18. Liver and Gall Bladder Flashcards
How is the liver’s blood supply divided up?
What does almost all dietry carbohydrate reach the liver as, and why is this good?
What is the fate of the absorbed carbohydrate in the liver?
75% from hepatic portal vein (drains gut). 25% from coeliac artery.
Glucose (broken down from sucrose, fructose, maltose etc.). Good b/c need only one set of enzymes/pathways to deal with it.
Glucose -> into hepatocyte -> phosphorylated -> glycolysis -> TCA etc. Or stored as glycogen (glyogenesis).
Label A-G
What does the portal tract consist of?
A: portal vein
B: bile duct (goes in opposite direction to portal vein, biliary epithelial cells make bile)
C: hepatic arteriole
D: hepatocyte
E: Kupffer cell - specialised macrophage
F: sinusoid (leaky - allows transfer of molecules and helps cells move)
G: central vein - leads to 3 hepatic veins which drain to inferior vena cava
Hepatic portal vein, hepatic artery, bile duct
What effect does insulin have on the liver.
What is transamination?
What does the blood test for liver function look for?
Signals fed state: promotes glycogen synthesis, supresses gluconeogenesis (pyruvate -> glucose), accelerates glycolysis - inceases fatty acid synthesis. Counteracted by glucagon
Transfer of amino group to a keto acid to make an amino acid (and a keto acid). Done via alanine and aspartate aminotransferases.
ALT and AST - measure of how inflamed/injured liver is (these enzymes are quite liver-specific - ALT more so, and if in blood liver cells must have burst open).
What is deamination?
What are the effects of excess ammonia?
How is ammonia produced and removed?
Take away amino group from amino acid via dehydrogenase, leaving a C and H structure and with ammonia
Excess NH3 depletes cell ketoglutarate (for TCA). NH3 in astrocytes leads to excess glutamine: increased osmotic pressure so pulls water in = astrocyte swelling
Produced by: deamination and gut bacteria. Removed by: NH3 reduced to NH4+ which is converted to urea so it can be extcreted (urea cycle in liver)
What does raised serum urea indicate?
What is the effect of liver failure on metabolism?
What is the difference between plasma and serum?
What does plasma contain?
Kidneys not working properly (not clearing substances they should clear)/making excess ammonia (hard to do)/excess protein intake (hard to do)/bleeding into stomach
Metabolise less, unable to make important proteins e.g. albumin and clotting factors
Both refer to non-cellular compoent of blood. Serum = plasma minus clotting factors
Cell-free part of blood: albumin, golbulins, clotting factors, water/glucose/electrolytes
What percentage of plasma proteins (albumin and clotting factors e.g fibrinogen) are made in the liver?
What 3 things keep fluid in blood? How will having no albumin affect this?
How does liver failure affect PTT?
90%
Ineraction of intergrity of vascular wall, oncotic potential of fluid, and hydrostatic pressure. No albumin = less able to keep fluid (affects oncotic potential) so goes to extravascular space -> peripheral oedema
Prolongs it b/c blood takes longer to clot. (PTT= partial thromboplastin time)
Lipids are not water soluble - how are they transported around?
What does the liver break fats (triglycerides) down into, and what are the consituents used for?
What form can the liver send out fat breakdown products to the tissues that need them?
What can the lipid-related things can the liver do?
Tag water soluble element to one end = lipids spontaneously form spherical structures = lipoprotein. (Or done via phosphorylation = phospholipid).
Fatty acids -> ACoA -> respiration / cholestrol synthesis
Glycerol -> glycerol-3-phosphate -> dihydroxyacetone phosphate -> into glycolysis or gluconeogenesis
LDL
Synthesise phospholipids, ketogenesis, convert excess glucose to fatty acids
What is ketogenesis?
How does the liver ‘help’ the body in time of plenty/need?
How do protein-only diets work?
Happens in absence of glucose (starvation), can be switched off by insulin. Breaks down lipids and proteins. Uses acetyl CoA to make ketone bodies e.g. acetoacetate and beta hydroxybutyrate. Ketone bodies back to ACoA in brain -> feed TCA and ETC
Plenty: send outs VLDL to other parts of body; Need: makes ketones
Induces starvation, pancreas thinks no sugar so reduces amount of insulin, liver in starvation mode, breakdown of peripheral fats in liver -> produce lots of ketone bodies
What happens if insulin is missing (e.g diabetes)?
Describe the journey of bile, from where it is produced to how it is excreted.
What does bile do? How much is produced/day?
How is bile modified?
Ketogenesis (b/c insulin turns off ketogenesis), Ketoacidosis (ketones form ketoacids -> acidified blood -> coma and renal impairment)
Bile secreted by hepatocytes in canaliculi -> bile ducts forming L and R hepatic duct -> merge to form common hepatic duct, and joined by cystic duct (which drains gall bladder) -> comomn bile duct -> to ampulla of vater and out through spincter of oddi -> to duodenum
Emulsifies fats and makes them water soluble. 800ml/day.
Cholangiocytes (biliary epithelial cells) add HCO3-
What 2 main hormones are involved in bile production?
What is bile composed of?
How are bile salts made?
Cholecystokinin (CCK): causes contraction of bile duct. Made in response to FA in lumen of duodenum -> gall bladder contracts -> sphincter of Oddi relaxes.
Secretin: in response to acid chyme entering duodenum from stomach -> stimulates biliary ductal cells to make bile
Water (>90%), bile salts, bilirubin, cholesterol, fatty acids, lecithin, Na+/K+/Ca2+/Cl-/HCO3- (electrolytes)
Cholesterol -> cholate/chenodeoxycholate -> conjugated to glycine/taurine -> secreted as sodium salts
What are bile salts important for?
What happens to bile after it has been secreted and done its ‘job’?
Where does the cholestrol come from, and what is it used for?
How do statins work? Give an example.
Absorption of lipophilic substances: fatty acids, monoglycerides, cholesterol, fat soluble vitamins (A, K, E, D)
Deconjugated and reabsorbed in terminal iluem -> portal vein -> liver for reorganisation etc.
Exogenous (diet), endogenous (liver). Uses: cell membranes, steroid hormones, skin, bile salts (80%)
Reduce serum cholesterol levels by directly inhibiting HMG-CoA reductase which is used to make cholestrol (in liver). E.g. simvastatin
What is bilirubin? Describe the break down process it is involved in.
What is jaundice?
What happens if flow of bile is obstructed?
Pigment, a breakdown product of Hb: RBC broken down in spleen. Non-Fe heame element of Hb -> biliverdin -> free billirubin bound to albumin-> conjugated bilirubin (to glucuronate) in liver -> urobilinogen in intestine -> faces/general circulation to kidney and urine/portal circulation
Yellowing of skin and sclera due to exess bilirubin
Get jaundice b/c bilirubin builds up and leaks out into bloodstream. Pale, floating stools because of fat in stools and not pigmented (bilirubin building up in blood).
What causes jaundice?
What are the 3 phases of drug metabolism in the liver?
How is paracetamol (acetaminophen) metabolised, and what happens if you take too much?
How is a paracetamol overdose treated?
Pre-hepatic: excess RBC breakdown. Hepatic: direct problem with liver. Post-hepatic: physical blockage e.g. stone in duct, cancer in wall of duct, or pressure from e.g. adhesion after surgery
Phase I: modification (e.g. hydroxylation by cytochrome P450), Phase II: conjugation (e.g. glutathione). Phase III: further modification/excretion
As it’s boken down it forms a toxic intermediate NAPQI, then conjugated with glutathione to detox NAPQI. If take too much - acute liver failure b/c limited pool of glutathione in hepatocytes.
NAC (N-acetyl cysteine) supplements glutathione pool and accelerates detox of NAPQI
Increased risk if take paracetamol with excess alcohol or malnourished
What are the outcomes of liver failure?
Hypoglycaemia - can’t maintain BG. Reduced albumin - oedema risk and fluid to wrong places. Impaired clotting. Jaundice. Hyperammoneamia (encephalopathy) - high NH3 level -> astrocyte swelling in brain -> pressure effects on nerve cells
