Liver Flashcards
Liver Function
o Regulation of carbohydrate and protein metabolism
o Regulation of cholesterol production and excretion through bile
o Degradation of hormones and detoxification and excretion of drugs and toxins
o Beta oxidation of fatty acids
o Bile production and secretion
o Vitamin storage
Liver Structure
o Sinusoids – contains mixed blood from portal vein and hepatic artery; bathes hepatocytes
o Space of Disse – space between sinusoids and hepatocytes that collects lymph produced by hepatocytes
o Kupffer cells – macrophages fixed to sinusoid membranes that clean blood of 99% bacteria and old RBCss
o Hepatocytes produce lymph; secretes bile into canaliculi and into bile duct; drug and chemical metabolism
Liver Vascular Function
o Blood flow to liver is from portal vein (1L/min) and hepatic artery (400ml/min); total = 1.5 L/min (~30% of cardiac output)
o Portal vein is part of Splanchnic circulation (vasculature around intestines, liver, and spleen); contains all the newly absorbed nutrients as well as bacteria and drugs
o Hepatic artery supplies systemic blood to liver
o Hepatic vein drains into vena cava with a pressure of ~ 0 mmHg; if pressure rises pathology can develop (asicitis – fluid in peritoneum; hepatomegaly – enlarged liver)
Pre-hepatic, intrahepatic, or post-hepatic hypertension
o Half of all body lymph production is done by liver
Carbohydrate Metabolism
– helps maintain glucose levels; provides energy source
Conversion of monosaccharides (galactose and fructose) glucose
Gluconeogenesis – amino acids and glycerol from triacylglycerides converted to glucose
Glycogen storage (~18 hour supply)
• Excess glucose converted to glycogen by glucokinase
• Epinephrine and glucagon stimulate phosphorylase and release of glucose into blood
Formation of chemical compounds from intermediates of carbohydrate metabolism
liver has GLUT2 transporters which are insulin-INDEPENDENT and allow for high capacity of glucose transport; also found in brain, pancreas, kidneys and basolateral side of enterocytes
Lipid Metabolism
– provides another energy source; provides building blocks for membranes, intracellular structures and steroid hormones; build up fat stores
High rate of beta-oxidation of fatty acids
Forms most lipoproteins (transport proteins)
• VLDL – high triacylglycerols; transports to adipose tissue
• LDL (BAD) – high cholesterol content; transport cholesterol to tissues
• HDL (GOOD) – 50% protein, less cholesterol
Synthesizes lots of cholesterol and phospholipids
• HMG-CoA reductase is rate limiting step in cholesterol synthesis; target of statin drugs
Converts unused carbohydrates and proteins to fat
Other Metabolic Functions
– reservoir for nutrients and detox plant; sequesters iron (toxic when free)
Vitamin storage – A, D, B12
Formation of blood coagulation products – fibrinogen, prothrombin, factor 7
Iron storage in ferritin pools
Drug, hormone, and waste removal (detoxification and excretion into bile)
Protein Metabolism
-essential for survival; would die within days from toxicity without it
Deamnation of amino acid – releases ammonia (NH3) which will be combined with CO2 to form urea and excreted in urine; CRITICAL to get rid of toxic ammonia
Forms 90% of plasma proteins (albumin – oncotic pressure) (immunoglobulins-immune defense) (fibrinogen-blood clotting)
Interconversion among different amino acids
Symptoms Occuring with Liver Failure
o Ascites, jaundice, portal hypertension (obstructive liver disease) o Bleeding/bruising (lack of clotting proteins produced) o Confusion/cognition problems (encephalopathy), weakness, nausea – (build of up toxins in body and acidosis due to buildup of unprocessed amino acids) o Cholestasis (reduced or blocked bile flow due to gallstones)
Cirrhosis
– most common cause of obstructed liver disease; leading to portal hypertension
Causes – alcoholism or hepatitis C infection
Kills hepatocytes and leads to scar tissue formation, inflammation and blockage of blood flow in liver
Ascitis
– increased hepatic vein pressure or increased portal vein pressure pooling of blood in liver capillaries increased hydrostatic capillary pressure pull fluid from plasma and Space of Disse into peritoneal cavity of the abdomen (contains both fluid and proteins)
Hepatomegaly
– increase in liver size due to fluid retention
Liver usually has 400ml of blood but can increase to ~1 L in pathologic conditions
General Jaundice Symptoms
yellowing of skin, nail beds, whites of eyes, etc. caused by increased bilirubin in the blood
Obstructive Jaundice
obstruction of bile ducts (cirrhosis, gallstones, cancer) causing bilirubin to be incorporated into blood instead of bile
Hepatic Jaundice
– reduces ability of cells to metabolize bilirubin (hepatitis, drug hepatotoxicity, cirrhosis)
Hemolytic Jaundice
– an increase in hemolysis of RBC that increases bilirubin production faster than the bile can excrete it (malaria, sickle cell, genetic disease