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Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Surface receptors are bound to the cell membrane, receive signals from their surrounding environment, and transmit those signals into the cell, often via the generation of 2nd messengers (like cyclic adenosine monophosphate (cAMP)) or through phosphorylation cascades. There are multiple different subclasses of surface receptors, and 3 of the most important classes include ligand-gated ion channel receptors, enzyme-linked receptors (the most common of which are receptor tyrosine kinases (RTKs)), and G-protein-coupled receptors (GPCRs). Intracellular receptors, on the other hand, are located within the cytoplasm and often act as transcription factors, directly interacting with DNA and affecting gene expression.
Diagnostic modalities such as chest X-rays provide static images of the thoracic cavity, including the lungs and airways. While providing a wealth of anatomical information necessary for the diagnosis of pulmonary disease, chest X-rays do not give much information about the individual's respiratory function. Pulmonary function tests are a group of diagnostic procedures yielding useful, quantifiable information about the rate of the flow of air through the individual's airways, lung capacity, and the efficiency of gas exchange in relation to time. The most commonly utilized tests include spirometry (before and after bronchodilator use), lung volumes, and quantitation of diffusing capacity for carbon monoxide (CO). The tests can be influenced by the individual's effort/fatigue, disease state, or anatomical malformation.
Invasive mechanical ventilation (IMV) is an advanced airway modality used for individuals with immediate or impending respiratory failure and/or in preparation for surgery. The IMV technique involves positive pressure ventilation delivered to the lungs through an endotracheal tube via a ventilator. The ventilator can be set to specific modes that determine how the machine assists with breathing. The modes are tailored to the individual's needs. The mode refers to the characteristics of mechanical ventilation and mainly includes trigger (how inspiration begins), cycle (how inspiration ends), and limit (when inspiration should be aborted). The most commonly used mode is assist-control ventilation, which is usually followed by pressure-support ventilation for weaning. Careful consideration should be exercised while planning extubation, as IMV is associated with complications.
In the human brain, information is transmitted in the form of bioelectrical impulses and chemical signaling molecules. These molecules, called neurotransmitters, are protein molecules used by neurons to emit a specific signal. The signals are picked up in the plasma membrane of adjacent neurons by receptors, which are complexes of protein subunits responsible for sensing relevant stimuli and setting in motion the cellular machinery required to produce the desired response.
Cancer immunotherapy is a rapidly advancing medical therapy that takes advantage of the immune system to contain or eliminate cancer cells. Currently, immunotherapies have been incorporated into treatment regimens for different types of cancer. Various therapeutic approaches exist, including using cytokines, vaccines, oncolytic viruses, T-cell manipulation or cellular adoptive immunotherapy, or antibodies to immune checkpoint molecules. These therapies provide new options for advanced cancers, including melanoma, renal cell carcinoma, prostate adenocarcinoma, lung cancer, urothelial carcinoma, Hodgkin lymphoma, and refractory B-cell ALL. With the immune system involved, these agents carry serious and potentially fulminant adverse effects and toxicities.
An abnormal amount of lipid in blood is called dyslipidemia, which includes abnormal levels of cholesterol, triglycerides, and/or lipoproteins. Dyslipidemia may be primary (familial) or secondary (acquired). Both primary and secondary causes can lead to the development of premature cardiovascular (atherosclerosis) disease. Familial causes are classified according to the Fredrickson system, which looks into the pathology and the lipids that are elevated. Certain types do not increase the risk of premature atherosclerotic disease but still impact overall cardiac risk and chance of cardiovascular events in the future. Screening, early diagnosis, and strict control and management are the keys to prevention of cardiovascular events.
Proteins are 1 of the 3 primary macronutrients in the body and are synthesized from individual building blocks called amino acids (AAs). Amino acids are bound together by peptide bonds, which link the amino end of one AA to the carboxy end of the next AA, generating a protein's primary structure. The strand of AAs then undergoes additional folding, ultimately generating complex 3-dimensional structures. Proteins have a wide variety of functions, including catalytic, structural, regulatory, transport, storage, and immunologic functions. They are digested by proteases and peptidases secreted by the stomach and pancreas and absorbed as individual AAs in the small intestines through specialized transporters. There are countless medical conditions related to protein abnormalities, including abnormalities related to enzymes, receptors, membrane channels, hormones, accumulation of proteins, and autoimmune disorders.
Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion (also known as hypovolemia) refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Dehydration is primarily caused by decreased water intake and presents with increased thirst and can progress to altered mental status and low blood pressure if severe. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. The clinical presentation has relatively nonspecific symptoms but will ultimately cause low blood pressure if severe. The diagnosis of these imbalances is based on lab findings in addition to clinical symptoms and signs, which can be subtle and unreliable. Management requires differentiation between these 2 conditions. The treatment is to administer fluids with tonicity similar to those lost; isotonic fluids are used for volume depletion, and hypotonic fluids are used for dehydration.
The hepatobiliary system is composed of the liver, gallbladder, and bile ducts (within the liver and external to the liver). The liver produces bile, which is a fluid made of cholesterol, phospholipids, conjugated bilirubin, bile salts, electrolytes, and water. Bile, which assists in digestion and helps eliminate waste products, is stored in the gallbladder. The hepatobiliary system can be affected by infections, cysts, solid masses, ischemia, and mechanical flow obstruction, which mandate the presence of reliable imaging tests to determine the etiology. The methods that evaluate structural changes in the liver and biliary tract include ultrasonography, CT scan, and MRI (including magnetic resonance cholangiopancreatography). Additionally, cholescintigraphy, a functional imaging study, helps identify gallbladder pathology by tracking the biliary pathway.
Noninvasive ventilation (NIV) is an advanced respiratory support that does not require an artificial, invasive airway. This technique is commonly used during acute respiratory failure. The most common forms of NIV are noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula (HFNC). In acute respiratory failure, NIV is frequently used to prevent intubation for invasive mechanical ventilation, if there are no contraindications. There are more established contraindications to NIPPV in comparison to HFNC, but NIPPV has demonstrated clear mortality benefit in chronic obstructive pulmonary disease and congestive heart failure exacerbations.
Imaging of the internal female reproductive organs (including the uterus, ovaries, and fallopian tubes) is indicated to diagnose common gynecologic complaints, most commonly in cases of abnormal bleeding, pelvic pain, and to evaluate masses, congenital anomalies, and infertility. Ultrasound is almost always the 1st-line imaging modality of choice, whereas MRI is typically reserved for complicated or indeterminate cases as a follow-up. Computed tomography is almost never used for primary gynecologic assessments. Fallopian tubes are not visible on either ultrasound or MRI if they are normal. The best way to assess tubal patency is by using hysterosalpingography, a fluoroscopic exam in which a dye is injected into the uterine cavity, followed by the study of its flow through the fallopian tubes.
Female breasts, made of glandular, adipose, and connective tissue, are hormone-sensitive organs that undergo changes along with the menstrual cycle and during pregnancy. Breasts may be affected by various diseases, in which different imaging methods are important to arrive at the correct diagnosis and management. Mammography is used for breast cancer screening and diagnostic evaluation of various breast-related symptoms. Ultrasonography is rarely used for screening, but it is typically used for diagnostic workup and during procedures (e.g., breast biopsy). MRI of the breasts is used as a supplementary screening tool for those at high risk for developing breast cancer. Additionally, in individuals with breast implants, inconclusive mammographic and/or breast ultrasound findings, and diagnosed breast cancer needing evaluation pretreatment and posttreatment, MRI is an important breast radiologic tool.
An airway, breathing, and circulation (ABC) assessment is the mainstay for evaluating and treating critically ill individuals. The airway assessment helps identify individuals with potential obstruction of the airway, which may benefit from airway management techniques to ensure adequate ventilation and oxygenation. Measures to relieve and prevent soft-tissue obstruction in an unconscious individual can include special positioning maneuvers and airway adjuncts (such as oropharyngeal or nasopharyngeal airways). By relieving obstruction, assisted breathing with a bag-mask is more effective. Endotracheal intubation provides a more definitive way to ensure airway patency and protection.
Congestive heart failure (CHF) is a progressive syndrome characterized by the failure of the heart to maintain the metabolic demands of the body either due to systolic or diastolic dysfunction. Treatment of CHF is centered around lifestyle modifications (salt and fluid restriction, smoking cessation, and weight loss) and pharmacologic management. Acute worsening of heart failure is often secondary to other medical conditions and is managed with aggressive diuresis and interventions to support cardiac and ventilatory functions. Angina is defined as chest pain or discomfort resulting from myocardial ischemia. Therapy for angina is targeted at limiting platelet aggregation and adhesion (with antiplatelet agents), reducing O2 demand (with beta-blockers), reducing preload (with nitrates), and preventing the progression of atherosclerotic disease (using statin therapy), along with the management of comorbidities.
Non-Hodgkin lymphomas (NHLs) are a diverse group of hematologic malignancies that are clonal proliferative disorders of mature or progenitor B cells, T cells, or natural killer (NK) cells. Most pediatric cases are aggressive and high-grade (but curable); in adults, low-grade subtypes are more common. Like Hodgkin lymphoma, which has distinct pathologic features and treatments, NHL often presents with constitutional signs of fever, night sweats, and weight loss. Clinical features include lymphadenopathy and hepatosplenomegaly, but some individuals present with extranodal involvement and abnormal lab findings. B-cell NHLs include diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma, mantle cell lymphoma, and marginal zone lymphoma. T-cell NHLs include adult T-cell lymphoma and mycosis fungoides. Diagnosis is made by lymph node biopsy, bone marrow biopsy, or both. Management is with chemotherapy or targeted drugs. Radiation therapy is used in adults but not in children, and stem cell transplantation is used for patients with aggressive disease.
Immune responses against pathogens are divided into the innate and adaptive immune response systems. The adaptive immune response, also called the acquired immune system, consists of 2 main mechanisms: the humoral- and cellular-mediated immune responses. Humoral immunity is mediated through B cells (producing antibodies), whereas cell-mediated immunity involves T cells, and this response is activated when the innate immune system fails to control an infection. As the 2nd line of defense, the adaptive immune system is slower and responds over a longer period of time, but the effect generally leads to specific immunological memory. The 2 important characteristics of adaptive response are specificity (with antigen recognition) and memory (immune response mounted with reinfection).
Diagnostic procedures in gynecology are useful in identifying the presence of disease, determining the progression of disease, and monitoring the response of the organs to treatment. The major diagnostic procedures include speculum examinations, sonography (ultrasound), colposcopy, cervical biopsy and endocervical curettage, loop electrosurgical excision procedures, vulvar biopsy, endometrial biopsy, hysteroscopy, and hysterosalpingography (HSG). All of these procedures can be performed in the office setting or in a radiology suite, though in certain situations they are performed in the OR if more sedation or increased monitoring is required.
Purines and pyrimidines are heterocyclic aromatic compounds, which, along with sugar and phosphate groups, form the important components of nucleotides. Purines include adenine and guanine, while pyrimidines include thymine (in DNA), uracil (in RNA), and cytosine. Purine nucleotide synthesis follows a series of reactions using carbon donors, amino acids (e.g., glutamine, aspartate), and bicarbonate. The de novo pathway generates inosine monophosphate (IMP), which is the precursor of adenosine monophosphate (AMP) and guanosine monophosphate (GMP). Purine synthesis is regulated in the 1st 2 steps. Synthesis of pyrimidine nucleotides also follows different reactions, producing uridine monophosphate (UMP), which is converted to uridine triphosphate (UTP) and cytidine triphosphate (CTP). For thymine, a part of deoxyribonucleotides, ribonucleoside reductase is required to reduce the ribose moiety. Degradation of nucleotides result in xanthine then uric acid production in purines, while pyrimidines produce the amino acids, Î²-alanine, and Î²-aminobutyrate.
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin secretion (type 1 DM), insulin resistance (type 2 DM), or both (latent autoimmune diabetes in adults (LADA)). The goal of diabetes management is to prevent chronic serious and potentially disabling complications due to damage to various organs. Adequate long-term control of blood glucose is crucial in the prevention of complications. Macrovascular complications include heart disease, stroke, peripheral vascular disease, and CKD in various stages, including end-stage renal disease that requires dialysis. Microvascular disease can cause retinopathy, neuropathy, or symptomatic cardiac disease, which are not seen during stress testing or angiogram that are used to diagnose large vessel diseases.
The uterus, cervix, and fallopian tubes are part of the internal female reproductive system. The fallopian tubes receive an ovum after ovulation and help move it and/or a fertilized embryo toward the uterus via ciliated cells lining the tubes and peristaltic movements of its smooth muscle. The uterus has a thick wall made of smooth muscle (the myometrium) and an inner mucosal layer (the endometrium). The most inferior portion of the uterus is the cervix, which connects the uterine cavity to the vagina. Externally, the cervix is lined by stratified squamous cells; however, the cervical canal is lined by columnar epithelium. The transition point is known as the squamocolumnar junction, which is the site of most cervical cancers. These organs are supplied by the uterine and ovarian arteries and innervated by the autonomic nervous system.
A complex system of coordinated electrical circuitry within the heart governs cardiac muscle activity. The heart generates its own electrical impulses within its pacemaker cells. The signal then travels through specialized myocytes, which act as electrical wiring, distributing the signal throughout the heart. Once the signal â€œleavesâ€ the specialized conduction system, it passes to each myocyte through channels called gap junctions (which connect myocytes to each other) and causes them to contract. An electrical impulse is created by the opening and closing of ion channels, allowing the flow of charged particles across the myocardial cell membrane. The flow of charged particles changes the voltage across the membrane and opens up additional voltage-gated channels, allowing the signal to propagate throughout the heart.
The human eye is a sensory organ whose primary function is vision. They eye has a spheroidal shape and is structured in 3 layers: a supporting outer fibrous layer, a middle vascular layer, and an inner neural layer. The eye can also be subdivided into 3 compartments: the anterior, posterior, and vitreous chambers. Surrounding the eyeball itself are the extraocular muscles, the lacrimal apparatus, various nerves and vessels, and the bony structure of the orbit. Light travels through the compartments of the eye to focus on the retina, which is the location where photoreceptors convert the stimulus into a neural impulse that is carried by the optic nerve to the brain.
Spinal cord injuries are complex injuries that involve damage to the neural tissue within the spinal canal. Spinal cord injuries are commonly the result of trauma. Clinical presentation varies depending on the site of injury and on whether the injury is complete or incomplete. Diagnosis is by clinical exam and imaging. Management is 2-fold, with immediate supportive care and stabilization of spine followed by long-term rehabilitation with physiotherapy and treatment of complications. Spinal cord injuries are associated with multisystem complications.
Circulation is the movement of blood throughout the body through one continuous circuit of blood vessels. Different organs have unique functions and, therefore, have different requirements, circulatory patterns, and regulatory mechanisms. Several of the most vital organs (including the brain, heart, and kidneys) have autoregulatory properties, meaning that they are able to maintain a relatively constant blood flow despite fluctuations in mean arterial pressure (MAP). In other cases, locally produced factors (such as adenosine, CO2, or NO) can produce local vasoconstriction or vasodilation, regulating blood flow under specific physiologic conditions.
Mean arterial pressure (MAP) is the average systemic pressure in the arteries. The MAP is tightly regulated to help maintain appropriate perfusion and is primarily determined by the cardiac output (CO) and the systemic vascular resistance (SVR). Cardiac output is determined by the HR and the stroke volume (the volume of blood ejected by the heart each beat). The HR is primarily regulated by the effects of the ANS on the sinoatrial node in the heart, while stroke volume is determined by the preload, afterload, and inotropy (or contractile strength) of each heartbeat. The SVR is regulated by a number of factors, including the ANS, the arterial baroreflex, circulating catecholamines, the RAAS, and several other hormones.
The adult human body is made up of 60% water and is divided into extracellular and intracellular fluid compartments. Extracellular fluid is present outside the cells and makes up â…“ of the total body water. Intracellular fluid is present inside the cells and makes up â…” of the total body water. Intracellular and extracellular fluids are separated into compartments by semipermeable membranes, and the transport of fluid and ions is maintained by channels in the cell membrane. Each compartment contains different concentrations of ions and osmolar molecules. The relative charge and osmolarity are maintained rigorously by the transport of water and substances between compartments. Hypernatremia, hyponatremia, and edema are the clinical conditions arising from disturbances in the maintenance of osmolarity of the body fluid compartments.
Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular resistance is directly related to the diameter of the vessel (smaller vessels have higher resistance). Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors.
Cardiac surgery is the surgical management of cardiac abnormalities and of the great vessels of the thorax. In general terms, surgical intervention of the heart is performed to directly restore adequate pump function, correct inherent structural issues, and reestablish proper blood supply via the coronary circulation. Common interventions treat ischemic and valvular heart disease as well as disorders of the great vessels.
Acute disseminated encephalomyelitis (ADEM) is an immune-mediated, inflammatory, monophasic, demyelinating condition that affects the white matter of the brain and spinal cord. As a rapidly progressive post-infectious encephalomyelitis, ADEM is characterized by demyelination in the brain and spinal cord as a result of inflammation following infection or immunization.
Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. These medications are also used for conditions requiring physiologic glucocorticoid replacement. Despite their extensive use, glucocorticoids can produce many and varied adverse effects and should be used judiciously. Because of their immunosuppressive effect, these medications may predispose individuals to infection and should be avoided in those with uncontrolled infections. In addition, long-term therapy can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, so discontinuation of therapy should be done carefully to avoid adrenal insufficiency.
A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Pathologic tachyarrhythmias resulting in hemodynamic instability can be caused by intrinsic cardiac abnormalities, systemic diseases, or medication toxicity. Supraventricular arrhythmias are called narrow-complex tachycardias and originate in the sinoatrial (SA) node, atrial myocardium, or atrioventricular (AV) node. Ventricular arrhythmias originate below the AV node and are characterized by a wide QRS complex. Diagnosis is made by physical exam and ECG. Management is directed toward the type of tachyarrhythmia present and its underlying cause.
Both gastrulation and neurulation are critical events that occur during the 3rd week of embryonic development. Gastrulation is the process by which the bilaminar disc differentiates into a trilaminar disc, made up of the 3 primary germ layers: the ectoderm, mesoderm, and endoderm. During this process, a structure called the notochord is formed in the midline in the mesodermal layer; the notochord is critical in inducing neurulation. Neurulation is the process by which some of the ectoderm in the trilaminar embryo develops into the neural tube and neural crest cells, which will go on to form all of the neural tissue in the body. This process is completed by the end of the 3rd week.
Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver function tests assess the levels of various hepatic proteins and enzymes to determine the state of liver metabolic activity, homeostasis, bile metabolism, and protein synthesis capacity. The standard hepatic panel includes the levels of total protein, bilirubin, albumin, ALT, AST, AST/ALT ratio, and alkaline phosphatase (ALP).
Sickle cell disease (SCD) is a group of genetic disorders in which an abnormal Hb molecule (HbS) transforms RBCs into sickle-shaped cells, resulting in chronic anemia, vasoocclusive episodes, pain, and organ damage. Sickle cell trait, which is the heterozygous condition, is the only 1 of the group that is generally benign and rarely associated with serious SCD-like complications. Triggers such as stress and hypoxia can induce or worsen the sickling of RBCs. Individuals with SCD are susceptible to infection, infarction of various organs, and bone marrow aplasia; lung involvement in acute chest syndrome can be rapidly fatal. Sickle cells can usually be seen on the peripheral blood smear, but Hb electrophoresis is needed for diagnosis. The management of painful episodes consists of IV fluids and analgesics, and in severe episodes, exchange transfusions may be required. Survival is improved by vaccination against bacterial infections, prophylactic antibiotics, and aggressive treatment of infections.
The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. The prostate consists of multiple lobes and is made up of glandular and fibromuscular tissue. The glandular tissue has ducts that empty into the prostatic portion of the urethra, and the fibromuscular tissue encircles the urethra.
The mediastinum is the thoracic area between the 2 pleural cavities. The mediastinum contains vital structures of the circulatory, respiratory, digestive, and nervous systems including the heart and esophagus, and major thoracic vessels including the superior vena cava, inferior vena cava, pulmonary arteries, pulmonary veins, and aorta. The mediastinum extends from the upper thoracic aperture to the diaphragm and is bordered by the lungs.
The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. The brain stem contains many nerves, pathways, reflex centers, and nuclei and serves as a major relay station for sensory, motor, and autonomic information. All cranial nerves, except I and II, originate from the brain stem. The brain stem also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle.
Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall laterally by the suspensory ligament of the ovary and to the uterus medially by the utero-ovarian ligament. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes), which are expelled and then â€œcapturedâ€ by the uterine tubes. The primary blood supply to the ovary is provided by the ovarian artery, a direct branch of the abdominal aorta; the ovarian artery anastomoses with the ascending branch of the uterine artery, providing excellent collateral blood flow.
The heart is a 4-chambered muscular pump made primarily of cardiac muscle tissue. The heart is divided into 4 chambers: 2 upper chambers for receiving blood from the great vessels, known as the right and left atria, and 2 stronger lower chambers, known as the right and left ventricles, which pump blood throughout the body. Blood flows through the heart in 1 direction, moving from the right side of the heart, through the lungs, and then returning to the left side of the heart, where it is pumped out to the rest of the body. As blood moves through the heart, 4 important valves prevent backflow. The heart muscle itself is supplied by the coronary arteries. The heart also has its own conduction system, triggering its own rhythmic contractions.
Nephritic syndrome is a broad category of glomerular diseases characterized by glomerular hematuria, variable loss of renal function, and hypertension. These features are in contrast to those of nephrotic syndrome, which includes glomerular diseases characterized by severe proteinuria, although there is sometimes overlap of > 1 glomerular disease in the same individual. The clinical presentations of nephritic syndrome are highly varied, from asymptomatic with urinary abnormalities to life-threatening critical illness. Diagnosis is suggested by hematuria, mild-to-moderate proteinuria, and certain serologies (e.g., ANCA); kidney biopsy is necessary in most cases. Management varies as widely as the clinical presentations, from watchful waiting in mild cases to immunosuppression and plasmapheresis in aggressive disease.
Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. The primary etiologies of nephrotic syndrome are minimal change disease, membranous nephropathy, and focal segmental glomerulosclerosis. The clinical presentation of nephrotic syndrome includes proteinuria (> 3.5 g/day), hypoalbuminemia (< 3 g/dL), and peripheral edema. Other frequently observed clinical findings are hyperlipidemia and thrombotic disease. Diagnosis is suggested by the clinical findings, and kidney biopsy is necessary in most cases. Management varies with the etiology and usually involves glucocorticoids or other immunosuppressant drugs.
Renal tubular acidosis (RTA) is an imbalance in physiologic pH caused by the kidneyâ€™s inability to acidify urine to maintain blood pH at physiologic levels. Renal tubular acidos3s exist in multiple types, including distal RTA (type 1), proximal RTA (type 2), and hyperkalemic RTA (type 4). Depending on the type of RTA, various mechanisms cause dysfunction of renal acidâ€“base handling, resulting in a nonâ€“anion-gap metabolic acidosis. All RTAs present clinically with some degree of metabolic acidosis; however, distal RTA and proximal RTA also have hypokalemia, while hyperkalemic RTA does not. Diagnosis is primarily through the history and laboratory analysis, including measurement of serum and urine anion gaps. Treatment involves the correction of chronic metabolic acidosis with alkali to prevent its long-term catabolic effects on bone and muscles, as well as addressing any underlying causes leading to the RTA.
Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. The clinical presentation varies by etiology as well as classification of the polyneuropathy, but generally manifests as sensorimotor disturbances (pain, paresthesia, numbness, weakness, and loss of coordination and balance), which have a gradual onset and progressive course. Distal nerves are affected most commonly, but the disease process may progress proximally with time or progression of the underlying etiologic disease entity. Diagnosis is made clinically, but laboratory studies, electrodiagnostic testing, and/or nerve biopsy may be required in some cases. Management varies depending on the etiology.
Fever is defined as a higher-than-normal body temperature. In modern medicine, fever is defined as a temperature > 38Â°C (100.4Â°F). It is a common symptom in the pediatric population as an isolated symptom or accompanied by other findings that can help narrow the differential diagnosis. Fever is most commonly the bodyâ€™s response to infectious processes; however, it can also be seen in other pathologic processes. In neonates and very young infants, the clinical presentation lacks specificity, so more diagnostic aids are deployed to rule out severe bacterial infection (SBI) and to begin treatment according to age and clinical evolution.
Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens are primarily given to treat hypogonadism, gender dysphoria in transgender men, and low testosterone in older men (controversial). Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5Î±-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism.
Neuropathy is a nerve pathology presenting with sensory, motor, or autonomic impairment secondary to dysfunction of the affected nerve. The peripheral nerves (outside the brain and spinal cord), are derived from several plexuses, with the brachial and lumbosacral plexuses supplying the major innervation to the extremities. Mononeuropathy (affecting a single nerve) and plexopathy (affecting the plexus) can occur from trauma, compression, and systemic diseases. The clinical presentation varies according to location, type of nerves affected, and cause of the damage. Diagnosis requires a thorough physical examination, and diagnostic tests include laboratory tests, imaging and a confirmatory nerve conduction study, and electromyography. Management depends on the etiology but centers around physical therapy, supportive care, and treatment of underlying issues.
Brain aneurysms, also known as intracranial or cerebral aneurysms, are dilations of the arteries along points of weakness in the brain. The majority of the aneurysms are berry (saccular) in nature and located within the anterior circulation of the circle of Willis. Unruptured aneurysms are typically asymptomatic, unless the aneurysm compresses surrounding structures. The majority of these aneurysms are detected on rupture and presentation of a subarachnoid hemorrhage (SAH). Rarely, they may be detected incidentally on brain imaging done for other reasons. Diagnosing an aneurysm is done via imaging with CTA or MRA. Management depends on the size, risk of rupture, risk of intervention complications, and individual preference. This may include risk factor modifications, surveillance with serial imaging, and interventional measures (such as surgical clipping or endovascular coiling). Ruptured aneurysms carry a high morbidity and mortality rate.
Transplantation is a procedure that involves the removal of an organ or living tissue and placing it into a different part of the body or into a different person. Organ transplantations have become the therapeutic option of choice for many individuals with end-stage organ failure. Transplantation can offer the individual a definitive treatment for a given disease entity. Over the past 50 years, organ transplantation has become established worldwide, with ever-improving results, conferring an immense benefit to hundreds of thousands of individuals. Both solid organs and bone marrowâ€“derived hematopoietic cells can be successfully transplanted for a number of different indications. Tolerance of the transplanted organ by the immune system of the host is achieved through the use of immunosuppressive and immunomodulating strategies. The main complications of transplantation are organ rejection or graft failure; however, chronic immunosuppression also carries the risk of serious complications, including potentially life-threatening infections.
The urogenital system is derived from intermediate mesoderm. The intermediate mesoderm differentiates into nephrogenic cords (which will go on to form the urinary system) and an adjacent area known as the gonadal ridge (which will go on to form the gonads). The nephrogenic cords elongate in a caudal direction and sequentially develop 3 different structures: the pronephros (rudimentary and nonfunctional), the mesonephros (forms the primitive urinary system), and the metanephros (forms the permanent kidney). Concurrently, the genital system develops in close association with the urinary system. Genital development depends on chromosomal sex, which determines whether the primitive gonads differentiate into testes or ovaries. The gonads then secrete certain hormones, which direct further development of both the internal and external genital structures.
Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. There are multiple targets in the immune system, as well as varied mechanisms in inhibiting inappropriate immune activity. Biologic agents are medications derived from living organisms that target particular components of the immune system. The targets can be tumor necrosis factor (TNF), interleukins (ILs), or B- or T-cell activity. Calcineurin inhibitors halt the activity of calcineurin, a phosphatase involved in T-cell activation. Corticosteroids interfere with the cell cycle of inflammatory cells and modify the activity of other immune components. mTOR inhibitors are proliferation signal inhibitors, reducing immune-cell proliferation. Some immunosuppressants, such as cytotoxic agents, have antineoplastic activity; these are used in rheumatoid arthritis, as prophylaxis for transplant rejection, and for malignant diseases.
Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. Risk factors for infection include conditions or agents that may lead to an immunocompromised state, disruption of the normal flora, and/or disturbance of the mucosal barrier. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). The diagnosis is made by identifying Candida on KOH preparation, cultures, or tissue biopsy. Treatment depends on the extent and site of infection, and includes topical or systemic antifungal medications
The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. The skin is composed of surface epithelium, exocrine components, connective tissue, muscles, and nerves. The primary role of the skin is to serve as a protective barrier between the internal body and the external environment; it also protects the body from excessive fluid loss.
Before the developing blastocyst reaches the uterine wall, it needs to undergo several stages of differentiation. After a continuous process of cleavage and compaction, the morula gives rise to the trophoblast and embryoblast, which are the primary components of the blastocyst. Uterine fluid passes through the zona pellucida to form the blastocyst cavity. When the blastocyst reaches the endometrium, implantation begins by the trophoblast dividing into the cytotrophoblast and syncytiotrophoblast, with the syncytiotrophoblast primarily being responsible for invading the endometrium. The embryoblast divides into the epiblast and hypoblast, which are responsible for creating the amniotic cavity and yolk sac, respectively.
The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. The kidneys also play a major role in homeostatic processes, including electrolyte concentration, blood pressure, and acid–base regulation. Grossly, they consist of an outer cortex and inner medulla. Microscopic functional units known as nephrons filter the blood through a structure called the glomerulus, and this filtrate is then modified and concentrated as it moves through a complex tubular system. The renal arteries supply the kidneys via a central opening, known as the renal hilum, on its medial side; large renal veins empty directly into the vena cava.
Targeted therapy exerts antineoplastic activity against cancer cells by interfering with unique properties found in tumors or malignancies. The types of drugs can be small molecules, which are able to enter cells, or monoclonal antibodies, which have targets outside of or on the surface of cells. Among the areas in malignant cells that are blocked or inhibited by targeted therapy are signal pathways (as seen in protein kinase inhibitors), which lead to decreased proliferation and subsequent tumor cell apoptosis. Other means of reducing cancer cells is by eliminating the capacity for DNA repair (seen in poly(ADP-ribose) polymerase inhibitors), blocking the ligand-receptor binding (growth factor inhibitors), and increasing immune activity against the neoplasm (immunotherapies). These agents are used in multiple types of cancer and in combination with traditional chemotherapeutic agents.
Gout medications include antiinflammatory and urate-lowering medications. Colchicine is an antiinflammatory medication that can be used for acute gout flares. The urate-lowering drug classes include the xanthine oxidase inhibitors, uricosuric agents, and uricases. These medications are beneficial for the prevention of gout exacerbations and work through a variety of mechanisms. Xanthine oxidase inhibitors are the most commonly used urate-lowering therapy; these work by inhibiting the enzyme necessary for the conversion of purines to uric acid. Uricosuric agents reduce reabsorption of uric acid by the proximal tubule, thereby increasing renal excretion. Lastly, the urases are recombinant enzymes that metabolize uric acid to allantoin. In addition to gout, urate-lowering treatment can also be used for other indications, such as the prevention of tumor lysis syndrome and uric acid nephrolithiasis.
Brown-Séquard syndrome (BSS) is a rare neurologic injury that causes hemisection of the spinal cord, resulting in weakness and paralysis of one side of the body and sensory loss on the opposite side. This syndrome is most often due to trauma, but it may also occur with disc herniation, hematoma, or tumor. Clinical presentation is consistent with ipsilateral damage to the corticospinal tracts and posterior columns (weakness, loss of proprioception, and vibration sensation) below the level of the lesion, and contralateral anterior column symptoms owing to the unilateral involvement of the spinothalamic tract (loss of pain and temperature sensation). Diagnosis is confirmed with MRI. Management depends on the etiology and site of injury, and timely intervention is associated with a favorable prognosis and recovery.
Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). The changes are due to the deposition of Igs, complement factors, or both, in the glomerular mesangium and along the glomerular capillary walls. The pathogenic variants include immune complex/monoclonal Ig-mediated (e.g., from infections, autoimmune diseases) and complement-mediated MPGN. In rare cases, MPGN is not associated with Igs and the complement system, such as in the case of endothelial injury. With multiple etiologies, the presentation and clinical course vary. Presenting features can be asymptomatic proteinuria and hematuria, nephrotic syndrome, nephritic syndrome, or chronic renal failure. Definitive diagnosis requires renal biopsy, although additional laboratory and imaging tests may point to the associated disease. Treatment is based on the underlying cause. Steroids, immunosuppressants, and kidney transplantation are among the commonly used treatment modalities.
Cell junctions are proteinaceous structures that physically hold 2 surfaces (cell-to-cell or cell-to-matrix) together. Cell junctions aid in communication and structural support and act as a barrier. They are classified as occluding (tight junctions), anchoring (adherens, desmosomes and hemidesmosomes), and communicating (gap junctions). Type II hypersensitivity has been noticed with autoantibody production against the components of anchoring junctions, resulting in pathology such as pemphigus vulgaris and bullous pemphigoid.
The vitreous body is a transparent, gelatinous substance that is present in the space between the lens and the retina, providing structural stability and maintaining the shape of the eye. Some conditions that can affect the vitreous body are posterior vitreous detachment, vitreous hemorrhage, synchysis scintillans, asteroid hyalosis, and persistent fetal vasculature. The conditions can be asymptomatic or present with floaters in the field of vision, photopsia, and decreased visual acuity. Funduscopy and slit-lamp microscopy are commonly used in the diagnosis of these diseases. Treatment methods depend on the condition and severity, but may include observation, vision correction, and surgery.
Phosphodiesterase (PDE) inhibitors are a group of drugs that act by inhibiting PDE enzymes. Phosphodiesterase inhibitors have various mechanisms of action depending on the subtype of PDE targeted, but their main action is increasing the amount of intracellular cAMP or cGMP, which in turn results in physiologic effects such as reducing inflammation, promoting smooth muscle relaxation, and vasodilation. Phosphodiesterase inhibitors are indicated in a wide variety of medical conditions, such as intermittent claudication, decompensated heart failure, chronic obstructive pulmonary disease, psoriasis, atopic dermatitis, erectile dysfunction, pulmonary artery hypertension, and benign prostatic hypertrophy. Contraindications, adverse effects, and warnings are category- and drug-dependent.
The testicles, also known as the testes or the male gonads, are a pair of egg-shaped glands suspended within the scrotum. The testicles have multiple layers: an outer tunica vaginalis, an intermediate tunica albuginea, and an innermost tunica vasculosa. The testicles are composed of testicular lobules (contain interstitial tissue) and seminiferous tubules (produce spermatozoa). Blood supply to the testicles is primarily provided by the testicular artery. Venous drainage is through testicular veins.
The breasts are found on the anterior thoracic wall and consist of mammary glands surrounded by connective tissue. The mammary glands are modified apocrine sweat glands that produce milk, which serves as nutrition for infants. Breasts are rudimentary and usually nonfunctioning in men. The shape and size of the breasts change during a womanâ€™s life and menstrual cycles. Breasts are supplied by the axillary, internal thoracic, and intercostal arteries, and they are innervated by branches of the cervical plexus.
Class 3 antiarrhythmics are drugs that block cardiac tissue K channels. The medications in this class include amiodarone, dronedarone, sotalol, ibutilide, dofetilide, and bretylium. The main mechanism of action includes blocking the cardiac K channels to prolong repolarization. However, some medications in this class also exert effects on Na channels, calcium channels, and adrenergic receptors. Indications vary among the medications, but include both atrial and ventricular arrhythmias. Because these medications prolong the QT interval, torsades de pointes is a potential complication of therapy.
Non-insulinotropic diabetes medications are used to treat type 2 diabetes by methods other than increasing insulin secretion. This group of medications includes the biguanides, thiazolidinediones, alpha-glucosidase inhibitors, sodium–glucose transport protein 2 inhibitors, and amylin analogs. Mechanisms of action vary, but they can include increasing peripheral insulin sensitivity, reducing glucagon release, inhibiting gluconeogenesis, slowing glucose absorption, and increasing satiety. Metformin is the initial medication of choice; others may be used as an alternative monotherapy or as adjunctive therapy. Most of these medications are not associated with severe hypoglycemia, except for amylin analogs or when medications are used in conjunction with other hypoglycemic agents.
Antimetabolite chemotherapy agents belong to the cell-cycle–specific drugs, which act on a specific phase of the cell cycle. Cancer cells more rapidly divide (or cycle) than normal cells, making them an easy target for chemotherapy. The different cell-cycle phases include G1, S, G2, and M. Antimetabolites target the S phase, when DNA replication occurs, thus inhibiting DNA synthesis of tumor cells. In this group, the drugs include antifolates (which block folic acid activity, an essential component of DNA and RNA precursors), pyrimidine and purine analogs (which interfere with the process of DNA synthesis), and ribonucleotide reductase inhibitors (which reduce production of deoxyribonucleotides). Cell-cycle–specific chemotherapy drugs cannot differentiate healthy from cancerous cells, thus adverse effects are seen. Myelosuppression is a common finding during treatment.
Alkylating agents are cell cycle–independent antineoplastic drugs that work primarily by binding alkyl groups to various parts of DNA. The overall action produces cross-linking of DNA, leading to inhibition of DNA replication and DNA damage. The general effect is cancer (CA) cell death. The subgroups of drugs are nitrogen mustards, nitrosoureas, alkyl sulfonates, triazines, ethylenimines, and methylmelamines. Platinum coordination complexes belong to the group of alkylating agents by producing the same effect, but their mechanism is via formation of covalent metal adducts with DNA. Myelosuppression and toxicity to organ systems such as the kidneys, liver, and lungs are common adverse reactions.
Microtubule and topoisomerase inhibitors target cellular structures and processes to inhibit cancer cell proliferation. Microtubule inhibitors act on the cytoskeleton, while topoisomerase inhibitors act on an enzyme that is important in DNA replication and transcription. The microtubule system, along with microfilaments and intermediate filaments, form the cellular cytoskeleton. These components are essential for cell division, movement, and signaling. Taxanes and vinca alkaloids interfere with microtubule function, and thus in effect, inhibit mitosis. Topoisomerase assists DNA replication by creating double- and single-stranded breaks to relieve supercoils. Inhibiting the enzyme causes termination of DNA replication and DNA damage. There are multiple chemotherapeutic agents in each class that commonly produce myelosuppression as an adverse effect.
There are multiple different types of malignancies that can affect the vulva. The most common histologic type is squamous cell carcinoma (SCC), which accounts for approximately 75%–85% of all vulvar cancers. Other types include melanoma, basal cell carcinoma, sarcoma, malignancy of the Bartholin glands, and Paget disease of the vulva (an adenocarcinoma). Squamous cell carcinoma is typically associated with either high-risk HPV infection or lichen sclerosus. Vulvar cancer presents as vulvar lesions that can have a variety of appearances, which may include warty or nodular masses, scaly plaques, pigmented lesions, and ulcers; pruritus is also common. Diagnosis usually requires a biopsy, and management is primarily with surgical excision. Unfortunately, lymph node metastasis occurs early in the natural history of the disease and is associated with a poor prognosis.
Insulinotropic diabetes medications treat type 2 diabetes mellitus by increasing insulin secretion, which results in decreased glucose levels. The group of medications includes sulfonylureas, meglitinides, glucagon-like peptide-1 (GLP-1) receptor agonists, and DPP-4 inhibitors. The agents are usually used in combination with other therapies for diabetes management. Sulfonylureas and meglitinides are associated with weight gain, while GLP-1 agonists may provide the added benefit of weight loss. Other side effects vary between the drug classes. None of the medications should be used in the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
Primary vaginal cancers are malignant tumors that originate from cells in the vagina. Squamous cell carcinoma (SCC) is by far the most common (80%–85%); other histologic types include adenocarcinomas, sarcomas (including sarcoma botryoides, typically seen in children), and melanomas. Vaginal SCC is most commonly associated with HPV infections, while clear cell adenocarcinomas are associated with in utero exposure to diethylstilbestrol (DES). Individuals typically present with vaginal bleeding and/or an irregular mass or lesion on exam; other symptoms may include abnormal discharge, pain, and urinary or defecatory symptoms. A biopsy is required for diagnosis. Staging is based on tumor size, extent of local invasion, and metastasis. Management may be surgical for stage I disease, but surgery is typically avoided in advanced disease, which is instead managed with radiation and chemotherapy.
Endometrial hyperplasia (EH) is the abnormal growth of the uterine endometrium. This abnormal growth may be due to estrogen stimulation or genetic mutations leading to uncontrolled proliferation. Endometrial carcinoma (EC) is the most common gynecologic malignancy in the developed world, and it has several histologic types. Endometrioid carcinoma (known as type 1 EC) typically develops from atypical endometrial hyperplasia, is hormonally responsive, and carries a favorable prognosis. Other histologic types are known as type 2 EC; they tend to present at more advanced stages, are not hormonally responsive, and carry a far worse prognosis. Women with both EH and EC tend to present with postmenopausal or irregular menstrual bleeding. Diagnosis is histologic. Management most often involves progestin therapy, surgery, and adjuvant radiation therapy (for advanced disease).
Spontaneous abortion, also known as miscarriage, is the loss of a pregnancy before 20 weeks' gestation. However, the layperson use of the term “abortion” is often intended to refer to induced termination of a pregnancy, whereas “miscarriage” is preferred for spontaneous loss. Most spontaneous abortions occur within the 1st 12 weeks of gestation and can be caused by several factors such as infection, trauma, and genetic and autoimmune causes. There are different types of spontaneous abortions, including threatened, inevitable, incomplete, complete, and missed abortions. Spontaneous abortions are diagnosed based on history, physical examination, and ultrasound findings. Management options include expectant, medical, or surgical therapy.
Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. There are several forms of insulin, and they differ in their time of onset, peak effect, and duration. Insulin can be classified as fast acting, short acting, intermediate acting, or long acting. A combination of classes can be used to maintain glucose control throughout the day. Common adverse effects include hypoglycemia, weight gain after initiation of an insulin regimen, and local injection site changes.
Ovarian cancer is a malignant tumor arising from the ovarian tissue and is classified according to the type of tissue from which it originates. The 3 major types of ovarian cancer are epithelial ovarian carcinomas (EOCs), ovarian germ cell tumors (OGCTs), and sex cord-stromal tumors (SCSTs). By far, EOCs are the most common, tend to present in postmenopausal women with advanced disease, and carry a poor prognosis. On the other hand, OGCTs and SCSTs frequently affect younger women, tend to present earlier, and carry a better prognosis. Affected individuals are frequently asymptomatic, although they may present with nonspecific symptoms such as fatigue, increasing abdominal girth, GI symptoms, and pelvic pain. Moreover, if the tumor secretes hormones, abnormal bleeding may be a presenting symptom. Diagnosis is suspected based on imaging studies and confirmed with histologic examination. Treatment is primarily surgical and often with adjuvant chemotherapy.
There are several benign vulvar diseases, but some of the most common are Bartholin cyst and abscess, lichen sclerosus, and lichen simplex chronicus. Bartholin cysts are formed due to an obstruction in the excretory duct that causes retention of their secretions (lubricating mucus). Bartholin cysts present as nontender fluctuant masses at the 4 and/or 8 o'clock positions in the labia. If a Bartholin cyst becomes infected, it can develop into an extremely painful abscess. Lichen sclerosus is a chronic dermatologic condition that causes progressive thinning and fibrosis of the vulvar, perineal, and perianal skin, and presents classically with itching and white plaques. Lichen simplex chronicus is a thickening of the vulvar skin due to chronic itching or rubbing, which often occurs in the setting of atopic or contact dermatitis.
Antitumor antibiotics, also known as antineoplastic antibiotics, are the product of soil microbes, Streptomyces bacteria. The commonly used types of antitumor antibiotics—bleomycin, dactinomycin, and anthracyclines—have a wide spectrum of activity against hematologic malignancies and solid tumors. Bleomycin differs from the rest of the drugs owing to its cell cycle–specific action during the G2 phase. Mechanisms of actions of these drugs include free radical damage to DNA, topoisomerase II inhibition, binding of DNA via intercalation, and alteration of cell membrane fluidity and transport of ions. Important adverse effects include cardiotoxicity (acute and chronic) and myelosuppression.
Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo is a clinical diagnosis, differentiated through history and physical examination findings, most notably nystagmus. Further testing may be required in malignant cases. Management depends on the etiology but certain maneuvers such as the Epley maneuver can be diagnostic and therapeutic.
The brachial plexus is a network of nerves that originate from the lower cervical and upper thoracic nerve roots. The causes of brachial plexopathies include traumatic injuries, birth-related injuries, iatrogenic procedures, neoplastic processes, and previous treatment with radiation. Patients present with sensory and motor deficits related to the site of the lesion and the nerves involved. Diagnosis is made based on clinical findings, imaging, and electrodiagnostic studies. Treatment is related to the underlying cause and may be medical or surgical.
The term “persistent vegetative state,” also called unresponsive wakefulness, describes the condition of individuals with severe anoxic brain injury who have progressed to a state of wakefulness without any meaningful response to their environment. A persistent vegetative state is distinguished from a coma in that individuals in a persistent vegetative state have intermittent sleep–wake cycles. The individual's eyes may be open and there may be some yawning, grunting, or other vocalizations. In both cases, the individual is alive, but the brain does not function fully. Persistent vegetative state is most commonly associated with anoxic brain injury due to cardiac arrest, trauma, metabolic causes, or infections. Diagnosis is made by fulfilling specific diagnostic criteria. Treatment is controversial and ethically challenging. Recovery of consciousness from a posttraumatic persistent vegetative state is unlikely after 12 months, while recovery from a nontraumatic persistent vegetative state after 3 months is exceedingly rare.
Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia may be inherited, acquired, or idiopathic. The diagnosis is made clinically, and genetic testing is recommended in individuals with a family history of dystonia. Management is with botulinum toxin or other drugs that target the various neurotransmitters involved in the pathogenesis of dystonia.
Posterior cord syndrome (PCS) is an incomplete spinal cord syndrome affecting the dorsal columns, the corticospinal tracts (CSTs), and descending autonomic tracts to the bladder. Posterior cord syndrome is rare but has a diverse range of etiologies, including demyelinating disorders, degenerative spinal conditions, neoplastic causes, vascular abnormalities, and hereditary neurodegenerative disorders. Clinical symptoms include gait ataxia, paresthesias with loss of position and vibration sense, and urinary incontinence. The diagnosis is made clinically and with neuroimaging. Management addresses treatment of the underlying cause.
Neurofibromatosis type 2 is a neurocutaneous disorder that can arise from mutations in the NF2 gene located in chromosome 22 and may be inherited in an autosomal dominant fashion or occur from de novo mutations. The main clinical features are bilateral vestibular schwannomas, intracranial/spinal meningioma, and intramedullary and extramedullary spinal tumors. Other features can include eye lesions such as cataracts, skin lesions, and peripheral neuropathy. Diagnosis is made clinically from history and examination and confirmed with MRI, molecular testing, and histopathology. Tumor surveillance and follow-up with screening of at-risk family members is recommended. Management includes surgical interventions, radiation therapy, and/or monoclonal antibody therapy with bevacizumab.
Neurofibromatosis type 1 (NF1), also known as phakomatosis, is a neurocutaneous disorder that is most commonly of autosomal dominant inheritance due to mutations in the NF1 gene. Neurofibromatosis type 1 presents a range of clinical manifestations with the most prominent features being various pigmented skin lesions called café au lait macules (CALMs), benign nerve-sheath tumors called neurofibromas, freckling of the inguinal and axillary regions, and iris hamartomas, referred to as Lisch nodules. At least half of the individuals with NF1 have learning disabilities. Neurofibromatosis type 1 may also cause osteodysplasia and malignant transformation of tumors. The diagnosis is based on the typical clinical presentation and can be confirmed with genetic testing. Management depends on the clinical presentation and may vary from surgical removal to chemotherapy/radiotherapy for tumors, occupational therapy and PT for motor impairments, treatment with growth hormone, and bracing in the case of bone abnormalities.
Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a clinical disorder that presents with symptoms due to increased intracranial pressure (ICP; ≥ 20 mm Hg) or CSF pressure (> 250 mm H2O), with no structural changes or other attributable causes. The condition is most commonly observed in obese women and after intake of certain drugs, such as growth hormones, tetracycline antibiotics, and high dosages of vitamin A. Classic manifestations include headache, vision loss or visual-field defects, and papilledema. Diagnosis is made by clinical exam, imaging, and lumbar puncture. Management is aimed at decreasing ICP and includes medication, therapeutic CSF removal, and shunting.
Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope is not a distinct disease entity; rather, it is a symptom of another pathologic process, whether it be transient or a more established disease process. Syncope may be accompanied by other symptoms, such as light-headedness, sweating, palpitations, nausea, feeling warm or cold, and visual blurring. Workup includes a detailed history and physical examination, electrocardiography, echocardiography, provocative testing (tilt-table test), or imaging of the suspected culprit vasculature. In many cases, a definite etiology is not found. Management is based on the underlying cause and can include physical countermaneuvers, stopping offending drugs, volume resuscitation, blood transfusion, and/or cardiac or vascular interventions.
Antiviral agents against human herpesviruses (HHVs) include acyclovir, cidofovir, and foscarnet. Human herpesviruses are DNA viruses in the Herpesviridae family. Herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and HHV-8 belong to the Herpesviridae family. Antivirals against the group generally act via inhibition of DNA polymerase. Acyclovir (the prototypical nucleoside analog) requires viral kinase for phosphorylation to become a triphosphate, which is incorporated in viral DNA. Cidofovir requires phosphorylation by host cellular kinase, which allows cidofovir to have activity against mutated viruses and become deficient in viral kinase. Foscarnet (a pyrophosphate analog) does not require phosphorylation. Nephrotoxicity is a shared adverse effect in the agents. Acyclovir can also cause obstructive crystalline nephropathy and foscarnet carries a risk of electrolyte abnormalities and seizures. The nephrotoxic effect of cidofovir can be reduced with IV saline and probenecid.
Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased ICP can lead to brain herniation and death if not treated promptly. Clinical presentation includes headache, drowsiness or altered level of consciousness, and papilledema. Diagnosis is suspected based on the clinical presentation and confirmed with urgent brain imaging. Immediate management includes measures to decrease ICP, medications including diuretics, and surgery.
Antivirals for hepatitis B include the nucleoside/nucleotide analogs, also known as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). Because of their similar chemical structure to nucleosides and nucleotides, NRTIs are able to integrate into viral DNA during the replication process. This process inhibits the function of viral RNA-dependent DNA polymerase, resulting in chain termination. All of these medications are administered orally and are excreted by the kidneys. Indications include chronic hepatitis B infection, and some (such as lamivudine) are also used for HIV. Adverse effects include GI symptoms, evidence of mitochondrial toxicity (such as lactic acidosis), and rebound infection upon discontinuation.
Intracerebral hemorrhage (ICH) refers to a spontaneous or traumatic bleed into the brain parenchyma and is the 2nd-most common cause of cerebrovascular accidents (CVAs), commonly known as stroke, after ischemic CVAs. Trauma, hypertension, vasculopathy, vascular malformations, tumors, coagulopathy, and hemorrhagic conversion of ischemic stroke may all be causative factors. Clinical presentation may vary depending on the size and location of the hemorrhage and may range from headache, neurologic signs and symptoms, and altered level of consciousness to coma. Treatment includes stabilization, stopping or reversing of anticoagulation, blood pressure control, monitoring in a neurologic ICU, and possible neurosurgical intervention. Intracerebral hemorrhage is associated with significant morbidity and mortality.
Intravenous fluids (IVFs) are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Crystalloids and colloids have different general compositions, which affect distributions through the body’s fluid compartments and guide clinical use. Crystalloid solutions are typically used for patients who are hypovolemic, dehydrated, or have ongoing fluid losses. Colloidal solutions may be used in cases of low oncotic pressure. Providers should choose fluid types based on the clinical scenario and best available evidence. All recipients of IVFs should be closely monitored to determine the goal and status of the fluid therapy.
Epidural hemorrhage (EDH) is an event characterized by bleeding into the epidural space between the dural layers of the meninges and the skull. The primary mechanism triggering bleeding is trauma (i.e., closed head injury), which causes arterial injury, most commonly middle meningeal artery injury. Epidural hemorrhage presents acutely, usually immediately (seconds to hours) following head trauma, with an altered level of consciousness that may span from a momentary loss of consciousness to coma. Diagnosis is based on clinical suspicion following head trauma and is confirmed with neuroimaging (i.e., noncontrast head CT). Management includes stabilization, stopping (possibly, the reversal) of all anticoagulants, monitoring in a neurologic ICU, and neurosurgical intervention.
To undergo fertilization, the sperm enters the uterus, travels towards the ampulla of the fallopian tube, and encounters the oocyte. The zona pellucida (the outer layer of the oocyte) deteriorates along with the zygote, which travels towards the uterus and eventually forms a blastocyst, allowing for implantation to occur. An ectopic pregnancy occurs if the zygote does not reach the uterus before the zona pellucida degrades.
Subdural hemorrhage (SDH) is bleeding into the space between the dural and arachnoid meningeal layers surrounding the brain. The most common mechanism triggering the bleeding event is trauma (e.g., closed head injury) causing a tearing injury to the extracerebral “bridging” veins, but rupture of small arteries within this space or intracranial hypotension may also be causative. Acute SDH presents, immediately following head trauma, with an altered level of consciousness that may span from a momentary loss of consciousness to coma, which makes it a potentially life-threatening condition. Chronic SDH may also occur, presenting with a more gradual neurologic deterioration. Diagnosis is based on clinical suspicion following head trauma and confirmed with neuroimaging (e.g., noncontrast head CT). Management includes stabilization, stopping (possibly reversing) all anticoagulants, monitoring in a neurologic ICU, and neurosurgical intervention.
Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. The basic pathophysiology of all etiologies of hyponatremia is an abnormal increase in total body water (TBW), which dilutes the total body sodium (TBNa+) concentration. The clinical presentation varies greatly, from asymptomatic to subtle cognitive deficits, seizures, and death. Management is guided by etiology, acuity, and duration of symptoms, usually involving oral fluid restriction or administration of IV fluids that contain Na. Sodium must be replaced slowly, as overly rapid correction of hyponatremia can lead to irreversible neurologic complications and death, known as the osmotic demyelination syndrome (ODS).
Rapidly progressive glomerulonephritis (RPGN) is a syndrome of severe glomerular disease with progressive loss of kidney function within weeks to months. Rapidly progressive glomerulonephritis is associated with nephrotic syndrome and is a manifestation of different diseases. Histologically, crescents (the proliferation of epithelial cells and the infiltration of monocytes/macrophages in the Bowman space) are found in the glomeruli and arise from immunologic injury. The major mechanisms of immunologic injury are classified into anti-glomerular basement membrane (anti-GBM) disease, pauci-immune crescentic glomerulonephritis, and immune complex-mediated injury. Rapidly progressive glomerulonephritis can manifest with hematuria, proteinuria, and varying degrees of edema and hypertension. Diagnosis is by presentation, laboratory tests, imaging, and renal biopsy. Prompt treatment is essential because RPGN can develop into end-stage renal disease within a short period of time. Modalities include corticosteroids, cyclophosphamide or other immunosuppressants, and plasmapheresis (depending on the underlying disease).
Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. The most classic symptom is a sudden-onset (thunderclap) headache along with neck stiffness, vomiting, a decreased level of consciousness, and seizure. As with any stroke, focal neurologic deficits are commonly present, and rapid neurologic deterioration may ensue without prompt diagnosis and intervention. An SAH should be suspected in any person presenting with thunderclap headache and neurologic symptoms, and the diagnosis can be confirmed with neuroimaging or lumbar puncture (LP). Treatment consists of reversal of anticoagulation, control of blood pressure, and neurosurgical intervention to contain the bleed and/or relieve elevated intracranial pressure (ICP). Even with prompt neurosurgical intervention, SAH carries a high mortality rate.
Gametogenesis is the development of gametes from primordial germ cells. This process differs between the sexes. In males, spermatogenesis produces spermatozoa. In females, oogenesis results in an ovum. The process starts with the migration of primordial germ cells from the yolk sac to the gonadal ridge. Oogenesis starts during the embryonic and fetal periods, whereas spermatogenesis starts at puberty. However, the phases of gametogenesis are similar, with germ cells progressing through mitosis, meiosis I, meiosis II, and maturation. This process results in gametes that are haploid, with 23 chromosomes.
Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. The major cellular response involves neutrophils and macrophages to phagocytose and lyse the injurious organism or repair necrosed tissue after injury. Inflammation can be pathologic if it is prolonged or when normal processes create an excessive response (such as with atherosclerosis). There are multiple mediators of inflammation that overlap with innate immunity when they respond to injurious stimuli. Inflammation can become chronic, resulting in the formation of granulomas, tissue damage, and the loss of organ function.
Paraneoplastic syndromes are a heterogeneous group of disorders caused by an abnormal immune response to a neoplasm. The substances produced are not due to the direct effect of the tumor, such as metastasis, mass effect, or invasion. Antibodies, hormones, cytokines, and other substances are generated and affect multiple organ systems. About 10% of cases of cancer are affected by paraneoplastic syndromes. The common cancers that present with paraneoplastic syndromes include cancer of the lung, breast, ovaries, kidney, liver, and stomach and lymphomas.
Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Most individuals are asymptomatic until complications arise, including esophageal varices, portal hypertensive gastropathy, ascites, and hypersplenism. The diagnosis is clinical, but it can be supported by ultrasound findings (and hepatic venous pressure gradient measurement in unclear cases). Management requires treating the underlying etiology and managing the complications. This can include nonselective beta blockers to prevent bleeding from varices, diuretics and sodium restriction for ascites, and transjugular intrahepatic portosystemic shunt for refractory complications.
Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C infection is diagnosed by testing for the presence of HCV antibodies and HCV RNA. Management is supportive but includes direct antiviral agents (DAAs) if infection does not resolve spontaneously.
Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. The virus can cause potentially life-threatening liver disease. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Management of acute hepatitis is typically supportive. Administration of antivirals or liver transplantation may be necessary in fulminant and chronic cases.
The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal incontinence can occur if this function is disturbed. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Peristaltic waves within the rectal muscularis, involuntary relaxation of the internal anal sphincter (controlled by the ANS), and voluntary relaxation of the external anal sphincter (controlled by the cerebral cortex) are essential for defecation to occur. The rich plexus of veins surrounding the anal canal can develop into hemorrhoids if dilated.
Heart sounds are brief, transient sounds produced by valve opening and closure and by movement of blood in the heart. They are divided into systolic and diastolic sounds. In most cases, only the first (S1) and second (S2) heart sounds are heard. These are high-frequency sounds and arise from aortic and pulmonary valve closure (S1), as well as mitral and tricuspid valve closure (S2). The third heart sound (S3) may be physiologic (e.g., athletes) or pathologic (e.g., congestive heart failure), and is related to abnormally rapid deceleration of early diastolic left ventricular inflow. The fourth heart sound (S4) is associated with contraction of the atria into partially-filled and non-compliant (stiff) ventricles. S4 is a pathologic sign in the young, but may be found in older individuals due to an age-related decrease in ventricular compliance. Additional sounds include murmurs (physiologic and pathologic), clicks, and snaps. These sounds are heard in individuals with structural abnormalities of the heart such as septal defects, valvular stenosis, and mitral regurgitation.
Pseudomembranous colitis is a bacterial disease of the colon caused by Clostridium difficile. Pseudomembranous colitis is characterized by mucosal inflammation and is acquired due to antimicrobial use and the consequent disruption of the normal colonic microbiota. C. difficile infections account for the most commonly diagnosed hospital-acquired diarrheal illnesses. C. difficile infections can range from asymptomatic colonization to diarrhea and progress to fulminant colitis with systemic sepsis in severe cases. The diagnosis is established based on stool studies. Management of pseudomembranous colitis is mainly using antibiotics. Fecal transplant is considered in a few cases, whereas surgical intervention is required in severe cases.
Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi.
Pituitary adenomas are tumors that develop within the anterior lobe of the pituitary gland. They are classified by size (either micro- or macroadenomas) and by their ability to secrete hormones. Non-functioning or non-secretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolved, leading to hyperpituitarism.
Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Extravascular destruction of RBCs is affected by macrophages of the liver, spleen, bone marrow, and lymph nodes. Other than the site of destruction, HA can also be classified according to the type of RBC defect that causes their destruction. If the RBC has an intrinsic and usually inherited defect such as a hemoglobinopathy, a membrane defect, or a metabolic defect, its destruction is called intracorpuscular hemolysis. If the RBC is normal but is damaged by an external force such as an antibody, mechanical trauma, or a pathogen, then its destruction is classified as extracorpuscular hemolysis, which is almost always an acquired disorder.
Gestational trophoblastic diseases are a spectrum of placental disorders resulting from abnormal placental trophoblastic growth. These disorders range from benign molar pregnancies (complete and partial moles) to neoplastic conditions such as invasive moles and choriocarcinoma. Diagnosis is confirmed by elevated serum beta human chorionic gonadotropin (hCG) and ultrasound findings, which are dependent on the disorder. Treatment is primarily through dilation and curettage and/or methotrexate.
Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Treatment is directed at the removal of excess fluid and decreasing oxygen demand of the heart. Prognosis depends on the underlying cause, compliance with medical therapy, and presence of comorbidities.
Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular fibrillation is most commonly caused by underlying ischemic heart disease. It leads to death within minutes unless advanced cardiac life support measures are started immediately.
Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease of unknown etiology. It leads to a necrotizing granulomatous inflammation of small and medium-sized blood vessels of the nose, sinuses, throat, lungs, and kidneys. Early stages of GPA often present with localized manifestations such as infections of the upper respiratory tract, skin lesions, and/or constitutional symptoms. Later stages can present with renal failure and severe respiratory disease. Early diagnosis and treatment of granulomatosis with polyangiitis (which involves the administration of corticosteroids and immunosuppressive agents such as methotrexate) may lead to a full remission but without treatment, the condition has a high mortality rate.
Malignant mesothelioma (usually referred to as simply "mesothelioma") is the malignant growth of mesothelial cells, most commonly affecting the pleura. The majority of cases are associated with occupational exposure to asbestos that occurred > 20 years before clinical onset, which includes dyspnea, chest pain, coughing, fatigue, and weight loss. Chest computed tomography (CT) scan shows multifocal pleural thickening and pleural effusion. Pleural biopsy is required for confirmation and to rule out metastases from lung or breast cancer. Treatment is rarely effective, with an average survival time of < 1 year.
Long QT syndrome (LQTS) is a disorder of ventricular myocardial repolarization that produces QT prolongation on electrocardiogram (ECG). Long QT syndrome is associated with an increased risk of developing life-threatening cardiac arrhythmias, specifically torsades de pointes. The condition may be congenital or acquired. Congenital LQTS is attributed to genetic mutations affecting cardiac ion channels. Acquired LQTS usually results from drug therapy and/or electrolyte abnormalities. Patients can be asymptomatic or present with palpitations, syncope, seizures, and even sudden cardiac death. Diagnosis is established with ECG along with medical and family history, laboratory workup, and other cardiac tests. Treatment is determined by etiology. Acquired LQTS requires removal of the offending drug and correction of electrolyte abnormalities. Congenital LQTS management involves avoidance of triggers of arrhythmia, intake of beta-blockers, and placement of an implantable cardioverter-defibrillator (ICD).
Crohn's disease is a chronic, recurrent condition that causes patchy transmural inflammation that can involve any part of the gastrointestinal tract. It is a type of inflammatory bowel disease (IBD) along with ulcerative colitis (UC). The terminal ileum and proximal colon are usually affected. Crohn's disease typically presents with intermittent, non-bloody diarrhea and crampy abdominal pain. Extraintestinal manifestations may include calcium oxalate renal stones, gallstones, erythema nodosum, and arthritis. Diagnosis is established via endoscopy with biopsy that shows transmural inflammation, characteristic “cobblestone” mucosa, and noncaseating granulomas. Management is with corticosteroids, azathioprine, antibiotics, and anti-TNF agents (infliximab and adalimumab). Complications include malabsorption, malnutrition, intestinal obstruction or fistula, and an increased risk of colon cancer.
5-alpha-reductase deficiency is an autosomal recessive intersex or “disorder of sex development” (DSD) condition caused by a loss-of-function mutation in a gene on chromosome 2. The affected subjects have a 46,XY karyotype, bilateral testes, and normal testosterone production but have impaired virilization during embryogenesis due to defective conversion of testosterone to dihydrotestosterone (DHT), which is a significantly more potent androgen. This leads to male pseudohermaphroditism or ambiguous genitalia in males. Also known as pseudovaginal perineoscrotal hypospadias, these patients present with a clitoris-like phallus, cryptorchidism, bifid scrotum, and a rudimentary prostate. No Müllerian structures are present.
Seborrheic dermatitis is a common chronic, relapsing skin disorder that presents as erythematous plaques with greasy, yellow scales in susceptible areas (scalp, face, and trunk). Seborrheic dermatitis has a biphasic incidence, occurring in two peaks: first in infants, then in adolescence and early adulthood. Although the exact etiology is unknown, pathologic mechanisms have been observed involving the sebaceous glands and Malassezia on the skin. Topical medications are used for acute exacerbation or maintenance treatment. These options aim to inhibit skin colonization (antifungal agents), reduce inflammation (steroids, calcineurin inhibitors), and loosen scales and crusts (keratolytic agents). Severe and refractory seborrheic dermatitis may warrant the use of systemic antifungal medications.
Type II hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by immunoglobulin G (IgG) and IgM antibodies directed against antigens on cells or extracellular materials. The reaction leads to cytotoxic processes involving antibodies and the complement system. Interference with the normal cellular operation generating either stimulatory or inhibitory dysfunction is another mechanism that occurs. The inciting antigen can be intrinsic or part of the host cell. Extrinsic antigens such as blood products or medications can provoke a similar reaction. For diagnosis, laboratory tests and invasive procedures are utilized, depending on the system affected. Management of resulting disease ranges from supportive care to antibiotics, immunosuppressive medications, and surgery.
By refraction, the light that enters the eye is focused onto a particular point of the retina. The main refractive components of the eye are the cornea and the lens. When the corneal curvature, the refractive power of the lens, does not match the size of the eye, ametropia or a refractive error occurs. The types of refractive errors include myopia (nearsightedness), hyperopia (farsightedness), and astigmatism (which can occur in both myopia and hyperopia). The use of a proper refractive device helps correct the visual impairment. Laser in situ keratomileusis (LASIK) is the most common corrective surgical procedure.
Type III hypersensitivity, also known as immune complex-mediated hypersensitivity, occurs when antibodies and antigens form immune complexes (ICs) in circulation and deposit in susceptible tissues. The complement system triggers the immune response, leading to leukocyte recruitment and tissue injury. There is no single clinical syndrome for this hypersensitivity. Symptoms reflect the impairment of multiple organ systems based on sites of IC deposition. Diagnostic workup depends largely on the history and includes laboratory tests, imaging, and biopsy of the affected organ. Treatment consists of removal or avoidance of offending agents and, in severe conditions, glucocorticoids or immunosuppressive therapy.
Neonatal polycythemia is a hematocrit (HCT) that is 2 standard deviations above the average values for gestation and postnatal age. Neonatal polycythemia can develop from increased fetal hematopoiesis (secondary to placental insufficiency, maternal endocrinopathies, genetic disorders, etc.) or passive erythrocyte transfusion (placental-, feto-, or maternal-fetal transfusion). Patients may be asymptomatic or present with plethora, cardiorespiratory distress, and other symptoms. Continuous monitoring of vital signs and metabolic derangements is important. Treatment includes partial exchange transfusion.
Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. A cytokine-mediated process is activated by T-helper cells while cytotoxic T cells directly release cytotoxins to infected or dysfunctional cells, causing cell lysis. Clinical manifestations depend on the system involved, so diagnostic tests rely on history and findings. Treatment includes controlling the effects of the immune response with glucocorticoids and immunosuppressive therapy while managing the associated disease complications.
Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. The typical presentation of blepharitis includes eyelid edema with itching and redness, crusts and scales around the eyelashes, and gritty sensation. Diagnosis is clinical, with a slit-lamp examination providing details of the structural changes affecting the eye. The mainstay of treatment is eyelid hygiene using warm compresses and eyelid scrubs. In moderate-to-severe cases, topical and oral antibiotics are utilized. Topical glucocorticoids also help improve symptoms but require an ophthalmology evaluation due to potential adverse effects.
Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Diagnosis is clinical. Management requires treating the underlying disease, managing complications, and, if required, liver transplantation.
Thoracic aortic aneurysm (TAA) is the abnormal dilation of a segment of the thoracic aorta, usually the ascending aorta. Most TAAs are due to degenerative aortic disorders, commonly in patients > 65 years of age. Genetic TAAs account for 20% of cases and are frequently found in younger patients. Most TAAs are asymptomatic (incidentally found in imaging) but could present with symptoms from its effects on surrounding structures. Aortic rupture is a life-threatening emergency. Among diagnostic imaging studies, computed tomography (CT) angiography is the most widely utilized. In asymptomatic cases, aortic expansion is monitored. Operative repair is recommended for symptomatic TAAs and increasing aortic diameter (criteria varies with location and underlying condition).
Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Uveitis can be caused by an infection or systemic disease, but in some cases the cause is idiopathic. Patients present with blurred vision, eye redness, and pain (frequently in anterior uveitis) or reduced vision and floaters (in intermediate and posterior uveitis). Diagnosis is by dilated funduscopy and slit-lamp examination. Treatment for anterior uveitis is topical steroids, while uveitis in deeper locations requires an injection. Uveitis from infections and systemic disorders requires etiology-directed therapy.
Benign breast epithelial lesions are grouped histologically as nonproliferative, proliferative without atypia, and atypical hyperplasia. The classifications are based on subsequent cancer risk in either breast. The nonproliferative type carries no risk, while fibroadenoma, the most common benign tumor, is a proliferative breast lesion (i.e., has a slight increase in malignancy risk). Because atypical hyperplasia shares some features with breast carcinoma in situ, future cancer potential is increased. Management ranges from frequent monitoring to surgical excision, depending on certain factors, including the inherent risk of the pathologic diagnosis. Other breast disorders without malignant possibility are associated with underlying infection or systemic disease, so treatment differs. Benign breast diseases are common but present diversely. It is important to distinguish between them to determine the likelihood of cancer and the best course of treatment.
Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Frequently, there is peripheral vision loss that eventually leads to loss of central vision. The 2 main types of glaucoma are open-angle and angle-closure. Overproduction or reduced excretion of the aqueous humor leads to open-angle glaucoma. Onset of symptoms is gradual. Angle-closure glaucoma results from blockage in the angle (of the iris and cornea), preventing drainage of the aqueous fluid. Diagnosis involves IOP determination (tonometry) and angle visualization with slit lamp (gonioscopy). Treatment includes topical medications that reduce IOP, and eye surgery.
A cataract is a condition defined as painless clouding or opacity of the lens. It causes visual impairment, as the lens provides part of the eye’s refractive power. Although all age groups can be affected, the age-related or senile type of cataract is the most common. Aside from age, there are multiple risk factors, including systemic diseases, medications, or trauma. Patients present with blurry vision, glare sensitivity, and color vision change. Ophthalmologic inspection often shows darkening of or opacities in the red reflex. Slit-lamp examination will show the extent and location of the cataract. The treatment is surgery, which is indicated when loss of vision function interferes with daily function.
Age-related macular degeneration (AMD) is visual impairment due to changes in the macula, the area responsible for high-acuity vision. It is marked by central vision loss with peripheral vision relatively spared. Risk factors include advanced age, smoking, family history, and cardiovascular disease. The 2 types of AMD are exudative (wet) or non-exudative (dry). The difference between these 2 types is the presence of choroidal neovascularization in wet AMD, which manifests as visual distortion or loss. The more frequently occurring dry AMD is usually asymptomatic but in a minority of cases leads to vision loss. There is no treatment for early dry AMD but Age-Related Eye Disease Study 2 (AREDS 2) supplements are recommended for advanced disease. Inhibitors of vascular endothelial growth factor are used for wet AMD.
Dacryocystitis is inflammation of the lacrimal sac due to nasolacrimal duct obstruction and the subsequent stasis of tears. The condition can have an acute or chronic onset. Acute dacryocystitis presents within hours or days with redness, swelling, tenderness, and excessive tearing. The chronic type has a gradual course, often manifesting with epiphora. By etiology, dacryocystitis can be congenital or acquired. Nasolacrimal duct obstruction affects 6% of newborns. Acquired cases occur due to trauma, systemic diseases, or tumors. Diagnosis is made clinically. In some cases, laboratory tests and imaging help determine abnormal structures and underlying disease. Initial treatment includes conservative measures such as Crigler massage, warm compresses, and antibiotics, if indicated. If these fail, surgical options are tried.
A cataract is a condition defined as painless clouding or opacity of the lens. Cataracts cause visual impairment, as the lens provides part of the eye’s refractive power. The condition is one of the most common causes of pediatric blindness. Cataracts can be present from birth (congenital) or can develop after infancy (acquired). Genetic mutations, systemic diseases, trauma, and medications can lead to cataract development. Children present with an abnormal red reflex, leukocoria, or decreased visual acuity. An ophthalmologic examination reveals the morphology and location of the cataract. Management depends on age of presentation and visual defects. When opacity is of a certain size or is causing visual impairment, strabismus, and nystagmus, cataract surgery is recommended.
Anal fistulas are abnormal communications between the anorectal lumen and another body structure, often to the skin. Anal fistulas often occur due to extension of anal abscesses but are also associated with specific diseases such as Crohn's disease. Symptoms include pain or irritation around the anus; abnormal discharge or purulent drainage; and swelling, redness, or fever if an abscess is present. Management is primarily surgical, with fistulotomy, but can include antibiotics if infection is present. Treatment is surgical. Complications after surgery include recurrence and incontinence.
Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. In the setting of an intact retina, detachment occurs when the vitreous pulls on the retina (traction) or when an underlying condition leads to increased leakage of fluid (exudative). Symptoms of photopsia, floaters, and visual defects can present over hours or gradually over weeks. Retinal detachment with visual loss is an emergency. Once macular detachment occurs, visual prognosis is poor. Symptomatic rhegmatogenous retinal detachment with intact central acuity warrants urgent surgery. For non-rhegmatogenous retinal detachments, treatment is directed toward the primary process.
In order to cope with their environment, cells undergo structural and functional changes. These cellular adaptations are reversible responses that allow cells to survive and continue to adequately function. Adaptive processes consist of increased cellular size and function (hypertrophy), increase in cell number (hyperplasia), decrease in cell size and metabolic activity (atrophy), or a change in the phenotype of the cells (metaplasia). If the stress or stimulus is removed, the cell can return to its original state. However, when the limits of the adaptive responses are exceeded, cellular function is adversely affected, leading to cellular injury.
A retinal vessel occlusion is a blockage in a major artery or vein of the retina. Depending on the location, the occlusion can be classified as central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), central retinal vein occlusion (CRVO), or branch retinal vein occlusion (BRVO). Typically, a retinal vessel occlusion is a thromboembolic event. Risk factors include hypertension, diabetes mellitus, and cardiac valvular disease. Central retinal artery occlusion is characterized by sudden, unilateral, painless loss of vision and/or transient vision loss (amaurosis fugax). Treatment options are limited in all cases and usually ineffective. When the macula is involved, prognosis is especially poor, leading to permanent vision loss.
A chalazion is one of the most common inflammatory lesions of the eyelid. It is caused by obstruction of the Meibomian or Zeis glands, leading to granulomatous inflammation and resulting in a firm, rubbery, slow-growing nodule that is typically non-tender. Diagnosis is based on history and physical exam findings. Most chalazia will resolve with conservative management.
The cubital fossa is the region anterior to the elbow joint. The cubital fossa is seen as the triangular depression between the brachioradialis and pronator teres muscles. Except for the ulnar nerve, which runs posteriorly, most of the major neurovascular structures transition from the arm to the forearm via the cubital fossa. The 4 important structures of the cubital fossa (from lateral to medial) are the radial nerve, tendon of the biceps brachii muscle, brachial artery, and median nerve.
A hordeolum is an acute infection affecting the meibomian, Zeiss, or Moll glands of the eyelid. Stasis of the gland secretions predisposes to bacterial infection. Staphylococcus aureus is the most common pathogen. The condition presents as a painful, localized, erythematous mass in the anterior (external hordeolum) or posterior (internal hordeolum) lamella of the eyelid. A hordeolum usually resolves spontaneously and can be managed with warm compresses, massage, and lid hygiene. In certain cases of significant swelling, topical antibiotics with steroids may be needed. If there is no resolution, incision, and drainage are performed.
The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle (follicular and luteal) and 3 phases of the endometrial cycle (desquamation or menses, proliferative, and secretory). The menstrual cycle is regulated by the hypothalamic-pituitary-ovarian axis via follicle-stimulating hormone (FSH) and luteinizing hormone (LH). A woman’s 1st menstrual cycle is referred to as menarche, and cycles continue until menopause.
Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Patients often present with progressive abdominal distention and weight gain. Abdominal exam may reveal shifting dullness and a positive fluid wave. Diagnosis is established with an ultrasound, and etiologies can be distinguished by ascitic fluid analysis from paracentesis. Treatment involves dietary sodium restriction, diuretics, and treatment of the underlying cause.
Psoriasis is a common T-cell–mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Plaques are well-circumscribed and salmon-colored, with silvery scales. Plaques commonly appear on the scalp and extensor surfaces of the extremities. Diagnosis is clinical. Treatment options are determined by the percentage of body surface area (BSA) affected and include topical corticosteroids, retinoids, calcineurin inhibitors, disease-modifying antirheumatic drugs (DMARDs), biologics, and phototherapy.
Hypertension has many adverse effects on the eye, of which retinopathy is the most common presentation. Hypertensive retinopathy consists of retinal vascular changes that develop as a direct effect of elevated blood pressure. In acute increases of blood pressure, autoregulation results in retinal arteriolar narrowing. In chronic hypertension, structural changes consistent with arteriosclerosis affect the retinal vasculature. Endothelial wall damage ensues and various signs appear including hemorrhages, cotton-wool spots, and exudates. In severe cases of uncontrolled hypertension, papilledema is seen. Management is focused on controlling hypertension. Patients with severe hypertensive retinopathy have an increased risk for coronary artery disease and stroke; therefore, detection and treatment of underlying hypertension are important.
Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic keratosis is usually diagnosed clinically but suspicious features warrant a biopsy to rule out invasive squamous cell carcinoma. The majority of AK lesions remain non-malignant, but it is difficult to distinguish those that will resolve from those that will become cancerous. Actinic keratosis has multiple types of treatment, including cryotherapy, shave removal, excision, topical medications, and photodynamic therapy. Lesions with features that are suggestive of cancer warrant removal and pathologic evaluation.
The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. The afferent pathway for visual function starts from the retina and moves through the optic tracts and lateral geniculate nuclei, terminating in the visual cortex. Light stimulus is conducted by the parasympathetic system to the midbrain, while psychosensory reaction is processed by the sympathetic system. Efferent pathways produce the appropriate response: miosis and mydriasis from the parasympathetic and sympathetic innervations, respectively. Pupillary disorders result from defects in areas of the visual afferent and efferent pathways. Presentation varies with pupillary size along with response to light and medication.
Tricuspid regurgitation (TR) is a valvular defect that allows backflow of blood from the right ventricle to the right atrium during systole. Tricuspid regurgitation can develop through a number of cardiac conditions that cause dilation of the right ventricle and tricuspid annulus. A blowing holosystolic murmur is best heard at the left lower sternal border. Mild TR may be asymptomatic or present with systemic venous congestion due to increased right atrial and venous pressures. Echocardiography can establish the diagnosis. Treatment focuses on heart failure management, and surgery is reserved for severe disease.
Nonalcoholic fatty liver disease is a spectrum of liver pathology that arises due to accumulation of triglycerides in hepatocytes. Risk factors include diabetes mellitus, insulin resistance, obesity, and hypertension, among others. Nonalcoholic fatty liver disease ranges from fatty liver or hepatic steatosis but can lead to nonalcoholic steatohepatitis (NASH), which features fatty deposits and inflammation. Progressive liver injury and fibrosis irreversibly develop into cirrhosis and, possibly, primary liver cancer. Patients are usually asymptomatic but may present with hepatomegaly and right upper quadrant discomfort. Although liver biopsy is the diagnostic gold standard, the diagnosis can also be established by clinical history, imaging, and laboratory tests. The mainstay of management is lifestyle modifications (weight loss and exercise) with control of associated comorbidities.
Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH), which only accounts for a small fraction of all cases of hypertension. Renovascular hypertension can be associated with abdominal bruits, renal insufficiency, or progressive renal atrophy. Diagnosis is by clinical presentation followed by imaging studies, including duplex ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), and sometimes catheter-based angiography. Revascularization is usually reserved for cases in which medical therapy has failed.
Valvular disorders can arise from the pulmonary valve, located between the right ventricle (RV) and the pulmonary artery (PA). Valvular disorders are diagnosed by echocardiography. Pulmonic regurgitation (PR) is the backflow of blood through the valve. Prior cardiac surgeries can lead to PR. Graham-Steell murmur, a high-pitched decrescendo murmur at the left sternal border, is a hallmark finding. Pulmonic regurgitation results in RV volume overload, from which RV failure eventually develops. Severe PR is also treated with surgical valve replacement.
Takotsubo cardiomyopathy (also known as stress cardiomyopathy, or “broken heart syndrome”) is a type of non-ischemic cardiomyopathy in which there is transient regional systolic dysfunction of the left ventricle. Patients present with symptoms of acute coronary syndrome, including chest pressure and shortness of breath. Electrocardiogram (ECG) may show ST-segment elevations. Coronary angiography can help in differentiating this condition from myocardial infarction. Echocardiogram can confirm the diagnosis by demonstrating characteristic apical wall motion abnormalities. Management includes the removal of inciting stressors and beta blockers.
Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. These pathogens have many virulence factors, including fimbriae, lipooligosaccharide envelope proteins, a polysaccharide capsule (unique to N. meningitidis), and IgA protease. Gonococcal infections are sexually or perinatally transmitted and include gonorrhea, pelvic inflammatory disease, septic arthritis, and neonatal conjunctivitis. Meningococcal infections are transmitted via respiratory and oral secretions. They most commonly cause meningococcemia with petechial hemorrhages and meningitis.
Budd-Chiari syndrome is a condition resulting from the interruption of the normal outflow of blood from the liver. The primary type arises from a venous process (affecting the hepatic veins or inferior vena cava) such as thrombosis, but can also be from a lesion compressing or invading the veins (secondary type). The patient typically presents with hepatomegaly, ascites, and abdominal discomfort. Onset is often subacute or chronic. Diagnosis is confirmed by Doppler ultrasound. Treatment involves addressing the underlying condition that caused the venous occlusion. Further management involves prevention of further clotting (anticoagulation), restoration of blood flow, and decompressing the liver. Liver transplantation is considered if initial treatment fails and/or the patient has decompensated liver cirrhosis.
The cell undergoes a variety of changes in response to injury, which may or may not lead to cell death. Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. The principal targets of cell injury are the cell membranes, mitochondria, protein synthesis machinery, and DNA. Multiple cellular abnormalities resulting from the damage result in cell death. The 2 main types of cell death are necrosis and apoptosis. Necrosis is an uncontrolled cell death characterized by inflammatory changes in a pathologic condition. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects.
Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Medical management is limited to using ursodeoxycholic acid, a disease-modifying agent. Definitive treatment is liver transplantation, which is performed in late stages (cirrhosis).
Acute cholangitis is a life-threatening condition characterized by fever, jaundice, and abdominal pain which develops as a result of stasis and infection of the biliary tract. Septic shock, liver abscess, and multi-organ dysfunction are potential serious complications. The diagnosis is confirmed with ultrasound showing dilation of the common bile duct (CBD) or gallstones, elevated liver function tests, and leukocytosis. Treatment includes hemodynamic stabilization, broad-spectrum antibiotics, urgent biliary drainage, and cholecystectomy to prevent recurrence.
Decompression sickness (DCS), known informally as “the bends,” is a condition caused by compression and decompression of gases contained in the body during descent and rapid ascent while diving. Clinical presentation of DCS may be nonspecific and variable, with a time of onset that can vary from immediately to 12 hours after surfacing. Diagnosis is made clinically. Management is early supportive therapy and hyperbaric recompression treatment carried out in a specialized facility.
Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. The 1st-degree block is due to delayed conduction through the AV node. The 2nd-degree block is characterized by progressive conduction delay or intermittently blocked conduction. The 3rd-degree block involves total interruption in conduction between the atria and ventricles, causing complete AV dissociation. Patients may be asymptomatic or may present with syncope, chest pain, dyspnea, and bradycardia depending on the severity of the block. Electrocardiography (ECG) establishes the diagnosis, and treatment is based on the type of block and hemodynamic stability of the patient.
Acute pancreatitis is an inflammatory disease of the pancreas due to autodigestion. Common etiologies include gallstones and excessive alcohol use. Patients typically present with epigastric pain radiating to the back. Diagnosis requires 2 of 3 criteria, including: characteristic abdominal pain, serum amylase and lipase 3 times the upper limit of normal, or characteristic radiology findings. Ranson’s criteria is commonly used to assess the severity. Management includes aggressive intravenous (IV) hydration, analgesia, nutritional support, and treatment of the underlying cause.
Congenital renal abnormalities arise from embryologic/genetic defects and cause a variety of isolated or syndromic renal disorders, including renal agenesis, dysgenesis, and ectopia. Congenital renal abnormalities are generally identified prenatally and represent approximately ⅓ of all prenatal anomalies. Because of the fetal kidney’s role in the production of amniotic fluid, oligohydramnios detected on prenatal ultrasounds often prompts the workup that identifies congenital renal anomalies. Unilateral renal involvement in the presence of a functioning contralateral kidney may only be an incidental finding later in life. In many cases, treatment is supportive.
Gastroenteritis is inflammation of the stomach and intestines, commonly caused by infections from bacteria, viruses, or parasites. Transmission may be foodborne, fecal-oral, or through animal contact. Common clinical features include abdominal pain, diarrhea, vomiting, fever, and dehydration. Diagnostic testing with stool analysis or culture is not always required, but can help determine the etiology in certain circumstances. The majority of cases of gastroenteritis are self-limited; therefore, the only required treatment is supportive therapy (fluids). However, antibiotics are indicated in severe cases.
The most common benign liver tumors include hepatic hemangiomas, focal nodular hyperplasia, and hepatic adenomas. These tumors are mostly asymptomatic and/or found incidentally on abdominal imaging. While these tumors are benign, large lesions can cause symptoms such as upper abdominal pain, or produce complications such as bleeding. Malignant potential is a concern for hepatic adenoma, depending on risk factors. The diagnosis is based on imaging studies, with characteristic findings defining the tumor. Biopsy generally is reserved for equivocal cases. Management is observation for most small, asymptomatic, and non-growing tumors. However, high-risk factors, symptoms, increasing tumor size, and complications dictate the need for surgical intervention.
Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Diagnosis is made by genetic testing of the index patient and their family members. Management consists of an earlier screening of individuals with defective MMR genes, as well as total colectomy if colorectal neoplasia is discovered. Prophylactic hysterectomy plus salpingo-oophorectomy are recommended for women beyond reproductive age.
Small bowel obstruction (SBO) is an interruption of the flow of the intraluminal contents through the small intestine, and is classified as mechanical (due to physical blockage) or functional (due to disruption of normal motility). The most common cause of SBO in the Western countries is post-surgical adhesions. Small bowel obstruction typically presents with nausea, vomiting, abdominal pain, distention, constipation, and/or obstipation. The diagnosis is established via imaging. Up to 80% of all cases will resolve with supportive management (bowel rest, intravenous (IV) hydration, and nasogastric decompression). However, surgery is required for persistent or complicated cases.
Klinefelter syndrome is a chromosomal aneuploidy characterized by the presence of 1 or more extra X chromosomes in a male karyotype, most commonly leading to karyotype 47,XXY. Klinefelter syndrome is associated with decreased levels of testosterone and is the most common cause of congenital hypogonadism. Symptoms are often not noticed until adolescence or adulthood. Individuals with this condition tend to present as tall, phenotypic men with small testes, decreased body hair, gynecomastia, and infertility. Treatment consists of life-long testosterone replacement therapy.
Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming “stuck.” Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Common causes of functional dysphagia include achalasia, scleroderma, and diffuse esophageal spasm (DES). Mechanical causes of dysphagia include esophageal rings, webs, strictures, and cancer. Oropharyngeal dysphagia may be due to structural abnormalities or abnormal neuromuscular function and coordination. The diagnostic workup depends on the patient’s presenting symptoms, but may include manometry, barium esophagram, or direct visualization with nasopharyngeal laryngoscopy or endoscopy. Treatment varies depending on the underlying cause.
Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. The replication cycle differs between viruses that infect bacteria (bacteriophages) and viruses that infect eukaryotic cells. Bacteriophages have either a lytic or lysogenic replication cycle, while eukaryotic viruses have a defined 6-step replication process.
A Meckel’s diverticulum is a persistent remnant of the omphalomesenteric (vitelline) duct. A Meckel’s diverticulum is usually located in the antimesenteric border of the ileum. The mucosal lining of the diverticulum may contain heterotopic mucosa (most commonly gastric). Though frequently asymptomatic, a Meckel’s diverticulum can cause ulceration and present with lower gastrointestinal (GI) bleeding. Other complications include diverticulitis or small bowel obstruction (SBO). A Meckel’s scan can detect the diverticulum in hemodynamically stable patients. For those with active bleeding, arteriography is the diagnostic option. The treatment for a symptomatic Meckel’s diverticulum is surgery.
The primary visual pathway consists of a relay system, beginning at the retina, whose ganglion cell axons form the optic nerve. The optic nerve fibers from each eye hemidecussate in the optic chiasm (OC), with nasal fibers joining the temporal fibers of the contralateral nerve. The nasal fibers continue as the optic tract on each side, synapsing with the lateral geniculate nucleus (LGN) of the thalamus. Signals are then transmitted to the primary visual cortex of the occipital lobe. The right and left visual fields are processed by opposite hemispheres. Lesions along the pathway result in vision loss or visual field deficits. Based on the type of presentation, the location of the lesion in the pathway can be ascertained.
Colorectal cancer (CRC) is the 2nd-leading cause of cancer-related death in the United States. Almost all cases of CRC are adenocarcinoma and the majority of lesions come from the malignant transformation of an adenomatous polyp. As most CRCs are asymptomatic, screening is essential in detecting early disease. Screening is recommended to start at the age of 45 years, utilizing various screening tools available with colonoscopy, flexible sigmoidoscopy, and fecal tests among them. For high-risk individuals, earlier and more frequent screening is recommended. Other stool-based strategies and visualization tests are also available for CRC screening.
The human immunodeficiency virus (HIV) is a species of Lentivirus, a genus of the family Retroviridae, which causes HIV infections and acquired immunodeficiency syndrome (AIDS). The virus has high genetic variability and is divided into 2 major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). The human immunodeficiency virus is a single-stranded, positive-sense, enveloped RNA virus, which targets and destroys WBCs, leading to frequent opportunistic infections and, eventually, death.
Aromatase deficiency is a very rare genetic condition with autosomal recessive inheritance. Aromatase deficiency is characterized by congenital estrogen deprivation with increased levels of testosterone due to decreased levels of the aromatase enzyme. Affected females present with abnormal development of the external genitalia, virilization, primary amenorrhea, and tall stature. Males usually develop symptoms later in life, including hyperinsulinemia and lipid metabolism disorders. Individuals affected by aromatase deficiency have an increased risk of developing osteoporosis. Treatment involves hormone replacement therapy.
Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations of APLS. Patients with APLS are at risk for both arterial and venous thrombosis, and after a thrombotic event, patients are managed with long-term anticoagulation therapy.
Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The pathophysiology of this disease is unclear, but a significant proportion of affected patients are positive for HLA-B27. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Ocular, mucocutaneous, GI, GU, and cardiac manifestations may also occur. The diagnosis is clinical, and efforts should be made to rule out alternative diagnoses. Management focuses on controlling symptoms, typically with nonsteroidal anti-inflammatory drugs. An active infection should also be treated, particularly Chlamydia trachomatis.
The plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a fleabite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Bubonic plague results in swollen and tender lymph nodes called buboes in the inguinal area. Pneumonic and septicemic plague can arise as the primary presentation, but also can result from hematogenous spread from the bubonic disease. Diagnosis includes clinical history and findings, culture, polymerase chain reaction (PCR), and serology. The mortality rate is high, so prompt diagnosis and treatment with antibiotics are necessary.
Toxic shock syndrome (TSS) is an acute, multi-systemic disease caused by the toxin-producing bacteria, Staphylococcus aureus and Streptococcus pyogenes. Staphylococcal TSS is more common and associated with tampons and nasal packing. Streptococcal TSS is commonly due to invasive group A streptococcal (GAS) infections, such as bacteremia and necrotizing fasciitis, and has a higher mortality rate. Patients present with fever, tachycardia, hypotension, an erythematous rash, and evidence of multi-system organ dysfunction. The diagnosis is based on clinical, laboratory, and culture data. Management involves intravenous fluid (IVF) resuscitation, antibiotics, vasopressor support, and identification and management of the potential infectious source.
Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Diagnosis is established by a combination of physical findings and serology. There is no curative treatment. Management options are limited and include immunosuppressive medications as well as specific organ- or symptom-directed drugs. The overall 5-year survival of patients with scleroderma is about 80%.
Erythema infectiosum is a rash illness caused by parvovirus B19. Erythema infectiosum is also known as fifth disease, being 5th in the historical list of rash-causing childhood infectious diseases: measles (1st), scarlet fever (2nd), rubella (3rd), Dukes' disease (4th), and roseola (6th). Transmission is through respiratory secretions. Diagnosis is generally clinical, suspected in patients presenting with an erythematous malar rash with circumoral pallor (“slapped cheek”). A rash over the trunk and extremities occurs afterward. The illness is self-limited and has no specific therapy. Complications can occur, however, due to the viral tropism for erythrocyte precursors. Patients with hemoglobinopathies can experience aplastic crisis, while the immunocompromised may have chronic infection producing pure red cell aplasia.
Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Currently, reverse transcriptase, protease, integrase, and entry inhibitors are used in combined ART (cART) regimens. Combination therapy (3-drug regimen) is used to prevent drug resistance and cross-resistance, which develop through genetic mutations.
A gastrinoma is a tumor that secretes excessive levels of the hormone gastrin and is responsible for Zollinger-Ellison syndrome (ZES). Gastrinomas are frequently associated with multiple endocrine neoplasia 1 (MEN 1) and can arise from the pancreas, stomach, duodenum, jejunum, and/or even from the lymph nodes. Gastrinoma tumors are often malignant and frequently metastasize to the liver, lymph nodes, and bone. Zollinger-Ellison syndrome (ZES) is characterized by high gastrin levels, elevated gastric acid production, peptic ulcers, gastroesophageal reflux, and diarrhea. Diagnosis is based on fasting serum gastrin levels. Management consists of surgical resection of the gastrinoma and/or symptomatic management for unresectable disease.
Hashimoto's thyroiditis, or chronic lymphocytic thyroiditis, is the most common cause of hypothyroidism in iodine-sufficient regions. The condition is an autoimmune disorder leading to destruction of the thyroid cells and thyroid failure. The gradual clinical course of Hashimoto's thyroiditis starts with a transient hyperthyroid state (“hashitoxicosis”) followed by subclinical hypothyroidism. Eventually, progression to overt hypothyroidism occurs, which is permanent. Patients may have a painless goiter, but in later stages, the gland is atrophic. Diagnosis is by laboratory tests showing elevated thyroid-stimulating hormone (TSH), low free thyroxine (T4), and positive antibodies against thyroglobulin and thyroid peroxidase. In uncertain cases, imaging is required. Radioactive iodine uptake will show low iodine uptake and ultrasound demonstrates diffuse symmetric enlargement. Biopsy shows lymphocytic infiltration with Hurthle cells. Treatment is lifelong thyroid hormone replacement.
Graves' disease is an autoimmune disorder characterized by the presence of circulating antibodies against the thyroid-stimulating hormone (TSH) receptors, thereby causing the thyroid gland to hyperfunction. Clinical features include hyperthyroidism (of which Graves' disease is the most common cause), orbitopathy, goiter, and dermopathy/pretibial myxedema. Manifestations reflect the muti-systemic effects of a hyperactive thyroid, including heat intolerance, sweating, palpitations, tremors, pretibial myxedema, and exophthalmos. Diagnosis is by thyroid laboratory tests showing a low TSH, elevated thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) and thyrotropin-receptor antibodies (particularly the thyroid-stimulating immunoglobulins subtype). If initial tests are nondiagnostic, radioactive iodine uptake (increased uptake) and thyroid ultrasound (diffuse thyroid enlargement) provide diagnostic information. Treatment options include thionamides, radioiodine ablation, and surgery.
Chlamydial infections are a group of infectious diseases caused by bacteria belonging to the Chlamydiaceae family. The 3 species that can infect humans are Chlamydia trachomatis, C. pneumoniae, and C. psittaci. The most common infection is an STI caused by C. trachomatis, which affects the genitourinary tract. Chlamydia is the most common sexually transmitted bacterial infection in the United States. Other species of Chlamydia mainly cause respiratory infections. Diagnosis is based on nucleic acid amplification tests. Management is with antibiotics. Untreated chlamydial infections may have serious consequences, including sterility, ectopic pregnancies, spontaneous abortions, and chronic pelvic inflammatory disease.
Polymyositis (PM) is an autoimmune inflammatory myopathy caused by T cell-mediated muscle injury. The etiology of PM is unclear, but there are several genetic and environmental associations. Polymyositis is most common in middle-aged women and rarely affects children. Patients present with progressive and symmetric proximal muscle weakness and constitutional symptoms. Complications may arise from respiratory, cardiac, or GI involvement. Diagnosis is based on clinical presentation and laboratory studies and confirmed using muscle biopsy. Management is with systemic glucocorticoids, immunosuppressants, and physiotherapy. All patients should undergo cancer screening because there is a strong association with malignancy.
A VIPoma is a rare neuroendocrine tumor arising primarily in the pancreas that releases large amounts of vasoactive intestinal polypeptide (VIP). This process leads to chronic watery diarrhea with concomitant hypokalemia and dehydration, as well as wheezing and flushing (known as Verner-Morrison or WDHA (chronic Watery Diarrhea, Hypokalemia, Achlorhydria) syndrome). Most tumors arise sporadically, but some are associated with MEN 1. Diagnosis is established by measuring serum VIP levels. Treatment consists of medical management of symptoms and complete surgical removal of the tumor when possible.
IgA nephropathy (Berger's disease) is a renal disease characterized by IgA deposition in the mesangium. It is the most common cause of primary glomerulonephritis in most developed countries. Patients frequently present in the second and third decades of life and, historically, with a preceding upper respiratory or GI infection. Common presenting features are gross hematuria or asymptomatic, microscopic hematuria on urinalysis. The course is often benign, with the definitive diagnostic procedure, renal biopsy, performed only in cases of severe, progressive renal disease. Treatment depends on the severity of proteinuria, renal function, and pathologic changes. ACE inhibitors or angiotensin-receptor blockers (ARBs) are given to reduce disease progression. Persistent proteinuria and increasing creatinine are indications for immunosuppressive therapy that includes glucocorticoids and, possibly, cytotoxic agents.
Subclavian steal syndrome occurs when narrowing/occlusion of the subclavian artery proximal to the origin of the vertebral artery causes a reversal of blood flow in the ipsilateral vertebral artery to continue perfusing the ipsilateral arm. The most common cause is atherosclerosis. Symptoms are rare, but when they occur are usually triggered by physical exertion of the arm and subsequent hypoperfusion of the arm or brain. Patients may present with claudication, pain, pallor, paresthesias, and weakened pulse in the affected extremity. Patients may also present with transient neurologic disturbances concerning for a stroke. Diagnosis is made by clinical findings and imaging (ultrasound, CT, MRI). In addition to appropriate management of atherosclerosis, symptomatic patients may need angioplasty/stenting or surgical revascularization.
Uterine leiomyomas (or uterine fibroids) are benign tumors arising from smooth muscle cells in the uterine myometrium. Leiomyosarcomas, however, are malignant tumors, arising de novo (not from fibroids). With a lifetime risk of > 70% for both African American and Caucasian women, fibroids are common. Conversely, leiomyosarcomas are rare. Leiomyosarcomas may present similarly to uterine fibroids making preoperative diagnosis challenging. Both conditions present with abnormal bleeding, pelvic pain, and/or bulk symptoms. A fibroid is identified as a hypoechoic, well-circumscribed, round mass on pelvic ultrasound. A leiomyosarcoma is usually diagnosed on a postoperative specimen. Depending on patient symptoms and preference, treatment for leiomyoma may include surgical resection or medical options to reduce bleeding and/or bulk. Management of leiomyosarcoma, which carries a poor prognosis, may include adjuvant chemotherapy based on stage.
A glucagonoma is a glucagon-secreting neuroendocrine tumor that originates from the α-cells in the pancreatic islets. Most glucagonomas are malignant, and many of them are part of the autosomal dominant condition known as multiple endocrine neoplasia syndrome type 1 (MEN 1). Elevated levels of glucagon lead to increased gluconeogenesis and glycogenolysis, resulting in an increase in free glucose in the bloodstream and the depletion of fat and amino acid stores. Patients often present with diabetes, a characteristic rash called necrolytic migratory erythema, weight loss, anemia, deep vein thrombosis, and neuropsychiatric symptoms. Laboratory findings demonstrate an elevated glucagon level, and imaging shows a pancreatic mass. Management is usually supportive and includes glucagon inhibition with octreotide (a somatostatin analog). Surgical resection is attempted if disease is localized, though this is frequently palliative. Chemotherapy and targeted molecular agents are also used in advanced disease.
Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Patients may have facial erythema, flushing, telangiectasia, papules, pustules, phymatous changes, and ocular manifestations. The diagnosis is clinical. Management includes avoidance of triggers, gentle skincare, topical (and/or oral) antibiotics, and laser (or surgical) therapies.
Dilated cardiomyopathy (DCM) is the most common type of non-ischemic cardiomyopathy and a common cause of heart failure (HF). The cause may be idiopathic, familial, or secondary to a variety of underlying conditions. The disease is characterized by the enlargement of 1 or both ventricles and reduced systolic function. Patients typically present with symptoms of HF such as shortness of breath, fatigue, weakness, and peripheral edema. Blood tests, ECG, X-rays, echocardiography, and other cardiac studies and procedures are typically done to obtain the diagnosis. Treatment includes medications used to reduce volume overload (e.g., diuretics) and manage HF (e.g., beta-blockers). Devices such as pacemakers and cardioverter-defibrillators may also be needed. In severe cases, a heart transplant is required. Complications include thromboembolic events and sudden cardiac death.
Becker muscular dystrophy (BMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. Abnormal, partially functional muscle dystrophin protein is produced, which leads to progressive muscle weakness and the eventual loss of ambulation. The clinical course is highly variable, but symptoms generally occur by adolescence. The diagnosis is based on muscle enzymes, genetic testing, and muscle biopsy (if necessary). Management of BMD is supportive and aimed at slowing disease progression and complications. Dilated cardiomyopathy is the leading cause of death.
A thyroid nodule is a disordered growth of thyroid cells that produces a mass in the thyroid gland. Most thyroid nodules are benign and detected either by the patient or by the clinician on examination. In other cases, a thyroid nodule is found in radiologic imaging incidentally. Ruling out of malignancy is important. Workup includes thyroid-stimulating hormone (TSH) and thyroid ultrasound followed by radioactive iodine (RAI) uptake scan or thyroid scan if initial tests suggest the presence of hyperthyroidism. Fine-needle aspiration biopsy (FNAB) is recommended in patients with suspicious ultrasound findings, "cold" nodules (iodine uptake < surrounding tissue) on thyroid scan, large nodules (generally > 1.5 cm), or risk factors for malignancy. Management is dictated by pathology findings and can range from periodic ultrasound monitoring to surgery.
Nephritic syndrome is a renal condition with signs and symptoms produced by inflammation of the glomeruli (glomerulonephritis) and increased permeability of the glomerular barriers. Defining features include hematuria, proteinuria (but below nephrotic range), RBC casts with dysmorphic RBCs on urine microscopy, and increased serum creatinine. Causes can be genetic, autoimmune, idiopathic, or post-infectious. The most common cause is acute post-streptococcal glomerulonephritis. General clinical findings include edema, hypertension, and oliguria. Diagnosis is made based on history, physical exam, and laboratory data. A renal biopsy is sometimes necessary to establish the underlying cause. There can be a combined nephritic-nephrotic picture, especially in the chronic presentation. Treatment and prognosis depend on cause and severity.
Dermatomyositis (DM) is an autoimmune and inflammatory myopathy. Although the etiology of DM is unclear, it has several genetic and environmental associations. Dermatomyositis is common in women around the age of 50 years. Patients present with symmetrical, proximal weakness, characteristic skin manifestations, and systemic symptoms. Diagnosis is based on clinical presentation and laboratory studies and confirmed on the basis of muscle biopsy. Myositis-specific antibodies, including anti-Mi-2, are specific markers in DM. Management is with systemic glucocorticoids, immunosuppressants, and physiotherapy. As there is a strong association of DM with malignancy, all patients should undergo cancer screening.
Alport syndrome, also called hereditary nephritis, is a genetic disorder caused by a mutation in the genes encoding for the alpha chains of type IV collagen, resulting in the production of abnormal type IV collagen strands. Patients present with glomerulonephritis, hypertension, edema, hematuria, and proteinuria, as well as with ocular (cataract, retinopathy) and auditory (sensorineural hearing loss) findings. Diagnosis is established with urinalysis, urine microscopy, and a renal function panel. A renal biopsy showing characteristic glomerular basement membrane splitting may be used to confirm the diagnosis. Treatment for Alport syndrome is focused on limiting disease progression with angiotensin receptor blockers and angiotensin-converting enzyme inhibitors. Hearing aids are used for hearing loss associated with Alport syndrome.
Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Primary risk factors include prolonged rupture of membranes and prolonged labor. Chorioamnionitis is diagnosed by clinical findings, including maternal fever. Chorioamnionitis is managed with antibiotics, and by ensuring continued labor progress (or initiating progress) toward delivery. Chorioamnionitis typically resolves soon after delivery. Significant maternal and fetal complications are possible, warranting prompt diagnosis and treatment.
Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Rashes can be classified by their distribution, configuration, and morphology. The diagnosis is often clinical and based on the patient’s history and physical exam findings. Management is dependent on identifying the correct condition and varies depending on the etiology.
Strongyloidiasis is a common parasitic disease caused by infection with the roundworm Strongyloides stercoralis. Transmission occurs through skin penetration, most commonly from walking barefoot. Strongyloides has a unique life cycle that can be entirely completed in the human host, migrating from the skin to the pulmonary system and then to the GI system. Symptoms include cutaneous irritation, constipation, diarrhea, dry cough, and wheezing, depending on where the parasite is in its life cycle. Effective eradication of the parasite can be obtained with anthelmintic medications, usually ivermectin.
Endometrial polyps are pedunculated or sessile projections of the endometrium that result from overgrowth of endometrial glands and stroma around a central vascular stalk. Endometrial polyps are a few millimeters to a few centimeters in size, can occur anywhere within the uterine cavity, and, while usually benign, can be malignant, particularly in postmenopausal women. Endometrial polyps present with abnormal uterine or postmenopausal bleeding, although many are asymptomatic and discovered incidentally. Endometrial polyps are best diagnosed with a saline-infusion sonogram, and are usually treated with hysteroscopic resection.
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Clinical presentation can consist of thrombocytopenia, hemolytic anemia, hematuria, gastrointestinal symptoms, neurological symptoms, and renal involvement. Diagnosis is established based on a combination of clinical symptoms and laboratory tests. Thrombotic thrombocytopenic purpura is a medical emergency and almost always fatal if appropriate treatment is not initiated promptly. Emergency management includes plasma exchange and immunosuppressive therapies.
Osteosarcoma is a primary malignant tumor of the bone characterized by the production of osteoid or immature bone by the tumor cells. The disease is most common in children and young adults and most frequently affects growth plates of the long bones, although it can involve any bone. Osteosarcoma can present with pain, swelling, and palpable mass, and sometimes with a pathologic fracture. Diagnosis is established with imaging studies and biopsy. Treatment involves systemic chemotherapy and surgical resection. Long-term survival can be expected with appropriate treatment in the absence of macrometastatic disease.
Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne can present as open or closed comedones, papules, pustules, nodules, or cysts. The diagnosis is based on clinical exam. Management depends on the severity, but includes skin care techniques, topical therapies, antibiotics, and retinoids.
Amyloidosis is a disease caused by abnormal extracellular tissue deposition of fibrils composed of various misfolded low-molecular-weight protein subunits. These proteins are frequently byproducts of other pathological processes (e.g., multiple myeloma). These misfolded proteins can become deposited in different tissues, interfere with normal organ functions, and cause tissue-specific diseases (e.g., renal amyloidosis causes proteinuria). Diagnosis is established clinically and confirmed with tissue biopsy. Treatment should be directed toward the underlying cause and the reduction of amyloid deposition.
Basal cell carcinoma is the most common skin malignancy. This cancer arises from the basal layer of the epidermis. The lesions most commonly appear on the face as pearly nodules, often with telangiectatic blood vessels and ulceration in elderly individuals. Diagnosis is established by tissue biopsy. Despite having low metastatic potential, basal cell carcinoma should be treated adequately because it is locally aggressive and destructive to tissues. Complete surgical excision is the main treatment method. Long-term prognosis is excellent with adequate management.
Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Furthermore, of that percentage, 25% may develop complications of the suppurative lymph nodes. Given the growth of H. ducreyi on a special medium (often not readily available), chancroid is diagnosed based upon clinical appearance and tests to rule out both syphilis and herpes (the most common causes of genital ulcers). Although the disease can resolve spontaneously, antibiotics (azithromycin or ceftriaxone) are the treatment of choice. Treatment should involve both patients and their sexual contacts.
Staphylococcal scalded skin syndrome (SSSS), also known as Ritter disease and staphylococcal epidermal necrolysis, is a toxin-mediated condition caused by Staphylococcus aureus. The exfoliative toxin produced disseminates and cleaves desmoglein 1 in the epidermis, causing separation and detachment of the skin. SSSS most commonly affects young children. Prodromal symptoms precede diffuse cutaneous erythema, tenderness, bullae formation, and superficial desquamation. The mucous membranes are spared. The diagnosis is made clinically and can be confirmed with culture data (targeting possible primary infection sites) and biopsy. However, cultures of bullae are not useful. Antibiotics and supportive care should be initiated as soon as the diagnosis is suspected.
An embolus is an intravascular solid, liquid, or gaseous material that is carried by the blood to a site distant from its point of origin. Emboli of all types warrant immediate medical attention. The majority of emboli dislodge from a thrombus, forming a thromboembolus. Other less common nonthrombotic types of emboli are cholesterol, fat, air, amniotic fluid, and tumor emboli. The cause of the embolus depends on the type, as does the clinical presentation, diagnosis, and management of each embolic condition. Due to their effects on circulation, all emboli have the potential to result in end-organ failure and death.
Hypoaldosteronism is a hormonal disorder characterized by low levels of aldosterone. These low levels can be caused by decreased aldosterone production or a peripheral resistance to aldosterone. When hypoaldosteronism occurs as a result of an acquired decrease in renin production, the condition is more commonly referred to as renal tubular acidosis (RTA) type 4. Patients are usually older, with underlying renal disease (e.g., diabetic nephropathy). Hypoaldosteronism usually presents as hyperkalemia with a mild hyperchloremic metabolic acidosis (normal anion gap). Most patients are asymptomatic and routine lab evaluation demonstrates hyperkalemia, prompting a further workup. The condition is diagnosed using serum and urine tests that demonstrate reduced aldosterone levels and a reduced transtubular potassium gradient, among other characteristic findings. Patients are managed based on their underlying etiology.
Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. While lungs are the most common site of infection, mycobacteria can colonize and infect other organ systems including the lymph nodes, skin, sinuses, eyes, ears, bones, CNS, and urinary tract.
Restrictive cardiomyopathy (RCM) is a fairly uncommon condition characterized by progressive stiffening of the cardiac muscle, which causes impaired relaxation and refilling of the heart during diastole, resulting in diastolic dysfunction and eventual heart failure. It most often occurs secondary to scarring, damage, and/or infiltration of the heart muscle, with amyloidosis being the most common cause. Infrequently, it may be idiopathic or inherited. Signs and symptoms include shortness of breath, low exercise tolerance, fatigue, and peripheral edema. Diagnosis is made through clinical suspicion and confirmed through ECG, X-ray, echocardiography, and cardiac MRI. Treatment includes medications for heart failure, implantable devices such as pacemakers and cardioverter–defibrillators, and heart transplantation in refractory cases.
Caustic agents are acidic or alkaline substances that damage tissues severely if ingested. Alkali ingestion typically damages the esophagus via liquefactive necrosis, whereas acids cause more severe gastric injury leading to coagulative necrosis. Ingestion of large volumes and high concentrations of caustic agents can lead to severe and extensive injuries. Additionally, aspiration affects the laryngeal and tracheobronchial structures. Signs and symptoms include oral pain, burns, dysphagia, vomiting, and abdominal pain. Severe injuries can present with shock, abdominal rigidity, respiratory distress, and/or altered mental status. Diagnosis is based on laboratory tests, abdominal and chest imaging, and endoscopy within 24 hours (if without contraindications) to determine the extent of damage. Management involves stabilizing the cardiorespiratory status, decontamination, and supportive therapy. Severe injury may require surgery.
In the context of acute or chronic kidney failure, renal function may diminish to a point at which it is no longer able to adequately support life. When this happens, renal replacement therapy is indicated. Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD).
Hyperaldosteronism is defined as the increased secretion of aldosterone from the zona glomerulosa of the adrenal cortex. Hyperaldosteronism may be primary (resulting from autonomous secretion), or secondary (resulting from physiological secretion due to stimulation of the RAAS). Classically, hyperaldosteronism presents with hypertension, hypokalemia, and metabolic alkalosis, although recent studies have suggested that hypokalemia is less common than originally thought in primary hyperaldosteronism. Patients with hypertension who are treatment resistant and/or associated with hyperkalemia should be screened for hyperaldosteronism by determining their plasma aldosterone concentration and plasma renin activity. Confirmatory tests and an abdominal CT scan are required to conclusively diagnose primary hyperaldosteronism. Management involves the use of aldosterone receptor antagonists and surgical excision of any aldosterone-secreting tumors.
Lactose intolerance (LI) describes a constellation of symptoms due to lactase deficiency (LD), the enzyme located in the brush border of the adsorptive cells in the small intestine. Lactose is the disaccharide present in milk and requires hydrolysis by lactase to break it down into its 2 absorbable constituents, glucose and galactose. Lactose intolerance typically presents with bloating, abdominal cramping, diarrhea, and flatulence. The diagnosis of LI can be suspected clinically based on symptoms after consumption of a lactose-containing meal. The most commonly used test for confirmation of the diagnosis is the lactose hydrogen breath test. The treatment goal is to eliminate symptoms while maintaining sufficient intake of calcium and vitamin D. Alternative diagnoses to LI should always be sought, as many people wrongly attribute their symptoms to LI.
The kidneys are primarily in charge of the maintenance of water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. Glomerular filtration is the process of converting the systemic blood supply into a filtrate, which will ultimately become the urine. Complex regulatory processes ensure that only the appropriate substances in the systemic blood are lost in the urine and that the urine flow is satisfactorily balanced to maintain adequate systemic volume status. Abnormalities of the glomerulus can cause several clinically important conditions.
Extranodal marginal zone lymphoma (EMZL) of mucosa-associated lymphoid tissue (also called MALToma, MALT lymphoma, and pseudolymphoma) is a group of non-Hodgkin’s lymphomas that have historically been grouped together because they appear to arise from postgerminal center marginal zone B cells and share a similar immunophenotype. MALT lymphoma is thought to arise in the setting of chronic immune stimulation, which is usually due to bacterial, viral, or autoimmune stimuli. MALT lymphomas present with symptoms due to localized involvement of glandular epithelial tissues in the specific site where they develop. Diagnosis of MALT lymphoma is made by morphologic, immunophenotypic, and genetic analysis of biopsy samples. Helicobacter pylori–positive gastric MALT lymphoma is treated with H. pylori eradication therapy, and H. pylori–negative gastric MALT lymphoma is treated with radiation therapy. Nongastric MALT lymphoma is treated based on the involved area and extent of disease. MALT lymphoma patients have a good prognosis, with a median survival of > 10 years.
Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Primary hyperparathyroidism is an inherent disease of parathyroid glands associated with abnormal secretion of PTH. Secondary hyperparathyroidism results from abnormalities of calcium metabolism, which, if left untreated, can progress to tertiary hyperparathyroidism, which is associated with hypertrophy of the parathyroid gland and oversecretion of PTH even if the primary cause is eliminated. Diagnosis is based on biochemical parameters, which include serum PTH, calcium, and phosphate levels as well as urinary calcium. Management relies mostly on surgical parathyroidectomy for primary and tertiary hyperparathyroidism. Management of secondary hyperparathyroidism is focused on treatment of the underlying disease.
Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). The etiology of thyroiditis is varied and includes autoimmune inflammation (most common), bacterial or viral infection, and drug-induced reactions. The inflammation of the thyroid leads to a sequential pathologic process that can result in signs and symptoms of hyperthyroidism followed by signs and symptoms of hypothyroidism. The resulting damage can be temporary or permanent, and the treatment depends on the underlying cause.
Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders.
Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is an autosomal recessive disorder leading to an impairment that affects mucociliary clearance. Primary ciliary dyskinesia is caused by defective ciliary function in the airways and is characterized by the loss of oscillation (immotility), abnormal oscillation (dyskinesia), or absence of cilia (aplasia). In most cases, PCD commonly presents with recurrent infections of the upper and lower respiratory tract. Clinical features include bronchiectasis, chronic rhinosinusitis, and situs inversus. There is no gold standard diagnostic test for PCD, as several tests are used in the diagnosis. Treatment is individualized, and the primary goal is to remove trapped mucus and treat infections. Patients with PCD usually have a regular lifespan.
A cell is a complex unit that performs several complex functions. An organelle is a specialized subunit within a cell that fulfills a specific role or function. Organelles are enclosed within their own lipid bilayers or are unbound by membranes. If a cell is viewed as an organism, the organelles are an equivalent of the cell’s internal organs. Cell organelles carry out various functions from maintaining the shape of the cell to reproduction, movement, protein synthesis, energy production, and the transport of substances in and out of the cell.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder affecting the neuromuscular junction and has a strong association with small cell lung carcinoma. Lambert-Eaton myasthenic syndrome affects the voltage-gated calcium channels at the presynaptic membrane. Presentation includes proximal muscle weakness and symptoms of autonomic dysfunction such as dry mouth and sluggish pupillary reflexes. Diagnosis includes nerve conduction studies/electromyography (EMG) and serum detection of antibodies. Management is mainly symptomatic with the use of potassium channel blockers and immunosuppressants. Prognosis is good for nonparaneoplastic LEMS but usually poor for paraneoplastic LEMS secondary to underlying malignancy.
Hypocoagulable conditions, also known as bleeding disorders or bleeding diatheses, are a diverse group of diseases that result in abnormal hemostasis. Hemostasis is the innate, stepwise process resulting in bleeding cessation from a damaged blood vessel. Physiologic hemostasis is dependent on the integrity of endothelial cells and subendothelial matrix, platelets, and coagulation factors. The hypocoagulable states result from abnormalities in one or more of these contributors, resulting in ineffective thrombosis and bleeding.
The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. The body produces approximately 15,000 mmol of CO2 daily, which is the majority of daily acid production; the remainder of the daily acid load (only about 70 mmol of nonvolatile acids) is excreted through the kidneys. In the setting of hypoventilation, this acid load is not adequately blown off, and respiratory acidosis occurs. Renal compensation occurs after 3–5 days, as the kidneys attempt to increase the serum bicarbonate levels. Patients are often asymptomatic, or they may present with neuropsychiatric manifestations or mild dyspnea. Diagnosis is made with arterial blood gas measurement. Management involves treating the underlying etiology, stabilizing the patient, and avoiding respiratory sedatives.
"The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. The body produces approximately 15,000 mmol of CO2 daily, which is the majority of daily acid production; the remainder of the daily acid load (only about 70 mmol of nonvolatile acids) is excreted through the kidneys. When hypoventilation occurs, excess carbon dioxide is blown off and respiratory alkalosis develops. The kidneys respond by decreasing serum bicarbonate (HCO3–) through increased HCO3– excretion or decreased excretion of H+. Patients present with an increased respiratory rate, dyspnea, light-headedness and potentially psychologic symptoms. Diagnosis involves a thorough history, an exam, and an arterial blood gas measurement. Management focuses on addressing the underlying abnormalities, stabilizing patients in acute distress, and potentially a small dose of short-acting benzodiazepines.
The identification and classification of skin lesions in a patient are important steps in the diagnosis of any skin disorder. Primary lesions represent the initial presentation of the disease process. Secondary lesions develop from irritated or manipulated primary lesions, and/or disease progression. Along with history, a comprehensive examination of the skin, appendages, and mucous membranes is required to differentiate between conditions. The key features noted during examination include the type, morphology, size, color, shape, arrangement, and distribution of the presenting lesions. At times, diagnostic procedures may be necessary.
A pyogenic liver abscess is a polymicrobial infection arising from contiguous or hematogenous spread. Pyogenic liver abscess is the most common type of visceral abscess. Patients may present with a triad of fever, malaise, and RUQ pain. Laboratory analysis can be informative with elevated WBC and abnormal liver function tests, and imaging may reveal solitary or multiple lesions on ultrasound or CT scan. On contrast imaging, the lesions generally appear well defined with rim enhancement. Diagnosis requires aspiration with Gram stain and culture and, in some cases, a drainage catheter may be placed. A combination of drainage and IV antibiotic therapy is the primary method of treatment. Surgical drainage or resection is utilized in specific cases.
The collective term “bronchial tree” refers to the bronchi and all of their subsequent branches. The bronchi are the airways of the lower respiratory tract. At the level of the 3rd or 4th thoracic vertebra, the trachea bifurcates into the left and right main bronchi. The right main bronchus is shorter and more vertical in direction than the left. Both of these bronchi continue to divide into secondary or lobar bronchi that bifurcate further and further in order to sufficiently spread the respiratory air completely into the left and right pulmonary lobes. The terminal segment of each bronchus contains millions of alveoli, the site of gas exchange.
Cholecystectomy is a surgical procedure performed with the goal of resecting and extracting the gallbladder. It is one of the most common abdominal surgeries performed in the Western world. Cholecystectomy is performed for symptomatic cholelithiasis, cholecystitis, gallbladder polyps > 0.5 cm, porcelain gallbladder, choledocholithiasis and gallstone pancreatitis, and rarely, for gallbladder cancer. Over 90% of cholecystectomies are now completed laparoscopically because of the procedure’s enhanced recovery time and decreased postoperative pain. Cholecystectomy has a low-risk profile, but the most dreaded complications include vascular and biliary ductal injuries.
The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. This daily load comes primarily from anaerobic metabolism, absorption of acids, and excretion of bases from the GI system. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Respiratory compensation occurs very quickly (within minutes) and mitigates changes in pH. In the acute period, metabolic disorders can cause severe symptoms. Management is aimed at correcting the underlying etiology.
The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. This daily load comes primarily from anaerobic metabolism, absorption of acids, and excretion of base from the GI system. Metabolic alkalosis develops when there is an increase in serum HCO3- levels. Metabolic alkalosis also occurs when there is an increased loss of acid, either renally or through the upper GI tract (e.g., vomiting), increased intake of HCO3-, or a reduced ability to secrete HCO3- when needed. Respiratory compensation occurs very quickly (within minutes) and mitigates changes in pH from the primary metabolic disorder. Management is aimed at correcting the underlying etiology.
Brain abscess is a life-threatening condition that involves the collection of pus in the brain parenchyma caused by infection from bacteria, fungi, parasites, or protozoa. The most common presentation is headache, fever with chills, seizures, and neurological deficits. Diagnosis is mainly based on imaging, as it is difficult to arrive at a definitive diagnosis based on clinical presentation alone. Management includes administration of empiric antibiotic therapy and surgical intervention. Immediate management is necessary; otherwise, severe neurologic complications ensue.
The identification and classification of a patient's skin lesions are important steps in the diagnosis of any skin disorder. Primary lesions represent the initial presentation of the disease process. Secondary lesions develop from irritated or manipulated primary lesions and/or manifestations of disease progression. The key features of skin lesions include type, morphology, color, shape, arrangement, and distribution. A comprehensive examination of the skin, appendages, and mucous membranes is done, with the type of procedure performed depending on the suspected diagnosis.
Leukoplakia is a potentially malignant lesion affecting the squamous epithelium usually within the oral cavity. Leukoplakia can be associated with a history of chronic tobacco and alcohol use, both of which can synergistically damage the epithelium. Leukoplakia presents as a white plaque that cannot be scraped off. Diagnosis is confirmed with a biopsy. The lesion can be surgically treated, but close observation is always recommended owing to the risk of malignant transformation.
Bowen disease and erythroplasia of Queyrat are 2 related entities that describe squamous cell carcinoma (SCC) in situ of the skin. Bowen disease usually presents in sun-exposed areas (e.g., face and forearms) as a red, scaly skin lesion. The lesion can occur in other areas as well. The genital region, particularly the penile shaft, is also affected. When the glans penis is involved, the lesion is called erythroplasia of Queyrat, with uncircumcised males being at high risk. Both genital lesions have HPV infection as a risk factor. Pathologic findings show full-thickness atypia without basement membrane invasion. Both entities may progress to invasive SCC. Thus, local destruction via surgical excision or topical chemotherapy should be performed.
Bowenoid papulosis is a sexually transmitted condition induced by HPV infection, which facilitates keratinocyte neoplastic transformation. On skin biopsy, Bowenoid papulosis manifests as low-grade dysplasia. Affected individuals present with genital papules of a red-to-brown color that are often asymptomatic. Although most cases resolve spontaneously, lesions should be followed up because there is a risk of transformation to invasive squamous cell carcinoma (SCC). Cryosurgery, excision, or topical therapy may be used to hasten the resolution of persistent cases of Bowenoid papulosis.
Polycystic kidney disease (PKD) is an inherited genetic disorder leading to the development of numerous fluid-filled cysts in the kidneys. The 2 main types of PKD are autosomal recessive polycystic kidney disease (ARPKD), which is often diagnosed antenatally or shortly after birth, and autosomal dominant polycystic kidney disease (ADPKD), which is often diagnosed in adulthood. Autosomal recessive polycystic kidney disease is primarily characterized by cystic dilatations of the renal collecting ducts and intrahepatic bile duct dilatation with hepatic fibrosis. Diagnosis is through physical exam and ultrasonography. Management requires a multidisciplinary approach to slow the progression of renal disease by controlling hypertension, proteinuria, and symptoms. The prognosis of ARPKD depends on the age at presentation, along with the degree of hepatic and renal involvement. Patients progressing to end-stage renal disease (ESRD) will need renal replacement therapy.
Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Diagnosis of meningitis is made on clinical grounds with a thorough neurologic examination. CSF analysis is an important diagnostic tool, as it is difficult to identify the exact cause clinically. Management of meningitis includes immediate broad-spectrum antibiotics and supportive therapy to prevent complications. Specific treatment depends on the etiology of meningitis. Delay in treatment can lead to permanent neurologic defects and death.
Human cells are primarily reliant on aerobic metabolism. Therefore, it is of vital importance to efficiently obtain oxygen from the environment and bring it to the tissues, while excreting the by-product of cellular respiration (carbon dioxide). Respiration involves both the respiratory and circulatory systems. There are 4 processes that supply the body with O2 and dispose of CO2. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration is represented by the O2 and CO2 exchange between the lungs and the blood.
A cell’s cytoskeleton is a network of intracellular protein fibers that provides structural support, anchors organelles, and aids intra- and extracellular movement. The cytosol is the liquid inside the cell membrane that surrounds the organelles and cytoskeleton. The cytosol is a complex solution where many biochemical processes take place.
Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. The total volume of water lost (usually via GI or renal routes) is regained through normal oral intake. Therefore, if a patient has access to water and an intact thirst mechanism, many etiologies of hypernatremia may remain hidden. The etiology of hypernatremia is often easily determined by clinical history. Treatment is primarily a replacement of the free water deficit by IV or oral routes.
Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. The venous circulation is a low-pressure system with much lower amounts of smooth muscle and elastic tissue, thinner walls, and larger lumens than arteries. Veins are capacitance vessels with significant compliance and the ability to distend and hold up to 70%–80% of blood volume at rest.
Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries are organized into capillary beds, which are extensive networks of branches and anastomoses. Blood flows from the metarterioles, into the capillaries, out the thoroughfare channel, and into venules. Continuous, fenestrated, and sinusoid (discontinuous) capillaries are the 3 primary types, and each has a slightly different structure. Capillary dysfunction can occur either as a result of or a contribution to the clinical manifestation of many clinical conditions.
Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Group A viruses cause herpangina; hand, foot, and mouth disease; and acute hemorrhagic conjunctivitis. Group B viruses cause myopericarditis, epidemic pleurodynia, and systemic neonatal disease. The diagnoses are usually made clinically. Viral culture and PCR can be performed for confirmation if the diagnosis is uncertain. Coxsackievirus infections are self-limiting and the management is supportive.
The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. E. coli is transmitted via a fecal–oral route, which can occur with unsanitary food preparation, contamination of meat or produce by manure, irrigating or washing crops/fruits with contaminated water, and consumption of contaminated water.
WBCs develop from stem cells in the bone marrow and are called leukocytes when circulating in the bloodstream. Lymphocytes are 1 of the 5 subclasses of WBCs. Lymphocytosis is an increase in the number or proportion of the lymphocyte subclass of WBCs, often as a result of an immune response to infection (known as reactive lymphocytosis). Common presentations include fever, lymphadenopathy, and upper respiratory symptoms. Usually transient, lymphocytosis resolves on its own in most cases after resolution of the infection. In other situations, it may signal a lymphoproliferative disorder (known as clonal lymphocytosis). Diagnosis is based on peripheral blood smear, flow cytometry, and potentially, a bone marrow biopsy. Management depends on the underlying cause.
Echoviruses are single-stranded positive-sense RNA viruses belonging to the genus Enterovirus. Transmission is most commonly through the fecal-oral route. The majority of patients are asymptomatic. Patients who are symptomatic can exhibit a wide range of illnesses ranging from nonspecific upper respiratory infections and exanthems to severe and life-threatening illnesses such as aseptic meningitis, encephalitis, and myocarditis. The diagnosis is usually made clinically, but laboratory confirmation using PCR and viral culture may be necessary for patients with severe disease. Most infections are self-limiting and require no specific therapy.
Chédiak-Higashi syndrome (CHS) is an autosomal recessive disorder caused by mutations affecting a lysosomal trafficking regulator protein. This protein plays a crucial role in the inability of neutrophils to kill phagocytosed microbes. Patients with CHS exhibit recurrent pyogenic infections, easy bleeding and bruising, and neurologic manifestations. The syndrome is also associated with oculocutaneous albinism. The diagnosis is made based on analysis of the patient’s blood or bone marrow smear and genetic testing. The treatment of choice is allogeneic hematopoietic cell transplantation.
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is marked by a severe urge to move the legs, and an unpleasant sensation only relieved by movement. Restless legs syndrome occurs after inactivity, especially during the evening and night, and is associated with sleep disturbance. The syndrome can be idiopathic, or due to secondary causes such as iron deficiency, pregnancy, diabetes mellitus, uremia, and Parkinson’s disease. Some drugs, most notably antidepressants and metoclopramide, can also trigger the syndrome. Management involves treatment of the underlying condition, supportive measures, and dopamine agonists.
Myeloperoxidase (MPO) deficiency is an inherited or acquired disorder caused by mutations in the MPO gene on chromosome 17, leading to a deficiency of MPO in neutrophils and monocytes. This deficiency particularly impairs destruction of pathogens in phagolysosomes. While the majority of patients are asymptomatic and do not suffer from an increased frequency of infections, a minority (particularly diabetic patients) can develop serious fungal infections. Histochemical staining of neutrophils for MPO can provide the diagnosis. There is no specific management for MPO deficiency, and prophylactic antibiotics are not indicated.
Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions such as maintaining electrical neutrality in cells, generating action potentials in nerves and muscles, and maintaining normal blood pH. The most important electrolytes are sodium, potassium, chloride, magnesium, calcium, phosphate, and bicarbonate. In order for these electrolytes to participate in biochemical reactions and cellular processes, regulatory mechanisms are in place, which help maintain homeostasis.
Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Primary/functional constipation can be divided into normal transit, slow transit, and outlet constipation. Constipation is a symptom, not a disease, and appropriate management requires an evaluation of possible etiologies, such as systemic disorders and drugs. Once secondary causes have been eliminated, idiopathic constipation can be managed with lifestyle modifications and medications.
Minimal change disease (MCD), also known as lipoid nephrosis, is the most common cause of nephrotic syndrome in children. The designation “minimal change” comes from the very little changes noticed in kidney biopsies under light microscopy. Hallmark clinical findings include edema, proteinuria, hypoalbuminemia, and hyperlipidemia. Diagnosis is based on clinical suspicion and supportive lab findings. Corticosteroid administration is the cornerstone of management, and the prognosis is largely favorable.
Intestinal ischemia occurs when perfusion fails to meet the demands of the intestines, resulting in ischemic tissue injury that can be life-threatening if bowel necrosis and/or perforation occurs. Symptoms can range from mild indigestion or diarrhea to severe abdominal pain. Imaging techniques including CT and angiography are used to detect stenosis or occlusion. The chronic form of intestinal ischemia benefits from medical therapies and revascularization procedures (stents, bypass surgery) while acute forms require urgent interventions to restore blood flow and remove any dead bowel tissue. Delay in the diagnosis and management of acute intestinal ischemia results in high mortality and severe complications, including intestinal perforation and sepsis.
Pneumocystis jiroveci is a yeast-like fungus causing pneumocystis pneumonia (PCP) in immunocompromised patients. Pneumocystis pneumonia is spread through airborne transmission and classically affects patients with AIDS, functioning as an AIDS-defining illness. Patients may present with insidious onset of fever, chills, dry cough, chest pain, and shortness of breath. The diagnosis is supported by an increased β-D-glucan level and diffuse, bilateral infiltrates on chest imaging in the immunocompromised patient. A definitive diagnosis can be given with microscopy of induced sputum or specimens from bronchoalveolar lavage (BAL). Management involves antimicrobial therapy with a trimethoprim-sulfamethoxazole combination, and supportive care. Addressing the etiology of immunodeficiency is paramount. Prophylaxis is often required to prevent infection or reinfection.
Hypercalcemia (serum calcium > 10.5 mg/dL) can result from various conditions, the majority of which are due to hyperparathyroidism and malignancy. Other causes include disorders leading to vitamin D elevation, granulomatous diseases, and the use of certain pharmacological agents. Calcium levels are regulated and affected by factors such as dietary intake and pH, and the levels of parathyroid hormone (PTH), vitamin D, and albumin. Symptoms vary depending on calcium levels and the onset of hypercalcemia. Generally, neuropsychiatric (confusion, altered mental status), GI (vomiting, abdominal pain), musculoskeletal (bone pain, weakness), and renal (polyuria, polydipsia) manifestations are seen. Confirmation of hypercalcemia is required. Correction of the value is based on the albumin levels or after determining the ionized calcium levels (the metabolically active form), which is followed by determining PTH levels. Subsequent laboratory tests and imaging studies are ordered based on history and presentation. Correction of hypercalcemia depends on its severity. Calcium levels > 14 mg/dL are treated using IV isotonic saline hydration, calcitonin, and bisphosphonates. Hemodialysis is considered in rare cases. Treatment of the underlying cause is recommended.
The pancreas is a composite organ containing a distinctive combination of cell lineages. The exocrine tissue comprises acinar cells, which secrete digestive enzymes into the intestine. The endocrine function is performed by the islets of Langerhans, which consist of distinct cell types secreting 4 different hormones into the circulation (α-cells, glucagon; β-cells, insulin; δ-cells, somatostatin; and γ-cells, pancreatic polypeptide). Endocrine hormones, as well as some exocrine enzymes, can be measured in body fluids and provide important diagnostic information in acute and chronic pancreatic disease.
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of RBCs. In addition, the WBC and platelet counts are also increased, which differentiate PV from erythrocytosis seen with chronic hypoxia and other chronic conditions. Polycythemia vera is presumed to have a genetic basis due to mutations in the Janus kinase-2 gene. The clinical presentation includes disease-related symptoms that can affect various organ systems. Sometimes, the disease can be an incidental finding during laboratory testing. Diagnosis is based on peripheral blood analysis and bone marrow biopsy findings. Management is with phlebotomy or drug therapy. The prognosis is generally good and patient survival is anticipated to improve further with the wide use of new therapies.
Astrocytomas are neuroepithelial tumors that arise from astrocytes, which are star-shaped glial cells (supporting tissues of the CNS). Astrocytomas are a type of glioma. There are 4 grades of astrocytomas. Grade I tumors are typically benign and present in children, while grade IV tumors (known as glioblastoma multiforme) are the most common primary malignant brain tumor in adults and have a particularly poor prognosis. The etiology of astrocytomas is usually unknown. The exact presenting symptoms depend on the tumor location and grade, but patients may exhibit headaches, seizures, and/or focal neurologic deficits. Diagnosis is made by MRI and tissue biopsy. Treatment depends on the grade of the tumor and may include any combination of surgery, radiation therapy, and/or chemotherapy.
The vertebral column is the most important anatomical and functional axis of the body, consisting of 7 cervical, 12 thoracic, and 5 lumbar vertebrae and limited cranially by the skull and caudally by the sacrum. The vertebral column provides structural support and protection for the spinal cord, which is housed in the spinal canal. The vertebral column and the spinal cord may be affected by various diseases, in which different imaging methods are important for correct diagnosis and management. Radiographs and CT scans are useful in evaluating bony structures, especially in excluding fractures and checking hardware. Additionally, CT scans also provide information on soft tissues. MRI is performed for evaluation of tumors, infection, disk herniations, and other soft tissue abnormalities including acute ligamentous or spinal cord injury.
Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Regardless of the etiology, progression of renal impairment is common and can ultimately lead to end-stage renal disease and the need for renal replacement therapy (e.g., transplantation or dialysis). The management of CKD includes treating the underlying etiology, aggressive risk factor modification, and addressing complications such as fluid overload and electrolyte imbalances.
Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle, where 30% of filtered salt is normally reabsorbed. Bartter syndrome is characterized by salt wasting and hypokalemia and presents with electrolyte abnormalities and their consequences, such as vomiting and dehydration. Diagnosis is made by lab testing that shows the typical hypokalemic metabolic alkalosis and hypercalciuria. Additional lab abnormalities include increased serum renin and aldosterone, but patients clinically have normal blood pressure. Management is focused on normalizing serum electrolyte levels. ACE inhibitors and angiotensin receptor blockers are used to improve hypokalemia and limit proteinuria.
Adenovirus (member of the family Adenoviridae) is a nonenveloped, double-stranded DNA virus. Adenovirus is transmitted in a variety of ways, and it can have various presentations based on the site of entry. Presentation can include febrile pharyngitis, conjunctivitis, acute respiratory disease, atypical pneumonia, and gastroenteritis. Severe manifestations include acute hemorrhagic cystitis, hepatitis, myocarditis, and disseminated infection. The diagnosis is confirmed with PCR and antigen testing. Most infections are self-limited, so management is generally supportive. Antiviral therapy is reserved for immunocompromised patients and severe infections.
Hairy cell leukemia (HCL) is a rare, chronic, B-cell leukemia characterized by the accumulation of small mature B lymphocytes that have “hair-like projections” visible on microscopy. The abnormal cells accumulate in the peripheral blood, bone marrow (causing fibrosis), and red pulp of the spleen, leading to cytopenias, including anemia, thrombocytopenia, neutropenia, and monocytopenia. HCL typically affects middle-aged men and presents with weakness, fatigue, opportunistic infections, and splenomegaly (which is often severe). Hairy cell leukemia is diagnosed by identifying hairy cells on a peripheral blood smear, characteristic cytopenias on CBC/DIFF, bone marrow biopsy, and immunophenotyping. Management consists of observation for asymptomatic patients and purine analogs for symptomatic patients. Both the disease itself and its treatments can cause immunosuppression, so prevention and prompt treatment of infections is also important.
Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4–5 cycles a night, and generally divided into non–rapid eye movement (NREM) sleep and REM sleep stages. NREM sleep, consisting of 3 stages, represents the period of transition from wakefulness, somnolence, and then deep sleep. REM sleep is characterized by rapid irregular eye movement, but with voluntary muscle atonia. The sleep stages and associated disorders are studied through the use of polysomnography, a multimodal test evaluating the brain waves, along with ocular and motor activities. Sleep disorders can be primary (which do not stem from any health problem) or can be attributable to underlying conditions or medications.
Orotic aciduria is an extremely rare genetic disorder that can result in crystalluria, megaloblastic anemia, developmental delay, and failure to thrive. The disorder is caused by an enzyme deficiency in the pyrimidine synthesis pathway resulting in the accumulation of orotic acid. Depletion of nucleotides leads to the symptoms of the disease. Diagnosis is made with genetic sequencing as well as urine studies. Options for treatment include uridine monophosphate and uridine triacetate.
Circadian rhythm sleep–wake disorders are a group of conditions marked by recurrent patterns of sleep disruption. These disorders can be due to an alteration of the circadian system (intrinsic) or a misalignment between an individual’s inner circadian rhythm and the environment (extrinsic). The disruption impairs the individual’s daily activities. There are 6 different subtypes, including delayed and advanced sleep–wake phase disorder, irregular and non-24-hour sleep–wake rhythm disorder, shift-work disorder, and jet lag. Diagnosis is generally clinical, but using tools such a sleep diary and actigraphy help in determining the disorder. Management for circadian rhythm sleep–wake disorders involves light therapy, behavioral modification, and pharmacotherapy, such as with melatonin.
Chronic granulomatous disease (CGD), as the name implies, is a chronic disorder that is characterized by granuloma formation. This disorder is a consequence of defective phagocytic cells that are unable to produce bactericidal superoxide because of a defect in nicotinamide adenine dinucleotide phosphate (NADPH), the oxidase responsible for the respiratory burst in phagocytic leukocytes. The diagnosis is made by testing neutrophil function for superoxide production. Patients with CGD are at increased risk of life-threatening infections with fungi and catalase-positive bacteria. Inflammatory complications such as CGD colitis are also possible. The introduction of antimicrobial prophylaxis and the use of azole antifungals has increased the overall life expectancy of these patients.
Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Chickenpox is the primary infection and occurs most commonly in children. The typical clinical presentation includes prodromal symptoms and a generalized, intensely pruritic vesicular rash. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. The diagnosis is primarily clinical. Management is supportive, although antiviral therapy can be used in certain patient populations. Complications can include secondary bacterial infections, encephalitis, or pneumonia. Varicella-zoster vaccine is recommended as a preventive measure in early childhood.
Norovirus is a nonenveloped, single-stranded, positive-sense RNA virus belonging to the Caliciviridae family. Norovirus infections are transmitted via the fecal-oral route or by aerosols from vomiting. The virus is one of the most common causes of non-bacterial gastroenteritis epidemic worldwide. Symptoms include watery and nonbloody diarrhea, nausea, vomiting, and low-grade fever. Although the infection is self-limiting, severe dehydration can occur. The diagnosis is usually presumptive, and viral detection using PCR or enzyme immunoassay may be used for patients with severe disease or immunocompromised status. Management is supportive and may include rehydration therapy.
Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. The diagnosis includes measurements of the waist circumference and BP along with serum levels of triglycerides, HDL cholesterol, and fasting glucose. Management consists mostly of lifestyle modifications such as moderate exercise and a balanced diet high in fibers and unsaturated fats and low in sugar.
Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Diagnosis relies on a thorough medical history and physical examination, which usually identify the underlying cause. When the cause is unknown, a biopsy may be necessary. Management is directed at the underlying infection, malignancy, or other cause.
Medulloblastomas are malignant primitive neuroectodermal tumors that arise in the posterior fossa in children. Medulloblastomas are the most common malignant brain tumors in children. Patients with medulloblastoma present with symptoms of increased intracranial pressure and cerebellar signs, which both evolve and worsen over weeks to a few months. Magnetic resonance imaging is the imaging modality of choice and typically shows a midline or paramedian cerebellar mass that enhances with contrast, but histopathological analysis after surgical resection is required for diagnosis. Treatment involves a combination of surgery, radiation therapy, and chemotherapy. Prognosis depends on a variety of factors, but with modern multimodality therapy, roughly 75% of children diagnosed with medulloblastoma survive into adulthood.
Meningiomas are slow-growing tumors that arise from the meninges of the brain and spinal cord. The vast majority are benign. These tumors commonly occur in individuals with a history of high doses of skull radiation, head trauma, and neurofibromatosis 2. Clinical symptoms of meningioma depend on the location and progression of the tumor, with a large proportion of meningiomas being asymptomatic. When symptoms do develop, they most commonly include headache, seizures, visual disturbances, and other focal neurologic deficits. Diagnosis is made based on neuroimaging (MRI is the gold standard) and biopsy. Management involves surveillance for asymptomatic patients and, for symptomatic patients, surgical resection. Radiation is also used in some cases.
Schwannomas (also known as neurilemmomas) are benign nerve sheath tumors in the peripheral nervous system (PNS), arising from Schwann cells that encase the peripheral nerves. Schwannomas are the most common tumors in the PNS. Although schwannomas are typically sporadic, they can be associated with neurofibromatosis type II and schwannomatosis. The clinical presentation of schwannomas depends on their specific location, but general signs and symptoms include a palpable mass on the skin, pain, and/or paresthesias due to nerve compression. The diagnosis is established primarily based on imaging studies (MRI or CT), and the treatment is usually surgical resection.
Acoustic neuroma, also referred to as vestibular schwannoma, is a benign tumor arising from Schwann cells of the vestibular component of the cranial nerve VIII. Acoustic neuroma forms within the internal auditory meatus and extends into the cerebellopontine angle. Vestibular schwannoma is mostly unilateral. Bilateral vestibular schwannomas are associated with neurofibromatosis type II. Symptoms arise due to compression of the cranial nerves V, VII, and VIII, and the cerebellum. The most common complaint is unilateral hearing loss but acoustic neuroma can also present with vertigo, decreased facial sensation, Bell’s palsy, and ataxia. Diagnosis of vestibular schwannoma is made with MRI of the brain with contrast. Treatment depends on the size of the tumor and symptom severity. Large tumors with severe hearing loss are treated with surgical excision or radiation therapy, while small tumors with mild symptoms can be observed over time.
Heavy metals poisoning is the toxic accumulation of metals in the body, which can occur due to ingestion or inhalation. These elements are normally found in nature and can have many applications (e.g., agriculture, medicine, industry); however, toxicity is rare. Common metals that the human body absorbs in toxic amounts are lead, arsenic, and iron. Presentation is variable and management involves the use of chelating agents.
Rotavirus belongs to the Reoviridae family and is a non-enveloped, double-stranded RNA virus. Transmission occurs through the fecal-oral route. Rotavirus is a common cause of severe gastroenteritis in children. Severe infections can result in dehydration and death. Diagnostic testing is not usually required, but the virus can be detected in stool samples using ELISA or PCR. Oral rehydration therapy is the mainstay of treatment. A live-attenuated vaccine is available to prevent rotavirus infections.
The kidneys regulate water and solute homeostasis through the processes of filtration, reabsorption, secretion, and excretion. After the filtration of blood through the glomeruli, the tubular system takes over and is responsible for adjusting the urine composition throughout the remainder of the nephron. Reabsorption, secretion, and excretion occur via active and passive transport mechanisms and respond dynamically to the body’s current needs to maintain homeostasis of the plasma composition and blood volume. The primary segments of the tubular system include the proximal tubule, loop of Henle, distal convoluted tubule, and collecting ducts. Each segment has unique transporters and functions.
Vasospastic angina, also known as Prinzmetal or variant angina, is an uncommon cause of chest pain due to transient coronary artery spasms. The pathophysiology is distinguished from stable or unstable angina secondary to atherosclerotic coronary artery disease (CAD). Clinical presentation is characterized by spontaneous episodes of chest pain from a transient decrease in blood flow to the epicardial arteries. Diagnosis is made by clinical history, normal exam, and ECG findings of ST-segment changes during an episode. Cardiac enzymes and angiography are usually normal. Management includes the prevention of vasospasm with calcium channel blockers and the relief of angina with nitrates.
Post-streptococcal glomerulonephritis (PSGN) is a type of nephritis that is caused by a prior infection with group A beta-hemolytic Streptococcus (GAS). The clinical presentation of PSGN can range from asymptomatic, microscopic hematuria to full-blown acute nephritic syndrome, which is characterized by red-to-brown urine, proteinuria, edema, and acute kidney injury. The diagnosis is made based on clinical findings in the setting of recent GAS infection. Management is supportive and involves treating the clinical manifestations. The prognosis is generally favorable, especially in children.
X-linked hypophosphatemic rickets (XLHR) is the most common of several hereditary disorders and is characterized by renal phosphate wasting, resulting in weak or soft bones. Formerly known as “vitamin D-resistant rickets,” XLHR is not currently considered true vitamin D resistance (related to inherited defects in the vitamin D metabolic pathway or calcitriol receptor). Typical clinical presentations occur during childhood and manifest as short stature, genu valgum, bone pain, and dental pain. Diagnosis is made by lab studies and confirmed by identification of the mutation in the PHEX gene. Management includes high doses of activated vitamin D (calcitriol) and phosphate. Patient monitoring by a multidisciplinary team is crucial to ensure adequate growth.
Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of
Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by excess production of monoclonal B lymphocytes in the peripheral blood. When the involvement is primarily nodal, the condition is called small lymphocytic lymphoma (SLL). The disease usually presents in older adults, with a median age of 70 years. Clinical presentation is often asymptomatic and diagnosis is made when abnormal lymphocytosis is seen on laboratory testing. Cytopenias can also be seen. The B cells are functionally incompetent lymphocytes and thus may result in recurrent infections. Treatment can vary from watchful waiting for early stages to chemotherapy for later stages. Median survival is around 10 years.
Oligodendrogliomas are malignant CNS tumors arising from neural glial cell precursors. Oligodendrogliomas often arise in the frontal lobes of the brain and have a generally favorable prognosis when compared to other gliomas. Oligodendrogliomas are the 3rd most common CNS tumor. The most frequent presenting symptom is a seizure; other symptoms include headaches, visual loss, and focal neurologic deficits. Diagnosis is established by brain biopsy that demonstrates a classic “fried egg” appearance (round nuclei with clear cytoplasm). Oligodendrogliomas are slow-growing, but because they are life-limiting, they are managed with a combination of surgical resection, radiation, and chemotherapy.
Endophthalmitis is an inflammatory process of the inner layers of the eye, which may be either infectious or sterile. Infectious endophthalmitis can lead to irreversible vision loss if not treated quickly. Based on the entry mode of the infectious source, endophthalmitis is divided into endogenous and exogenous types. Exogenous endophthalmitis occurs via direct inoculation of infectious organisms during cataract surgery, ocular trauma, or intravitreal injection. Endogenous endophthalmitis results from hematogenous seeding. Sterile endophthalmitis may result from toxins or retained lens material after an ocular operation. Clinical features vary depending on the type and course of the disease. Features may include decreased vision, conjunctival injection, ocular pain, hypopyon, and corneal edema. The diagnosis primarily depends on history and ophthalmological examination, and treatment is based upon the underlying cause. Sterile endophthalmitis generally resolves spontaneously while infectious endophthalmitis is treated with antimicrobials (antibiotics or antifungals). Vitrectomy may be needed in severe disease.
Imaging of the brain is most commonly used for evaluating trauma, stroke, and benign or malignant tumors. Before the advent of CT and MRI, X-ray scanning was widely used to study the skull and spinal bones. Today, CT and MRI, especially the latter, are the preferred imaging methods for the study of the cranial vault and its contents. In conditions where emergent management is decided on the basis of presentation and imaging, CT has the advantage of rapid scan time and wider availability. CT also has good sensitivity and specificity and relatively lower cost. MRI though, provides better parenchymal characterization especially in cases where initial findings are negative on CT (such as in acute ischemia).
Hemangioblastomas are vascular neoplasms of the CNS. Hemangioblastomas are rare and are often associated with von Hippel-Lindau disease (VHL). The most common presentation is a headache and, depending on the size and location of the tumor, patients may present with sensory deficits and motor weakness. Imaging is the main screening method, with histopathologic evaluation required for definitive diagnosis. Surgery is often indicated in the management of hemangioblastomas, though depending on the size, number, and location of the tumors, radiation therapy may also be warranted. Prognosis is usually good in solitary hemangioblastomas, but tumors associated with VHL are often associated with a worse prognosis and a higher risk of recurrence.
Folate and vitamin B12 are 2 of the most clinically important water-soluble vitamins. Deficiencies can present with megaloblastic anemia, GI symptoms, neuropsychiatric symptoms, and adverse pregnancy complications, including neural tube defects. Deficiencies are more likely to occur in specific patient populations, especially B12 deficiencies, which are more common in patients on vegan diets and in those with conditions related to the stomach and/or terminal ileum that affect absorption. These vitamins generally do not cause toxicity when consumed in excess amounts, even in supplemental form, as they are effectively excreted by the kidneys.
Human papillomavirus (HPV) is a nonenveloped, circular, double-stranded DNA virus belonging to the Papillomaviridae family. Humans are the only reservoir, and transmission occurs through close skin-to-skin or sexual contact. Human papillomaviruses infect basal epithelial cells and can affect cell-regulatory proteins to result in cell proliferation. There are > 200 serotypes that can cause several conditions, including cutaneous warts, anogenital warts, and neoplasms.
Neuroblastoma is a malignancy that arises from the neural crest cell derivatives along the sympathetic chain (neuroblasts) and is most commonly located in the adrenal medulla. The tumor often presents in childhood with a flank mass that crosses the midline. Neuroblastoma can also manifest as opsoclonus-myoclonus paraneoplastic syndrome. The tumor is diagnosed through biopsy, and supporting data include measuring the catecholamine breakdown products such as vanilmandelic acid (VMA) and homovanillic acid (HVA) in urine. Imaging studies are needed to localize the tumor. Management depends on several factors such as the stage of malignancy and the patient’s age at the time of diagnosis. Prognosis is favorable in the early stages of neuroblastoma.
An orbital fracture is a break in the continuity of one or multiple bones of the eye socket, caused by direct or indirect trauma to the orbit. Patients frequently present with lacerations around the eye, orbital pain, edema, ecchymosis, diplopia on upward gaze, numbness around the eye, and signs of muscle entrapment. Diagnosis is based on clinical exam and imaging. The mainstay of management is to prevent further injury to the eye while determining whether surgery is needed. Complications include orbital compartment syndrome, blindness, and persistent diplopia.
Neutropenic fever is a medical emergency defined as a fever > 38.3℃ (100.9℉) or higher than 38.0℃ (100.4℉) for more than 1 hour in neutropenic patients. Neutropenic fever is a common life-threatening complication of hematologic malignancies and in patients undergoing chemotherapy. Patients are often asymptomatic, and the only sign is the presence of fever. Diagnosis should include a detailed history, physical examination, and routine laboratory tests, in addition to symptom-directed workup with cultures. Initial management includes the administration of empiric antibiotics adjusted according to clinical response and culture results.
Acromegaly and gigantism are caused by an excessive production of growth hormone (GH) by the pituitary gland. Tall stature is a clinical sign observed in some patients with gigantism. Increased GH and insulin-like growth factor-1 (IGF-1) are responsible for inducing hypersomatotropism. Acromegaly is usually produced by pituitary tumors secreting GH or, less commonly, by extrapituitary disorders. Gigantism typically results in children from excess GH before growth-plate closure; acromegaly typically results from excess GH after growth-plate closure. Diagnosis involves neuroimaging of the pituitary and laboratory tests to evaluate the hypothalamic-pituitary axis. Treatment depends on the operative status of the tumor (if present), or a nonoperative treatment strategy may be utilized.
An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Electrocardiograms are simple, inexpensive, noninvasive, and readily obtained. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. In the healthy state, an ECG records predictable, reproducible waves and complexes, which correspond to electromechanically coupled physiologic events in the heart. Under pathologic conditions, the ECG can detect arrhythmias, ischemia, inflammation, and more.
Parasomnias are a pattern of sleep disorders marked by unusual actions, activities, or physiological events that occur during sleep or sleep-wake transitions. Parasomnias are divided into which sleep phase the symptoms occur, either rapid eye movement (REM) or non-REM (NREM). Symptoms may include simple or complex abnormal movements, such as sleep talking, sleepwalking, sleep terrors, and dream enactment, or emotions, dreams, and autonomic activity. Diagnosis involves a thorough history taking from the patient and the partner. In some cases, polysomnography is required, especially if comorbid sleep disorders are suspected. Some conditions resolve over time without any treatment. For those that require intervention, options include lifestyle or risk modifications, different forms of therapy, and medications. Choice of management is affected by patient preferences.
Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. The disorder can be acute (< 3 months), which can progress to the chronic form (≥ 3 months). Multiple risk factors contribute to having insomnia, including medical illnesses, psychiatric disorders, medications, and the sleep environment. Diagnosis starts with a detailed history and sleep diagnostic aids (sleep diary, sleep problems questionnaire). The 1st line of management is nonpharmacologic, i.e., identifying the stressor(s), implementing sleep hygiene, and utilizing cognitive behavioral therapy. Medications are used with nonpharmacologic intervention or after initial management has failed.
Laxatives are medications used to promote defecation. Most often, laxatives are used to treat constipation or for bowel preparation for certain procedures. There are 4 main classes of laxatives: bulk-forming, stimulant, osmotic, and emollient. Often, a combination of these medications is required to have the desired effect. All laxatives can result in bloating. Laxative overuse can induce diarrhea and dehydration. Non–anion gap metabolic acidosis occurs owing to bicarbonate loss in the feces, while metabolic alkalosis occurs because of volume contraction.
Severe congenital neutropenia (SCN) affects myelopoiesis and has many different subtypes. SCN manifests in infancy with life-threatening bacterial infections. The treatment proven to be effective is the administration of granulocyte colony-stimulating factor, which elevates the decreased neutrophil count. Kostmann disease (SCN3) has an autosomal recessive inheritance pattern, whereas the most common subtype, SCN1, has autosomal dominant inheritance.
Fat-soluble vitamins are absorbed and stored in adipose tissue (fat) and the liver. These vitamins can be released from storage and used when necessary. The 4 important fat-soluble vitamins are A, D, E, and K. Each vitamin has its own function, and deficiencies can lead to significant clinical manifestations. Diagnosis of deficiencies is by clinical presentation and lab testing, and management of vitamin deficiency is with supplementation. Because these vitamins are fat-soluble and stored in the body, overuse of supplemental vitamins may lead to toxicity and adverse effects, especially with vitamins A and D.
Stable and unstable angina are considered an important symptom of coronary heart disease (CHD) and present with chest pain due to transient myocardial ischemia. These disorders can be a warning sign for the risk of heart attack (MI) in the future. Clinically, stable and unstable angina are differentiated by exacerbating factors, duration of symptoms, and response to rest and medications. Diagnosis is by history and examination, ECG, stress testing with possible additional nuclear medicine imaging, echocardiography, or coronary angiography. Management with lifestyle modifications and aggressive risk factor reduction (of hypertension, diabetes, and hyperlipidemia) is indicated to prevent the risk of progression to MI and death.
MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Diagnosis is by clinical history, ECG changes, an increase in cardiac enzymes, and evidence of wall motion abnormalities on imaging. Management depends on the timing of the presentation and local resources with regard to thrombolytic therapy versus percutaneous intervention. All patients receive nitrates, pain control, aspirin, anticoagulation, and beta-blockers (unless contraindicated).
Malabsorption involves many disorders in which there is an inability of the gut to absorb nutrients from dietary intake, potentially including water and/or electrolytes. A closely related term, maldigestion is the inability to break down large molecules of food into their smaller constituents. Malabsorption and maldigestion can affect macronutrients (fats, proteins, and carbohydrates), micronutrients (vitamins and minerals), or both. These disorders present with weight loss, diarrhea, weakness, and fatigue. There are many causes, and the goal of management is to reduce symptoms, with specific treatments aimed at the underlying cause.
Testicular cancer is the most common solid malignancy affecting men 15–35 years of age. Most of the testicular cancers are of the germ cell tumor type, and they can be classified as seminomas and nonseminomas. The most common presentation of testicular cancer is a painless testicular mass. Diagnosis is via physical exam, testicular ultrasonography, and serum tumor markers. Additional imaging helps with staging and assessment of metastasis. Treatment consists of surgical inguinal orchiectomy, and further adjuvant therapy is based on disease pathology and stage. Subsequent strategies include disease surveillance, radiotherapy, and chemotherapy. Disease prognosis is excellent, as testicular cancer is one of the most curable solid neoplasms.
Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Clinical presentation consisting of fatigue, bleeding, fever, and infection is related to anemia, thrombocytopenia, and a lack of functional WBCs. The onset of symptoms takes days to weeks. Additional findings in AML may include gingival hypertrophy and skin infiltration (leukemia cutis). Diagnosis is via peripheral blood smear and bone-marrow biopsy examination (shows myeloblasts). The precursor cells contain Auer rods. Immunophenotyping, histochemistry, and genetic analysis all aid in identifying and guiding the treatment of AML. Management is chemotherapy administered in phases (induction, consolidation, and maintenance) based on subtypes. Prognosis varies according to the age of onset and type of leukemia.
Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia is most commonly seen in diabetic patients as a result of inadequate oral intake with insulin administration, but it can also be seen in hypermetabolic states, such as sepsis, or malnutrition states, such as chronic alcohol use or prolonged fasting. Hyopoglycemia may present with a variety of nonspecific symptoms, including adrenergic symptoms (sweating, tachycardia, tremulousness) and neuroglycopenic symptoms (dizziness, confusion, lethargy, loss of consciousness). Diagnosis is based on serum glucose measurement and clinical presentation. Management depends on the severity of symptoms. A patient with normal mental status may be able to take oral glucose gel or sugary drinks, but a patient with altered mental status will need IV dextrose and frequent serum glucose checks.
Gitelman syndrome is a rare genetic autosomal recessive disorder that affects the sodium–chloride cotransporter in the distal convoluted tubule of the nephron and causes electrolyte abnormalities. The syndrome presents clinically with symptoms of hypokalemia and hypomagnesemia. Diagnosis is based on the clinical presentation of the syndrome with lab testing as well as genetic testing for family counseling. The mainstay of management is potassium and magnesium supplementation to prevent development of symptoms. The prognosis is good, but hypokalemia must be monitored to prevent cardiac arrhythmias and potential cardiac arrest.
Mitochondrial myopathies are conditions arising from dysfunction of the mitochondria (the energy-producing structures) and are characterized by prominent muscular symptoms and accompanied by various symptoms from organs with high energy requirements. The organs disproportionately affected include the skeletal muscles, brain, and heart. Mitochondrial myopathies are caused by mutations in the nuclear DNA or mitochondrial DNA, which typically result in reduced production of energy needed by cells. Presentation can be an isolated myopathy, encephalomyopathy, ophthalmoplegias, or a multisystem disease. Diagnosis involves in-depth medical and family history, along with laboratory and genetic studies. On biopsy, there is subsarcolemmal and intermyofibrillar proliferation of mitochondria seen as “ragged-red fibers.” This condition indicates a compensatory response to energy failure. There is no definitive treatment. Management consists of physical therapy and a multidisciplinary approach in addressing accompanying symptoms.
Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Typical mucocutaneous infections are characterized by an acute localized appearance of clusters of small, painful vesicles on an erythematous base. Although overlap exists, HSV-1 is classically associated with oropharyngeal lesions, whereas HSV-2 is mostly responsible for genital herpes, an STI. Systemic and severe infections including encephalitis, meningitis, and neonatal herpes may also occur. The diagnosis is made based on clinical presentation and history, which can be confirmed by the microscopic examination of a stained smear of a fresh vesicle, nucleic amplification test using PCR, direct immunofluorescence, or serologic tests. The therapy for mucocutaneous lesions is usually symptomatic, but antiviral therapies involving acyclovir, valacyclovir, or famciclovir are useful if given early, and are always part of the therapy for serious systemic infections.
Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. Cryptococcus neoformans is typically found in pigeon droppings and acquired by inhaling dust from contaminated soil. The majority of affected patients are immunocompromised. Patients with AIDS, chronic steroid use, and organ transplant are particularly affected. The primary virulence factor is an antiphagocytic capsule, consisting of repeating capsular polysaccharide antigens. The infection typically affects the lungs and presents as a primary lesion or pneumonia. Dissemination can occur to involve the brain and meninges, skin, bones, and visceral organs. Treatment for cryptococcal meningitis is usually amphotericin B and flucytosine, followed by fluconazole. Cryptococcosis is an AIDS-defining illness and typically associated with CD4 count < 100 cells/μL.
Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. These syndromes are caused by mutations in specific genes associated with tumor suppression or cell cycle regulation. All patients with FAP will develop colon cancer by age 35–40 years if left untreated. Management is with a surveillance program and colectomy.
Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. The syndromes are caused by mutations in specific genes associated with tumor-suppression or cell-cycle regulation. Peutz-Jeghers syndrome is caused by disruptions in the STK11 gene and is associated with colonic (colorectal) and noncolonic (pancreatic, gastric, breast, uterine, cervical, lung, ovarian, and testicular) cancers. Management is with close surveillance and surgery.
Acute lymphoblastic leukemia/lymphoma (ALL/LBL) are hematologic malignancies characterized by the uncontrolled proliferation of lymphoid precursor cells. Acute lymphoblastic leukemia/lymphoma, the most common forms of cancer affecting children, show the presence of increased lymphoblasts. In ALL/LBL, lymphoblasts replace the normal marrow, eventually entering the circulation and infiltrating other organs. The clinical presentation includes fatigue, bleeding, fever, and infections, all of which are related to anemia, thrombocytopenia, and the lack of functional WBCs. The onset of symptoms takes days to weeks. Mass effects of malignant infiltration (in bone, liver, spleen) are common; thus, hepatosplenomegaly and lymphadenopathy are seen. Diagnosis is by peripheral blood smear examination and bone marrow biopsy, which show the presence of lymphoblasts. Immunophenotyping, histochemistry, and genetic studies aid in the classification and guidance of treatment. Management is mainly by chemotherapy, which is administered in phases (induction, consolidation, and maintenance). Prognosis varies according to the age of onset and type of leukemia. The cure rate in children is 85%.
Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. The disorder can usually be managed with lifestyle modification and medications, but occasionally, vascular intervention or surgery are required. Age, sex, smoking, obesity, and diet are contributing factors to hypertension, which can lead to heart attack, stroke, congestive heart failure, and CKD if not managed properly. Many individuals with hypertension are undiagnosed or undertreated.
Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Hypergonadotropic hypogonadism results when the gonads fail, and hypogonadotropic hypogonadism results from failures in the hypothalamic–pituitary–gonadal axis. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Diagnosis is guided by the history, physical exam, measurement of hormone levels, and an evaluation for an underlying etiology. Management is with hormone replacement.
A toxidrome is a group of clinical signs and symptoms associated with a toxic ingestion or exposure. There are 5 traditional toxidromes: anticholinergic, cholinergic, opioid, sympathomimetic, and sedative-hypnotic. Toxidromes often arise from ingestion of overdose amounts, accumulation of medications with resultant elevated serum levels, adverse drug reactions, or interactions between 2 or more medications. Rapid recognition of a toxidrome can help determine the specific poison or class of toxin that was ingested. On presentation of a suspected toxidrome, appropriate airway, breathing, and circulation assessment is initiated. Decontamination is performed, and the patient is stabilized. Diagnosis is accomplished with clinical findings based on medication and exposure history, vital signs, mental status, and physical examination. Testing generally includes toxicology and drug levels, electrolytes, and ECG. Management consists of supportive care and antidote administration if indicated.
Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Clinical presentation may include vertical or horizontal diplopia (double vision). Diagnosis of strabismus is established clinically with the eye cover–uncover test. Management includes therapy with cycloplegic eye drops, eye patching, or surgery. Untreated strabismus can lead to amblyopia, which is cortical blindness with no structural defect.
Internuclear ophthalmoplegia (INO) is an ocular movement disorder that affects the conjugate horizontal gaze, meaning the eyes are incapable of moving in a simultaneous and coordinated manner on the horizontal plane. This disorder is usually caused by a lesion in the brain stem involving the medial longitudinal fasciculus (MLF) and is characterized by impaired adduction ipsilateral to the MLF lesion and abduction nystagmus contralateral to the MLF lesion. Internuclear ophthalmoplegia is a clinical diagnosis. However, investigations involving neuroimaging, especially MRI, help establish the diagnosis. Management of INO varies depending on the cause. The prognosis mainly depends on the etiology. For instance, trauma patients do not have a very favorable prognosis, whereas patients with ischemic and demyelinating causes have a favorable recovery.
Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix “-dronate” or “-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates are indicated for postmenopausal osteoporosis, glucocorticoid-induced osteopenia/osteoporosis, and Paget disease of the bone. Adverse effects include hypocalcemia, hypophosphatemia, avascular necrosis of the femur, and osteonecrosis of the jaw. Contraindications include hypersensitivity reactions and esophageal disorders. Bisphosphonates may interact with aminoglycosides, aspirin, and proton pump inhibitors.
Carbonic anhydrase inhibitors (CAIs) block the carbonic anhydrase enzymes in the proximal convoluted tubule, inhibiting the reabsorption of sodium bicarbonate (NaHCO3), which results in diuresis and metabolic acidosis. Carbonic anhydrase inhibitors also block the carbonic anhydrase present in the eyes and glial cells, resulting in decreased aqueous humor and CSF production, respectively. Acetazolamide is the prototypical CAI. Carbonic anhydrase inhibitors are mainly used for the treatment of altitude sickness, edema in patients with metabolic alkalosis, glaucoma, and, sometimes, as an adjuvant treatment for certain types of epilepsies and increased intracranial pressure. Carbonic anhydrase inhibitors are not used for the treatment of hypertension.
Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Common side effects among the disease-modifying antirheumatic drugs include bone marrow suppression and hepatotoxicity. Leflunomide, methotrexate, and tumor necrosis factor (TNF)-ɑ inhibitors are avoided in pregnancy due to their potential teratogenicity. Hydroxychloroquine and sulfasalazine are safe for use during pregnancy.
Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Known for their remarkable efficacy, opioids induce their effects (analgesia, euphoria, and sedation) by interacting with opioid receptors (μ, κ, and δ) in the nervous system. Opiates/opioids have adverse effects that include respiratory depression, nausea and vomiting, decreased GI motility and constipation, tolerance, dependence, and addiction.
Antepartum hemorrhage is defined as vaginal bleeding that occurs after 20 weeks of gestation and is unrelated to labor. The most important causes are placental abruption (most common), placenta previa (2nd most common), vasa previa, and uterine rupture. Placental abruption and uterine rupture are diagnosed clinically. Placenta previa and vasa previa are usually diagnosed as part of routine screening on a midtrimester ultrasound, and digital exams in these women must be avoided. All of these conditions can lead to maternal and/or fetal hemorrhage, necessitating emergency C-section and maternal and/or fetal resuscitation.
Male sexual dysfunction is any disorder that interferes with the male sexual response cycle and includes desire disorders, erectile disorders, and ejaculatory disorders. Sexual dysfunction has a varied etiology and may be due to psychological causes, endocrine diseases, neurogenic dysfunction, chronic medical illness, or medication/substance abuse. These disorders often cause significant distress to the patient and sexual partner. Treatment options include psychotherapy, physical therapy, and pharmacotherapy based on the causes of dysfunction.
Diarrhea is described as passage of large amounts stools that are often loose, liquid, or watery, resulting in excess loss of fluids and electrolytes. Diarrhea is one of the most common illnesses in children, representing the largest percentages of morbidity and mortality worldwide in the pediatric age group. The majority of cases are infectious, caused by rotavirus, while the rest are caused by bacteria (Escherichia coli, Salmonella) and parasites (Entamoeba histolytica). Management is largely based on rehydration; antibiotic therapy is used only when indicated. Prognosis is excellent if diarrhea promptly treated.
Loop diuretics are a group of diuretic medications primarily used to treat fluid overload in edematous conditions such as heart failure and cirrhosis. Loop diuretics also treat hypertension, but not as a 1st-line agent. The medication inhibits sodium reabsorption through the NKCC2 cotransporter in the thick ascending limb of the loop of Henle (TAL), leading to significant diuresis. Careful monitoring is important because loop diuretics result in increased excretion of sodium, potassium, chloride, calcium, magnesium, and water. In addition to electrolyte and fluid abnormalities, loop diuretics can lead to nephrotoxicity and ototoxicity.
Tay-Sachs disease is an autosomal recessive lysosomal storage disorder caused by genetic mutations in the hexosaminidase A (HEXA) gene, leading to progressive neurodegeneration. This disease is highly prevalent in the Ashkenazi Jewish population. Classic symptoms in infants include rapid degeneration of cognitive and neuromuscular abilities, progressive blindness, and a macular cherry-red spot on physical examination. Diagnosis is made by measurement of hexosaminidase A and beta-hexosaminidase enzyme activity. Currently, there is no cure for this disease, and treatment is aimed at improving the patient’s quality of life.
Von Willebrand disease (vWD) is a bleeding disorder characterized by a qualitative or quantitative deficiency of von Willebrand factor (vWF). Most cases are hereditary, but acquired forms have been described. Von Willebrand factor is a multimeric protein involved in the plate adhesion phase of hemostasis by forming a bridge between platelets and damaged portions of the vessel wall. Von Willebrand factor also regulates the levels of coagulation factor VIII (FVIII) by acting as its carrier. Clinical features vary depending on the plasma vWF levels. Most cases are asymptomatic, but patients may present with petechiae, gingival bleeding, epistaxis, or menorrhagia. The diagnosis primarily depends on the clinical history and laboratory assays, including quantitative measurement of vWF, vWF ristocetin cofactor activity (vWF:RCo) assay, and FVIII coagulant assay. Management is based on the subtype of the disease. The most common agents used are desmopressin acetate and concentrates containing recombinant vWF and FVIII.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but serious acquired hemolytic anemia with periodic exacerbations. This anemia is caused by nonmalignant clonal expansion of ≥ 1 hematopoietic stem cells that have acquired a somatic mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene. Clonal expansion of affected stem cells are deficient in glycosylphosphatidylinositol-anchored proteins (GPI-APs). Deficiency of the GPI-APs CD55 and CD59, which regulate complement, results in intravascular hemolysis. The classic triad of PNH is hemolytic anemia, marrow failure, and thrombophilia. Patients may be treated with the monoclonal antibody eculizumab or with stem cell transplantation, in addition to being treated for associated complications.
Familial juvenile polyposis, also known as juvenile polyposis syndrome, is an autosomal dominant condition characterized by the growth of hyperplastic, hamartomatous polyps in the colon. Polyposis syndromes are a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, and are associated with other extracolonic features. These syndromes are caused by mutations in specific genes associated with tumor suppression or cell cycle regulation. Familial juvenile polyposis is commonly associated with mutations in the SMAD4 (chromosome 18q) and BMPR1A (chromosome 10q) genes. Diagnosis is made by visualizing 5 or more polyps on colonoscopy, or any number plus a positive family history. Management is surgical in order to reduce the likelihood of GI bleeding and obstruction.
Although hepatocellular carcinoma (HCC) is by far the most common malignant liver tumor, there are several rare malignant tumors that are important to keep in mind when making a differential diagnosis. These tumors include cholangiocarcinoma; hepatoblastoma and mesenchymal tumors, such as epithelioid hemangioendothelioma (EHE); and angiosarcoma. While these conditions differ in their etiology and pathology, they often present similarly, with nonspecific symptoms such as fatigue, weight loss, and abdominal discomfort. Diagnosis is by imaging, which can be supported by a biopsy. Surgical excision is the only curative approach for these tumors.
An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. An increase in the concentration of these substances to toxic levels can occur accidentally or intentionally, resulting in both acute and chronic presentations. Some substances can be detected using specific laboratory tests, whereas the detection of others relies on nonspecific findings. Thus, it is important to recognize substance poisoning by history, individual risk factors, and physical examination. Antidotes along with supportive care and monitoring are part of the management.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by poor social skills, restricted interests/social interactions, and repetitive/stereotyped behaviors. The condition is termed a “spectrum” because of the wide variability in the severity of symptoms exhibited. Some patients suffer from severe impairment in language and intellectual levels, while others have normal or even advanced intellect. The etiology is not well understood and there is no known cure. Early diagnosis and intervention are important in improving the patient’s symptoms.
Triptans and ergot alkaloids are agents used mainly for the management of acute migraines. The therapeutic effect is induced by binding to serotonin receptors, which causes reduced vasoactive neuropeptide release, pain conduction, and intracranial vasoconstriction. Triptans are the preferred therapy, followed by ergot alkaloids, but both agents have good efficacy. Due to the vasoconstriction effect, the medications should not be used concurrently or be prescribed to patients with cardiovascular disease.
Endometritis is an inflammation of the endometrium, the inner layer of the uterus. The most common subtype is postpartum endometritis, resulting from the ascension of normal vaginal flora to the previously aseptic uterus. The 2nd subtype is endometritis unrelated to pregnancy, which is further subdivided into acute and chronic forms. Pelvic inflammatory disease usually precedes acute endometritis, while the chronic form is often idiopathic but may be associated with chlamydia, tuberculosis, radiation therapy, or intrauterine devices. Clinical features include fever, abdominal pain, abnormal vaginal bleeding, and vaginal discharge. Diagnosis is based on history and physical examination. Imaging is performed to exclude abscesses, septic pelvic thrombophlebitis, and retained products of conception. Management includes hydration and antibiotic therapy.
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that leads to demyelination of the nerves in the CNS. Young women are more predominantly affected by this most common demyelinating condition. The etiology of MS is unclear; however, both genetic and environmental factors are believed to play a role. The clinical presentation varies widely depending on the site of lesions, but typically includes neurological symptoms that affect vision, motor functions, sensation, and autonomic function. The diagnosis is made via MRI of the entire CNS (brain and spine) as well as CSF examination. Management involves corticosteroids for acute exacerbations and disease-modifying agents to reduce these exacerbations and slow disease progression. The average life expectancy of individuals with MS is decreased by 5–10 years.
Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ≤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Etiologies include uteroplacental insufficiency, drugs, fetal malformations (especially related to the renal/urinary systems), fetal chromosomal abnormalities, and maternal "toxoplasmosis, other agents, rubella, cytomegalovirus, and herpes simplex" (TORCH) infections. Management involves close antenatal monitoring. Complications include pulmonary hypoplasia, preterm delivery, and musculoskeletal deformities due to prolonged compression. Oligohydramnios is also frequently associated with growth restriction and fetal intolerance to labor, necessitating cesarean delivery. Prognosis is extremely poor when diagnosed in the 1st and 2nd trimesters, but generally favorable in the 3rd trimester.
Congenital malformations of the female reproductive system are any congenital anomalies that affect the ovaries, fallopian tubes, uterus, cervix, hymen, and/or vulva. Any of these anomalies can affect the normal reproductive and sexual functions of affected women. The cause is usually unknown. Clinically, these patients typically present with menstrual and/or fertility issues, with the exact presentation varying based on the patient’s anatomy. Diagnosis is primarily based on history, physical examination, and imaging with pelvic ultrasonography and/or pelvic MRI. Management depends on the type of defect(s) present and often involves surgical correction and/or hormone replacement. Most malformations can be managed well and have a good prognosis. Associated complications are infertility and the psychosocial and emotional impact of having “abnormal” genitalia.
Cerebral palsy (CP) refers to a group of conditions resulting in motor impairment affecting tone and posture and limiting physical activity. Cerebral palsy is the most common cause of childhood disability. It is caused by a nonprogressive CNS injury to the fetal or infant brain. It is classified according to muscle tone, its distribution, and the presumed time of injury (spastic diplegia is the most common), and it is present in around 3 per 1,000 live births. Diagnosis is made by a detailed history and physical exam with an MRI scan confirming CNS insult. Interventions are multidisciplinary and prognosis depends on the degree of disability.
Normal placental structure and function are essential for a healthy pregnancy. Some of the most common placental abnormalities include structural anomalies (such as a succenturiate lobe or velamentous cord insertion), implantation anomalies (such as placenta accreta and placenta previa), and functional anomalies (such as placental insufficiency). The placenta is typically seen well on ultrasound, and placental assessment is part of routine antenatal screening, which is when most structural and implantation anomalies are identified. Because of the extensive maternal and fetal circulation through the placenta, placental abnormalities can significantly increase the risk of serious antepartum or postpartum hemorrhage. Placental abnormalities also frequently impact decisions regarding the timing and route of delivery.
Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythropoiesis starts with hematopoietic stem cells, which develop into lineage-committed progenitors and differentiate into mature RBCs. The process occurs in stages, and extrusion of the nuclei and organelles occurs prior to maturation. Thus, mature RBCs lack nuclei and have a biconcave shape. RBCs carry hemoglobin, and the shape allows efficient oxygen transport. Billions of RBCs are produced daily, as the life span is 120 days. Senescent or deformed RBCs are removed by macrophages in the spleen, liver, and bone marrow.
The myeloid lineage produces a diverse group of blood cells (leukocytes) involved in the defense of the body against foreign substances or infectious agents. Monocytes, neutrophils, eosinophils, basophils, and mast cells all arise from the common myeloid progenitor (CMP), which develops from bone marrow stem cells. However, leukocytes have different functions. Neutrophils kill invading bacteria and fungi, eosinophils increase in parasitic infections, basophils and mast cells are key to allergic response as sources of histamine, and monocytes are released from bone marrow to become macrophages in the tissues. The development in the bone marrow is regulated by different cytokines.
Iron deficiency anemia is the most common type of anemia worldwide. This form of anemia is caused by insufficient iron due to a decreased supply, an increased loss, or an increased demand. Iron deficiency anemia is seen across all ages, sexes, and socioeconomic strata; however, children, women of childbearing age, and patients from lower socioeconomic strata are at higher risk. Symptoms include pallor, particularly of the mucous membranes, easy fatigability, and headaches. Iron studies are the key to diagnosis. Treatment is based on the underlying cause of iron deficiency and consists of supplementation.
Renin-angiotensin-aldosterone system inhibitors constitute an important drug class for the treatment of cardiovascular disease. They are 1st-line antihypertensive agents, in addition to being used in the treatment of MI, heart failure, diabetic nephropathy, and stroke. Renin-angiotensin-aldosterone system inhibitors include ACEis, ARBs, direct renin inhibitors (DRIs), angiotensin receptor and neprilysin inhibitors (ARNIs), and aldosterone antagonists, which affect different components of the RAAS pathway. In general, the use of RAAS inhibitors results in decreased vasoconstriction and serum blood volume. Common adverse effects include hyperkalemia, cough, angioedema, and pancreatitis, which are all more common with the use of ACEis than ARBs.
During pregnancy, fetal development and growth are sustained completely by the mother until birth. The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. The placenta is also called “the fetal lung” because it allows for gas exchange between the maternal and fetal circulation. Diseases or defects in the placenta often have severe, and even fatal, complications.
Hypertrophic scars (HSs) and keloids are raised, red, and rigid (3 Rs) scars that develop during cutaneous wound healing and are characterized by a local abnormal proliferation of fibroblasts with over-production of collagen. Over-expression of growth factors, such as transforming growth factor-beta (TGF-β), and decreased production of molecules that promote matrix breakdown, such as matrix metalloproteinases, appear to be involved in the etiology in both an HS and a keloid. Genetics has a strong influence on keloid predisposition, with people of darker skin complexion having a higher predisposition. Keloids occur mostly on the upper torso, shoulders, head, and neck. Treatment of keloids is often ineffective, but moderate success can be achieved with surgical excision, especially when combined with adjuvant non-surgical management.
Trace elements are minerals required in small amounts (1–100 mg/day in adults) to carry out biologic functions. These elements act as cofactors for essential enzymes as well as being components of hormones and antioxidant molecules. Trace elements have essential roles in oxygen transport, energy metabolism, and immune responses. Iron, chromium, copper, and iodine are among these elements. Overt deficiencies in resource-rich countries are rare because of varied food supply, food fortification, and supplement use. However, deficiencies can develop in certain medical conditions. Toxicity can also occur when there is exposure to concentrations larger than those physiologically required.
Arrhythmogenic right ventricular cardiomyopathy is an inherited disorder of the heart muscle that affects the right ventricle (RV); it can cause rhythm disturbances and sudden cardiac death (SCD). The disorder results from mutations in the genes that encode desmosomal proteins involved in cell-to-cell adhesion. Symptomatic patients develop palpitations, arrhythmias leading to syncope, dyspnea, or chest pain. Diagnosis is based on clinical, ECG, echocardiographic, and imaging findings. Management aims to prevent SCD and symptom-causing arrhythmias. Treatment includes implantable cardioverter-defibrillator (ICD) placement, radiofrequency ablation to correct arrhythmias, and antiarrhythmic medications if possible. Prevention of disease progression with lifestyle changes is important, and cardiac transplantation may be necessary after 15 years.
The hepatitis E virus (HEV) is a small nonenveloped virus that contains linear, single-stranded, positive-sense RNA, making it similar to norovirus. Transmission of HEV is via the fecal–oral route and is clinically similar to that of hepatitis A. However, unlike hepatitis A, hepatitis E is quite severe, especially in pregnant women, and may cause fulminant hepatitis along with hepatic encephalopathy over a period of approximately 8 weeks. Management is mainly preventive and includes avoiding contaminated drinking water, good sanitation, and adequate personal hygiene.
Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. B and T lymphocytes play a role in adaptive immunity, and NK cells provide host defense against atypical proteins such as tumor cells. While all developmental stages begin in bone marrow, lymphocyte maturation differs. B lymphocytes and NK cells differentiate in bone marrow before migrating to secondary lymphoid organs (such as lymph nodes). T lymphocytes, however, proceed to the thymus for further maturation.
Calcimimetics are medications that mimic the action of calcium on tissues, particularly in the parathyroid gland. By activating calcium-sensing receptors, calcimimetics inhibit the release of parathyroid hormone. Due to this mechanism, this drug class is mainly indicated for management of hyperparathyroidism. Adverse effects include hypocalcemia, GI symptoms, adynamic bone disease, and QT prolongation. Cinacalcet is metabolized by the cytochrome P450 (CYP450) system, which results in several drug interactions.
Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Common macrolides are erythromycin, clarithromycin, and azithromycin. Side effects include GI upset, QT prolongation, and hepatotoxicity. Resistance mechanisms include ribosomal methylation or mutation, inactivation of the drug through enzyme production, or removal of the drug through efflux pumps.
Worldwide, the most frequent cause of death is heart disease. Thus, the common conditions that are evaluated in healthcare facilities are often related to the heart or the cardiovascular system: hypertension, atherosclerotic disease, and heart failure. In radiologic terms, this region is likely the most frequently studied aspect of human anatomy in healthcare delivery settings. Multiple methods are used, including X-ray, CT, MRI, echocardiography, nuclear imaging, and angiography. Each test has its advantages and disadvantages and is obtained on the basis of the clinical presentation, acuity of symptoms, and risks and benefits to the patient. It is important to know the roles of imaging studies to help determine the proper treatment.
Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. The diagnosis can be confirmed using hemoglobin electrophoresis, which will reveal the presence of abnormal α- or β-globin chains.
Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Common side effects include GI irritation, prolonged bleeding, and AKI.
B lymphocytes, also known as B cells, are important components of the adaptive immune system. In the bone marrow, the hematopoietic stem cells go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs for activation and further maturation. The process entails antigen stimulation, with or without the help of T cells. The T-cell–independent activation generates a short-lived immune response (via plasma cells), and this is seen with antigens such as bacterial lipopolysaccharides. T-cell–dependent activation, on the other hand, produces both plasma cells and memory cells. Activated B cells then proliferate in the germinal centers, but not all become effector B cells. Through somatic hypermutation, B cells undergo additional mechanisms to increase the affinity of the antibody to the antigen. Only those with high-affinity B-cell receptors subsequently advance for terminal differentiation. B cells then go through class switching (from IgM to another class of Ig) under the influence of cytokines. After class switching, the B cells become plasma cells (which produce antibodies) or memory cells (which mount a robust secondary immune response).
The primary lymphoid organs, also referred to as central lymphoid/lymphatic organs, are the tissues responsible for the production of lymphoid cells from progenitor cells, incuding the bone marrow and the thymus. In the bone marrow, hematopoietic stem cells progress to become oligopotent progenitors (in the case of lymphocytes, the common lymphoid progenitor). B lymphocytes stay and undergo processes for differentiation before migrating to the secondary lymphoid organs (such as lymph nodes). The progenitor cells that are to become T lymphocytes proceed to the thymus for further maturation.
The lymphatic system consists of the lymphoid organs containing the cells of the immune system and the lymphatic vessels, which transport interstitial fluid (as lymph) back to the venous circulation. Lymphatic vessels are spread extensively throughout the body, draining and filtering lymph, facilitating homeostasis, and aiding in defense against circulating pathogens. Fluid flow is unidirectional, enabled by valves in the collecting lymphatic vessels. In vessels without valves, the muscle contraction of organs and adjacent blood vessels help in the fluid movement. To return to the venous circulation, the lymph is collected by the major lymphatic ducts: right lymphatic duct (collects from the right side of the head and neck, the right side of the thorax, and the right upper extremity) and the thoracic duct (collects from the rest of the body). Pathologic conditions involving the lymphatic system are associated with infections, lymphatic damage, or injury and malignancies.
Hypertensive disorders of pregnancy include chronic hypertension, preeclampsia/eclampsia, gestational hypertension, and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. These syndromes pose a significant risk to the pregnant woman and her fetus. Hypertension is defined as a BP > 140/90 mm Hg and can be diagnosed before (chronic) or after (gestational) the 20th week of gestation. Preeclampsia is gestational hypertension with proteinuria or end-organ damage. Eclampsia is preeclampsia with seizures. HELLP syndrome is a severe manifestation of preeclampsia leading to hemolysis, low platelets, and liver injury. Management is with antihypertensives and magnesium sulfate for seizure prophylaxis. The definitive treatment for all hypertensive disorders of pregnancy is delivery.
Corneal anomalies are conditions in which the function of the cornea is impaired due to various congenital or acquired pathologies. Corneal anomalies are classified based on anomalies of size, clarity, ectatic anomalies, corneal dystrophies, and acquired conditions. Pathological changes can result in opacity or clouding of the cornea and, hence, reduce visual acuity. Corneal anomalies are usually diagnosed based on clinical findings. Management includes correction of refractive errors and treatment of the underlying conditions.
Major neurocognitive disorders (NCDs), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. There are several distinct etiologies for major NCDs. While there are known risk factors and measures to prevent major NCDs, there are no effective curative treatments.
Interleukins are a type of cytokines (signaling proteins) that communicate messages between different parts of the immune system. The majority of interleukins are synthesized by helper CD4 T lymphocytes along with other cells such as monocytes, macrophages, and endothelial cells. Interleukins underlie the development and differentiation of T and B lymphocytes and hematopoietic cells.
Alpha-1 antitrypsin deficiency is a genetic disorder caused by inherited genetic mutations of the SERPINA1 gene, causing the defective production of the protease inhibitor alpha-1 antitrypsin (AAT). These mutations can lead to deficiency of the enzyme causing lung disease, production of an abnormal form of the enzyme leading to liver dysfunction, or both. Patients commonly present with emphysema, spontaneous pneumothorax, cirrhosis, hepatitis, or hepatocellular carcinoma. There is no known cure. Management is supportive and includes infusion of AAT, treatment of comorbidities, and liver transplantation. Prognosis may vary based on the form of disease contracted and the severity of symptoms.
Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. There are many causes of delirium. Early recognition and accurate diagnosis constitute the 1st steps to adequate management. The primary goal of treatment is to identify and reverse the underlying cause and prevent future episodes. Pharmacotherapy is reserved for the most severe cases of agitation.
Carcinogenesis is the development of cancer by transforming healthy cells into cancer cells. This complex process occurs because of mutations in DNA that prevent the normal process of cell division. Normal cells have programmed cell death, but cancer cells proliferate without regulation. The genetic changes that cause cancer may occur in reproductive cells of the ova and sperm and propagate to progeny. Somatic changes are acquired during an individual’s lifetime because of exposure to carcinogenic chemicals, tobacco, radiation, and other factors. Mutations in oncogenes that promote cell growth and tumor suppressor genes that reduce cell growth are important mechanisms in the dysregulation of cell division and lead to cancer. Cancers are classified by their cell type and their location.
The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. The primary indication for use is treatment of urinary tract infection (although significant resistance has emerged). In addition, the drugs are used to treat and prevent opportunistic infections such as toxoplasmosis encephalitis and pneumocystis pneumonia in immunosuppressed individuals. The most common adverse events are hypersensitivity reactions, fever, rash, GI upset, and hematologic reactions. The drugs are generally contraindicated in pregnancy, young/ill infants, and individuals with megaloblastic anemia or severe renal impairment.
Ovarian cysts are defined as collections of fluid or semiliquid material, often walled off by a membrane, located in the ovary. These cysts are broadly categorized as either functional or neoplastic. Neoplastic ovarian cysts are subcategorized as either benign or malignant. When the cysts occur as a result of normal physiologic processes, they are called functional, whereas if there is abnormal growth of ovarian cells, the cyst is referred to as neoplastic. In women of reproductive age, neoplastic ovarian cysts are typically benign; however, the risk of malignancy increases in the postmenopausal period. While most ovarian cysts do not cause symptoms, some women report vague symptoms such as lower abdominal pain or abdominal fullness. Complications of functional cysts include torsion and rupture. Neoplastic cysts may be either benign or cancerous. A diagnosis of ovarian cancer requires consultation with a specialist because treatment involves coordination of surgery and chemotherapy. Treatment is dependent on the etiology of the ovarian cyst and may range from surgical intervention to supportive care only.
Hirschsprung disease (HD), also known as congenital aganglionosis or congenital megacolon, is a congenital anomaly of the colon caused by the failure of neural crest-derived ganglion cells to migrate into the distal colon. The lack of innervation always involves the rectum and extends proximally and contiguously over variable distances. Most cases are diagnosed in the neonatal period, with a classic triad of symptoms including delayed passage of meconium, abdominal distension, and bilious vomiting. Individuals having less severe degrees of functional obstruction may not be diagnosed until later in infancy or childhood when they present with symptoms of chronic refractory constipation, abdominal distension, and failure to thrive. The diagnosis of HD is confirmed by the absence of ganglion cells on rectal biopsy after noninvasive testing such as anorectal manometry and the use of contrast enema. Surgical resection of the aganglionic segment is the standard treatment.
Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. There are numerous maternal adaptations to pregnancy, both anatomic and physiologic, which occur to help support the developing fetus and prepare the mother's body for ultimate delivery. Pregnancy is not a pathologic condition, but good routine prenatal care can help achieve the best outcomes for both the mother and infant. Prenatal care includes appropriate lab and ultrasound testing, anticipatory guidance, and offering solutions or advice for common pregnancy discomforts.
The head and neck examination is the portion of the physical examination done to observe for signs of head and neck disease or illness. The head and neck examination consists of inspection, palpation, and auscultation. The information gathered from the physical examination of the head and neck, along with the information from the history, is used by the physician to generate a differential diagnosis and treatment plan for the patient.
Pancreatic cancer, consisting mostly of invasive pancreatic ductal adenocarcinoma (PDAC), arises from the ductal cells of the exocrine pancreas and is the 4th leading cause of cancer-related deaths in the United States. Pancreatic cancer has the highest mortality rate among the major cancers, with a 5-year survival rate of only 8%–10%. Clinical presentation includes symptoms of abdominal pain, jaundice, and weight loss. Diagnosis is made by CT, MRI, and endoscopic ultrasonography (EUS). Management by surgical resection, usually with neoadjuvant or adjuvant chemotherapy, provides the only chance for cure in the 15%–20% of patients who have resectable disease at the time of diagnosis. Other rare malignant tumors arising from the exocrine pancreas are acinar cell carcinoma and pancreatoblastoma.
Pancreatic neuroendocrine tumors (PanNETs) arise from the endocrine pancreas (islet cells) and represent 2%–5% of primary pancreatic neoplasms; the other 95%–98% of pancreatic neoplasms are from the exocrine pancreas. The majority of PanNETs are nonfunctional (50%–75%), while others that are functional may be benign or malignant. Benign or malignant PanNETs include insulinomas, gastrinomas, malignant pancreatic neuroendocrine carcinomas, and very rare tumors named glucagonomas, somatostatinomas, and VIPomas, after the hormones they secrete. Diagnosis is made clinically, with lab testing for hormone secretion, as well as imaging or upper endoscopy. Management is surgical or with newer molecularly targeted therapies.
Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5–5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. If minor in severity, hypokalemia is usually asymptomatic. However, acute reductions in K+ level or severe hypokalemia can lead to cardiac arrhythmias, muscle weakness, rhabdomyolysis, paralysis, and respiratory failure. Diagnosis is by clinical history and lab testing. Management is guided by severity and includes treating urgent symptoms, replacing the K+ deficit, and treating the underlying cause.
The hepatitis A virus (HAV) is a nonenveloped virus of the Picornaviridae family with single-stranded RNA. The virus replicates in the liver, is excreted in the bile, and is found in high concentrations in the stool of acutely infected individuals. The 2 main routes of infection are consumption of contaminated food or water and direct contact with an infected person. HAV causes an acute, highly contagious hepatitis with unspecific prodromal symptoms such as fever and malaise followed by jaundice and elevated liver transaminases. Most individuals recover fully within a few months, and the immunity resulting from HAV infection is lifelong. Unlike hepatitis B and C, HAV infection does not result in chronic infection or chronic liver disease. Preventive vaccination is available for HAV and is recommended for individuals with increased risk of exposure and, in some countries such as the United States, for all children > 12 months of age.
Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or “uncontrolled” hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Despite the prolonged presence of hypertension, there may be no signs or symptoms of end-organ damage (e.g., brain, eyes, heart, kidneys) until function becomes decompensated or severely impaired. Individuals may present with clinical symptoms such as chest pain due to MI or focal neurologic changes associated with a cerebral infarction or intracranial hemorrhage. Diagnosis is made using serial blood pressure measurements and testing for end-organ damage. Management includes lowering the blood pressure and treating specific organ damage.
Gastric acid medications include proton pump inhibitors (PPIs) and H₂ receptor antagonists (also known as H₂ blockers). The drugs work through different mechanisms to suppress acid secretion by parietal cells in the stomach. The most common indications include peptic ulcer disease, GERD, and dyspepsia. Adverse effects of PPIs include malabsorption, acute interstitial nephritis, and an increased risk of Clostridioides difficile infection. Adverse effects of H₂ blockers include CNS effects, bradycardia/hypotension, gynecomastia, and galactorrhea. Both classes are associated with drug interactions related to the cytochrome P450 system.
Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Uremia refers specifically to the constellation of symptoms that occur with severe renal dysfunction. The etiologies of AKI are classified as prerenal, intrinsic renal, or post-renal, and there is a varied clinical presentation depending on the severity of kidney dysfunction. Acute kidney injury is diagnosed initially by a change in serum creatinine levels, and then the etiology is determined by clinical history, lab testing, imaging, and possibly kidney biopsy. The management of AKI depends on the etiology; however, attention to the individual's volume status and serum electrolytes is always important. If management is unsuccessful and AKI progresses to CKD, then renal replacement therapy with dialysis or kidney transplantation is necessary.
T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. A functional mature T cell develops from a step-by-step process creating a T-cell receptor (TCR) complex, selecting T cells with appropriate affinity to self-antigens associated with major histocompatibility molecules (positive selection), and expressing either CD4 or CD8. In this series, cells predisposed to autoimmunity undergo apoptosis (negative selection). When released from the thymus, the naive mature T cells travel to the secondary lymphoid organs for activation. Two signals, an antigen-specific binding of TCR and costimulation, are required to be activated (ready to mount an immune response). In the case of CD8+ T cells, additional cytokine stimulation is necessary. Depending on the cytokines they are exposed to during antigen stimulation, the undifferentiated mature T cell (Th0) develops into cells with different functions: CD4+ become T helper (Th) cells and CD8+ become cytotoxic, or cytolytic, cells. Th cells have other subtypes; the most characterized are Th1, Th2, Th17, follicular Th cells, and regulatory T cells. Other types include natural killer T cells and memory T cells. These mature differentiated T cells ensure effective surveillance and immediate response to pathogens, tumor cells, and foreign tissues and provide immunologic memory.
Colon polyps are growths of mucosal tissue in the colon, the most common site of polyps in the GI tract. Polyps can be classified as neoplastic or nonneoplastic and may be associated with genetic syndromes. Hyperplastic polyps are nonneoplastic and are the most common type overall, whereas adenomas are the most common type of neoplastic polyp and have the potential to progress to cancer. For most people without hereditary syndromes, colon cancer screening should begin at age 50 (at age 45 for Black individuals) and in adolescence for those with the rare familial adenomatous polyposis (FAP) syndrome. Diagnosis is by biopsy, and management includes frequent surveillance in people with adenomatous polyps or screening every 10 years in the general population until age 75.
Tension headache is the most common of the primary primary headache disorders and one of the most common disorders presenting for medical evaluation worldwide. Tension headaches are generally described as bilateral, nonthrobbing, and of mild to moderate severity. There is no aura or other associated features. The diagnosis is clinical, often self-diagnosed by the patient or in the primary care setting. Management consists of abortive analgesics, such as NSAIDs and aspirin for isolated attacks, and preventative measures, such as behavioral changes, biofeedback, and preventative administration of medication for more chronic attacks.
Antithyroid agents are used in the management of hyperthyroidism, particularly that due to Graves’ disease. This group of medications includes the thionamides (methimazole and propylthiouracil), potassium iodide, and radioactive iodine. Thionamides are currently the preferred choice for hyperthyroid management; these drugs work by blocking thyroid hormone synthesis. Propylthiouracil also blocks the conversion of T4 to T3 and, because it less readily crosses the placenta, is the preferred therapy in the 1st trimester of pregnancy. Potassium iodide mainly works through inhibiting thyroid hormone release. Potassium iodide is most often used as a pretreatment prior to thyroid surgery or as an adjunct to hyperthyroid management. Radioactive iodine causes damage to thyroid tissue, thereby definitively reducing thyroid function.
Cluster headache is a primary headache disorder characterized by moderate-to-severe unilateral headaches that occur in conjunction with autonomic symptoms. Cluster headache can last from weeks to months, during which the affected individual may experience attacks up to several times a day, followed by a pain-free remission period. Autonomic symptoms typically manifest as ocular and nasal phenomena (e.g., ptosis, miosis, nasal congestion, rhinorrhea) on the same side as the headache. Men are more commonly affected by cluster headaches than women. The diagnosis is clinical and often easy to establish owing to the distinct features of the presenting headache. The 1st-line treatment involves administration of oxygen by nasal cannula and/or abortive therapy using a triptan. Preventative strategies (e.g., glucortoicoids, verapamil) are crucial, as cluster headache is a chronic condition associated with significant morbidity and a high rate of suicide.
Corneal abrasions, erosions, and ulcers are classified as corneal epithelial defects. These defects are differentiated according to their depth: abrasions are into the corneal surface epithelium, erosions involve the corneal epithelium and epithelial basement membrane, and ulcers extend into the underlying stroma. Corneal defects are commonly caused by injury to the eye by foreign bodies, spontaneous causes such as corneal epithelial dystrophy, or infections. These injuries are diagnosed with proper history taking and physical examination. Slit-lamp examination is used for confirmation. Treatment includes use of topical lubricants, analgesics, antibiotics, and an eye patch. Minor surgical procedures are used in treating erosions. Complications include infections, loss of vision, perforation, and irregular astigmatism.
As the most common cause of dementia, Alzheimer disease affects not only many individuals but also their families. Alzheimer disease is a progressive neurodegenerative disease that causes brain atrophy and presents with a decline in memory, cognition, and social skills. Several genetic defects and risk factors have been described, although there is no clear cause in the majority of cases. The main pathologic features are neuritic plaques, extracellular deposits of amyloid peptides, and neurofibrillary tangles. The clinical features are memory impairment, loss of executive function and judgment, impaired cognitive function, and behavioral changes. Diagnosis is based on clinical examination, neuropsychiatric testing, and imaging. There is no curative therapy, but symptomatic management with medications may slow progression; these include cholinesterase inhibitors, the N-methyl-D-aspartate (NMDA) receptor antagonist memantine, and a recently approved anti-amyloid monoclonal antibody.
Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. The work of hormones allows the body to maintain homeostasis and regulate growth and development. Hormones are typically either made from amino acids or derived from cholesterol (the latter group being known as steroid hormones). Hormones exert their effects by binding to receptors either on the cell surface (most amino acid–based hormones) or within the cytosol (steroid hormones). Ultimately, binding to receptors triggers changes in gene expression or enzymatic activity within the cell.
Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. The innate immune response is activated within minutes to hours after exposure to an infection, which curtails microbe invasion at the initial stages. The pathogen has specific components recognized by pattern recognition receptors (PRRs). After identification of a microbial invasion, noncellular components (including the complement system and cytokines) act in concert with cellular elements to achieve cell recruitment, direct microbial killing, or phagocytosis induction. The steps all aim to eliminate the pathogen. Antimicrobial mechanisms in phagocytosis include acidification and respiratory/oxidative burst. The process terminates with destruction of the threat while maintaining immunologic homeostasis. The defense is also important in activating the adaptive immune system.
A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Diagnosis is clinical, relying on history and physical exam, but also may use EEG and other tools. Management includes both abortive and preventive medications but may not be required in self-limited cases with no etiology found during workup.
A comprehensive examination of the eyes and their functions is important for all individuals with ocular symptoms, and to screen for visual acuity, glaucoma, and retinal pathology. A routine examination includes testing for visual acuity, peripheral vision, and color vision, plus an examination of the external eye, conjunctiva, sclera, iris, pupil, and extraocular movements. Primary care clinicians evaluate and refer for visual acuity issues, and treat minor eye conditions such as infections, hordeola (styes), and corneal abrasions. Slit-lamp exams are performed by eye specialists or emergency providers to examine the cornea, anterior chamber, lens, and fundus. Dilated exams help examine the retina. Annual examinations are recommended for individuals with diabetes for early detection and treatment of retinopathy.
Antidiarrheal agents include several drug classes, including opioid agonists, somatostatin analogues, adsorbents, and bile acid sequestrants. These medications mainly work through antimotility and/or antisecretory effects. Somatostatin analogues are particularly helpful for secretory diarrhea due to endocrine hormone-producing malignancies, while bile acid sequestrants can be used for conditions causing bile acid malabsorption diarrhea. Antidiarrheals can decrease the clearance of infectious pathogens and toxins and should be avoided in invasive infectious diarrhea.
Cancer is the 2nd leading cause of death in the US after cardiovascular disease. Many malignancies are treatable or curable, but some may recur. Thus, all malignancies must be assigned a grade and stage in order to guide management and determine prognosis. The tumor grade classifies a tumor by its histology and is part of the internationally accepted TNM staging system, which is used to characterize the extent of the disease. Metastatic disease refers to cancer that has spread beyond its primary tumor site.
Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Type I IFNs have been extensively studied; these proteins bind to cell-surface receptors when triggered by a viral infection. After stimulation, pathways are activated to produce proteins (e.g., ribonuclease) that inhibit viral replication. An antiviral state is created in both infected and uninfected cells. Type I IFN also has antitumor properties. The antiviral activity of type II IFN (IFN-ɣ) is not as potent as that of type I, but IFN- ɣ is crucial in macrophage activation. The recently discovered IFN-ƛ is noted to have activity against intestinal viruses. With a wide range of biologic effects, interferons are used in therapy for malignancies, infections, and other immune-related conditions (e.g., multiple sclerosis).
Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder. Although the cause is unknown, several genetic and environmental risk factors are currently being studied. Individuals present clinically with resting tremor, bradykinesia, rigidity, and postural instability. Parkinson disease is diagnosed clinically on the basis of characteristic signs and symptoms. The postmortem finding of Lewy bodies in the brain is the only confirmation for the disease. Treatment includes supportive physical and emotional care plus medications such as levodopa/carbidopa, monoamine oxidase type B inhibitors, and dopamine agonists.
An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. The clinical presentation includes neurologic symptoms with varying degrees of motor and sensory loss corresponding to the area of the brain that is affected and the extent of tissue damage. Diagnosis is made by physical examination and imaging. Management is ideally with thrombolytic therapy to restore blood flow, depending on the time frame and clinical situation. Long-term rehabilitation with physical, occupational, and speech therapies is important after the acute event.
Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. A migraine attack might be preceded by a so-called aura—neurologic phenomena of visual, auditory, sensual, or motor quality. There is a strong hereditary component in the etiology of migraines. Migraine headache is a clinical diagnosis with several variants. Management strategies include abortive therapy such as NSAIDs and triptans to manage acute episodes as well as preventive strategies to minimize morbidity and pain-related disability.
Vasculitides are a group of conditions characterized by vasculitis, ischemia, and damage to the organs supplied by the affected vessels. The affected arteries are of different sizes and locations and vary by the type of vasculitis. Vasculitides can be a primary condition or secondary to another underlying disease. There is no clearly known pathophysiology. The diagnosis should be considered in any individual with palpable purpura, pulmonary infiltrates, ischemic events, and multisystem disease. Prompt recognition and therapy of the vasculitides are imperative, as they are often serious and sometimes fatal diseases. Management includes immunosuppressive, antiviral, and/or antiinflammatory agents.
Ventricular tachycardia is any heart rhythm faster than 100 beats/min, with 3 or more irregular beats in a row, arising distal to the bundle of His. Ventricular tachycardia is the most common form of wide-complex tachycardia, and it is associated with a high mortality rate. Ventricular tachycardia is often caused by myocardial ischemia, structural disease, congenital conditions, or electrolyte derangement. Individuals may present with chest pain, dyspnea, palpitations, syncope, and hemodynamic instability. Diagnosis is based on characteristic ECG findings of wide-complex QRS, fusion, and capture beats. Management may require antiarrhythmic medications or electrical cardioversion to avoid complications such as heart failure, multiorgan failure, and cardiac arrest.
The vulva is the external genitalia of the female and includes the mons pubis, labia majora, labia minora, clitoris, vestibule, vestibular bulb, and greater vestibular glands. The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery.
Hepatitis D virus (HDV) is a small enveloped, single-stranded RNA virus. Hepatitis D virus is considered a satellite virus, as it requires the presence of hepatitis B virus (HBV) for assembly and secretion. Therefore, in order for an individual to contract hepatitis D, coinfection or superinfection with HBV is required. Like HBV, HDV is transmitted parenterally, through unprotected sexual intercourse, or perinatally. Clinical presentation is that of a classical viral hepatitis, including coinfection of HDV and HBV, which is considered the most serious form of hepatitis because of the high mortality rate. For acute cases, management is supportive, whereas for chronic cases, pegylated interferon alfa (PEG-IFN-α) is needed.
Huntington disease (HD) is a progressive neurodegenerative disorder with an autosomal dominant mode of inheritance and poor prognosis. It is caused by cytosine-adenine-guanine (CAG) trinucleotide repeats in the huntingtin gene (HTT). The most common clinical presentation in adulthood is a movement disorder known as chorea: abrupt, involuntary movements of the face, trunk, and limbs. Psychiatric and cognitive features are also characteristic, and patients with HD are at an increased risk for suicide throughout the course of the disease. The diagnosis is primarily clinical, often with a positive family history followed by genetic confirmation. Management by an interdisciplinary team is supportive, with the goal of maintaining quality of life. Treatment of depression, agitation, and psychosis is the 1st priority for patients with Huntington disease over the treatment of chorea.
Brain death is a legal and clinical term describing the irreversible cessation of all cerebral and brainstem functions, including the ability of the brain stem to regulate vegetative and respiratory activities. Brain death can be due to a variety of etiologies causing catastrophic injuries to the brain, including brain ischemia due to cardiopulmonary arrest, drugs, sepsis, and trauma. The diagnosis is made at the bedside based on the clinical context and performance of a neurological exam. Additional ancillary studies may be needed to support the diagnosis and diagnostic criteria may vary among states and countries. A diagnosis of brain death must be established prior to consideration of organ donation.
Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Diagnosis is confirmed with EEG. While some epileptic disorders resolve over time, many require lifelong antiepileptic medication for management or, in some refractory cases, surgical procedures.
Tumor necrosis factor (TNF) is a major cytokine, released primarily by macrophages in response to stimuli. The presence of microbial products and dead cells and injury are among the stimulating factors. This protein belongs to the TNF superfamily, a group of ligands and receptors performing functions in inflammatory response, morphogenesis, and cell proliferation. Tumor necrosis factor interacts with 2 receptors, which initiate signal transduction pathways leading to different cellular responses (inflammation, cell survival, or apoptosis). Inappropriate or unrestrained activation of TNF signaling produces chronic inflammation, as seen in autoimmune conditions (e.g., rheumatoid arthritis, psoriasis). The mechanism of TNF inhibition has been used in treating these inflammatory diseases.
The pituitary gland, also known as the hypophysis, is considered the “master endocrine gland” because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. The pituitary gland has 2 lobes: the anterior lobe (the adenohypophysis) and the posterior lobe (the neurohypophysis). Each lobe has its own regulation, set of secretory products, and feedback loops. Abnormalities in the pituitary gland can lead to a wide range of clinical conditions, some of which include hyperprolactinemia, acromegaly, hyperthyroidism or hypothyroidism, and central diabetes insipidus.
Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. Antibodies undergo processes that improve antigen affinity and provide appropriate defense by class switching. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. General functions include opsonization, neutralization of infectivity of the pathogens, cytotoxicity, and complement activation. Specific classes have unique defensive mechanisms.
Cell-mediated immunity is an integral part of the adaptive immune system, mounting a highly specific defense against pathogens. Cell-mediated immunity develops over a longer period of time than innate immunity. Cell-mediated adaptive response occurs in cells/tissues (intracellular infections or aberrant cells (e.g., tumors)) and involves the T cells or T lymphocytes. The cells, which arise from bone marrow, migrate to the thymus for further maturation. A T cell receptor is assembled and activation is facilitated by antigen-presenting cells in secondary lymphoid organs. Influenced by cytokines, activated T cells can differentiate into subsets (e.g., CD4+ T helper cells, CD8+ cytotoxic T cells, memory T cells). T helper cells aid in the eradication of pathogens by helping the partners of immune cells (e.g., macrophages and granulocytes). With mechanisms activating the caspase pathway, cytotoxic T cells have the capacity to kill microbes. Memory T cells develop after initial exposure to the antigen and become effector T cells on reinfection. T cells also activate B cells (a major component in humoral immunity), which enhance the ability to eliminate pathogens.
Humoral adaptive immunity is an integral part of the adaptive immune system, which mounts a highly specific defense against pathogens but takes a longer time to respond (compared to the innate immune system). Humoral immunity is the arm of the immune system protecting the extracellular fluids of the lymphatics (lymph), interstitium, and circulatory system (plasma) from microbial contamination mediated through soluble molecules. The B cells play a major role, producing antibodies or immunoglobulins. Arising from the bone marrow, B cells originate from the common lymphoid progenitor and undergo stages to assemble the B cell receptor. To become fully functional, activation follows, and this can be T cell–dependent (which produces memory cells) or T cell–independent (producing a short-lived response). When activated, B cells go through processes enhancing antigen affinity, class switching, and differentiation to plasma cells and memory cells. Plasma cells produce the antibodies, while memory B cells respond to reinfection. There are different immunoglobulin isotypes, generally providing immune protection through complement activation, opsonization, neutralization of toxins or viruses, and induction of cell lysis.
High-risk headaches, sometimes also referred to as red-flag headaches, encompass secondary causes of headache that can result in irreversible end-organ damage, neurologic deficits, loss of vision, and even death. Entities such as subarachnoid hemorrhage, meningitis/encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. Diagnosis of a high-risk headache requires a high degree of clinical suspicion and is made by conducting a thorough clinical evaluation followed by a targeted workup for the most likely etiology. Management depends on the etiology but consists of prompt treatment of the underlying cause and stabilization of accompanying organ dysfunction.
Movement disorders can be characterized as hypokinetic or hyperkinetic and often require pharmacologic management to improve the individual’s level of function. Common movement disorders include essential tremor, tics (Tourette syndrome), Parkinson disease, Huntington disease, and Wilson disease. Each of these conditions requires unique pharmacologic interventions depending on the pathophysiology and symptom severity. For example, Parkinson disease requires restoration of dopaminergic activity, while symptoms of Huntington disease are ameliorated by reducing dopamine concentrations. Although these agents can be highly beneficial, no agent is innocuous and some have potentially severe adverse events.
The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck, spanning the regions between the C5 and T1 vertebrae and encircling the anterolateral trachea. The left and right lobes of the thyroid gland are connected by a central isthmus. Important processes in metabolism, growth, cardiac function, and calcium homeostasis are regulated by the thyroid hormones (thyroxine and triiodothyronine) and calcitonin.
The gonadal hormones are produced by the human gonads: the testes and the ovaries. The primary hormones produced by these organs include androgens, estrogens, and progestins. Testosterone is the primary androgen, and it plays a critical role in the development of the primary and secondary male sex characteristics as well as of spermatogenesis. Estradiol and progesterone are the primary female hormones, which are responsible for egg development, the menstrual cycle, and breast development. The gonadal hormones are part of the hypothalamic-pituitary-gonadal (HPG) axis and are regulated by the pituitary hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In turn, FSH and LH are both regulated by gonadotropin-releasing hormone (GnRH) secreted from the hypothalamus.
Class 2 antiarrhythmics include beta-blockers, which exert their therapeutic effects by blocking epinephrine and norepinephrine from binding to the beta-adrenergic receptors in cardiac tissue. The outcome is an antiarrhythmic effect, which results from decreased sinoatrial node activity and increased atrioventricular conduction time and refractory period. Additional effects include decreased cardiac contractility, afterload, and blood pressure. Class 2 antiarrhythmics are used in the management of atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular arrhythmias. Adverse effects include bradycardia, hypotension, bronchospasm, fluid retention, and fatigue. Beta-blockers should not be used in individuals with decompensated heart failure, shock, and severe bradycardia.
The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Different nuclei within the hypothalamus play roles in hormone regulation and secretion, autonomic regulation, thermoregulation, food and water intake, sleep and circadian rhythms, memory, and emotional behavior. The hypothalamus has both neural and circulatory connections with the pituitary gland. Abnormalities in the hypothalamus can lead to a wide range of clinical conditions.
The immune system is equipped with a varied repertoire of defense mechanisms against pathogens. Functionally, the immune system is differentiated into the innate and adaptive components. Innate immunity, the 1st protective layer of defense, is a system that recognizes threatening microbes, distinguishes self-tissues from pathogens, and subsequently eliminates the foreign invaders. The response is nonspecific and uses different layers of protection: barriers such as the skin, pattern recognition receptors (PRRs) as well as circulating proteins (e.g., complement) that relay signals of a threat, and immune cells that help eliminate the microbe. Pathogen-associated molecular patterns (PAMPs) in microorganisms and damage-associated molecular patterns (DAMPs) from injured tissues are identified, and the appropriate cells are recruited. Involved cells include phagocytes and accessory cells. The offending pathogens are engulfed by phagocytes for destruction. In antigen-presenting cells (the most potent of which is the dendritic cell), parts of the pathogen material or peptides are transported to the cell surface. Through a unique antigen-loading mechanism specific to MHC I or II, the processed antigen peptides are then presented to the appropriate T cells, leading to T-cell activation. This interaction links innate immunity with adaptive immunity.
As a general term, headache is a descriptor tied to hundreds of clinical entities. A headache is one of the most common reasons people present for medical attention. All headaches fall into 1 of 2 classification systems; primary and secondary headache syndromes. The presentation, degree of severity, underlying pathogenesis, potential clinical sequelae, management, and prognosis are as variable as the underlying headache entities.
Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder presenting with a facial birthmark called a port-wine stain (PWS), neurological abnormalities such as seizures, and eye abnormalities such as glaucoma. Not all of these symptoms have to be present in an affected individual, and some may develop later in life. While the condition is congenital, it is not inherited, as the causative mutation in the gene GNAQ is somatic and sporadic. Diagnosis is suspected based on symptoms and neuroimaging and confirmed with genetic testing. Management is targeted at symptom management and prevention of seizures and hemiparesis.
Diffuse proliferative glomerulonephritis (DPGN) is a histopathologic classification of glomerulonephritis (GN) characterized by an increased cellular proliferation affecting > 50% of the glomeruli. Mesangial, endothelial, and epithelial cells are notably increased. The most common causes are lupus nephritis class IV and IgA nephropathy. Individuals may present with symptoms related to the renal disease, such as fatigue, nausea, vomiting, hematuria, proteinuria, hypertension, and edema. Other manifestations related to the underlying disease can be present. Diagnosis is made by laboratory tests, renal imaging, and renal biopsy. Microscopic findings show hypercellularity of mesangial and endothelial cells, with capillary loop thickening. Early aggressive therapy is indicated and is based on the specific etiology.
The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. The pancreas is covered with a very thin connective tissue capsule that extends inward as septa, partitioning the gland into lobules. This organ has both exocrine and endocrine tissue. The exocrine portion is organized in grape-like clusters of acini, which are small sacs surrounding the terminal ends of pancreatic ducts. The cells lining the acini and ducts secrete products that make up pancreatic juices, which play a major role in digestion. The endocrine portion of the gland consists of circular islets interspersed between acini, which secrete glucagon, insulin, and somatostatin.
Ischemic cell damage is the injury of a cell arising from reduced blood flow. The process involves hypoxia from interrupted blood supply, lack of nutrients, and accumulation of toxic metabolites. Damage to the cell can be reversible (function returns when blood flow resumes) or irreversible (the reversibility threshold has passed). While blood flow can be restored and allow cell recovery, reperfusion injury is possible in previously ischemic tissues. By producing calcium overload, oxidative stress and inflammatory mechanisms involving immune cells, cytokines, and the complement system, reperfusion can also lead to cell death (often by necrosis). Susceptibility to ischemia is affected by different factors, which include high metabolic activity, the presence of collateral circulation, watershed areas, and the magnitude of ischemia. The organ most susceptible to ischemia is the brain. Other susceptible organs include the heart, kidneys, liver, and the large intestine.
Tuberous sclerosis or tuberous sclerosis complex (TSC) is an autosomal dominant disorder with mainly neurocutaneous symptoms. Mutation in the TSC genes causes excessive tumor-like growths in the brain, eyes, heart, kidney, and lungs. Cutaneous manifestations include hypopigmentation (i.e., ash leaf spots, confetti lesions) or excessive growth (i.e., angiofibroma, shagreen patch). The diagnosis is made on clinical suspicion and confirmed by genetic testing. Management entails a multidisciplinary approach that targets monitoring and treatment of the various manifestations of the disorder. mTOR inhibitors such as sirolimus and everolimus are used to treat severe manifestations.
Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic condition resulting from a deletion or mutation in the VHL gene. Individuals diagnosed with VHL disease have tumors and cysts in various parts of their bodies and may present with hemangioblastomas, renal cell carcinoma (RCC), pheochromocytoma, endolymphatic sac tumors of the middle ear, pancreatic tumors, and papillary cystadenomas of the epididymis or the broad ligament. The diagnosis is by genetic testing, laboratory evaluation of BUN, laboratory evaluation for the presence of catecholamines in the blood or urine, fundoscopic exam of the eye to detect hemangioblastoma of the retina, and CT/MRI to detect any other tumors. Management of the disease includes surgical removal of tumors.
Eicosanoids are cell-signaling molecules produced from arachidonic acid. With the action of phospholipase A2, arachidonic acid is released from the plasma membrane. The different families of eicosanoids, which are prostaglandins (PGs), thromboxanes (TXA2s), prostacyclin (PGI2), lipoxins (LXs), and leukotrienes (LTs), emerge from a series of reactions catalyzed by different enzymes. The LTs and LXs are products of the lipoxygenase (LOX) pathway. The remaining eicosanoids are produced from the COX pathway, which involves 2 enzymes, COX-1 and COX-2. Eicosanoids are involved in various physiological and pathological processes. Thromboxanes cause platelet aggregation and are potent vasoconstrictors. Leukotrienes mediate allergic responses, while LXs have anti-inflammatory activities. Principal actions of PGs include vasodilation, smooth muscle contraction, and inflammation. Prostacyclin, a member of the PG family, has a potent vasodilatory effect. Both biologic actions and inhibitions of eicosanoids are mechanisms used in pharmacologic agents for various medical conditions and desired clinical effects.
Autoimmunity is a pathologic immune response toward self-antigens, resulting from a combination of factors: immunologic, genetic, and environmental. The immune system is equipped with self-tolerance, allowing immune cells such as T cells and B cells to recognize self-antigens and to not mount a reaction against them. Defects in this mechanism, along with environmental triggers (such as infections) and genetic susceptibility factors (most notable of which are the HLA genes) can lead to autoimmune diseases. These conditions are more commonly seen in women. Autoimmune diseases are chronic, with clinical manifestations consistent with the associated immune response. Among these conditions are Graves’ disease (autoantibodies against thyroid hormone receptors), myasthenia gravis (antibodies against acetylcholine receptors), type 1 diabetes (pancreatic β-cell destruction by immune cells), and systemic lupus erythematosus (multiorgan damage driven by immune complexes and autoantibodies).
The kidneys, solid organs located in the lower back, are extremely important in regulating homeostasis through their role in maintaining blood volume, electrolyte balance, acid–base equilibrium, blood-pressure regulation, and removal of metabolic waste from the blood. Evaluation of renal function and early detection of kidney dysfunction is of primary importance. Tests of renal function are useful in identifying the presence of renal disease, monitoring the response of kidneys to treatment, and determining the progression of renal disease.
The adrenal glands are a pair of retroperitoneal endocrine glands located above the kidneys. The outer parenchyma is called the adrenal cortex and has 3 distinct zones, each with its own secretory products. The outer zona glomerulosa secretes mineralocorticoids (primarily aldosterone); the middle zona fasciculata secretes glucocorticoids (primarily cortisol); and the innermost zona reticularis secretes androgens. Beneath the cortex lies the adrenal medulla, which secretes catecholamines involved in the fight-or-flight response. The medullary cells function more like neurosecretory postsynaptic neurons rather than traditional endocrine cells. The adrenal glands have a rich vascular supply and complex relationships with their surrounding organs.
The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. On a microscopic level, the stomach wall has several layers, including a mucosa, submucosa, muscularis, and serosa. The stomach is filled with glands that secrete a variety of substances involved in the digestive process. The arterial supply to the stomach is primarily from vessels originating from the celiac trunk.
Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Diagnosis is made clinically with a thorough neurologic examination, including assessment of the brain stem to evaluate for the presence of brain death. Definitive management depends on the underlying cause.
Penile anomalies and conditions may be congenital or acquired and can affect the urethral opening, prepuce, shaft, or glans or the penis. Examples include phimosis, paraphimosis, epispadias, hypospadias, balanitis, Peyronie disease, and priapism. The severity of clinical symptoms varies, but diagnosis of each of these conditions is usually based on the history and physical examination. Treatment varies from medical therapies to surgical intervention. These diagnoses are important to be aware of, since a few (such as phimosis and balanitis) are relatively common, while others (such as paraphimosis and priapism) can have severe complications if not treated in a timely fashion.
Muscle tissue is one of the basic tissue types. Histologically, the muscles of the body can be classified into 3 types: skeletal, smooth, and cardiac. The 3 types of muscle tissue are based on the morphologic and functional properties of the cells. One of the defining characteristics of muscle tissue is its contractility, which generates forces that move the musculoskeletal system as well as cause movement in the vasculature and multiple organ systems. This contractility is due to specialized proteins known as myofilaments, which create organized structures that have the ability to lengthen and contract.
Microsporidia are a group of obligate intracellular organisms that were recently reclassified as fungi. Microsporidia is made up of around 15 clinically relevant species, with the most common being Enterocytozoon bieneusi. There is much we do not understand about this group of organisms, and knowledge is evolving. Microsporidia species are ubiquitous, with a wide range of reservoirs. Immunocompromised individuals (particularly those with AIDS and a CD4 count < 100 cells/µL) most commonly develop symptomatic microsporidiosis. GI diseases range from acute, self-limited watery diarrhea to chronic diarrhea causing malabsorption and wasting. Extraintestinal manifestations and dissemination can also occur, affecting the eyes, respiratory tract, brain, biliary tract, urinary tract, and/or muscles. Diagnosis occurs through identification of spores on examination of the stool. Antimicrobials, such as albendazole and fumagillin, can be used to treat infections with most microsporidia species.
Locked-in syndrome (LIS) is a rare neurological disorder in which patients are awake and conscious but are unable to move their limbs or speak. The disorder is a result of brain injury to the ventral aspect of the pons and caudal ventral midbrain; etiologies include brainstem stroke, tumors, intracranial bleeding, and demyelinating disorders. Consciousness and the ability to think and reason remain intact, as do the abilities to blink and move the eyes. Diagnosis is made clinically, and the initial management is supportive care for breathing and feeding. Definitive management depends upon the underlying cause and is followed by several months of rehabilitation. Prognosis is generally poor, although some patients are able to achieve significant improvement in some functions.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). All 3 diseases cause life-threatening small-vessel vasculitis with a wide range of systemic manifestations, which can involve the lungs, kidneys, skin, and heart. Diagnosis is suspected by clinical presentation and a positive cytoplasmic (c)- or perinuclear (p)-ANCA test. Biopsy of involved tissue confirms the diagnosis. Glucocorticoids and immunosuppressive therapy are the mainstays of treatment.
Goodpasture syndrome, also known as anti-glomerular basement membrane (GBM) disease, is an autoimmune disease characterized by circulating antibodies directed against glomerular and alveolar basement membranes. The autoantibodies are thought to be generated in response to an inciting stimulus in genetically predisposed individuals. Affected individuals present with symptoms of rapidly progressive glomerulonephritis and alveolar hemorrhage. Constitutional symptoms such as malaise, chills, fever, arthralgia, and weight loss may also be present. Detection of anti-GBM antibodies and renal biopsy findings of crescent glomerulonephritis with linear IgG deposition along the basement membranes provide the diagnosis. Management includes plasmapheresis and immunosuppressants. Renal transplantation is an option in individuals who develop end-stage renal disease.
Normal pressure hydrocephalus (NPH) is a neurodegenerative disorder characterized by the triad of gait abnormalities, dementia, and urinary urgency or incontinence. Normal pressure hydrocephalus can be either idiopathic or secondary to intraventricular or subarachnoid hemorrhage. Symptoms may be similar to those of Alzheimer and Parkinson's diseases. Diagnosis of NPH is clinical, in addition to lumbar puncture testing and neuroimaging. Management is with surgical shunt placement to drain excess CSF from the cerebral ventricles.
Hypertension, or high blood pressure, is a common disease manifesting as elevated systemic arterial pressure. Hypertension is most often asymptomatic and discovered as part of a routine physical examination, or during triage for an unrelated medical encounter. Age, gender, smoking, obesity, and diet are all contributing factors to hypertension and can lead to heart attack, stroke, congestive heart failure, and CKD if not managed properly. If blood pressure cannot be controlled with lifestyle modifications, medications are employed for the management of hypertension. The 1st-line medication classes include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBs). Contraindications, adverse effects, and drug-to-drug interactions are agent specific.
The scrotum is a sac hanging outside the body that contains parts of the male reproductive system. The scrotum’s main function is to support testicles outside the body so that spermatogenesis can be completed under optimal conditions. The scrotum can be affected by various pathologic conditions, and imaging is a valuable tool in reaching the appropriate diagnosis. The most important imaging method is ultrasonography +/– Doppler mode because scrotal structures are superficial with no intervening gas. MRI is useful when ultrasound is indeterminate.
The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Bile is secreted by hepatocytes into thin channels called canaliculi. These canaliculi lead into slightly larger interlobular bile ductules, which are part of the portal triads at the “corners” of hepatic lobules. The bile leaves the liver via the right and left hepatic ducts, which join together to form the common hepatic duct. The common hepatic duct joins with the cystic duct to form the common bile duct, which empties into the small intestine. If the sphincters leading into the intestines are closed, bile will travel via the cystic duct into the gallbladder for storage.
Lipid metabolism is the processing of lipids for energy use, energy storage, and structural component production. Lipid metabolism uses fats from dietary sources or from fat stores in the body. A complex series of processes involving digestion, absorption, and transport are required for the proper metabolism of lipids. Triacylglycerols are transported in body fluids by molecules called lipoproteins. Within the GI tract, metabolism of triacylglycerols may occur, facilitated by a group of enzymes called lipases. This process relies on preprocessing to make hydrophobic lipids soluble in order to accommodate hydrolysis and further processing.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a sporadic or inherited neurodegenerative disease of upper motor neurons (UMNs) and lower motor neurons (LMNs). Amyotrophic lateral sclerosis is the most common progressive motor neuron disease in North America, primarily affecting men and individuals of Caucasian ethnicity. This disease is characterized by the coexistence of UMN and LMN signs and symptoms. The diagnosis is made clinically. Management is supportive and symptomatic, progressing to end-of-life care.
Central cord syndrome (CCS) is a neurological syndrome caused by an injury to the center of the spinal cord, affecting the spinothalamic tracts ((STTs) sensory) and medial aspect of the corticospinal tracts ((CSTs) motor), most often due to trauma in patients with cervical spondylosis. A less frequent but classic cause of CCS is syringomyelia. Clinical manifestations are motor deficits in the arms more so than the legs and variable sensory deficits below the level of injury. Diagnosis is made clinically and is supported with neuroimaging. Definitive management can be medical or surgical, depending on the severity of the injury. Rehabilitation is the key to maintaining functionality and improving chances of recovery.
Anterior cord syndrome (ACS) is an incomplete cord syndrome predominantly affecting the anterior (ventral) ⅔ of the spinal cord while sparing the dorsal columns. Anterior cord syndrome can be caused by occlusion of the anterior spinal artery or by trauma, which results in disc herniation and bone fragments disrupting the spinal cord. Clinical manifestations include loss of both motor and sensory function below the level of injury. Diagnosis of ACS is by clinical exam and neuroimaging with MRI. Management is directed at resolving the underlying cause. Preservation of motor function is a priority, but the prognosis is poor.
Ion channel myopathies are a heterogeneous group of disorders that are caused by genetic defects in sodium, chloride, and calcium ion channels in the myocyte membranes resulting in myotonia. These myopathies present clinically with symptoms of muscle pain, weakness, stiffness, cramps, and spasm. Diagnosis is made on the basis of clinical presentation, lab testing, electromyography, and genetic testing. Management involves both prevention with diet and exercise modifications and treatment with diuretics in some cases.
Blood supply to the brain can be divided into an anterior and a posterior circulation, which interconnect to form the circle of Willis. The anterior circulation is derived from the internal carotid arteries and consists mainly of the anterior and middle cerebral arteries. The posterior circulation is derived from the vertebral arteries and consists primarily of the cerebellar and posterior cerebral arteries. The primary venous drainage of the brain occurs via the internal jugular vein.
The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. The wall of the esophagus is made up of 4 primary layers: mucosa (lined with squamous epithelium), submucosa, a thicker muscularis layer, and an outer layer of connective tissue. The esophagus also has a sphincter at each end, which allows it to help control the passage of food into the stomach.
The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. The colon also contains many mucus-secreting glands to lubricate the stool passing through it. The colon receives its blood supply from colic branches of the superior and inferior mesenteric arteries, which form an important anastomosis along the transverse colon. The colon is regulated by the ANS and receives both sympathetic (inhibitory) and parasympathetic (stimulatory) input.
Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants are used in the treatment and prevention of thrombotic and embolic diseases including cardioembolic ischemic stroke, acute coronary syndrome, and venous thromboembolism, among other conditions. Patients with atrial fibrillation or thrombophilias may require indefinite or lifelong anticoagulation. Accordingly, the route of administration, drug interactions, pharmacokinetics, and availability of reversal factors should be considered while selecting the anticoagulant therapy.
DiGeorge syndrome (DGS) is a condition caused by a microdeletion at location q11.2 of chromosome 22 (thus also called 22q11.2 syndrome). There is a defective development of the third and fourth pharyngeal pouches, leading to thymic and parathyroid hypoplasia (causing T-cell immunodeficiency and hypocalcemia, respectively). Conotruncal anomalies present as congenital heart defects. Other manifestations consist of characteristic facial features, frequent infections, and neuropsychiatric disorders.
Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant cell arteritis causes headaches, scalp tenderness, jaw pain, vision problems, and potentially blindness. The diagnosis is made with temporal artery biopsy. Prompt treatment with glucocorticoids can relieve symptoms and prevent vision loss.
Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. The diagnosis is based on clinical suspicion, and once suspected, immediate empiric treatment is warranted to prevent catastrophic and long-term neurologic sequelae. Encephalitis is managed with supportive measures and antiviral therapy. Focal neurologic defects are common after encephalitis, and hence, physiotherapy is usually required.
Seizures occur when uncontrolled excessive synchronous neuronal activity in the brain causes sudden transient changes in motor function, sensation, behavior, or mental status. Seizures are classified primarily as generalized or focal and may occur once or be recurrent (epilepsy). Prolonged or recurrent seizures lasting > 30 minutes are called status epilepticus. Diagnosis depends on thorough history, physical exam, and EEG findings. Treatment is directed at the underlying trigger, and medications are administered as necessary. Most children that seize recover without any sequelae, but prognosis depends on the initial cause and the presence of underlying neurologic pathology.
Respiratory distress syndrome (RDS), also known as hyaline membrane disease, is caused by the lack of adequate pulmonary surfactant production in an immature lung. The syndrome is most commonly seen in preterm infants. The incidence is inversely related to gestational age, with the highest risk in neonates born at less than 28 weeks. Prenatal assessment of lung maturity and steroid administration can improve outcome if an early delivery cannot be prevented. Diagnosis is clinical. Affected newborns show signs of respiratory distress at birth, or soon thereafter, with nasal flaring, grunting respirations, and retractions. Treatment includes antenatal steroids, exogenous surfactant, and respiratory support. Neonatal RDS is associated with high morbidity and mortality in preterm infants.
Sideroblastic anemias are a heterogeneous group of bone marrow disorders characterized by abnormal iron accumulation in the mitochondria of erythroid precursors. The accumulated iron appears as granules in a ringlike distribution around the nucleus, giving rise to the characteristic morphological feature of a ring sideroblast. Sideroblastic anemias may be due to inherited defects in heme synthesis or can be acquired through alcoholism, lead poisoning, medications, or vitamin deficiencies. The anemia is commonly microcytic with low to normal reticulocyte count. Serum iron levels are typically elevated. A bone marrow examination showing ring sideroblasts establishes the diagnosis. Management involves treating the underlying condition, avoiding causative medication and/or toxins, and phlebotomy in cases of iron overload.
The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of 16–20 semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. The posterior wall of the trachea is free of cartilage. In this area, the paries membranaceus forms a plate out of smooth tracheal muscle and connective tissue and forms the border to the dorsally running esophagus.
Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. To perform this function, the lungs need to be able to capture as much O2 as possible, a task that is easily achieved owing to their elastic morphology. Each lung is enclosed within the visceral pleura and completely fills 1 of the non-symmetrical pleural cavities, which are situated on the left and right sides of the mediastinum. The lungs encase the bronchial tree and are divided functionally and anatomically into lobes.
Malignant lesions of the penis arise from the squamous epithelium of the glans, prepuce, or penile shaft. Penile cancer is rare in the United States, but there is a higher prevalence in lower socioeconomic regions. The most common histologic subtype is squamous cell carcinoma. Uncircumcised men and those with HPV infections are at highest risk of penile neoplasms. Diagnosis is a combination of physical exam, history, imaging studies, and tissue biopsy. Proper TNM staging is necessary to determine the correct treatment, which ranges from local topical therapy to multimodal surgery/radiation/chemotherapy.
Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Diffuse alveolar damage involves damage to the endothelial and alveolar epithelial cells and is associated with inflammation and the development of hyaline membranes lining the inner alveolar walls. The reparative stage follows after weeks, with fibrosis possibly occurring later. Clinically, the following triad of findings favors a diagnosis of ARDS: acute or rapidly progressive dyspnea, hypoxic respiratory failure (partial pressure of O2/fraction of inspired O2 ratio < 300 mm Hg), and bilateral alveolar opacities on chest imaging. Management involves determination and treatment of the cause while providing adequate oxygen, reducing further lung damage, and avoiding fluid overload. Most patients require mechanical ventilation. Acute respiratory distress syndrome is associated with high mortality or long-term complications potentially developing even after treatment.
Urinary tract infections (UTIs) represent a wide spectrum of diseases, from self-limiting simple cystitis to severe pyelonephritis that can result in sepsis and death. Urinary tract infections are most commonly caused by Escherichia coli, but may also be caused by other bacteria and fungi. Depending on the location of the infection, patients can present with dysuria, urinary urgency, increased urinary frequency, suprapubic pain, and fever. Urinalysis and urine culture along with the clinical presentation help in the diagnosis of UTIs. Management options include oral or IV antibiotics such as trimethoprim-sulfamethoxazole, nitrofurantoin, and ceftriaxone. In certain instances, further workup may be needed to determine the underlying conditions that predispose an individual to UTIs.
Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Only 5%–15% of patients with hemoptysis have life-threatening bleeding. However, hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. The most common causes of hemoptysis include bronchiectasis, lung cancer, tuberculosis, and aspergillosis. Diagnosis involves chest imaging and bronchoscopy. In cases of life-threatening bleeding, treatment is initially directed at stabilizing the patient and, if bleeding is ongoing, hemostasis can often be achieved with minimally invasive techniques (e.g., arterial embolization).
Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies, which can be due to low dietary intake, underlying malabsorptive conditions, and medications. Clinical presentation includes anemia and GI symptoms, with neurologic manifestations more commonly seen in B12 deficiency. Laboratory tests show macrocytic anemia (elevated mean corpuscular volume) and low B12 and folate levels. Confirmatory tests can be performed if levels are borderline. Treatment focuses on identifying the cause of the deficiency and replacing the deficient vitamin either orally or parenterally.
Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000–450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Clinical manifestations of thrombocytopenia include easy bruising or bleeding, petechiae, purpura, and when severe, spontaneous mucosal and/or internal bleeding. Diagnosis is made with a CBC and blood smear; additional testing may be required to determine the underlying etiology if it is not evident from the clinical scenario. Management involves treating the underlying etiology and platelet transfusions.
Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves platelet adhesion, activation, and aggregation to the damaged vascular endothelium, forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade resulting in the formation of a more stable plug. Finally, as the vasculature is repaired, the clot is broken down in the fibrinolytic phase.
Esophageal rupture or perforation is a transmural defect that occurs in the esophagus, exposing the mediastinum to GI content. The most common cause of esophageal perforation is iatrogenic trauma by instrumentation or surgical procedures. Perforation can also be due to foreign body ingestion or non-iatrogenic trauma produced by severe vomiting. Esophageal perforation presents with substernal chest pain that can have a sudden or insidious onset. Diagnosis can be achieved through a CT scan of the chest and neck, chest X-ray, or esophagogram. Management commonly includes surgical repair of the transmural esophageal defect. However, conservative therapy may also be considered for a hemodynamically stable patient with a minor defect. The main complication of esophageal perforation is acute mediastinitis. The mortality rate can range from 10%–50%.
Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of an infected female Anopheles mosquito, malaria is caused by single-celled microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis after a history of exposure in an area endemic to malaria, which is often cyclical. Prophylaxis is of utmost importance. Treatment with oral medications is available, but malaria can be severe and fatal without a timely diagnosis, especially in young children.
Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. DIC is always triggered by another (often serious) condition, including severe sepsis, trauma, malignancy, or obstetric complications. Acute DIC often presents dramatically, with rapid onset of spontaneous bleeding from multiple locations throughout the body simultaneously. A chronic form of DIC also exists, typically in patients with late-stage malignancies. Management involves stabilizing the patient, replacing consumed platelets and coagulation factors, and treating the triggering condition.
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. Myasthenia gravis presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Diagnosis is established based on clinical presentation, detection of antibodies, and electrophysiologic studies. Management is aimed at increasing the activity of acetylcholine at the neuromuscular junction and suppression of antibodies. This disease can be associated with thymomas and thymic hyperplasia, and thymectomy is sometimes indicated. Myasthenia gravis can progress to a life-threatening cholinergic crisis with respiratory failure, but this is preventable with appropriate management. Prognosis is generally good with treatment, and some patients can achieve a long-term remission.
Vomiting, or emesis, is the forceful oral expulsion of gastric contents. Vomiting is a common presenting symptom in pediatrics. The frequency and characteristics of vomiting may point toward a specific pathology, just as its presence can be another symptom of a greater clinical situation. The majority of vomiting symptoms are benign and self-limited. A good history and physical examination can bring into focus the underlying cause and workup. Management is with antiemetics and treating the underlying cause, if needed. The most common complications are dehydration and malnutrition.
Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Patients typically present with shortness of breath initially during exercise and then at rest. Diagnosis may involve an echocardiogram, ECG, chest X-ray, pulmonary function tests, a ventilation-perfusion scan, laboratory testing for conditions associated with PAH, and/or cardiac catheterization. Management is often complex and aimed at treating the underlying etiology. Several classes of vasodilatory agents may be used for patients with primary PAH, including calcium channel blockers and vasoactive prostaglandins.
Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. A number of etiologies exist, including diseases of the lungs, cardiovascular, and nervous system. Patients with respiratory failure may present with dyspnea, tachypnea, and altered mentation. The diagnosis is made with arterial blood gas and supplemented with laboratory and imaging studies to elicit an etiology. Management involves treating the underlying cause, supplemental oxygen administration, and mechanical ventilation for severe cases.
A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. Additionally, the cell membrane allows the cell to communicate with other cells and also helps in tissue formation. Membranes are formed when glycerophospholipids and sphingolipids interact and expose their polar heads to the aqueous extracellular environment while sequestering their nonpolar tails toward the middle of the membrane. Proteins that are anchored in the membrane are responsible for cell signaling and interactions, transmembrane transport of substances, and for providing cellular structure.
Nephrolithiasis is the formation of a stone, or calculus, anywhere along the urinary tract caused by precipitations of solutes in the urine. The most common type of kidney stone is the calcium oxalate stone, but other types include calcium phosphate, struvite (ammonium magnesium phosphate), uric acid, and cystine stones. Nephrolithiasis presents with colicky flank pain, which radiates to the groin, and hematuria due to damage to the ureters. Diagnosis is made by noncontrast CT of the abdomen and pelvis or by renal ultrasound, and urinalysis is performed to exclude concomitant urinary tract infection (UTI). Management depends on the size of the stone. Small stones likely to pass on their own are managed conservatively with hydration and analgesics. Large stones unlikely to pass spontaneously are managed with extracorporeal shock wave lithotripsy (ESWL), ureterorenoscopy, or percutaneous nephrolithotomy. Nephrolithiasis can be complicated by hydronephrosis or acute pyelonephritis. Adequate hydration is the best prophylactic intervention to prevent kidney stones.
Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Most cases are idiopathic, though infections, bronchial obstruction, congenital disorders, and systemic conditions can contribute. Patients present with slowly progressive symptoms of cough and sputum production. The diagnosis is made from characteristic radiographic findings, such as bronchial wall thickening and luminal dilatation. Management focuses on improving clearance of mucus, relieving airway obstruction, treating infection, and managing the underlying etiology. Management can include chest physiotherapy, bronchodilators, and antibiotics.
Renal Na+ and water regulation work in tandem to control how fluid is distributed throughout the compartments of the body. Sodium is the body’s dominant extracellular solute, and is responsible for the osmotic force that keeps differing amounts of water in each compartment. Changes in Na+ balance are sensed by the body through changes in blood volume. Changes in water balance are sensed by the body through changes in plasma osmolality. Both ultimately send feedback signals to the kidneys to ensure that homeostasis is maintained. Abnormalities in these processes can result in problems in volume status (e.g., hypertension, pulmonary edema, pitting edema) and dysnatremias (hyponatremia and hypernatremia).
Pericardial effusion is the accumulation of excess fluid in the pericardial space around the heart. The pericardium does not easily expand; thus, rapid fluid accumulation leads to increased pressure around the heart. The increase in pressure restricts cardiac filling, resulting in decreased cardiac output and cardiac tamponade. Signs and symptoms usually occur in the setting of cardiac tamponade and include dyspnea, hypotension, muffled heart sounds, jugular venous distension, and pulsus paradoxus. The diagnosis of pericardial effusion is confirmed with echocardiography. Small effusions in stable patients are treated medically. Larger effusions and cardiac tamponade may require pericardiocentesis or pericardiotomy.
Acute abdomen, which is in many cases a surgical emergency, is the sudden onset of abdominal pain that may be caused by inflammation, infection, perforation, ischemia, or obstruction. The location of the pain, its characteristics, and associated symptoms (e.g., jaundice) are important tools that help narrow the differential diagnosis. Patients will typically have severe tenderness with associated rigidity and rebound tenderness. Laboratory evaluation will demonstrate leukocytosis, acidosis, and in some cases, abnormal hepatic function tests. Imaging helps narrow the differential diagnosis; first-line imaging is always an upright chest X-ray to evaluate for pneumoperitoneum. The treatment and prognosis of acute abdomen strongly depend on the underlying cause, but the vast majority of these cases constitute a surgical emergency with associated morbidity and mortality.
Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. The myocardium becomes ischemic when oxygen supply does not meet oxygen demand. Diagnosis is based on history and ECG findings; cardiac stress tests and catheterizations may also be needed. Treatment is primarily based on reducing the heart's oxygen demand and increasing the delivery of oxygen.
Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. The course of myocarditis may vary based on the etiology and timeline of symptom progression. The diagnosis is supported by clinical findings, laboratory evaluation, and cardiac imaging. A definitive diagnosis by endomyocardial biopsy is rarely required. Management is supportive and aimed at addressing complications.
Adrenal insufficiency (AI) is the inadequate production of adrenocortical hormones: glucocorticoids, mineralocorticoids, and adrenal androgens. Primary AI, also called Addison’s disease, is caused by adrenal gland disorder (autoimmune disease, infections, and malignancy, among others). Adrenal insufficiency can also occur because of decreased production of adrenocorticotropic hormone (ACTH) from disease in the pituitary gland (secondary) or hypothalamic disorders and prolonged glucocorticoid therapy (tertiary). Diagnosis is by demonstrating hypocortisolism (via cortisol and ACTH levels and ACTH-stimulation test) and determining the etiology (adrenal autoantibodies, imaging). Glucocorticoid replacement is needed in all forms of AI. Additionally, in primary AI, mineralocorticoid is given to prevent volume depletion, salt loss, and hyperkalemia. Adrenal crisis is a medical emergency; management requires prompt IV hydration and administration of IV glucocorticoids without waiting for initial hormone results.
Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. It manifests itself as vessel stenosis and a source of thromboembolic disease. Its clinical manifestations depend on the specific vessels affected and include most notably coronary artery disease, carotid disease, and peripheral vascular disease. It is the most common primary disease of the arterial vascular system and is responsible for coronary heart disease, the leading cause of death worldwide.
Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). The list of causes is extensive, ranging from familial disorders to underlying diseases and infections. Patients often present with chest pain, dyspnea, palpitations, and/or syncope. Some patients may be completely asymptomatic, while others may present with sudden cardiac death as the first sign of an underlying condition. Diagnosis is made through the use of ECG and cardiac imaging such as echocardiography and cardiac MRI. Management involves medications typically used to treat heart failure, as well as implantable devices. In severe cases, heart transplantation may be necessary.
Thyroid cancer is a malignancy arising from the thyroid gland cells: thyroid follicular cells (papillary, follicular, and anaplastic carcinomas) and calcitonin-producing C cells (medullary carcinomas). Rare cancers are derived from the lymphocytes (lymphoma) and/or stromal and vascular elements (sarcoma). Driver mutations involving the receptor tyrosine kinase pathway (such as RET and BRAF) and a family history of cancer or related syndromes increase the risk. Exposure to ionizing radiation and iodine deficiency are also considered risk factors. The major types can present as thyroid nodules or enlarged cervical lymph nodes. The diagnostic approach includes thyroid-stimulating hormone, ultrasonography, and biopsy. Treatment options are surgical removal of the thyroid gland, with the addition of radioactive iodine therapy and systemic therapy, depending on the type and extent of the thyroid malignancy.
Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma, which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and unbound T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.
Multiple endocrine neoplasia syndromes are autosomal dominant inherited conditions characterized by 2 or more hormone-producing tumors involving the endocrine organs. There are different types of MEN, namely MEN1–4. The MEN1 syndrome is associated with MEN1 gene mutation and has a predilection for primary hyperparathyroidism, pituitary adenomas, and pancreatic tumors (the 3 P’s). Due to the RET proto-oncogene mutation, MEN2 syndrome can be further categorized as MEN2A and MEN2B. Medullary thyroid carcinoma and pheochromocytoma are common features. The MEN2A variant is associated with primary hyperparathyroidism, whereas MEN2B (also considered MEN3) is associated with neuromas and Marfanoid habitus. The newer and rare entity, MEN4, has features of MEN1 but results from CDKN1B mutations. The diagnosis is clinical, and tumors are detected based on imaging and correlating hormone levels. Genetic testing plays a crucial role in MEN2 syndromes in determining further management. Treatment is dependent on the tumors that are present and genetic mutation.
Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Deficiency of PTH results in hypocalcemia, which leads to increased neuromuscular excitability and osteosclerosis, as well as cardiac and neuropsychiatric manifestations. Treatment is based on calcium and vitamin D supplementation.
Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE and a personal or family history of atopy. Skin dryness, erythema, oozing, crusting, and lichenification are present. Pruritus is a cardinal symptom. Diagnosis is established clinically. The mainstays of management are avoidance of triggers, emollients, and topical corticosteroids.
A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Hashimoto’s thyroiditis is associated with a benign hypothyroid goiter, while Graves’ disease produces a toxic or hyperthyroid goiter. Nontoxic goiter is euthyroid and is usually due to iodine deficiency (the most common cause of goiter). Diagnostic tests include thyroid function tests and measurement of thyroid antibodies. Ultrasound, CT, and/or MRI help if lab results are ambiguous and if worrisome features such as obstructive symptoms are present. Radioactive iodine uptake distinguishes hyperthyroid causes. Treatment depends on the underlying condition; options include observation, medication, surgery, and radioiodine ablation.
Crohn's disease is a chronic, recurrent condition that causes patchy transmural inflammation that can involve any part of the gastrointestinal tract. It is a type of inflammatory bowel disease (IBD) along with ulcerative colitis (UC). The terminal ileum and proximal colon are usually affected. Crohn's disease typically presents with intermittent, non-bloody diarrhea and crampy abdominal pain. Extraintestinal manifestations may include calcium oxalate renal stones, gallstones, erythema nodosum, and arthritis. Diagnosis is established via endoscopy with biopsy that shows transmural inflammation, characteristic “cobblestone” mucosa, and noncaseating granulomas. Management is with corticosteroids, azathioprine, antibiotics, and anti-TNF agents (infliximab and adalimumab). Complications include malabsorption, malnutrition, intestinal obstruction or fistula, and an increased risk of colon cancer.
Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative colitis causes diffuse friability, erosions with bleeding, and loss of haustra, which are visible on endoscopy. Patients typically present with bloody diarrhea, colicky abdominal pain, tenesmus, and fecal urgency. Diagnosis is established via endoscopy with biopsy and by ruling out other causes of bloody diarrhea. Management is primarily through topical mesalamine, 6-mercaptopurine, or colectomy for severe cases. Complications include fulminant colitis, toxic megacolon, intestinal perforation, and increased risk of colorectal cancer.
Ichthyosis vulgaris is the most common type of keratinization disorders. The condition occurs due to an autosomal dominant mutation in the filaggrin gene, which results in skin-barrier dysfunction. Patients present in early childhood with rough, dry, and scaly skin that worsens during cold, dry months. The diagnosis is usually clinical, but often aided with a skin biopsy showing hyperkeratosis and a diminished stratum granulosum. Emollients, moisturizers, keratolytics, and retinoids are the mainstays of management.
Urticaria is raised, well-circumscribed areas (wheals) of edema (swelling) and erythema (redness) involving the dermis and epidermis with associated pruritus (itch). Urticaria is not a single disease but rather is a reaction pattern representing cutaneous mast cell degranulation resulting in the release of histamine and other vasoactive substances from mast cells and basophils in the dermis resulting in extravasation of plasma into the dermis. Urticaria can be caused by myriad inciting events, such as allergic reactions, infections, exposure, and many others. The diagnosis is made clinically. H1-antagonists are used as 1st-line treatment.
Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiomyopathy, which is characterized by an asymmetric increase in thickness (hypertrophy) of the left ventricular wall, diastolic dysfunction, and often left ventricular outflow tract obstruction. Hypertrophic cardiomyopathy is caused by various gene mutations affecting the contractile components of the heart, known as sarcomeres. Inheritance of HCM is typically autosomal dominant, although sporadic mutations also occur. Patients may be asymptomatic, present with dyspnea and chest pain or suffer sudden cardiac death without prior symptoms. Diagnosis is made based on ECG, echocardiography, stress test, and cardiac MRI. Symptomatic HCM is typically treated with beta-blockers as the 1st-line therapy. Additional management depends on the presence of left ventricular outflow tract obstruction.
Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. The treatment of cardiac arrest begins with basic life support (BLS) when out-of-hospital and advanced cardiac life support (ACLS) when in-hospital. Basic life support comprises checking the patient’s mental status, activating the emergency response system, and cardiopulmonary resuscitation (CPR). An automated external defibrillator (AED) should be used once available. High-quality CPR (with early defibrillation in shockable rhythms) is crucial to survival in cardiac arrest. Advanced cardiac life support includes CPR, securing the airway, administering medications (such as epinephrine), and identifying and treatment of the cause of cardiac arrest. Post-cardiac arrest care follows return of spontaneous circulation (ROSC).
Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto's disease (autoimmune thyroiditis) is the leading cause in non–iodine-deficient regions. Primary hypothyroidism occurs with thyroid gland disorders, while the central type arises from pituitary and hypothalamic conditions. Thyroid hormones are integral in metabolic processes and in the development of the brain and other organs. Congenital hypothyroidism can result in significant mental disability due to the loss of thyroid hormones. The features of acquired hypothyroidism also reflect the effects of slowed organ function, such as fatigue, bradycardia, cold intolerance, and exertional dyspnea. Diagnosis is by thyroid function testing. Elevated thyroid stimulating hormone and low free thyroxine (T4) levels are noted. Treatment is with synthetic T4.
Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Important clinical exam findings include a new or changed heart murmur and common extra-cardiac signs, such as Osler nodes, Janeway lesions, splinter hemorrhages, and Roth spots. The diagnosis is based on clinical findings, blood cultures, and echocardiography showing valvular vegetations. Management includes intravenous antibiotics for infectious cases, addressing the underlying etiology for noninfectious cases, and surgical repair when necessary.
Immune thrombocytopenic purpura (ITP), formerly known as idiopathic thrombocytopenic purpura, is a condition that develops secondary to immune-mediated destruction of platelets, resulting in thrombocytopenia (platelet count < 100,000/mm³). Immune thrombocytopenic purpura can be either primary or secondary due to drugs or underlying disease. The diagnosis is usually one of exclusion. Many patients with ITP are asymptomatic. When present, symptoms are primarily related to bleeding (e.g., bruising, petechiae, epistaxis), but fatigue is also common. The severity of thrombocytopenia in patients with ITP is variable. When platelet counts drop to < 20,000/mm³, the risk of serious bleeding increases. Treatment may include platelet transfusion, steroids, IV immune globulins, and/or splenectomy. Some cases remit spontaneously; others generally have a good prognosis with appropriate therapy.
Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Sexual contact is a common route of spread for HPV. While seen in all populations and ages, condylomata acuminata is most often seen in adolescence. HPV types 6 and 11 are responsible for 90% of warts and are considered low risk for malignancy; however, other types of HPV should be considered. Lesions rarely self-resolve; however, they can be removed via cryotherapy or topical antimitotic agents. While there is currently no treatment for HPV infection, it can be prevented through vaccination.
Nephrotic syndrome is a renal disorder caused by conditions that increase the permeability of the glomerular filtration barriers. Nephrotic syndrome affects all age groups but has a higher pediatric prevalence. This disorder can be due to both primary (renal) and secondary (systemic) causes. Minimal change disease (MCD), is the most common presentation in children. Hallmark features include proteinuria of > 40 mg/m²/day, hypoalbuminemia, hypercholesterolemia, and edema. Diagnosis is based on history, physical exam, laboratory tests confirming nephrotic-range proteinuria and workup for systemic disease. Genetic testing is recommended in some cases. Steroids are the initial treatment in a classic presentation of the typically steroid-responsive MCD. In other cases, renal biopsy is indicated. Management and prognosis vary depending on the underlying cause and response to steroids.
Pityriasis rosea is an acute, self-limited skin disease. The etiology is not known, and it commonly occurs in young adults. Patients initially present with a single, ovoid “herald patch.” This is followed by diffuse, pruritic, scaly, oval lesions over the trunk (often in a “Christmas tree” distribution on the back) and extremities. The diagnosis is clinical. Pityriasis rosea is a self-limiting condition; therefore, usually no treatment is required. However, topical steroids and antihistamines may be used for pruritus, if needed.
Melasma is a benign skin condition characterized by hyperpigmentation of sun-exposed regions due to excess melanin production and deposition. The condition mainly affects women during their reproductive years, particularly those with darker skin tones. Hyperpigmented patches typically occur on the face, especially the cheeks, chin, forehead, and upper lip. The diagnosis is clinical. Management includes sun protection and topical depigmenting agents.
Septic arthritis is an infection of the joint due to direct inoculation, contiguous extension, or hematogenous spread of infectious organisms into the joint space. This process causes an acute, inflammatory, monoarticular arthritis. A variety of organisms have been implicated, most commonly Staphylococcus aureus. Previously damaged joints (e.g., rheumatoid arthritis) are at the highest risk of infection. Patients present with a swollen, warm, and tender joint, most commonly involving the knee. Positive cultures from arthrocentesis are diagnostic, with antibiotic therapy tailored to the specific organism. Repeated joint aspiration, or surgical drainage, is required in some cases. If the joint space is infected with a prosthetic in place, debridement and prosthesis removal may also be required.
Albinism refers to a group of inherited disorders that result in the disruption of melanin production, causing hypopigmentation and visual impairment. The condition is classified according to the clinical phenotype. Oculocutaneous albinism results in hypopigmentation of the skin, eyes, and hair. Ocular albinism affects only the eyes. The diagnosis is clinical. Management is mainly supportive, with sun protection being a key component. Patients with albinism have an increased risk of skin cancer and require frequent skin examinations.
Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The most common pathogenic species is H. influenzae, which is transmitted through respiratory droplets and can cause epiglottitis, meningitis, otitis media, and pneumonia. H. ducreyi is transmitted through sexual contact and is the cause of chancroid, a type of genital ulcer.
Cushing's syndrome or hypercortisolism is a disorder characterized by features resulting from chronic exposure to excess glucocorticoids. Cushing's syndrome may be exogenous, due to chronic glucocorticoid intake, or endogenous, due to increased adrenal secretion of cortisol or adrenocorticotropic hormone (ACTH) production from the pituitary gland or ectopic sources. Exogenous or iatrogenic hypercortisolism is the most common cause. Typical clinical features of hypercortisolism include central obesity, thin and bruisable skin, abdominal striae, secondary hypertension, hyperglycemia, and proximal muscle weakness. The initial diagnostic approach is to establish hypercortisolism via urinary and salivary cortisol tests along with low-dose dexamethasone suppression test. Once the elevated cortisol levels are confirmed, the etiology is determined based on ACTH levels, confirmatory biochemical tests, and subsequent imaging studies. Treatment options depend on the cause, and include surgery and medical therapy.
Carcinoid tumors are small, well-differentiated, slow-growing neuroendocrine tumors (NET). Carcinoid syndrome describes the signs and symptoms associated with unregulated vasoactive hormone production by neuroendocrine tumors. Carcinoid tumors are most commonly found in the GI and bronchopulmonary tracts. Vasoactive substances produced by NET of the GI tract do not cause carcinoid syndrome until the tumors metastasize to the liver. Symptoms of carcinoid syndrome include flushing, diarrhea, and wheezing. Treatment consists primarily of surgical tumor resection and therapy with somatostatin analogs. Prognosis depends on the tumor location, aggressiveness, and overall disease burden.
The hemophilias are a group of inherited, or sometimes acquired, disorders of secondary hemostasis due to deficiency of specific clotting factors. Hemophilia A is a deficiency of factor VIII, hemophilia B a deficiency of factor IX, and hemophilia C a deficiency of factor XI. Patients present with bleeding events that may be spontaneous or associated with minor or major trauma. Management is focused mainly on treatment of acute bleeding events and prevention of bleeding events via replacement of deficient factors.
Vitiligo is the most common depigmenting disorder and is caused by the destruction of melanocytes. The etiology is unknown; however, genetic and autoimmune factors may play a role. Patients present with hypo- or depigmented macules or patches which often occur on the face, hands, knees, and/or genitalia. The diagnosis is clinical. Management depends on the severity and can include sun protection, topical or oral steroids, topical calcineurin inhibitors, immunosuppressants, and phototherapy.
Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Imaging can confirm the presence of a pleural effusion, and pleural fluid analysis can help in the evaluation of an etiology. Management is dependent on the underlying condition and whether the effusion is causing respiratory distress. Drainage of the effusion may provide symptomatic relief.
Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Osteoclastic activity results in bone resorption, bone pain, pathologic fractures, and metabolic disturbances. Excessive secretion of antibodies results in proteinuria and associated kidney damage as well as production and tissue deposition of amyloid fibrils. Metabolic disturbances combined with tissue amyloid deposition cause end-organ damage. Diagnosis is established by plasma electrophoresis and bone marrow biopsy. Treatments to slow down the disease progression are available; however, there is no cure for MM. The median survival is approximately 3 years.
Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Diagnosis is via physical exam and history. Management is guided by clearly discussing patient expectations after explaining the benefits and risks. Treatment includes conservative management with lifestyle modifications, oral medications, and injectables. Invasive surgical penile implants may be considered when conservative measures fail. Ultimately, both the patient and partner must be in tune with the treatment modalities to optimize their overall satisfaction.
Hypersensitivity pneumonitis (HP), previously called extrinsic allergic alveolitis, is an immunologically induced inflammatory disease affecting the alveoli, bronchioles, and lung parenchyma. It is caused by repeated inhalation of an inciting agent in a susceptible host that triggers first a type III (complement-mediated) hypersensitivity reaction in the acute phase and then a type IV (delayed) reaction in the subacute and chronic phases. The clinical presentation of acute HP includes cough, fever, and malaise, while subacute and chronic forms present as insidious onset of a cough and dyspnea over weeks to months. Diagnosis is aided by high-resolution CT scans and bronchoalveolar lavage. Management includes avoiding the inciting agent and administration of steroids in subacute and chronic cases. Early treatment has a good prognosis, but long-term exposure can cause permanent scarring and fibrosis.
Gonorrhea is a sexually transmitted infection (STI) caused by the gram-negative bacteria Neisseria gonorrhoeae (N. gonorrhoeae). Gonorrhea may be asymptomatic but commonly manifests as cervicitis or urethritis with less common presentations such as proctitis, conjunctivitis, or pharyngitis. Without antibiotic treatment, complications can occur. Complications for men may include epididymitis, prostatitis, balanitis, and periurethral abscess. Women may develop pelvic inflammatory disease, which can cause perihepatitis and fertility issues. Disseminated gonococcal infection is associated with fever, dermatitis, tenosynovitis, septic arthritis, and (rarely) endocarditis or meningitis. Gonorrhea diagnosis is made by microscopy, culture, or nucleic acid amplification tests. Management generally involves ceftriaxone, but treatment with doxycycline should be pursued if a coinfection with Chlamydia trachomatis (C. trachomatis) is not excluded.
Molluscum contagiosum is a viral infection limited to the epidermis and is common in children below 5 years of age. Lesions appear as grouped, flesh-colored, dome-shaped papules with central umbilication. Molluscum contagiosum is mild in immunocompetent patients and self resolves within months. Immunocompromised individuals present with extensive lesions and systemic disease, which require treatment. Molluscum contagiosum is highly transmissible; therefore, patient education is key in its management. Cryotherapy with liquid nitrogen is the 1st-line treatment.
Bullous pemphigoid and pemphigus vulgaris are two different blistering autoimmune diseases. In bullous pemphigoid, autoantibodies attack the hemidesmosomes, which connect epidermal keratinocytes to the basement membrane. This attack results in large, tense subepidermal blisters. In pemphigus vulgaris, autoantibodies attack the desmosomal proteins, which connect the keratinocytes to one another. This attack results in a more severe, potentially fatal condition with fragile, flaccid blisters, usually with significant mucosal involvement. Diagnosis is made with biopsy and IF staining to identify and localize the antibodies. Management involves immunosuppression with corticosteroids and other steroid-sparing immunomodulatory agents.
Angioedema is a localized, self-limited (but potentially life-threatening), nonpitting, asymmetrical edema occurring in the deep layers of the skin and mucosal tissue. The common underlying pathophysiology involves inflammatory mediators triggering significant vasodilation and increased capillary permeability. Clinically, angioedema presents with swelling around the eyes, lips, tongue, mouth, bowel wall, extremities, or genitalia. Angioedema may also compromise the airway. Urticaria will be present when the angioedema is mediated by mast cells, but not when it is due to increases in bradykinin. Diagnosis is usually clinical but additional testing may include skin/serum testing for specific antigens and C4 level assessment. Management depends on the underlying mechanism but may include treatment for anaphylaxis, removing any offending agents, antihistamines, glucocorticoids, and/or therapies that target bradykinin.
Abnormal uterine bleeding is the medical term for abnormalities in the frequency, volume, duration, and regularity of the menstrual cycle. Abnormal uterine bleeding is classified using the acronym PALM-COEIN, with PALM representing the structural causes and COEIN indicating the non-structural causes. Etiologies include polyp (P), adenomyosis (A), leiomyoma (L), malignancy/hyperplasia (M), coagulopathy (C), ovulatory dysfunction (O); endometrial pathology including endometritis and atrophy (E), iatrogenic causes (I), and etiologies not otherwise classified (N). Diagnosis usually requires careful history-taking and examination, basic laboratory work, transvaginal ultrasound, and endometrial biopsy based on age and risk factors. Management depends on the underlying etiology, but often includes oral contraceptive pills, levonorgestrel-containing intrauterine devices, and surgery.
Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Primary syphilis begins with a chancre, a painless ulcer on the genitals. Progression to secondary syphilis manifests as a generalized maculopapular rash, which includes the palms and soles. The development of tertiary syphilis can cause severe neurologic (neurosyphilis), cardiovascular, and/or gummatous disease. The diagnosis is through both treponemal and nontreponemal testing. Penicillin G is the antibiotic of choice. The duration of management varies based on the stage of the disease.
Alcoholic liver disease is a spectrum of disorders ranging from fatty liver to cirrhosis secondary to chronic alcohol abuse. Excessive and prolonged consumption of alcohol results in impairment of the lipolysis pathway, causing inflammatory changes within the hepatocytes. Patients typically present during the hepatitis stage with jaundice, fever, and abdominal pain. Diagnosis is based on a history of alcohol abuse and confirmed by laboratory derangement with an AST/ALT ratio > 2. Alcoholic liver disease carries a high mortality rate if patients present with severe hepatitis. Management aims at alcohol abstinence for reversal (at certain stages) and addressing contributing factors (such as viral infections or drugs) to minimize damage to the hepatocytes. Approximately 10% of patients regress with alcohol abstinence during the hepatitis stage. Cirrhosis is frequently irreversible.
Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis most often presents clinically with frequent fractures and loss of vertebral height. Diagnosis is established by measuring bone mineral density. Management includes lifestyle modifications, maintaining adequate levels of calcium and vitamin D, and the use of bisphosphonates.
Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytomas are frequently familial and associated with genetic syndromes. Approximately 90% of pheochromocytomas are benign and surgical resection is the only curative treatment. Prognosis is generally good for benign, sporadic tumors that have been completely resected. Familial forms are associated with higher recurrence rates and malignant potential.
Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder that is caused by a mutation in the DMD gene. The mutation leads to the production of abnormal dystrophin, resulting in muscle-fiber destruction and replacement with fatty or fibrous tissue. Affected individuals present with progressive proximal muscle weakness leading to the eventual loss of ambulation, as well as contractures, scoliosis, cardiomyopathy, and respiratory failure. A marked elevation in CK may be observed. Genetic testing is used to confirm the diagnosis. Management is supportive and aimed at slowing disease progression and complications. Duchenne muscular dystrophy is fatal with a life expectancy of about 20 years of age.
Erysipelas is a bacterial infection of the superficial layer of the skin extending to the skin's superficial lymphatic vessels. This infection presents as a raised, well-defined, tender, and bright red rash. Typically on the legs or face, but erysipelas can occur anywhere on the skin. This infection occurs when bacteria enter through the points of skin breakdown. The most common bacteria causing this infection is group A Streptococci (especially Streptococcus pyogenes). Diagnosis is based mostly on the history and physical exam. Management includes antibiotics.
Necrotizing fasciitis is a life-threatening infection that causes rapid destruction and necrosis of the fascia and subcutaneous tissues. Patients may present with significant pain out of proportion to the presenting symptoms and rapidly progressive erythema of the affected area. Most patients will also have systemic signs of infection, including fever, hypotension, altered mental status, and multisystem organ failure. The diagnosis is primarily clinical since patients can quickly progress to septic shock without source control. This type of infection is a surgical emergency and requires emergent surgical debridement, parenteral antibiotics, and close hemodynamic monitoring.
Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Histopathologic examination should be done for all suspected cases, as many lesions, such as actinic keratosis, mimic the appearance of SCC. Surgical excision is the mainstay of treatment. Overall prognosis is excellent for completely excised lesions, but certain high-risk features may predispose to metastatic disease and poor outcomes.
Benign or nonacute scrotal masses are represented by hydroceles, varicoceles, and spermatoceles. Key components to evaluation are physical exam and scrotal ultrasound. Hydroceles represent extra fluid in the tunica vaginalis, leading to a swollen scrotum. Varicoceles have a dilatation of the pampiniform venous plexus, giving the “bag of worms” appearance on exam. Spermatoceles present as an epididymal cyst, commonly arising from the head of the epididymis. Hydroceles, varicoceles, and spermatoceles are usually asymptomatic and do not require treatment unless they are causing pain or other complications.
Cervical cancer, or invasive cervical carcinoma (ICC), is the 3rd most common cancer in women in the world, with > 50% of the cases being fatal. In the United States, ICC is the 13th most common cancer and the cause of < 3% of all cancer deaths due to the slow progression of precursor lesions and, more importantly, effective cancer screening. There are 2 major histologic types of ICC: squamous cell carcinoma (SCC) and adenocarcinoma. High-risk human papillomaviruses (hrHPVs) cause > 99% of SCCs and > 85% of adenocarcinomas. Early cervical neoplasia is asymptomatic, and diagnosis is made using routine screening methods, including the cervical Papanicolaou test with cytology, hrHPV testing, and biopsy. Treatment of precursor or dysplastic lesions depends on the severity of the dysplasia and the age of the patient. Management of ICCs depends on the stage and varies from excisional biopsy by cervical cone biopsy for microinvasive ICC to radical hysterectomy for more advanced cases. If there is extracervical spread, radiation and chemotherapy would be recommended.
Rickets and osteomalacia are disorders of decreased bone mineralization. Rickets affects the cartilage of the epiphyseal growth plates in children, while osteomalacia affects the sites of bone turnover in children and adults. Although most cases of rickets and osteomalacia are due to vitamin D deficiency, other genetic and nutritional disorders as well as medications can cause these disorders. Rickets commonly presents with skeletal deformities and growth abnormalities, while osteomalacia can present with bone pain, difficulty with ambulation and pathologic fractures. Diagnosis is made based on a combination of clinical findings, laboratory tests and imaging. Treatment includes vitamin D, calcium, and phosphorus supplementation.
Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. The clinical presentation can vary greatly. Notable clinical features include malar rash, nondestructive arthritis, lupus nephritis, serositis, cytopenia, thromboembolic disease, seizures, and/or psychosis. Diagnosis is based on clinical criteria, and includes tests to determine ANAs, SLE-specific antibodies, and specific clinical findings. The goal of management is to control symptoms and prevent organ damage, using corticosteroids, hydroxychloroquine, and immunosuppressants.
Intussusception occurs when a part of the intestine (intussusceptum) telescopes into another part (intussuscipiens) of the intestine. The condition can cause obstruction and, if untreated, progress to bowel ischemia. Intussusception is most common in the pediatric population, but is occasionally encountered in adults. The pediatric patient typically presents with acute cyclical abdominal pain and vomiting, while adults present with symptoms of bowel obstruction. The diagnosis in children is frequently clinical but may be supported by an abdominal ultrasound showing a classic target sign. Management options in children include contrast or pneumatic enema, with surgical options reserved for failure of the non-operative measures, complications such as gangrene or perforation, and treatment of underlying pathology. In adult patients, surgery is usually required.
Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis and Neisseria gonorrhoeae, as well as organisms associated with bacterial vaginosis, such as Gardnerella vaginalis. Common symptoms are lower abdominal pain, cervical discharge, and irregular vaginal bleeding. Complications of PID can include ectopic pregnancy, chronic pelvic pain, and infertility. Diagnosis is primarily clinical in addition to PCR testing of cervical specimens and sometimes imaging or laparoscopy. Due to its polymicrobial nature, PID treatment is with combination antibiotic regimens.
Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Molecular profiling of the cancer provides further distinction of the tumor's biological behavior, prognosis, and treatment options. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Regional and metastatic spread cause additional symptoms and complications depending on the location and organ(s) affected. Related paraneoplastic syndromes include hypercalcemia, hyponatremia, Lambert-Eaton syndrome, Cushing's syndrome, polydermatomyositis, and dermatomyositis. Definitive diagnosis and staging are made by biopsy, genetic mutation with biomarker testing, and imaging. Management is guided by the cancer stage and associated molecular profile. Lung cancer carries an overall poor prognosis.
Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Deep vein thrombosis (DVT) is diagnosed in > 50% of patients presenting with symptoms, in whom the lower-extremity deep-venous system is the most common source of thrombus. Some individuals are asymptomatic, but the most common presenting symptom is dyspnea. The symptoms can be acute or chronic, and diagnosis is usually based on radiographic findings. Initial management is supportive and focuses on restoring oxygenation and hemodynamic stability. Both medical (systemic anticoagulants) and interventional therapies (catheter-based approach, surgery) are used to reestablish vessel patency.
Hemorrhoids are normal vascular cushions in the anal canal composed of dilated vascular tissue, smooth muscle, and connective tissue. They do not cause issues unless they are enlarged, inflamed, thrombosed, or prolapsed. Patients often present with rectal bleeding of bright red blood, or they may have pain, perianal pruritus, or a palpable mass. Risk factors include family history, low-fiber diet, and constipation. The two main types of hemorrhoids are external, usually with perianal pain, and internal, which are usually painless. The main diagnostic tools are history, physical exam, and endoscopic procedures if indicated for further investigation. If symptoms are acute, excision can be performed for external hemorrhoids. Otherwise, conservative management is recommended. Surgical methods are reserved for more severe hemorrhoids or those unresponsive to primary treatment.
Whipple's disease is a rare malabsorption syndrome with systemic manifestations (neurologic, cardiac, and musculoskeletal) caused by the bacterium Tropheryma whipplei. Patients often present with weight loss, diarrhea/steatorrhea, and arthralgias, as well as neurologic and cardiac manifestations. Whipple's disease is diagnosed with biopsy after the visualization of periodic acid–Schiff (PAS)-positive foamy macrophages in the involved tissues or with PCR for the bacterial DNA. It is managed with antibiotics, namely ceftriaxone or penicillin G and sulfamethoxazole.
Hypopituitarism is a condition characterized by pituitary hormone deficiency. This condition primarily results from a disease of the pituitary gland, but it may arise from hypothalamic dysfunction. Pituitary tumors are one of the most common causes. The majority of cases affect the anterior pituitary lobe (adenohypophysis), which accounts for 80% of the gland. The hormones produced from this lobe are growth hormone, follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone (TSH), adrenocorticotropic hormone, and prolactin. When the posterior lobe (neurohypophysis) is also damaged, loss of antidiuretic hormone and oxytocin occurs. All of these hormones regulate the activities of different organs, and thus the effects of pituitary hypofunction are multisystemic. The diagnosis is made through a combination of clinical findings, hormone levels, provocation tests, and brain imaging. Treatment is hormone replacement and addressing the etiology.
Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Associated symptoms, including fever, nausea and vomiting, weight loss, and bloody stools are also important to elicit from the history. Most causes of acute diarrhea are infectious and do not require additional workup. Since diarrhea is usually a self-limited condition, management is generally supportive. However, chronic diarrhea can require laboratory studies, stool studies, imaging, or procedures to determine the cause. Management ultimately hinges on treating the underlying pathology, though symptomatic and empiric therapies may be utilized under the right circumstances.
Chronic venous disease is a spectrum of disorders characterized by venous dilation and/or abnormal vein function in the lower extremities resulting from venous hypertension. "Chronic venous insufficiency" refers to the more severe forms of chronic venous disease. Skin changes typically distinguish chronic venous insufficiency from milder forms of venous disease (like varicose veins) and include skin pigmentation, stasis dermatitis, lipodermatosclerosis, and eventually, the development of ulcers. Diagnosis is usually based on physical exam findings alone, although venous duplex ultrasonography can provide additional information about the etiology, location, and extent of disease. The mainstay of management is compression therapy. A variety of