Liver Physiology By: Dr Asma Jabeen

Learning Objectives To describe the functional anatomy of liver To discuss the functions of liver

Introduction The largest organ 2% of total body weight

The Functional Anatomy Of Liver Functional unit is liver lobule

Liver Lobule 0.8 to 2 millimeters in diameter. Cylindrical structure 0.8 to 2 millimeters in diameter. 50,000 to 100,000 individual lobules in human liver. Constructed around a central vein that empties into the hepatic veins and then into the vena cava.

Liver Lobule

Liver Lobule

Veins of hepatic lobule Portal vein from GIT Portal venules Hepatic sinusoids Central vein

Arterial supply Hepatic arterioles in the interlobular septa. Supply arterial blood to septal tissues Most of these empty directly into the hepatic sinusoids

Liver Lobule

Liver Sinusoids Extremely porous endothelial lining Pores 1 micrometer in diameter. Beneath this lining, lying between the endothelial cells and the hepatic cells, there are narrow tissue spaces called the spaces of Disse.

Spaces of Disse Perisinusoidal spaces. The millions of spaces of Disse connect with lymphatic vessels in the interlobular septa.

Blood Flow In Liver About 1050 milliliters of blood flows from the portal vein into the liver sinusoids each minute, Additional 300 milliliters flows into the sinusoids from the hepatic artery, The total averaging about 1350 ml/min. This amounts to 27 per cent of the resting cardiac output.

Functions of liver

Formation and secretion of bile Bile acids, bile pigments dissolved in alkaline electrolyte solution 500 ml/day Digestion and absorption of fats Major excretory route for lipid soluble waste products

2. Nutrient and Vitamin Metabolism Carbohydrate Metabolism Storage of large amount of glycogen Conversion of galactose and fructose to glucose Gluconeogenesis Glucose buffer function of liver

Fat Metabolism Oxidation of fatty acids to supply energy for other body functions Synthesis of large quantities of cholesterol, phospholipids, and most lipoproteins Synthesis of fat from proteins and carbohydrates

Protein Metabolism Deamination of amino acids Formation of urea for removal of ammonia from the body fluids Formation of plasma proteins Interconversions of the various amino acids and synthesis of other compounds from amino acids

3. Inactivation of various substances: Hormones: Several hormones either chemically altered or excreted by the liver like: Thyroxin Essentially all the steroid hormones Liver damage cause overactivity of these hormonal systems

Mineral Metabolism One of the major routes for excreting calcium from the body is secretion by the liver into the bile, which then passes into the gut and is lost in the feces.

Drug Inactivation The active chemical medium of the liver is well known for its ability to detoxify or excrete into the bile many drugs, including sulfonamides penicillin ampicillin erythromycin.

4. Storage Functions: The vitamin stored in greatest quantity in the liver is vitamin A Sufficient quantities of following vitamins can be stored to prevent their deficiency Vitamin A for as long as 10 months. vitamin D for 3 to 4 months, vitamin B12 for at least 1 year

Iron Storage Greatest proportion of iron stored in liver Apoferritin combines reversibly with iron to form ferritin If low iron in circulating fluids, released from ferritin Blood iron buffer

5. Synthesis of plasma proteins: Clotting factors Steroid binding and other hormone binding proteins

6. Blood cleansing function Large phagocytic macrophages Kupffer cells lining the hepatic sinusoids cleanse blood as it passes through sinusoids. Less than 0.1 % of bacteria in portal blood enters systemic circulation

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Fate of RBC – Billirubin formation and excretion

Jaundice Jaundice refers to a yellowish tint to the body tissues, including a yellowness of the skin and deep tissues. Cause: Large quantities of bilirubin in ECF either conjugated or unconjugated. normal bilirubin: 0.5 mg/dl

Diagnostic differences between different types of Jaundice Van den Bergh reaction: The lab test that is used to differentiate between conjugated and unconjugated bilirubin Direct Van den Berg reaction : Conjugated bilirubin Indirect Van Den Berg reaction: Unconjugated billirubin

In Hemolytic Jaundice: All the bilirubin is in Unconjugated form In Obstructive jaundice: Billirubin is mostly conjugated Tests for urobilinogen in urine are negative Clay coloured stools because of absence of stercobilin & other bile pigments Significant quantities of conjugated bilirubin appear in urine

Liver Cirrhosis When liver parenchymal cells are destroyed, they are replaced by fibrous tissues that eventually contracts around blood vessels greatly impeding flow of portal blood through the liver. This disease process is called cirrhosis of liver

Causes of liver cirrhosis: Chronic alcoholism Excess fat accumulation & inflammation in liver (Non alcoholic steatohepatitis-NASH) Ingestion of poisons(carbon tetrachloride) Infectious hepatitis Obstruction or infection of the bile ducts

Portal Hypertension & Ascites 1. Impedance in portal circulation due to clot etc- portal hypertension 2. Rise of capillary pressure to 15 to 20 mmHg above normal, edema of gut wall and transudation of fluid from gut serosa- Ascites 3. Increased pressure in hepatic vein- large amount of transudate into lymph- “sweating” from the surface of liver-Ascites

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