Liver and biliary system week 3 Flashcards
What is a liver lobule?
What are liver lobules surrounded by?
Liver lobule: classical anatomical unit
- Liver lobule is surrounded by the portal space (aka portal tetrad) (occupied by hepatic arteries, portal veins (low in O2, high in nutrients), bile ducts and lymphatic vessels).
What are portal lobules?
What are they defined by?
Portal lobule: unit defined by bile flow
bile flows from periphery of triad toward portal space where bile canaliculi are also present
central vein collects blood from the liver and delivers it to the vena cava/
What is a hepatic acinus?
What is it defined by?
Describe each zone and the processes that occur in each zone.
Hepatic acinus: functional unit defined by blood flow. Has functional zonation. Zone I hepatocytes are exposed to highest oxygen concentrations, are very active in gluconeogenesis and oxidative energy metabolism, and urea synthesis (closest to portal spaces). Zone III are more active in glycolysis and lipogenesis (processes requiring less oxygen) (closest to central veins).
Explain the directionality of blood flow and bile flow within liver lobules.
blood flow: from portal veins and hepatic arteries, through sinusoids, and toward central veins (which then drain into the vena cava). blood from these vessels mixes together.
bile flow: from hepatocytes to portal spaces/tetrads where bile ducts are contained
Explain the energy metabolism and substrate interconversion functions of the liver.
Carbohydrate metabolism
- glucose production through gluconeogenesis and glycogenolysis
- glucose consumption through glycolysis and glycogen synthesis
Protein metabolism
- deamination and transamination of amino acids
- de-novo synthesis of nonessential amino acids
Lipid metabolism
- uptake of cholesterol and triglycerides by endocytosis of chylomicron remnants, HDL and LDL
- excretion of cholesterol via bile
Explain the synthetic functions of the liver.
- synthesis of plasma proteins (e.g. albumin, clotting factors, globulin, angiotensinogen, insulin-like growth factor, binding proteins)
- cholesterol and triglyceride synthesis and secretion as VLDL
- synthesis and secretion of bile
Explain the transport and storage functions of the liver.
- storage of glucose as glycogen
- storage of iron (ferritin)
- storage of vitamins (A, D, E, K, B12)
- enterohepatic circulation of bile acids
- binding proteins for transport of various substances in bloodstream (e.g. steroid- and thyroid-hormone binding globulin, transferrin, ceruloplasmin, apolipoproteins)
Explain the protective and clearance functions of the liver.
- detoxification of ammonia through urea cycle
- metabolism and excretion of bilirubin (= breakdown product of hemoglobin)
- transformation and excretion of hormones, drugs and toxins (biotransformation into inactive forms, increase of water solubility by conjugation with glucuronic acid, glycine and glutathione)
- clearance of bacteria, antigens, damaged cells, proteins in portal circulation by phagocytotic and endocytotic activity of Kupffer cells and hepatocytes
What is cirrhosis of the liver? What is it characterized by?
What 2 things are clincial signs of cirrhosis the consequence of?
What are possible etilogies of cirrhosis?
Cirrhosis of the liver = irreversible distortion of normalvliver architecture characterized by hepatic injury, fibrosis and nodular regeneration. Clinical signs are consequence of
• portal hypertension
• hepatocellular dysfunction
Etiology: - infectious (e.g. viral hepatitis, toxoplasmosis)
- drugs and poisons (e.g. alcohol, methotrexate)
- genetic diseases (e.g. Wilson’s disease, hemochromatosis, glycogen storage diseases)
What is portal HTN?
What does it result in?
Portal hypertension: rise in intrahepatic vascular resistance. Increased blood pressure within sinusoids is transmitted back to the portal vein (portal vein lacks valves!), and further back to other vascular beds, resulting in enlargement of the spleen (splenomegaly) and portal-to-systemic shunting.
Explain why ascites and ankle edema are seen in individuals with portal HTN.
Portal HTN leads to increased leaking of fluid outside of blood vessels. Additionally, hepatcellular dysfunction leads to a decrease in oncotic pressure=increased filtration.
Explain the intrahepatic biliary duct system.
The fxn of the gallbladder is storage of bile.
When does bile flow into the gallballder?
How is bile concentrated in the gallbladder?
What hormone causes contraction of the gallbladder?
- Bile flows into the gallbladder when sphincter Oddi is closed.
- Bile is concentrated (up to 20-fold) in gallbladder by absorption of water.
- Cholecystokinin causes contraction of gallbladder and discharge of bile into small intestine.
What are the types of gallstones? What is the most common?
Cholelithiasis = presence of gallstones
Types of gallstones:
- cholesterol gallstones (most common)
- bile pigment gallstones (unconjugated bilirubin)
- mixed stones
List 3 factors involved in the formation of cholesterol stones.
- supersaturation of bile with cholesterol
- stasis
- crystallization-promoting factors in bile (a number of lipoproteins have been reported as putative crystallizing factors).
Explain why supersaturation of bile with cholesterol can lead to gallstone formation.
Why are gallstones more likely to form in the gallbladder than outside of it?
- Cholesterol is very insoluble in bile and is maintained in solution in micelles only at certain concentrations of bile salt and lecithin (e.g. point P in figure below). At cholesterol concentrations above grey area, bile is supersaturated and contains small crystals of cholesterol.
- Bile is more concentrated (up to 20-fold) in gallbladder –> stones are more likely to form in the gallbladder than outside
What are risk factors for cholesterol gallstones?
Risk factors for cholesterol gallstones:
Increasing age
Sex (F > M) (female hormones decrease gallbladder contraction)
Multiparity
Diabetes mellitus
Diet (e.g. high in animal fat)
Obesity
Drugs (e.g. contraceptive pill)
Acromegaly treated with octreotide
Rapid weight loss
Ileal disease or resection
Liver cirrhosis
