Liver Physiology Dr Maddi Anupindi
Describe the blood supply to the liver and its regulation
The basic functional unit of the liver is the lobule which is composed of a roughly hexagonal arrangement of plates of hepatocytes that radiate around a central vein. The central vein empties into the hepatic vein which then empties into the IVC. At the vertices between adjacent lobules are portal triads which consist of branches of the portal vein, bile duct and hepatic artery. Blood from the portal vein and hepatic artery flow and mix in the sinusoids that radiate from the portal triad and drain into the central vein. Sinusoids also contain endothelial cells and Kupffer cells and the endothelium is fenestrated.
Source – Circulation Research 103(9):929-39 · November 2008
Blood flow to the liver is derived from both the hepatic artery and portal vein. Total blood flow to the liver is 1.5L/minute which is almost 25% of cardiac output, of which about 30% is supplied by the hepatic artery and 70% is supplied by the portal vein.
The hepatic artery is a branch of the coeliac trunk. It is a high pressure, high resistance system, that has a muscular coat and contributes 40-50% of the liver’s oxygen supply. It has a baseline oxygen saturation of 98%. The portal vein is valveless and drains blood from the intestines, spleen, stomach, pancreas and gallbladder. It is a low pressure, low resistance system and contributes about 50-60% of the liver’s basal oxygen supply. It has a baseline oxygen saturation of 85% during fasting but this decreases with increased gastrointestinal activity. The mean pressure in the portal vein is 10mmHg whereas the mean pressure in the hepatic artery is 90-100mmHg.
Given the liver’s high resting flow rate, an increase in oxygen demand results in an increased oxygen extraction. Control of liver’s blood flow is via control of hepatic arterial inflow, portal venous inflow and the inter-relationship between these two circuits.
Hepatic arterial flow:
Portal venous flow:
Outline the effect of liver blood flow on drug clearance
Hepatic clearance of a drug is a product of the hepatic extraction ratio and the hepatic blood flow. The hepatic extraction ratio is the fraction of the drug in the blood entering the liver which is irreversibly removed during one pass through the liver. It is determined by the concentration difference of the drug entering and leaving the liver divided by the concentration entering the liver. For drugs with an extraction ratio towards one, most of the drug is eliminated during a single pass through the liver. For those with an extraction ratio closer to 0, most escapes elimination after a single pass. The hepatic extraction ratio is dependent on the extent of protein binding of the drug, as hepatocytes only have access to the unbound fraction, and on the intrinsic clearance of the drug. The effect of liver blood flow on drug metabolism depends on the extraction ratio for that drug.
Outline the functions of the liver
Describe the physiology of bile and its metabolism
Bile is an aqueous secretion that originates from hepatocytes and is modified distally by absorptive and secretory transport systems in the bile duct epithelium. Approximately 400ml – 1L of bile is produced a day by the liver. It is 97% water in which are dissolved bile acids, bilirubin, cholesterol, lecithin, organic ions, electrolytes, enzymes, proteins and toxins.
The two principal liver bile acids are cholic acid and chenodeoxycholic acid which are formed from cholesterol.
The bile acids combine with glycine and taurine to form conjugated bile acids, the salts of which are secreted into bile. Bile is initially secreted by hepatocytes and contains large quantities of bile acids, cholesterol and other organic molecules. As it flows through bile ducts a watery sodium bicarbonate solution is added. It eventually enters the cystic duct and the gallbladder where it is concentrated and stored or the duodenum where it aids in lipid digestion. About 95% of bile salts are then reabsorbed in the small intestine and undergo enterohepatic circulation while the remainder are excreted in faeces.
The roles of bile are:
The regulation of bile formation and secretion involves:
Outline the consequences of liver disease