Liver: Anatomy

Development

• Develops from the 3rd to 8th week during embryogenesis
  • Originates from the foregut Foregut Development of the Abdominal Organs endoderm Endoderm The inner of the three germ layers of an embryo. Gastrulation and Neurulation
  • Appears as the hepatic diverticulum Hepatic diverticulum Development of the Abdominal Organs, 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: Anatomy
• The falciform ligament is called the ventral mesentery Mesentery A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. Peritoneum: Anatomy during the fetal period Fetal period Prenatal and Postnatal Physiology of the Neonate.
• 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: Anatomy contains the umbilical vein umbilical vein Venous vessels in the umbilical cord. They carry oxygenated, nutrient-rich blood from the mother to the fetus via the placenta. In humans, there is normally one umbilical vein. Prenatal and Postnatal Physiology of the Neonate during gestation, which is the main fetal blood source (see table below).

Gross Anatomy

Location

The liver is the largest gland in the body. It extends from the right to the left hypochondriac region (¾ of the liver is in the right superior quadrant).

• Immediately adjacent to the inferior surface of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy → location is breath-dependent (rises during exhalation, lowers during inhalation)
• Superior limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation: height of the 5th intercostal space during exhalation
• Inferior limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation: curve of the right costal arch during inhalation 
• Surfaces: diaphragmatic and visceral
  • Intraperitoneal Intraperitoneal Peritoneum: Anatomy except for the bare area, porta hepatis, and 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: Anatomy fossa 
  • Enclosed in the Glisson capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides (external layer of fibrous Fibrous Fibrocystic Change connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology)
• Weight: 1.5 kg (average)

Four lobes

• Superficially divided by fissures and ligaments
• Functionally determined by the left and right branches of the hepatic vein Hepatic vein Veins which drain the liver. Budd-Chiari Syndrome and Cantlie’s line (an imaginary line that crosses 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: Anatomy fossa and inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy)

1. Right lobe: largest
2. Left lobe: separated from the right by the falciform ligament on the diaphragmatic surface
3. Caudate lobe: between the venous ligament and groove for the inferior vena cava Inferior vena cava The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy ( IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy)
4. Quadrate lobe: between 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: Anatomy 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: Anatomy fossa

Impressions of adjacent structures and organs

• Gastric: left lobe, anterior to the esophageal impression
• Colic: inferior margin of the right lobe (right colic flexure)
• Duodenal: right lobe, lateral to 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: Anatomy (1st segment of the duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy)
• Renal: center of the right lobe (superior pole of the right kidney)
• Suprarenal: superior to the renal impression (right adrenal gland)

Eight segments (Couinaud classification)

• Based on a transverse plane Transverse plane Anterior Abdominal Wall: Anatomy through the bifurcation of the main portal vein
  • Exception: Caudate lobe receives blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure from both vascular branches.
• 8 functionally independent segments, each with its own vascular inflow, outflow, and biliary drainage 
• Segment I is the caudate lobe and can only be seen from the posterior view.
• Segments can be surgically resected without affecting the viability of the remaining liver.

Porta hepatis

The porta hepatis (also called the hepatic portal) is a transverse fissure Fissure A crack or split that extends into the dermis Generalized and Localized Rashes that separates the caudate and quadrate lobes and serves as a passageway for the following: 

• Common hepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct (exits the liver, located anteriorly and laterally)
• Hepatic artery proper (enters the liver, located anteriorly and medially) 
• Hepatic portal vein (enters the liver, located posteriorly, between the duct and artery)
• Hepatic nerve plexus (contains postganglionic sympathetic innervation from the celiac plexus and preganglionic parasympathetic innervation from the vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy)
• Lymphatic vessels Lymphatic Vessels Tubular vessels that are involved in the transport of lymph and lymphocytes. Lymphatic Drainage System: Anatomy of the liver

Ligaments of the liver

Definition: Ligaments of the liver are double layers of visceral peritoneum Visceral peritoneum Peritoneum: Anatomy that fix the position of the liver by attaching it to the surrounding structures.

Microscopic Anatomy

Hepatic (classical) lobule

• Small hexagonal units of the liver, measuring 1–2.5 mm each, separated by thin strands of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
• Central vein: Each lobule has a vein in the center that receives mixed blood from the sinusoids (via branches from the portal vein and hepatic artery), drains into the 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: Histology, and leaves the liver via the IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy.
• Portal triad: cluster of vessels located at the 6 vertices of each hepatic lobule:
  • Interlobular branch of the portal vein: supplies the lobule with deoxygenated blood, rich in nutrients
  • Interlobular branch of the hepatic artery proper: supplies the lobule with oxygenated blood
  • Interlobular bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct: drains the bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy from the biliary ductules in the opposite direction of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
  • Additionally: lymphatic vessels Lymphatic Vessels Tubular vessels that are involved in the transport of lymph and lymphocytes. Lymphatic Drainage System: Anatomy and a branch of the vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy

Portal vein lobule

• The portal vein lobule is a lobule viewed from a 2nd perspective, with the portal triad in the center and the central veins Central Veins Central Venous Catheter at the 3 vertices
• Shaped like a triangle
• Functional unit for bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy transport
• Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy is drawn to the center of the triangle, into the interlobular bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct.

Hepatic acinus

• The hepatic acinus is a lobule viewed from a 3rd perspective, with the central veins Central Veins Central Venous Catheter and portal triads at the 4 vertices.
• Diamond-shaped
• Functional unit for blood exchange
• Blood moves from the triads to the vein through 3 zones:
  1. Zone 1: the periphery of the hepatic lobule, highest nutrient/oxygen levels
  2. Zone 2: transitional zone Transitional zone Anal Cancer
  3. Zone 3: the center of the hepatic lobule, lowest nutrient/oxygen levels
     • Most sensitive to ischemic damage

Hepatocytes

• Polyhedral cells organized into plates separated by sinusoids
• Shape and number of the nuclei vary
• Each cell has an apical biliary pole, which drains into one or more bile canaliculi Bile Canaliculi Minute intercellular channels that occur between liver cells and carry bile towards interlobar bile ducts. Also called bile capillaries. Gallbladder and Biliary Tract: Anatomy, and a basolateral blood pole, which receives blood from the sinusoids.

Sinusoids

• Capillaries Capillaries 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: Histology with discontinuous endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology between hepatocyte plates
• Receive oxygen-rich blood from the interlobular arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology and nutrient-rich blood from the interlobular 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: Histology and conducts in toward the central veins Central Veins Central Venous Catheter
• Kupffer cells Kupffer cells Specialized phagocytic cells of the mononuclear phagocyte system found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells. Benign Liver Tumors: specialized macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation between the endothelial cells, which phagocytose old or damaged erythrocytes Erythrocytes 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. Erythrocytes: Histology
• Pit cells: liver-specific natural killer cells Natural killer cells A specialized subset of T-lymphocytes that exhibit features of innate immunity similar to that of natural killer cells. They are reactive to glycolipids presented in the context of the major histocompatibility complex (MHC) class I-like molecule, CD1D antigen. Lymphocytes: Histology that adhere to the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology, are dependent on Kupffer cells Kupffer cells Specialized phagocytic cells of the mononuclear phagocyte system found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood, and dispose of worn out red blood cells. Benign Liver Tumors, and have tumor Tumor Inflammation cell-lysing capability 
• Perisinusoidal or space of Disse: space filled with blood plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products that lies between the sinusoids and hepatocytes
  • Contains Stellate or Ito cells: store vitamin A Vitamin A Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies and play a role in collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology production (important in the development of 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)

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 Abdominal Aorta The aorta from the diaphragm to the bifurcation into the right and left common iliac arteries. Posterior Abdominal Wall: Anatomy → 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: Histology
  • Additional tributaries: inferior mesenteric, cystic Cystic Fibrocystic Change, 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: Histology

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: Histology → IVC IVC The venous trunk which receives blood from the lower extremities and from the pelvic and abdominal organs. Mediastinum and Great Vessels: Anatomy
• Portosystemic anastomoses Portosystemic anastomoses Systemic and Special Circulations: alternative routes of circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment 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: Histology 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: Histology 
  • 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: Histology 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: Histology
  • 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: Histology 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: Histology
  • The intraparenchymal hepatic branches of the right division of the portal vein and the retroperitoneal Retroperitoneal Peritoneum: Anatomy 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: Histology 
  • 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: Histology with the retroperitoneal Retroperitoneal Peritoneum: Anatomy 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: Histology
  • The ductus venosus Ductus venosus Development of the Heart 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: Anatomy 

Lymphatic drainage

Hepatic lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy: located around the porta hepatis → celiac cluster of lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy → cisterna chyli (dilated sac that receives lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs from the gastrointestinal [GI] trunk and 2 lumbar lymphatic trunks) → thoracic duct Thoracic Duct The largest lymphatic vessel that passes through the chest and drains into the subclavian vein. Lymphatic Drainage System: Anatomy 

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 Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides innervated by the most inferior intercostal nerves
• HAP has α and β adrenergic receptors Receptors 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. Receptors innervated by splanchnic nerves

Biliary drainage

Bile canaliculi Bile Canaliculi Minute intercellular channels that occur between liver cells and carry bile towards interlobar bile ducts. Also called bile capillaries. Gallbladder and Biliary Tract: Anatomy → intrahepatic bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy ducts → left and right hepatic ducts → common hepatic duct → common bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct → duodenum Duodenum The shortest and widest portion of the small intestine adjacent to the pylorus of the stomach. It is named for having the length equal to about the width of 12 fingers. Small Intestine: Anatomy

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 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury 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. Acid-Base Balance into urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle
• Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism breakdown
• Breakdown of bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism (glucuronidation) → excretion into bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy

Metabolism

• Carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of 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 Synthesis Polymerase Chain Reaction (PCR) of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance from amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids, lactate, or glycerol)
  • Glycogenesis Glycogenesis Glycogen Metabolism ( synthesis Synthesis Polymerase Chain Reaction (PCR) of glycogen from glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance)
  • Glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism (breakdown of glycogen into glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance)
  • Glycolysis Glycolysis Glycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins. Glycolysis (breakdown of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance into pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis, producing adenosine Adenosine A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Class 5 Antiarrhythmic Drugs triphosphate (ATP))
• Proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis:
  • Production of albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests; globulins; acute phase Acute phase Short Bowel Syndrome proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis; transaminases Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis; coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis I ( fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis), II ( prothrombin Prothrombin A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Hemostasis), V, VII, VIII, IX, X, XI, XII, and XIII; protein C; protein S Protein S Protein S augments the activity of protein C. Hemostasis; and antithrombin Antithrombin Endogenous factors and drugs that directly inhibit the action of thrombin, usually by blocking its enzymatic activity. They are distinguished from indirect thrombin inhibitors, such as heparin, which act by enhancing the inhibitory effects of antithrombins. Anticoagulants
  • 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 Lipids Lipids are a diverse group of hydrophobic organic molecules, which include fats, oils, sterols, and waxes. Fatty Acids and Lipids:
  • Lipogenesis Lipogenesis De novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements. Nonalcoholic Fatty Liver Disease (storage of free fats Fats The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (dietary fats) as a source of energy. Energy Homeostasis as triglycerides Triglycerides Fatty Acids and Lipids) 
  • Ketogenesis Ketogenesis Ketone Body Metabolism ( synthesis Synthesis Polymerase Chain Reaction (PCR) of ketone bodies Ketone bodies The metabolic substances acetone; 3-hydroxybutyric acid; and acetoacetic acid (acetoacetates). They are produced in the liver and kidney during fatty acids oxidation and used as a source of energy by the heart, muscle and brain. Ketone Body Metabolism) 
  • Fatty acid synthesis Synthesis Polymerase Chain Reaction (PCR) and degradation 
  • Production of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance, lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism, and cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism

Storage

• Glycogen 
• Lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism 
• 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 Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements and copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements

Hormone production

• Thrombopoietin Thrombopoietin A humoral factor that stimulates the production of thrombocytes (blood platelets). Thrombopoietin stimulates the proliferation of bone marrow megakaryocytes and their release of blood platelets. The process is called thrombopoiesis. Platelets: Histology
• Insulin-like growth factor 1
• Angiotensinogen

Erythropoiesis Erythropoiesis The production of red blood cells (erythrocytes). In humans, erythrocytes are produced by the yolk sac in the first trimester; by the liver in the second trimester; by the bone marrow in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction. Erythrocytes: Histology

• Site of fetal RBC production from week 6 of gestation until birth
• Extramedullary erythropoiesis Erythropoiesis The production of red blood cells (erythrocytes). In humans, erythrocytes are produced by the yolk sac in the first trimester; by the liver in the second trimester; by the bone marrow in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction. Erythrocytes: Histology may occur in adulthood after bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis irradiation, in various bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis disorders (e.g., myelofibrosis, myelodysplastic syndrome, polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma 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 Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination and percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination. The purpose of liver palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination is to approximate liver size and feel for tenderness and masses. The purpose of liver percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination 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 Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis, glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids dehydrogenase, and AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests/ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests ratio)
  • Parameters of cholestasis (e.g., γ-glutamyl transpeptidase, alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, and direct and indirect bilirubin Indirect Bilirubin Liver Function Tests)
  • Parameters of hepatic synthesis Synthesis Polymerase Chain Reaction (PCR) ( albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests, cholinesterase Cholinesterase Liver Function Tests, and coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis)
• Normal abdominal imaging: Imaging is essential for accurately detecting focal liver lesions (e.g., abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease, tumor Tumor Inflammation), 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 Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) ultrasonography
  • Computed tomography (CT) scan
  • Radionuclide liver scanning
  • Abdominal radiography
  • Magnetic resonance imaging (MRI)

Disorders

Neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors

• Benign Benign Fibroadenoma liver tumors: cavernous hemangiomas, hepatocellular adenomas, and focal nodular hyperplasia Focal nodular hyperplasia Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as hepatocytes, small bile ducts, and kupffer cells among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen. Benign Liver Tumors. 
• 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 Cholangiocarcinoma A malignant tumor arising from the epithelium of the bile ducts. Rare Malignant Liver Tumors; hepatoblastoma Hepatoblastoma A malignant neoplasm occurring in young children, primarily in the liver, composed of tissue resembling embryonal or fetal hepatic epithelium, or mixed epithelial and mesenchymal tissues. Rare Malignant Liver Tumors; angiosarcoma; hemangioendothelioma; liver metastases from GI, breast, and lung malignancies; and rare hepatic tumors (carcinosarcomas, teratomas Teratomas A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). Ovarian Cancer, yolk sac Yolk Sac The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. Embryoblast and Trophoblast Development 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 Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

• Viral hepatitis: mainly caused by primarily hepatotropic Hepatotropic Hepatitis A Virus viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology 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 Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop non-specific symptoms, such as nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, 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, and abdominal pain Abdominal Pain Acute Abdomen. Other viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology 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 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 virus Virus 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. Virology.
• Bacterial 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:
  • Pyogenic liver abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease (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)
  • Diffuse involvement, such as by Salmonella enterica serotype typhi Salmonella enterica serotype typhi A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. Salmonella, Mycobacterium tuberculosis Mycobacterium 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 Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, 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 capsulatum Histoplasma capsulatum Histoplasma/Histoplasmosis
• Parasitic 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, 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 Infection with flukes (trematodes) of the genus schistosoma. Three species produce the most frequent clinical diseases: Schistosoma haematobium (endemic in Africa and the Middle East), Schistosoma Mansoni (in Egypt, northern and southern Africa, some West Indies islands, northern 2/3 of South america), and Schistosoma japonicum (in Japan, China, the Philippines, Celebes, Thailand, Laos). S. mansoni is often seen in Puerto Ricans living in the United States. Schistosoma/Schistosomiasis), 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 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. Plasmodium/Malaria)

Inflammatory disorders

• Alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) 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 use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder.
• Nonalcoholic fatty liver Nonalcoholic fatty liver Fatty liver finding without excessive alcohol consumption. Nonalcoholic Fatty Liver Disease 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 Diabetes 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, and elevated triglycerides Triglycerides Fatty Acids and Lipids.
• 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 Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques 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 Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides 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 PID 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).

Hereditary disorders

• Hemochromatosis Hemochromatosis A disorder of iron metabolism characterized by a triad of hemosiderosis; liver cirrhosis; and diabetes mellitus. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. Hereditary 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 Inheritance disorder 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 HFE gene Hereditary Hemochromatosis, resulting in increased intestinal iron absorption Iron absorption 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. Skin: Structure and Functions, diabetes Diabetes 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 mellitus, arthralgia Arthralgia Pain in the joint. Rheumatic Fever, 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). Cardiomyopathy: Overview and Types.
• 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 Inheritance metabolic disorder in which copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements excretion is impaired, leading to copper Copper A heavy metal trace element with the atomic symbol cu, atomic number 29, and atomic weight 63. 55. Trace Elements accumulation in the liver.
• Dubin-Johnson syndrome Dubin-Johnson Syndrome Jaundice: 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 Inheritance disorder that involves elevated levels of conjugated bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism 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 Infection with flukes (trematodes) of the genus schistosoma. Three species produce the most frequent clinical diseases: Schistosoma haematobium (endemic in Africa and the Middle East), Schistosoma Mansoni (in Egypt, northern and southern Africa, some West Indies islands, northern 2/3 of South america), and Schistosoma japonicum (in Japan, China, the Philippines, Celebes, Thailand, Laos). S. mansoni is often seen in Puerto Ricans living in the United States. Schistosoma/Schistosomiasis, and portal vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus, but may be idiopathic Idiopathic Dermatomyositis.
• 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: a condition caused by chronic damage to the 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 is characterized by hepatic parenchymal necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage, which ultimately leads to fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans and liver insufficiency.
• Budd–Chiari syndrome: a rare condition resulting from hepatic vein Hepatic vein Veins which drain the liver. Budd-Chiari Syndrome 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.