protein synthesis in the liver Flashcards
which proteins does the liver produce (3)
- plasma proteins
- clotting factors
- complement factors
examples of plasma proteins (7)
- albumin
- globulins
- fibrinogen
- CRP (an infection marker)
- Clotting factors – Factors II, VII, IX and X are Vitamin K dependent
- Thrombopoietin
- Angiotensinogen
what is the most abundant plasma protein
albumin
what stimulates protein synthesis
insulin and growth hormone
role of the plasma proteins synthesised by the liver (2)
- play an important role in maintaining the amino acid equilibrium in the blood.
in times of tissue amino acid depletion, these proteins can be degraded and released back into the blood as amino acids for tissues to use in protein synthesis.
- provide oncotic pressure in the blood, meaning they hold water in the plasma.
functions of albumin (2)
- binding & transport of large, hydrophobic compounds such as bilirubin, fatty acids, hormones & drugs (NSAIDS & warfarin)
- maintenance of colloid osmotic pressure
what is colloid osmotic pressure
the effective osmotic pressure across blood vessel walls which are permeable to electrolytes but NOT large molecules.
It is almost entirely due to plasma proteins
how does albumin maintain osmotic pressure
albumins presence in the plasma means that the water concentration of the blood plasma is slightly lower than that of the interstitial fluid meaning there is a net flow of water
OUT OF the interstitial fluid INTO the blood plasma
how does fluid move across the capillary wall
there are 4 opposing forces called Starling forces
what are the 4 Starling forces
- Capillary hydrostatic pressure (favouring fluid movement out of the
capillary) - Interstitial hydrostatic pressure (favouring fluid movement into the
capillary - Osmotic force due to plasma protein concentration (favouring fluid
movement into the capillary) - Osmotic force due to intestinal fluid protein concentration (favouring
fluid movement out of the capillary
what results in in bulk filtration of fluid OUT OF the capillaries
at the arterial ends of the capillaries the hydrostatic pressure from the
capillary is 38 mmHg - greater than that from the interstitial fluid
(which is virtually zero since there is very little fluid in the interstitial spaces
since it quickly picked up by the lymphatics etc.)
and the interstitial fluid protein concentration is 3mmHg
and the osmotic pressure due to plasma proteins is 28mmHg
so net outward pressure EXCEEDS the net inward pressure
causing bulk filtration of fluid out of the capillaries
what results in bulk absorption of fluid INTO the capillaries
at the venous end, the only difference in Starling forces is the capillary hydrostatic pressure which has decreased from 35 to around
15mmHg due to the resistance encountered as blood flow through the
capillary wall.
The other three forces are virtually the same as above
so the net inward pressure EXCEEDS the net outward pressure
so bulk absorption of fluid INTO the capillaries occurs
impact of reduced albumin due to liver failure
liver failure
reduction in albumin
less albumin in blood - (hypoalbuminaemia)
causes decrease in capillary oncotic pressure
since there will be less of a
difference in the concentration of water between plasma and interstitial fluid
causes the accumulation of water in the interstitial fluid
resulting in oedema. Hypoalbuminaemia = Oedema
what can cause albumin to decrease (4)
- nephrotic syndrome
- haemorrhage
- gut loss
- burns
what is nephrotic syndrome
where there is an increased glomerular
permeability
which allows proteins to filter through the basement membrane
meaning the loss of up to several grams of protein a day can occur
what is gut loss
a rare syndrome in which the wall of the gut is unusually permeable to large molecules resulting in albumin loss
how do burns reduce albumin
extensive tissue damage with damage to capillaries can cause loss of protein through the walls of the capillaries
what are globulins
a group of proteins in the blood made by the liver and the immune system
what are the 3 types of globulins
- Alpha (1 and 2)
- Beta
- Gamma
where are alpha and beta globulins made
in the liver
where are gamma globulins made
in the immune system
function of alpha and betta globulins
- Blood transport of:
- Lipids by lipoproteins
- Iron by transferrin
- Copper by caeruloplasmin - work as enzymes
- a few have antibody functions
function of gamma globulins
vital role in natural and acquired immunity to infection.
immunoglobulins (antibodies) - help to fight off infection
which clotting factors does the liver produce
all of them except
calcium (IV)
and
von Willebrand factor (VIII)
also produces bile salts
why does the liver produce bile salts
they are essential for vitamin K absorption and digestion because it is fat soluble
what happens in biliary obstruction
Vitamin K is not appropriately absorbed
so the Vitamin K dependant clotting factors are not adequately synthesized,
so more bleeding.
why does liver disease lead to a tendency of bleeding
as fewer clotting factors are produced
what is essential in order to produce clotting factors
vitamin K is essential to the carboxylase enzyme that is used to make clotting factors II (prothrombin), VII, IX, X and protein C
(10,9,7,2)
what are complement factors
plays an important role in the immune response to pathogens,
a plasma protein which sticks to pathogens, that is recognised by neutrophils, it helps mark pathogens to kill
describe the route of albumin
- leaves circulation via interstitium
- collected by lymphatics
- returned via thoracic duct
- the rate is the transcapillary escape rate
what causes albumin to decrease
- decreased synthesis
- increased catabolism
- increased loss
consequences of lower albumin
- decreased colloid oncotic pressure
- decreased ligand banding
what is protein turnover
the continuous degradation and re-synthesis of all cellular proteins
describe the rate of protein turnover
turnover is very variable and reflects usage/demand
what causes an increase in the rate of protein turnover
- when tissues are undergoing structural re-arrangement e.g.
when tissue is damaged due to trauma - due to severe burns since there attempts at re-modelling the
skin, its complicated by the fact that significant amounts of protein can be lost in the exudate from the damaged tissue
what are the primary methods of protein breakdown
- Lysosomal Pathway
- Ubiquitin- Proteasome Pathway
where is lysosomal breakdown carried out
out in the reticulo-endothelial system of the liver
this is comprised of the sinusoidal endothelial cells, Kupffer cells & pit cells
what do Sinusoidal endothelial cells do
remove soluble proteins and fragments from the blood
through the sieve plates on their luminal surface -they are
important for removing; fibrin, fibrin degradation products, collagen & IgG
complexes.
Once in the liver these proteins are then fused into lysosomes containing lysozyme which are hydrolytic enzymes that break down the protein into amino acids
what do kuppfer cells do
they are the livers resident macrophages and perform a similar function
except there phagocytose particulate matter thereby packaging them in to
phagosomes in the cell which contain hydrolytic enzymes which will break down the protein into amino acids
where does the Ubiquitin-Proteasome Pathway occur
in cytoplasm of cells
which proteins are degraded quicker
those that are defective because of incorrect amino acid sequences or because of damage to normal function (denatured)
why do different proteins degrade at different rates
depends on the structure of
the protein - a denatured (unfolded) protein is more readily digested than a protein with an intact conformation
how does Ubiquitin-Proteasome degradation occur
Proteins are targeted for degradation by the attachment of a small peptide called ubiquitin to the protein.
This peptide directs the protein to a protein complex called a
proteasome - “the cellular executioner”,
which unfolds the protein and breaks it
down into small peptides
