Lecture 1: Liver Anatomy and Physiology

8 Segements made into lobules Each lobule is represented as a hexagonal cluster of hepatocytes which is connected to a central vein, hepatic portal vein, bile duct, hepatic artery.

Lecture slides

Blood is conveyed to the lobules by branches of the hepatic portal vein and the hepatic artery. It then flows through sinuses, bathing the hepatocytes, to the central vein of the lobule, a branch of the Hepatic vein which drains into the Inferior Vena Cava. The hepatocytes secrete bile into bile canuliculi running between the hepatocytes, and these drain into branches of the bile duct. Refer to lecture slides for diagram

Lonely cells, very temperamental when outside the body Cells die immediately and function is lost in order of hours.

hepatocyte stellate fat storing cell Kupffer cell liver endothelial cell

Also called parenchymal cells. Make up 70 to 80 percent of the liver’s cytoplasmic mass. Are involved in synthesizing protein, cholesterol, bile salts, fibrinogen, phospholipids and glycoproteins.

Transportation of WBC and increasing immune tolerance. Secrete cytokines, which is a forem of cellular communication signal.

Reticuloendothelial cells of the liver Secrete mediators of immune response system Phagocytize bacteria, foreign material Blood flowing through intestinal capillaries picks up many bacteria in intestines

Exist in the space between parenchymal cells and sinusoidal endothelial cells Vitamin A-storing cells, lipocytes, interstitial cells, fat-storing cells, promote ion movement and proliferation of chemical responses to stress.

Production of bile Production of cholesterol, carbohydrate, proteins Regulate blood levels of amino acids Processing of haemoglobin for use of its iron content Conversion of ammonia to urea Detoxification of drugs Regulate blood clotting

storage of glycogen gluconeogenesis site role in glucose homeostasis.

The liver is central to the processing of dietary fats to lipoproteins

De-animation of amino acids

Deamination of amino acids, conversion of the non-nitrogenous part of those molecules to glucose or lipids. Formation of urea for removal of ammonia from the body fluids Formation of plasma proteins – not gamma globulins Interconversions of the various amino acids and synthesis of other compound from amino acids

Ammonia detoxification disorder and failure of urea formation (ammonia comes from bacterial degradation of nitrogen substances in intestines, from intestine mucosa during glutamine degradation, from degradation of amino acids in kidneys and muscles) Hyperamonemia increase of ammonia blood concentration (>50 μmol/l) Hepatic encephalopathy Toxic effect of ammonia in the brain (Binding of ammonia to glutamate = glutamine) Mental changes (capriciousness, disorientation, sleeping disorders, chaotic speech, personality changes) Motoric changes (increased in muscle reactivity, hyperreflexion, tremor) Hepatic coma to death Endogenous = viral hepatitis and poisoning (hepatic cells desintegration) Exogenous = final status of chronic cirrhosis (ammonia and other toxic substances bypass the liver through the extrahepatic anastomoses)

Lecture slides

Storage of glycogen Glucose buffer function = removing excess of glucose from blood, storage, fast return when the blood concentration decreases Conversion of galactose/fructose to glucose

glycogenesis: Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the large polymer, glycogen glycogenolysis: When blood concentrations of glucose begin to decline, the liver activates other pathways which lead to depolymerization of glycogen to glucose gluconeogenesis: Synthesizing glucose out of such things as amino acids and non-hexose carbohydrates

Hyperglycaemia: in patients with cirrhosis after carbohydrate rich meal. liver insufficiency → decrease of glucose utilization → hyperglycemia → hyperinsulinemia → down-regulation of insulin receptors → insulin resistance Hypoglycemia in alcohol abusers – alcohol suppresses citrate cycle and thereby impairs gluconeogenesis from amino acids. After depletion of glycogen storages comes hypoglycemia that threatens the patient’s life

Oxidation of fatty acids to supply energy for other body function Synthesis of large quantities of cholesterol (80% of cholesterol synthesized in the liver is converted into bile salts), phospholipids, and most lipoproteins Inactivation of steroids and their excretion of the body Synthesis of lipoproteins, fat from proteins and carbohydrates Remainder is excreted in bile as cholesterol or after conversion to bile acids.

Initial portion is from hepatocytes (contains bile acids, cholesterol, organic constituents).Mostly bile acids Additional secretion is a watery solution of sodium and bicarbonate – secreted by secretory epithelial cells lining the ductules and ducts. Neutralising gastric acid

Water, electrolytes, cholestrol, phospholipids, bile acids, bilirubin

• Fat emulsifation/absorption 2. Neutralisation of gastric acid

Cholecystokinin (CCK) Most potent stimulant for bile secretion Stimulus for release = fat in duodenum Secretin Stimulated in response to acid in duodenum Stimulates bile duct (and pancreas) to secrete bicarb and H20 Expands volume of bile and bile flow increases Acetylcholine secreting nerve fibers Not as potent, from vagi and enteric nervous system ie smell food gastric system kicks in and pH drops, releases bicarbonate