liver physiology Flashcards
functions of the liver
- filtration/storage of blood
- metabolism pf CHO/fats/hormones/foreign chemicals/ammonia
- bile formation and disposal of lipid soluble things
- storage of vitamins and Fe
- formation pf blood proteins
hepatic circulation
uses venous blood to metabolise products of digestion that come from the portal vein
blood is mostly deoxygenated
how does the liver get oxygen
also has an arterial supply
most - 80% - is nutrient rich blood
other 20% Is oxygen rich arterial blood
where does the blood from the liver go
to the vena cava
liver blood resistance
needs to be low pressure to allow diffusion
los resistance
liver provides limited resistance to blood flow
mixing arterial and venous blood
very different pressures
lots of fluid is produced - lots of lymph
resident macrophages of the liver
kupffer cells
modified resident macrophages
removal of >99% of GIt bacteria
involved in iron metabolism 0 accumulation of ferritin
flow control in the liver
- NA vasoconstriction contracts venous and hepatic artery - fight or flight response, diverts blood away from the liver
- no known vasodilator fibres
- when the metabolism is high, liver produces adenosine which binds to receptors and vasodilator to increase flow
- sinusoids can be isolated
NA vasoconstriction in the liver
contracts venous and hepatic artery
fight or flight response
countercurrent flow
of bile
goes in the opposite direction to blood flow
lymph
removes volume without moving nutrient
when there is too much plasma glucose
liver absorbs some through glucose channels
stored as glycogen - glycogenesis
when there is not enough plasma glucose
liver liberates some and puts it into the blood stream
break down glycogen by glycogenolysis
glucose-6-phosphatase
enables glycogen to go back too glucose
only present in the liver
without glucose-6-phosphatase
muscles can break down glycogen but only to glucose-6-phosphatase, not all the way to glucose
glucose-6-phosphate
doesn’t go through glucose transporters, trapped inside the cell and must be used in situ
gluconeogenesis
when glucose is made from fat (glycerol), some amino acids, lactate - via pyruvate
formation/interconversion of CHO intermediates
liver can convert between different types of monosaccharides
can be converted to glucose because it is he principle monosaccharide used throughout the body
beta oxidation
breakdown of FAs to acetyl CoA
acetyl CoA used to synthesis
fats and cholesterol
breakdown of cholesterol
not possible in the human body
uses of cholesterol
made into bile salts and excreted directly into bile and steroid hormones
cholesterol stored as
cholesterol esters
protein metabolism
deaminated
remove carbon skeleton and use as fuel
transamination
conversion between non-essential amino acids
removal of ammonia
converted into urea which is dumped into plasma and excreted into the kidneys
use of amino acids
used to make new proteins
all plasma proteins are synthesised in the liver eg. transferrin, albumin, angiotensin
ammonia-urea metabolism
NH3 is neurotoxic and is very permeable and can pass the BBB
converted to urea - only occurs in the liver
sources of ammonia
liver, colon, kidney etc
mainly liver
where is ammonia converted into urea
only in the liver
what happens to urea
excreted into plasma
most of it is excreted in the kidneys
some of it enters the GI and diffuses across the plasma membrane where it is broken down by bugs or is reabsorbed
kupffer cells
macrophages
kill bugs
drug metabolism
gets rid of lipid soluble drugs
liver metabolising blood borne hormones
Vit D and A when acting as hormones
all steroids
insulin and glucagon
cytochrome P450
enzymes
metabolise steroids
storage of vits and mins
stores vit A 5-10 months supply vit B12 - 1 year supply vitamins D - 2-4 months vitamin K stores iron
iron is bound to _ in the liver
ferritin - globular protein
ferroxidase
Fe2+ > Fe3+ (safe storage)
ferroductase
Fe3+ > Fe2+ (soluble release)
ferric iron
oxidised form
completely insoluble
storage form
ferrous iron
reduced form
water soluble - useful for transport
liver iron sensing
stores/releases iron is a controlled fashion
liver sense elevated plasma and releases hepcidin which switches off iron channels in the gut and in the liver (ferroportin)
bile
for emulsification and absorption
emulsifies fats in chyme
increases access to lipase
facilitates uptake of digested fat products by intestinal epithelial cells
excretion of waste products from blood
bilirubin - Hb breakdown product
excess hydrophobic stuff - cholesterol, drugs, xenobiotics, toxins
HDL uptake by
SR-B1
BSEP
exports bile salts
once bile is exported
can be stores in the gallbladder or released
production of bile salts
expensive too produce - mostly reabsorbed
ASBT
apical sodium dependant bile salt transporter
in the ileum
scavenger - secondary active transport
puts bile salt into the blood stream where it goes to the liver via the portal vein
haem disposal
Hb phagocytosed, split into global and haem
ferrous reused by being picked up with ferritin and sent to the liver
the rest of the Hb is toxic
enzymes converted it to bilirubin
haem-oxigenase and biliverdin reductase both located in the spleen
haem-oxygenase
ring cleavage and Fe-release
biliverdin reductase
reduces biliverdin to bilirubin
bilirubin is bound to _ in the plasma
albumin
once albumin-bound bilirubin enters the liver
transport proteins for the bilirubin - organic anion transport protein
bilirubin enters the cell
add glnucaronic acid to make bilirubin di-gluconeride and/or bilirubin gluconeride
why cant you dump bilirubin into bile
is will be reabsorbed into plasma
why conjugate the bilirubin
so it can’t cross plasma membranes and be reabsorbed into plasma
how do you conjugate the bilirubin
by using glucuronyl transferase on smooth endoplasmic reticulum
multidrug-resistance protein -2
pumps conjugated bilirubin into canaliculus in order to secrete into bile
how is conjugated bilirubin secreted into bile
via multi-drug resistance-protein 2
what do bacteria do to the conjugated bilirubin
deconjufate and and metabolise it to form urobilinogen which can be reabsorbed and sent back to the liver again
bacteria turn conjugated bilirubin into
urobilinogen
what happens to absorbed urobilinogen
sent back to the liver to attempt to remove again, some also lost via kidneys
jaundice
yellow tinted issues from excess bilirubin which causes a yellow pigment which dissolves into fatty tissues and eyes and skin
jaundice cause by either
- haemolytic - excessive RBC destruction/myolysis
- hepatic - impaired uptake, disturbed processes
- disturbed secretion, obstruction, obstructive jaundice
assay of plasma of someone with haemolytic jaundice
excess free bilirubin
assay plasma of someone with hepatic jaundice caused by impaired uptake
excess free bilirubin
assay of plasma of someone with hepatic jaundice caused by disturbed secretion, obstruction - Obstructive Jaundice
excess free conjugated bilirubin
jaundice of the neonate
newborn infants have poorly developed bilirubin conjugation enzymes and jaundice is common - premature infants more affected
infants more commonly affected by jaundice
premature infants
problems with infants with jaundice
unconjugated bilirubin in the brain causes permanent damage
what is it called when there is unconjugated bilirubin in the brain causing damage
kernicterus - eten fatal
how to prevent brain damage in neonates
phototherapy
blue light converts the bilirubin to a photo isomer which is water soluble and can be excreted in the kidneys
