Lecture 21.1: Liver Anatomy and Function PDF

Lecture 21.1: Liver anatomy and function Hepatic circulation Blood circulates to the liver via two separate routes. Firstly, the liver cells receive oxygenated blood from the hepatic artery, a branch of the cephalic trunk/arteries along the descending aorta. The superior mesenteric artery,...

Lecture 21.1: Liver anatomy and function Hepatic circulation Blood circulates to the liver via two separate routes. Firstly, the liver cells receive oxygenated blood from the hepatic artery, a branch of the cephalic trunk/arteries along the descending aorta. The superior mesenteric artery, inferior mesenteric artery, and other branches of the cephalic artery provide oxygenated blood to the rest of the GI organs, including the stomach, pancreas, small intestine, and large intestine. The blood circulating through these organs is collected in veins that converge to form the hepatic portal vein. The blood received by the hepatic portal vein contains compounds absorbed by the GI tract and hormones secreted by the various endocrine glands. It’s important to know that a portal system is defined as blood circulated through two separate organs before being returned into venous circulation. In this case, blood enters the liver via the cephalic trunk AND via the hepatic portal vein (the blood in the latter having already passed through other organs). Blood from the hepatic portal vein AND hepatic arteries is circulated through the sinusoids (a type of capillary with large gaps between the endothelial cells; sinusoids are also present in your hypothalamus) of the liver. This blood is drained into the central vein of the liver lobules and transported to the hepatic vein and then into the inferior vena cava. Here is an overview of the movement of blood: Hepatic artery: brings oxygenated blood to GI organs deoxygenated blood collected via: cephalic trunk and hepatic protal vein portal: means 2 veins converge into 1 all blood passes through liver sinusoids 1 Organization of liver lobes and lobules The liver is composed of four lobes, and each lobe is further divided into thousands of hexagonal lobules. Each corner of a hexagonal lobule is vascularized by a branch of the portal vein, a branch of the hepatic artery, and a bile duct. Recall that the blood from the hepatic artery is oxygenated, and the blood from the hepatic portal veins is deoxygenated and full of GI-absorbed compounds. Smaller vessels branching off the hepatic portal vein and hepatic artery converge to form the sinusoids, through which blood is moved towards a centrally-placed central vein. Groups of hepatocytes are arranged such that some make contact with the sinusoids and others make contact with the bile canaliculi (vessel branches off the bile ducts). Hepatocytes will absorb various compounds from the blood and detoxify others while also secreting bile into the bile canaliculi. Kupffer cells (a type of phagocyte) line the sinusoid walls and help remove defective blood cells, bacteria, and other foreign materials. around 4000 lobules Each hexagonal lobules: branch of poratl vein, branch of hepatic artery and bile duct Janitors: kupffer cells: phagocyte 2 Functions of the hepatocytes The cells of the liver perform functions related to 1) metabolism and 2) storage. 1. Metabolism: This can be further classified according to carbohydrate, lipid, and protein metabolism, and includes processes that synthesize and break down compounds. a. Carbohydrate metabolism: the liver stores glucose as glycogen in the fed state and breaks down glycogen into glucose in the fasting state. It also creates glucose from noncarbohydrates, including amino acids, glycerol, and lactic acid, during gluconeogenesis. It can also metabolize glucose to create triglycerides (lipogenesis) during the fed state. b. Lipid metabolism: The liver will metabolize fatty acids to create ketones in a process called ketosis that occurs primarily during the fasting state. The liver can also synthesize lipoproteins (like very-low density lipoproteins) to help package triglycerides and cholesterol (made by the liver). The components of triglycerides, glycerol and fatty acids, can be synthesized from glucose and amino acids. Cholesterol can be used to create bile. c. Protein metabolism: The liver is responsible for synthesizing the plasma proteins, including albumin, globulins, and fibrinogen. It also synthesizes many components of the coagulation cascade, including prothrombin and several clotting factors. It is also largely responsible for the interconversion of essential amino acids into nonessential amino acids. The processes that modify amino acids include transamination and deamination and they are necessary to synthesize glucose, ketones, and fatty acids. Furthermore, ammonia, produced via the catabolism of amino acids is converted into urea by the liver. During red blood cell recycling, the heme portion of hemoglobin is converted into biliverdin, which is quickly converted into unconjugated bilirubin. The hepatocytes convert this unconjugated bilirubin into conjugated bilirubin, which is much more soluble in water. This conjugated bilirubin is excreted by the kidneys or secreted as a component of bile. d. Miscellaneous: Cholecalciferol, a steroid intermediary produced by exposure to ultraviolet light, is metabolized to vitamin D by the hepatocytes. This form of vitamin D is further converted into calcitriol by the kidneys. The liver is also responsible for detoxifying toxic medications and compounds absorbed by the GI tract. Lastly, the liver contributes to the half-life of hormones, as it is responsible for breaking them down. 2. Storage: This not only pertains to the liver’s ability to store glycogen in the hepatocytes, but also fat-soluble vitamins, like vitamins A, D, and K. 3 Assessing liver function We monitor liver health by verifying two characteristics, 1) its protein-synthesizing capacity (including enzymes) and 2) its excretory capacity, while a patient’s history and physical examination can provide clues to liver function. The level or magnitude of liver injury is determined by ratios of liver to non-liver enzymes and its physical characteristics (determined largely through imaging technologies). Elevated serum liver enzymes is indicative of liver damage; these enzymes include: - aspartate aminotransferase (AST) and alanine aminotransferase (ALT) catalyze the transamination of their respective amino acids. The half-life of a compound is the amount of time taken to remove half the concentration of a compound from the blood (via filtration or decomposition), and AST and ALT have relatively long half-lifes. The AST:ALT ratio can help diagnose the condition or stage of liver disease. For example, an AST:ALT ratio below one (2) is indicative acute liver damage (tylenol toxicity or early-stage viral hepatitis) or alcohol-related liver damage. A ratio above five (>5) is indicative of a condition unrelated to the liver, like myocardial infarction or rhabdomyolysis; this is because AST is an enzyme found in several other organs, like muscles, kidney, and brain, while ALT is largelyText specific to the liver. - albumin and prothrombin (a clotting factor that is a precursor to thrombin) can also act as proxies for liver health, whereby drops in either protein indicate liver dysfunction. Indicators of the liver’s excretory capacity include the following: serum bilirubin, γ-glutamyltransferase, and alkaline phosphatase. Unconjugated bilirubin is a byproduct of heme breakdown (a component of hemoglobin), and the liver takes it up and converts it enzymatically into conjugated bilirubin, a more soluble form. Elevated levels of unconjugated bilirubin (without a rise in conjugated bilirubin) might indicate hemolysis, concurrent with a drop in erythrocytes and rise in lactate dehydrogenase. Elevated levels of conjugated bilirubin (without a rise in unconjugated bilirubin) might indicate the inability of the liver to excrete it into the intestine with bile, causing its accumulation in the bloodstream; this is called cholestasis (an inability to transport bile). Serum γ-glutamyltransferase (GGT) is elevated in cholestasis, viral hepatitis, and non-alcoholic liver disease, while alkaline phosphatase is a membrane enzyme on hepatocytes lining the biliary ductules, and its presence in the blood can indicate similar conditions as GGT. 4 Review questions 1. The external anatomy of the liver is organized into lobes, and the lobes are further organized as lobules, which are hexagonal in shape. Compounds are distributed and directed towards the liver for a number of reasons. What series of structures will bile salt travel through in order to emulsify fats in the small intestine? i. hepatocyte iv. sinusoid vii. bile duct ii. enterocyte v. portal vein viii. small intestine lumen iii. bile canaliculi (ductule) vi. central vein ix. colon lumen A. i, iv, v, viii B. ii, iii, vii, viii C. i, iii, vii, viii hepatocyte, bile canaliculi, bile duct, small intestine D. ii, iv, v, ix E. ii, vi, vii, viii 2. What series of structures will blood travel through in order to supply the liver with oxygen and leave the liver with carbon dioxide? i. hepatocyte v. hepatic portal vein vii. hepatic vein ii. hepatic artery vi. central vein viii. small intestine lumen iii. sinusoid iv. bile duct ix. vena cava A. ii, iii, v, vii, ix B. ii, iii, vi, vii, ix hepatic artery, sinusoid, central vein, hepatic vein, vena cava C. ii, v, vi, vii, ix D. iii, v, vi, vii, ix E. iii, vi, v, viii, ix 5 Answer key: C, B 6