Development

• Develops from the 3rd to 8th week during embryogenesis
  • Originates from the foregut endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation
  • Appears as the hepatic diverticulum, which later becomes the liver and the gallbladder Gallbladder 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. Gallbladder and Biliary Tract
• The falciform ligament is called the ventral mesentery during the fetal period.
• The round ligament Round ligament A fibromuscular band that attaches to the uterus and then passes along the broad ligament, out through the inguinal ring, and into the labium majus. Uterus, Cervix, and Fallopian Tubes contains the umbilical vein during gestation, which is the main fetal blood source (see table below).

Neurovasculature

Blood supply

The liver has a special dual blood supply that provides a mix of oxygenated, deoxygenated, and nutrient-rich blood. 

• Hepatic artery proper (HAP): supplies 25% of the liver’s blood supply and carries oxygenated blood 
  • Abdominal aorta → celiac trunk → common hepatic artery →  HAP
• Portal vein: supplies 75% of blood supply, carries oxygen-poor, nutrient-rich blood drained from the abdominal organs
  • Formed most commonly by the union of the splenic and superior mesenteric veins Veins 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. Veins
  • Additional tributaries: inferior mesenteric, cystic, and left and right gastric veins Veins 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. Veins

Venous drainage

• Sinusoids → central vein of each lobule → hepatic veins Veins 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. Veins → IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels
• Portosystemic anastomoses: alternative routes of circulation ensuring venous drainage of abdominal organs even if blockage occurs in portal system. Anastomosis between:
  • The left gastric veins Veins 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. Veins and the lower esophageal veins Veins 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. Veins 
  • The superior rectal veins Veins 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. Veins and the inferior and middle rectal veins Veins 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. Veins
  • The paraumbilical veins Veins 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. Veins and the small epigastric veins Veins 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. Veins
  • The intraparenchymal hepatic branches of the right division of the portal vein and the retroperitoneal veins Veins 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. Veins 
  • The omental and colonic veins Veins 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. Veins with the retroperitoneal veins Veins 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. Veins
  • The ductus venosus and the IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels 

Lymphatic drainage

Hepatic lymph nodes: located around the porta hepatis → celiac cluster of lymph nodes → cisterna chyli (dilated sac that receives lymph from the gastrointestinal [GI] trunk and 2 lumbar lymphatic trunks) → thoracic duct 

Innervation

• Hepatic plexus (travels with the hepatic artery and portal vein)
• Sympathetic fibers from the celiac plexus and superior mesenteric plexus
• Parasympathetic fibers from the anterior and posterior vagal trunks
• Glisson capsule innervated by the most inferior intercostal nerves
• HAP has α and β adrenergic receptors innervated by splanchnic nerves

Biliary drainage

Bile canaliculi → intrahepatic bile ducts → left and right hepatic ducts → common hepatic duct → common bile duct common bile duct The largest bile duct. It is formed by the junction of the cystic duct and the common hepatic duct. Acute Cholangitis → duodenum

Functions of the Liver

Detoxification

The liver eliminates degradation products obtained via resorption from the GI tract. It makes fat-soluble substances water-soluble through enzymatic modification. This allows for excretion via biliary tracts or through urine.

• Cytochrome p450 system: inactivates orally administered drugs via the first-pass effect
• Degradation of ammonia Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as ammonium hydroxide. Physiology of Acid-Base Balance into urea
• Ethanol breakdown
• Breakdown of bilirubin (glucuronidation) → excretion into bile

Metabolism

• Carbohydrates:
  • Gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis (synthesis of glucose from amino acids, lactate, or glycerol)
  • Glycogenesis (synthesis of glycogen from glucose)
  • Glycogenolysis (breakdown of glycogen into glucose)
  • Glycolysis (breakdown of glucose into pyruvate, producing adenosine triphosphate (ATP))
• Proteins: 
  • Production of albumin; globulins; acute phase proteins; transaminases; coagulation factors I (fibrinogen), II (prothrombin), V, VII, VIII, IX, X, XI, XII, and XIII; protein C; protein S; and antithrombin
  • Amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids degradation
• Lipids:  
  • Lipogenesis (storage of free fats as triglycerides) 
  • Ketogenesis (synthesis of ketone bodies) 
  • Fatty acid synthesis and degradation 
  • Production of bile acids, lipoproteins, and cholesterol

Storage

• Glycogen 
• Lipoproteins 
• Vitamins A, K, B12, B9 ( folate Folate 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. Folate and Vitamin B12), E, and D 
• Iron and copper

Hormone production

• Thrombopoietin
• Insulin Insulin 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. Insulin-like growth factor 1
• Angiotensinogen

Erythropoiesis Erythropoiesis 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. Erythrocytes

• Site of fetal RBC production from week 6 of gestation until birth
• Extramedullary erythropoiesis may occur in adulthood after bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow irradiation, in various bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow disorders (e.g., myelofibrosis, myelodysplastic syndrome, polycythemia vera Polycythemia vera 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), and chronic anemias (e.g., thalassemia Thalassemia 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. Thalassemia, sickle cell disease Sickle cell disease 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 Disease).

Clinical Relevance

Clinical evaluation

• Abdominal examination Abdominal examination The abdominal examination is the portion of the physical exam evaluating the abdomen for signs of disease. The abdominal examination consists of inspection, auscultation, percussion, and palpation. Abdominal Examination: The examination of the liver is mostly based on palpation and percussion. The purpose of liver palpation is to approximate liver size and feel for tenderness and masses. The purpose of liver percussion is to measure the liver size.
• Liver function tests Liver function tests 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: can be divided into 3 categories:
  • Parameters of hepatocellular damage (transaminases, glutamate dehydrogenase, and AST/ALT ratio)
  • Parameters of cholestasis (e.g., γ-glutamyl transpeptidase, alkaline phosphatase, and direct and indirect bilirubin)
  • Parameters of hepatic synthesis (albumin, cholinesterase, and coagulation factors)
• Normal abdominal imaging: Imaging is essential for accurately detecting focal liver lesions (e.g., abscess, tumor), but is limited in detecting and diagnosing diffuse hepatocellular disease (e.g., hepatitis, cirrhosis Cirrhosis 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. Cirrhosis).
  The types of imaging used are:
  • Hepatobiliary ultrasonography
  • Ultrasound elastography
  • Doppler ultrasonography
  • Computed tomography (CT) scan
  • Radionuclide liver scanning
  • Abdominal radiography
  • Magnetic resonance imaging (MRI)

Disorders

Neoplasms

• Benign liver tumors Benign Liver Tumors 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. Benign Liver Tumors: cavernous hemangiomas, hepatocellular adenomas, and focal nodular hyperplasia. 
• Liver cancer: hepatocellular carcinoma Hepatocellular carcinoma Hepatocellular carcinoma (HCC) typically arises in a chronically diseased or cirrhotic liver and is the most common primary liver cancer. Diagnosis may include ultrasound, CT, MRI, biopsy (if inconclusive imaging), and/or biomarkers. Hepatocellular Carcinoma (HCC) and Liver Metastases; intrahepatic cholangiocarcinoma; hepatoblastoma; angiosarcoma; hemangioendothelioma; liver metastases from GI, breast, and lung malignancies; and rare hepatic tumors (carcinosarcomas, teratomas, yolk sac tumors, carcinoid tumors Carcinoid tumors 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. Carcinoid Tumors and Syndrome, and lymphomas). 

Infections

• Viral hepatitis: mainly caused by primarily hepatotropic viruses A, B, C, D, and E, resulting in targeted 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 of the liver. Patients develop non-specific symptoms, such as nausea, vomiting, anorexia, and abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. Other viruses may cause hepatitis, including the Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus, cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus, and yellow fever virus Yellow Fever Virus Yellow fever is a disease caused by the yellow fever virus, a single-stranded, positive-sense RNA virus of the genus Flavivirus. Humans and primates serve as reservoirs, and transmission occurs from the bite of an infected female mosquito. Most patients present with fever and flu-like symptoms. Yellow Fever Virus.
• Bacterial infections:
  • Pyogenic liver abscess Pyogenic liver abscess 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. Pyogenic Liver Abscess (caused by many different types of pyogenic bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview)
  • Diffuse involvement, such as by Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella enterica serotype typhi, Mycobacterium Mycobacterium 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. Mycobacterium tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
• Fungal infections, including Candida Candida 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. 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). Candida/Candidiasis spp., Histoplasma Histoplasma Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. The fungus exists as a mold at low temperatures and as yeast at high temperatures. H. capsulatum is the most common endemic fungal infection in the US and is most prevalent in the midwestern and central states along the Ohio and Mississippi River valleys. Histoplasma/Histoplasmosis capsulatum
• Parasitic infections, including Schistosoma Schistosoma Schistosomiasis is an infection caused by Schistosoma, a trematode. Schistosomiasis occurs in developing countries with poor sanitation. Freshwater snails are the intermediate host and are transmitted to humans through skin contact with contaminated fresh water. The clinical presentation occurs as a result of the host's immune response to antigens from the eggs. Schistosoma/Schistosomiasis spp. ( schistosomiasis Schistosomiasis Schistosomiasis is an infection caused by Schistosoma, a trematode. Schistosomiasis occurs in developing countries with poor sanitation. Freshwater snails are the intermediate host and are transmitted to humans through skin contact with contaminated fresh water. The clinical presentation occurs as a result of the host's immune response to antigens from the eggs. Schistosoma/Schistosomiasis), Plasmodium spp. ( 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. Malaria)

Inflammatory disorders

• Alcoholic liver disease Alcoholic Liver 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. Alcoholic Liver Disease: progressive disease characterized by 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 damage of the liver due to long-term excessive alcohol abuse.
• Nonalcoholic fatty liver disease Nonalcoholic Fatty Liver 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. Nonalcoholic Fatty Liver Disease: progressive disease of the liver characterized by the accumulation of fat in the liver without the excessive intake of alcohol; often associated with obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity, diabetes, and elevated triglycerides.
• Autoimmune hepatitis Autoimmune hepatitis Autoimmune hepatitis (AIH) is a rare form of chronic liver disease in which the immune system attacks the liver causing inflammation. It predominantly affects women. Clinical presentation ranges from asymptomatic cases to patients that present with symptoms of acute liver failure (jaundice, right upper quadrant pain). Autoimmune Hepatitis: progressive necroinflammatory process leading to chronic hepatitis or cirrhosis Cirrhosis 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. Cirrhosis. Characterized by the presence of circulating autoantibodies and high serum globulin concentrations. 
• Fitz-Hugh-Curtis syndrome (perihepatitis): characterized by 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 of the liver capsule that occurs in women as a rare complication of pelvic inflammatory disease Pelvic inflammatory disease 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, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease (PID).

Hereditary disorders

• Hemochromatosis: a genetic autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancedisorder due to a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations of the HFE gene, resulting in increased intestinal iron absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption. Presents with hepatomegaly, liver cirrhosis Cirrhosis 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. Cirrhosis, bronzed 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. Structure and Function of the Skin, diabetes mellitus Diabetes mellitus 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 β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, arthralgia, and 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). Overview of Cardiomyopathies.
• Wilson’s disease: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancemetabolic disorder in which copper excretion is impaired, leading to copper accumulation in the liver.
• Dubin-Johnson syndrome: a rare, autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancedisorder that involves elevated levels of conjugated bilirubin in the serum that lead to a melanin-like pigment depositing in the liver, causing what is known as “black liver.”

Miscellaneous disorders

• Portal hypertension Portal hypertension 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. Portal Hypertension: an increase in the pressure in the portal vein. Most commonly caused by cirrhosis Cirrhosis 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. Cirrhosis, schistosomiasis Schistosomiasis Schistosomiasis is an infection caused by Schistosoma, a trematode. Schistosomiasis occurs in developing countries with poor sanitation. Freshwater snails are the intermediate host and are transmitted to humans through skin contact with contaminated fresh water. The clinical presentation occurs as a result of the host's immune response to antigens from the eggs. Schistosoma/Schistosomiasis, and portal vein thrombosis, but may be idiopathic.
• Cirrhosis: a condition caused by chronic damage to the liver. Cirrhosis is characterized by hepatic parenchymal necrosis, which ultimately leads to fibrosis and liver insufficiency.
• Budd–Chiari syndrome: a rare condition resulting from hepatic vein obstruction that leads to hepatomegaly, ascites Ascites 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). Ascites, and abdominal discomfort.