Trypanosoma cruzi/Chagas disease

General Characteristics and Epidemiology

Basic features of Trypanosoma cruzi

• Parasitic protozoan
• Taxonomy:
  • Family: Trypanosomatidae Trypanosomatidae Trypanosoma brucei/African trypanosomiasis
  • Genus: Trypanosoma
• General characteristics:
  • Thin, irregularly shaped
  • Single, polar flagellum
  • Undulating membrane
• Morphologic forms:
  • Epimastigote Epimastigote Trypanosoma brucei/African trypanosomiasis (extracellular, noninfectious form Noninfectious Form Trypanosoma brucei/African trypanosomiasis)
  • Trypomastigote ( infectious form Infectious Form Trypanosoma brucei/African trypanosomiasis)
  • Amastigote Amastigote Obligate intracellular non-flagellate ovoid organism in human or animal host Leishmania/Leishmaniasis (intracellular form that replicates)

Associated disease

American trypanosomiasis is called Chagas disease.

Epidemiology

• Geographic distribution:
  • South America
  • Central America
• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: Approximately 8 million people are infected.
  • Previously, more prevalent in rural communities
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are becoming more widespread because of migration.
• Morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status is higher in children.

Pathogenesis

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli

• Humans
• Domesticated and wild mammals

Transmission

• Primarily vector-borne Vector-Borne Antimalarial Drugs: triatomine bugs (reduviid bug or “kissing bug”)
• Less common:
  • Blood transfusion
  • Organ transplantation Organ Transplantation 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. Organ Transplantation
  • Ingestion of contaminated food or drink
  • Vertical
  • Laboratory exposure

Host risk factors

• Living in an endemic region
• Poor housing conditions
• Prolonged exposure to vectors

Life cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation and pathophysiology

• Reduviid bug feeds on an infected human or mammal host → bug becomes infected with trypomastigotes Trypomastigotes Trypanosoma brucei/African trypanosomiasis
• Transform into epimastigotes in the midgut Midgut Development of the Abdominal Organs → replicate 
• Differentiate into trypomastigotes Trypomastigotes Trypanosoma brucei/African trypanosomiasis in the hindgut Hindgut Development of the Abdominal Organs
• During a blood meal on a human host, bug defecates
• Trypomastigote entry into the host occurs through contact of infected feces with:
  • Bug bite wound
  • Conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy
  • Mucous membranes
• Invasion of cells at the site of inoculation → become intracellular amastigotes → asexual replication ( binary fission Binary fission Cell Types: Eukaryotic versus Prokaryotic)
• Differentiation into trypomastigotes Trypomastigotes Trypanosoma brucei/African trypanosomiasis → disseminate through the bloodstream to other organs
• Immune reaction → tissue damage
• Chronic dissemination of T. cruzi is associated with:
  • Fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of cardiac tissue → cardiomyopathy Cardiomyopathy 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). Cardiomyopathy: Overview and Types
  • Fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans involving cardiac conduction pathways → arrhythmias
  • Invasion of nerve plexuses (often GI tract) → megaesophagus and megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon

Clinical Presentation

Acute infection

The incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period is approximately 1–2 weeks, and the infection lasts 8–12 weeks.

• Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic.
• Inflammation Inflammation 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. Inflammation and pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema) may occur at the site of inoculation
  • Chagoma: 
    • Subcutaneous inflammatory nodule Nodule Chalazion
    • Typically on the face or extremities
  • Romaña’s sign: 
    • Unilateral swelling Swelling Inflammation of the eyelid secondary to chagoma
    • Occurs when the conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy is the site of inoculation
• Nonspecific signs and symptoms:
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
  • Lymphadenopathy Lymphadenopathy 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. Lymphadenopathy
• Severe disease (↑ risk of mortality Mortality All deaths reported in a given population. Measures of Health Status):
  • Myocarditis Myocarditis 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. Myocarditis
  • Pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade
  • Meningoencephalitis Meningoencephalitis Encephalitis

Chronic infection

A minority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop chronic infection, which presents 10–20 years after the initial inoculation period. 

• Chronic Chagas cardiomyopathy Chagas cardiomyopathy A disease of the cardiac muscle developed subsequent to the initial protozoan infection by trypanosoma cruzi. After infection, less than 10% develop acute illness such as myocarditis (mostly in children). The disease then enters a latent phase without clinical symptoms until about 20 years later. Myocardial symptoms of advanced chagas disease include conduction defects (heart block) and cardiomegaly. Achalasia (primary cause of mortality Mortality All deaths reported in a given population. Measures of Health Status)
  • Enlargement of all chambers → biventricular heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
  • Apical aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms → thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus
  • Conduction abnormalities
    • Left anterior fascicular block Left anterior fascicular block Bundle Branch and Fascicular Blocks
    • Right bundle branch block Bundle branch block A form of heart block in which the electrical stimulation of heart ventricles is interrupted at either one of the branches of bundle of His thus preventing the simultaneous depolarization of the two ventricles. Bundle Branch and Fascicular Blocks
    • Atrioventricular block Atrioventricular block 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. Atrioventricular block (AV block)
    • Ventricular arrhythmias
• Megaesophagus 
  • Dysphagia Dysphagia 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. Dysphagia
  • Regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Recurrent aspiration → aspiration pneumonia Aspiration pneumonia A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper respiratory tract. Pneumonia
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
• Megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon
  • Obstipation Obstipation Large Bowel Obstruction
  • Bloating Bloating Constipation
  • Volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus → bowel ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage
  • Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries

Congenital Congenital Chorioretinitis disease

Congenital Congenital Chorioretinitis disease occurs in a minority of infants born to infected mothers.

• Low birth weight
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
• Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
• Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types

Diagnosis and Management

Diagnosis

Confirmatory tests:

• Blood smear Blood smear Myeloperoxidase Deficiency visualization of trypomastigotes Trypomastigotes Trypanosoma brucei/African trypanosomiasis using Giemsa stain Giemsa stain Borrelia
• Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus for antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. 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. Immunoglobulins: Types and Functions
  • ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus
  • Indirect fluorescent antibody Indirect fluorescent antibody A form of fluorescent antibody technique commonly used to detect serum antibodies and immune complexes in tissues and microorganisms in specimens from patients with infectious diseases. The technique involves formation of an antigen-antibody complex which is labeled with fluorescein-conjugated anti-immunoglobulin antibody. Chikungunya Virus (IFA)
• PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) for parasitic DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
• Xenodiagnosis
  • Uninfected reduviid bugs take a blood meal from the patient.
  • The bug is later examined for the presence of T. cruzi.

Supporting evaluation:

• ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. 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. Electrocardiogram (ECG) showing conduction abnormalities
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests with cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
• Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) to evaluate for chamber enlargement and ventricular dysfunction
• Esophageal and colon Colon 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. Colon, Cecum, and Appendix: Anatomy dilation can be evaluated with:
  • Barium esophagography or colonic enema
  • Esophageal or anorectal manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia
  • Endoscopy Endoscopy Procedures of applying endoscopes for disease diagnosis and treatment. Endoscopy involves passing an optical instrument through a small incision in the skin i.e., percutaneous; or through a natural orifice and along natural body pathways such as the digestive tract; and/or through an incision in the wall of a tubular structure or organ, i.e. Transluminal, to examine or perform surgery on the interior parts of the body. Gastroesophageal Reflux Disease (GERD) or colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening

Management

Acute infection:

• Benznidazole
• Nifurtimox

Chronic disease:

• Effective treatments are limited.
• Antitrypanosomal drugs are less effective in chronic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
• Focus is on management of irreversible complications:
  • Cardiomyopathy Cardiomyopathy 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). Cardiomyopathy: Overview and Types:
    • General heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) management
    • Consider cardiac transplantation
    • Pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias for high-degree atrioventricular block Atrioventricular block 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. Atrioventricular block (AV block)
  • Megaesophagus management is aimed at ↓ the lower esophageal sphincter Lower Esophageal Sphincter Esophagus: Anatomy tone:
    • Nifedipine Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) or isosorbide
    • Pneumatic dilation
    • Surgery
  • Megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon:
    • High-fiber diet
    • Hydration
    • Laxatives Laxatives 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. Laxatives
    • Enemas
    • Suppositories Suppositories Medicated dosage forms that are designed to be inserted into the rectal, vaginal, or urethral orifice of the body for absorption. Generally, the active ingredients are packaged in dosage forms containing fatty bases such as cocoa butter, hydrogenated oil, or glycerogelatin that are solid at room temperature but melt or dissolve at body temperature. Large Bowel Obstruction
    • Manual disimpaction, as needed
    • Surgery

Prevention

• Vector control with insecticides
• Bug nets
• Screen blood and organ donors in endemic regions
• Screen and treat women prior to pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

Comparison of Flagellated Protozoa

Differential Diagnosis

• African trypanosomiasis African trypanosomiasis African trypanosomiasis, or African sleeping sickness, is a parasitic infection caused by the protozoa Trypanosoma brucei. Initial infections present with localized inflammation (chancre), cervical lymphadenopathy, intermittent fevers, and other nonspecific findings. If untreated, CNS involvement occurs, which is characterized by sleep disturbances, behavioral changes, coma, and death. Trypanosoma brucei/African trypanosomiasis: infection caused by Trypanosoma brucei Trypanosoma brucei African trypanosomiasis, or African sleeping sickness, is a parasitic infection caused by the protozoa Trypanosoma brucei. There are 2 notable subtypes, T. brucei gambiense and T. brucei rhodesiense. Transmission is primarily vector borne through the tsetse fly. Trypanosoma brucei/African trypanosomiasis and transmitted by the tsetse fly Tsetse fly Bloodsucking flies of the genus glossina, found primarily in equatorial africa. Several species are intermediate hosts of trypanosomes. Trypanosoma brucei/African trypanosomiasis. Signs and symptoms include a trypanosomal chancre Chancre The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. Syphilis, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, lymphadenopathy Lymphadenopathy 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. Lymphadenopathy, facial swelling Swelling Inflammation, and erythematous rash Rash Rocky Mountain Spotted Fever. CNS involvement is associated with “sleeping sickness” syndrome. The diagnosis is confirmed with identification Identification Defense Mechanisms of organisms in a fluid sample (e.g., blood, CSF). Management depends on the stage of disease and can include pentamidine, suramin, eflornithine, or melarsoprol.
• Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia: primary esophageal motility Motility The motor activity of the gastrointestinal tract. Gastrointestinal Motility disorder that develops from the degeneration of the myenteric plexus Myenteric plexus One of two ganglionated neural networks which together form the enteric nervous system. The myenteric (Auerbach’s) plexus is located between the longitudinal and circular muscle layers of the gut. Its neurons project to the circular muscle, to other myenteric ganglia, to submucosal ganglia, or directly to the epithelium, and play an important role in regulating and patterning gut motility. Gastrointestinal Neural and Hormonal Signaling. Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia results in impaired lower esophageal sphincter relaxation Sphincter relaxation Gastrointestinal Motility and absence of normal esophageal peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically present with dysphagia Dysphagia 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. Dysphagia with solids and liquids along with regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). Diagnosis is established by high-resolution manometry Manometry Measurement of the pressure or tension of liquids or gases with a manometer. Achalasia. Management options include pneumatic balloon dilation, surgical myotomy, and botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism injection. 
• Large bowel obstruction Large Bowel Obstruction Large bowel obstruction is an interruption in the normal flow of intestinal contents through the colon and rectum. This obstruction may be mechanical (due to the actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis, also known as pseudo-obstruction). Malignancy and volvulus are the most common causes of mechanical large bowel obstruction. Large Bowel Obstruction: interruption in the normal flow Flow 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, Flow, and Mean Arterial Pressure of intestinal contents through the colon Colon 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. Colon, Cecum, and Appendix: Anatomy and rectum Rectum 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 continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy. This obstruction may be mechanical (due to actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis Peristalsis A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction. Gastrointestinal Motility, also known as pseudo-obstruction). Typical symptoms include intermittent lower abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, abdominal distention Abdominal distention Megacolon, and obstipation Obstipation Large Bowel Obstruction. Diagnosis is established with imaging. Mechanical large bowel obstruction Large Bowel Obstruction Large bowel obstruction is an interruption in the normal flow of intestinal contents through the colon and rectum. This obstruction may be mechanical (due to the actual physical occlusion of the lumen) or functional (due to a loss of normal peristalsis, also known as pseudo-obstruction). Malignancy and volvulus are the most common causes of mechanical large bowel obstruction. Large Bowel Obstruction requires surgery in most cases.
• Toxic megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon: complication of severe colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis, frequently associated with Clostridium difficile Clostridium difficile A common inhabitant of the colon flora in human infants and sometimes in adults. The type species clostridioides difficile is formerly known as Clostridium difficile. It is a causative agent for clostridioides infections and is associated with pseudomembranous enterocolitis in patients receiving antibiotic therapy. Clostridia, inflammatory bowel disease, or ischemic colitis Colitis Inflammation of the colon section of the large intestine, usually with symptoms such as diarrhea (often with blood and mucus), abdominal pain, and fever. Pseudomembranous Colitis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with toxic megacolon Megacolon Megacolon is a severe, abnormal dilatation of the colon, and is classified as acute or chronic. There are many etiologies of megacolon, including neuropathic and dysmotility conditions, severe infections, ischemia, and inflammatory bowel disease. Megacolon present with severe abdominal distention Abdominal distention Megacolon and pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways with associated systemic toxicity Toxicity Dosage Calculation ( fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, and altered mental status Altered Mental Status Sepsis in Children). The diagnosis is established with the history, physical findings, and imaging. Treatment depends on the cause, but can include supportive care and surgery.
• Leishmaniasis Leishmaniasis Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The mildest form is cutaneous leishmaniasis (CL), characterized by painless skin ulcers. The mucocutaneous type involves more tissue destruction, causing deformities. Visceral leishmaniasis (VL), the most severe form, presents with hepatosplenomegaly, anemia, thrombocytopenia, and fever. Leishmania/Leishmaniasis: infection caused by Leishmania Leishmania Leishmania species are obligate intracellular parasites that are transmitted by an infected sandfly. The disease is endemic to Asia, the Middle East, Africa, the Mediterranean, and South and Central America. Clinical presentation varies, dependent on the pathogenicity of the species and the host’s immune response. Leishmania/Leishmaniasis species, which are obligate intracellular parasites transmitted by the sandfly Sandfly Leishmania/Leishmaniasis. The mildest form is cutaneous leishmaniasis Cutaneous leishmaniasis An endemic disease that is characterized by the development of single or multiple localized lesions on exposed areas of skin that typically ulcerate. The disease has been divided into old and new world forms. Old world leishmaniasis is separated into three distinct types according to epidemiology and clinical manifestations and is caused by species of the l. Tropica and l. Aethiopica complexes as well as by species of the l. Major genus. New world leishmaniasis, also called american leishmaniasis, occurs in south and central america and is caused by species of the l. Mexicana or l. Braziliensis complexes. Leishmania/Leishmaniasis, characterized by painless skin Skin 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. Skin: Structure and Functions ulcers. The mucocutaneous type involves more tissue destruction and deformities. Visceral leishmaniasis Visceral leishmaniasis A chronic disease caused by Leishmania donovani and transmitted by the bite of several sandflies of the genera phlebotomus and lutzomyia. It is commonly characterized by fever, chills, vomiting, anemia, hepatosplenomegaly, leukopenia, hypergammaglobulinemia, emaciation, and an earth-gray color of the skin. The disease is classified into three main types according to geographic distribution: indian, mediterranean (or infantile), and african. Leishmania/Leishmaniasis (VL) presents with hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, thrombocytopenia Thrombocytopenia 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. Thrombocytopenia, and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever. Management is based on clinical severity. Systemic treatment ( amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes) is needed for VL.
• Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria: mosquito-borne infectious disease caused by Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs species. Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria often presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, rigors Rigors Fever, diaphoresis, jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, and renal impairment. A blood smear Blood smear Myeloperoxidase Deficiency shows a single pleomorphic Pleomorphic Bacteroides ring. Rapid testing for Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs Antimalarial drugs Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person’s bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. Antimalarial Drugs.