liver lecture Flashcards
gross anatomy
present in upper right and left quadrants
what protects liver
thoracic ribcage
where does liver lie
very near diaphgram
4 lobed structure
right, left
what separates right and left lobe and attaches to diaphragm
falciform ligament
caudate lobe
in middle
quadrate lobe
bottom
blood delivery
hepatic portal vein, hepatic artery proper
blood removal
hepatic vein (into inferior vena cava)
couinaud classification
8 functionally independent segments - each can be resected without damaging those remaining
functional segments
centrally (portal vein, hepatic artery, bile duct), peripherally (hepatic vein)
blood supply
25% of resting cardiac output
dual blood supply
20% arterial blood from hepatic artery (left and right branches); 80% venous blood draining from gut through hepatic portal vein
where does blood from liver drain into
inferior vena cava via hepatic vein
purpose of dual blood supply
hepatic artery provides oxygenated blood to allow function as hepatic portal vein has low oxygen concentration - anything absorbed by gut must pass through liver before entering systemic circulation
micro-anatomy structures: morphological
lobules, portal tracts/triads
micro-anatomy structures: functional
acinis, blood flow, bile flow
lobule shape and structures on outer section
hexagonal, portal triad (hepatic portal vein branch, hepatic artery branch, bile duct)
where does blood from hepatic portal vein and artery mix
sinusoid - absorbed nutrients into hepatic cells, then to internal central canal; bile duct secretes bile to external
hepatocytes from external to internal
periportal to centilobular
where are portal tracts
around edges of adjoining lobules
4 key roles in liver
digestion, storage and biosynthesis, energy metabolism, degradation and detoxification
cell types of liver
hepatocytes (80% of mass), endothelial cells (line blood vessels and sinusoids), cholangiocytes (line biliary structures), Kupffer cells (fixed phagocytes), hepatic stellate cells (vitamin A storage cells, may be activated to fibrogenic myofibroblastic phenotype)
Kupffer cells or hepatic stellate cells
flattened, dense cell nuclei that appear to be in sinusoids
hepatocytes
large cells with pale and rounded nuclei
hepatocytes
cords (sheets) of hepatocytes radiating from central vein
acinus
functional unit less clearly defined - 2 adjacent 1/6ths of lobules
acinus zones
1 (closest to portal triad), 2, 3 (closest to vein)
acinus zone most susceptible to ischaemia
zone 3
acinus zone most susceptible to viral hepatitis
zone 1
what produces bile
hepatocytes
where does bile flow
along canaliculus to bile duct (opposite direction to blood flow)
non-parenchymal cells
Kuppfer cells, endothelial cells, hepatic stellate cells
hepatic stellate cell
vitamin A storage, when activated produce ECM (fibrogenesis); respond to pro-inflammatory environments, laying down excessive ECM, promoting fibrosis and cirrhosis (loss of functional liver tissue replaced by fibrotic tissue)
sinusoidal endothelial cell
fenestrated to allow lipid and other large molecule movement to and from hepatocytes
Kupffer cell
phagocytosis including erythrocyte breakdown, secretion of cytokines promoting hepatic stellate cell activation, causing proliferation, contraction and fibrogenesis
glucose metabolism
increase after meal, taken up by liver and muscle to be stored as glycogen (24 hours) then gluconeogenesis
hepatocyte glucose metabolism: muscle and liver
glucose uptaken, glycolysis to pyruvate, TCA cycle/fermentation/lactate (if lactate uptaken by liver, converted to pyruvate, then to glucose (gluconeogenesis - energy dependent) and released again
hitting the wall when running a marathon
when muscle and liver glycogen store exhausted, as must switch to metabolism of other substrates (e.g. fat - not as much energy per mole oxygen, and also slower process)
amino acid source
diet or, in fasted state, from muscle
amino acids in liver
generates secreted proteins (plasma proteins, clotting factors, lipoproteins)
transamination purpose
some don’t come from diet - body must produce others from diet amino acids
reversible transamination by transaminases
amino acid 1 (essential) + keto acid 1 - amino acid 2 (non-essential) + keto acid 2
amino acids from a-keto glutarate
glutamate, proline, arginine
amino acids from pyruvate
alanine, valine, leucine
amino acids from oxaloacetate
aspartate, methionine, lysine
muscle deamination - energy dependent
removal of amino group, converting pyruvate to glucose, removing nitrogen as urea
glucose-alanine cycle in liver
pyruvate and glutamate (from amino acid breakdown) converted to alanine in muscle, then adding to a-ketoglutarate in liver to form pyruvate and glutamate
fate of glutamate in liver
removal of amine group (4 ATP) to form urea, pyruvate converted to glucose (6 ATP) then secreted so muscle cells can uptake glucose
fat storage
contains more energy, stored in adipose and liver
when glycogen stores full
excess glucose and amino acids converted to fats in liver for storage
production of acetyl CoA from fat in liver
triglyceride broken down into fatty acids (and glycerol) in adipose tissue - sent to liver - B-oxidation to acetyl CoA for use in TCA
other outcome of acetyl CoA
2 produced and combined to produce acetoacetate (ketone - mobile method of acetyl CoA transfer) - used by tissues to liberate acetyl CoA
lipoprotein synthesis in liver
glucose converted to pyruvate (and glycerol) - converted to acetyl CoA - converted to fatty acids or cholesterol
glycerol fate
tri-acyl glycerol, then add apoproteins and phospholipids, which then combine with fatty acids and cholesterol from acetyl CoA, producing lipoproteins including VLDL (transport fatty acids to tissues)
outcome of VLDL
become tri-glycerides in adipose tissue, or become LDL (transport cholesterol to tissues - bad)
other outcome of lipoproteins
HDL (empty so pick up excess cholesterol - good)
cholesterol functions
membrane integrity, hormones
liver function as storage
store fat soluble vitamins (A (to vitamin B12), D, E, K), iron as ferritin (for erythropoiesis), copper
liver function as detoxification
phase 1: attempts to make more hydrophilic (easier to excrete) by P450 enzymes; phase 2: attach water soluble side chain to make less reactive and leave blood until reaches kidney for excretion in urine
