Liver Flashcards
name the three types of proteins made by the liver
albumin
most clotting factors
complement proteins - mark pathogens in the immune response
function of albumin
carry unconjugated bilirubin
plasma protein
are proteins stored as they are?
no, always have a function
if no function, used for energy or stored as fat
how are faulty proteins degraded?
ubiquitin
- in cell cytoplasm
- small protein ubiquitin selectively binds to defective protein
signals to proteases that protein needs breakdown
lysosomal
- reticuloendothelial system (liver)
- sinusoid endothelial cells remove protein from blood
- protein fused into lysosomes
- phagocytosed by Kuppfer cells
name functions of the liver
storage
- vitamins
- fats
- carbohydrates
- minerals such as iron and copper
synthetic
- produces proteins such as clotting factors, plasma proteins and complement proteins
immune
- resident macrophages: Kuppfer cells
hormonal regulation
- oestrogen
digestion
- produces bile
metabolism
- carbohydrate
- fat
- protein
- hormone
toxin/ drug metabolism and excretion
which clotting factor is not produced by the liver?
Von Willebrand - produced by endothelial cells
what is the reticuloendothelial system?
resident macrophages residing in tissues systemically
e.g liver Kuppfer cells and alveolar macrophages
in which quadrant is the liver found?
right upper quadrant
why is the liver important with regards to vitamin K?
bile salts produced in the liver are necessary to absorb vitamin K
vitamin K is required to produce clotting factors 10, 9, 7, 2
fate of amino acids
catabolised for energy breakdown - enters Krebs
excreted as urea
when metabolising amino acids for energy, which is the key intermediate we always start with?
alpha ketoglutarate
mechanism of amino acid catabolism
transamination then oxidative deamination
describe transamination
include the fate of the products
alpha ketoglutarate accepts amine from alanine
forms glutamate and pyruvate
catalysed by alanine transferase
alphaketoglutarate + alanine —> glutamate + pyruvate
pyruvate for
- gluconeogenesis
- aerobic respiration
describe oxidative deamination
glutamate hydrolysed to reform alphaketoglutarate and ammonia
catalysed by glutamate dehydrogenase
glutamate + water –> alpha ketoglutarate + ammonia
toxic ammonia is removed to enter urea cycle
what is a negative nitrogen balance?
catabolism
more nitrogen out than in
what is a positive nitrogen balance?
anabolism
more nitrogen in than out
what determines nitrogen balance?
protein intake
loss or gain of total body protein
draw the urea cycle
.
major amino acids in the urea cycle
arginine, ornithine, citrulline
‘CITARGORN’
why is ammonia harmful?
neurotoxic, can cross blood brain barrier
what is the glucose alanine cycle?
involves muscle protein being degraded to provide more glucose to generate additional ATP for muscle contraction
describe the glucose alanine cycle
- reverse transamination in muscles
glutamate + pyruvate –> alanine + alphaketoglutarate - alanine to liver (in blood)
- transamination in liver
alanine + alphaketoglutarate —> glutamate + pyruvate
glutamate is oxidatively deaminated to remove excess ammonia in the urea cycle
pyruvate is converted to glucose in the liver (gluconeogenesis) - glucose back to muscle cells
- glycolysis (to pyruvate)
which are the fat soluble vitamins?
A,D,E,K
functions of lipids
energy reserve - fatty acid beta oxidation
shock absorber
cell membrane components - phospholipids and cholesterol
hormones, metabolism
energy content of lipids
9kcal/g
structure of lipoproteins
outer glycoprotein, inner lipid
what is ‘good’ cholesterol and why?
HDLs - high density lipoproteins
highest protein to lipid ratio
where are HDLs synthesised?
liver
function of HDLs
remove cholesterol from cells to take to the liver
where are LDLs produced?
plasma
function of LDLs
deposit cholesterol in cells
what are VLDLs
very low density lipoproteins
carry triglycerides to adipose tissue
what are IDLs?
VLDL intermediates
converted to LDL
when does beta oxidation of fatty acids occur?
in the fasted state
high glucagon and low insulin
name types of beta oxidation of fatty acids
peroxisomal
mitochondrial - main
what is a xenobiotic?
foreign substance to be excreted
modified by the liver to be less lipophilic and more hydrophilic to increase solubility
e.g drugs
what are the phase 1 biotransformation reactions?
addition/ exposure of a functional group
most commonly produces a hydroxyl group
small increase in hydrophilicity
oxidation, reduction or hydrolysis
microsomal enzymes in endoplasmic reticulum - CYP450 enzymes
what are phase 2 conjugation reactions?
conjugation to produce hydrophilic metabolites
large increase in hydrophilicity
glucoronidation - most common
examples of conjugation molecules
- glucaronic acid
- sulphate
non microsomal enzymes - enzyme UGT
alcohol detoxification - a different type
metabolism of alcohol does not fit into type 1 or 2 detoxification
does not need to be conjugated for excretion
alcohol –> acetaldehyde –> acetate –> carbon dioxide and water
enzymes for the first two steps: alcohol dehydrogenase, acetaldehyde dehydrogenase
does alcohol need to be conjugated for excretion?
no
constituents of bile
bile salts
cholesterol
xenobiotics
electrolytes
phospholipids
bilirubin
what is the portal triad?
hepatic portal vein, hepatic artery, bile duct
where are portal triads found?
vertexes of hepatic lobules
histological appearance of liver tissue
hexagonal lobules
lobules have a central hepatic vein (not hepatic portal vein)
in the corners of the lobules we find the portal triad
what is the hepatoduodenal ligament and what does it contain?
part of the lesser omentum
connects the porta hepatis of the liver to the duodenum
contains
- portal vein
- hepatic artery (right and left)
- common hepatic duct
what percentage of bile is excreted?
about 5
where is bile reabsorbed? what percentage?
ileum
95%
function of CCK
relaxes the sphincter of Oddi
gallbladder contraction
chole, “bile”; cysto, “sac”; kinin, “move”
how is bile reabsorbed?
into portal blood
using apical Na+ bile acid transporter (ASBT)
function of iron in body
muscle myoglobin
erythrocytes
what is directly proportional to the total iron stores in the body?
ferritin levels
what causes low ferritin?
iron deficiency
what amount of ferritin suggest depletion?
and absence of stored iron
less than 20ug/L
12ug/L
functions of vitamins
gene activators
free radical scavengers
coenzymes or cofactors in metabolic reactions
vitamin a sources
retinol
carotenoids
functions of vitamin a
vision
- used to form rhopsodin in the rod cells in the retina
spermatogenesis
prevention of foetal resorption
vitamin a excess
joint and bone pain
reversible yellowing of the skin
abdominal pain
function of vitamin d
calcium absorption
vitamin d deficiency
demineralisation of bone
- rickets in children
- osteomalacia in adults
function of vitamin e
antioxidant
vitamin e requirements
4mg/ day in men
3mg/ day
causes of vitamin e deficiency
fat malabsorption
which vitamins does the liver store?
ADEK fat soluble
which clotting factors are vitamin K dependent?
2, 7, 9, 10
1972
deficiency of what substance causes neural tube defects?
folate
which clotting factors are produced by the liver?
1, 2, 4, 5, 6, 7
functions of fat
energy reserve
hormone metabolism
part of cell membranes
inflammatory cascades
steroid hormones - cholesterol
where is cholesterol made?
liver
what percentage of cholesterol is endogenous?
90%
what percentage of cholesterol is dietary?
10%
what is the only way cholesterol is exported?
through bile excretion
what is enterohepatic circulation?
movement of bile acid molecules from the liver to the small intestine and back to the liver
how are triglycerides and cholesterol carried through the circulatory system?
lipoproteins
energy content of lipids
9kcal/g
what carries lipids from the gut to muscle and adipose tissue?
chylomicrons
order
HDL
VLDL
LDL
chylomicron
in order of highest to lowest lipid to protein ratio
highest lipid to protein ratio means more lipid compared to protein
chylomicron
VLDL
LDL
HDL
what happens to chylomicron remnants?
taken up by liver by receptor mediated endocytosis - recognition of ApoB by hepatocyte surface receptors
