Plasma Proteins Notes

Plasma proteins

Synthesised in the liver

Functions

-Colloid osmotic pressure

-Transport

-Haemostasis

-Defence

Examples

a) Albumin

b) Transport proteins e.g Transferrin/Transcobalamin

c)Protease inhibitors: alpha1-antitrypsin

d) Clotting factors: Prothrombin, Factors 7,9,10, Fibrinogen

1) Albumin

Plasma concentrations = 40g/L

Synthesis= 12g/day

Function: Transportation of:

-Long chain fatty acids: mobilised from the adipose tissue

-Bilirubin: prevents liver intoxicity

-Steroids

-Lipophilic drugs

-Copper

2) Catbolism of Haeme

Haeme consists of a prophyrin ring made up of four pyrollic groups joined together by methine bridges. The porphyrin ring is chelated to Fe 2+ at the centre

-Catbolism of Haeme produces bilirubin which comes from the

-80% senescent RBC, 20% cytochromes, myoglobin, catalase

-The initial reaction is ring cleavage by ER by Haeme oxygenase with Fe2+/NADPH Long linear molecule

-Bilirubin: Lipophilic molecule so is highly insoluable in water, bright yellow compound- transported in the blood by binding to albumin. The binding site on albumin is also used by various drugs (sulphonamides- antibiotics)

-Excretion of bilirubin

i) Liver cells:

-Transported to liver bound to albumin. Within the cytoplasm they bind to protein ligandin

-Propionyl side gropus are conjugated with glucuronic acid (hydrophilic) to form bilirubin monoglucuronides and bilirubin diglucoronides- more water soluable. These are excreted into Bile canaliculi by specific transport mechanisms.

-In the gut the conjugated bilirubin is mostly not reabsobed and is degraded by gut bacteria to colourless urobilinogens (Unconjugated)

-These are absorbed and re-excreted in bile whih small fraction excreted in the kidney

-Some of the urobilinogens are oxidised to urobilins-give colour to urine and faeces

Toxicity of bilirubin

Hyperbilirubinaemia and jaundice

a) Excess unconjugated bilirubin

-Unconjugated bilirubin is highly lipophic- can cross the blood brain barrier- affects mostly the cochlear nucli, hippocampus, basal ganglia, brain stem, cerebral nuclei of the brain

-Excess unconjugated bilirubin results in kernicterus- occurs in neonates/infants- symptoms are hypotonia, loss of refexes, athetoid movements, high pitched cry, reflex opisthotonus, lethargy, atonia, death

-survivors may be deaf and have athetosis

SYMPTOM: Unconjugated bilirubin is not excreted in urine as it is not water soluable, so urine is colourless,

CAUSE:

-immaturity of the conjugating enzymes-physiological jaundice of the neonate

-Increased bilirubin load due to haemolytic anaemias- life span of RBC shorter, so constant release of Haeme, constant generation of bilirubin

-Genetic defects of conjugating enzymes- Gilbert’s syndrome

b) Excess conjugated biliribin

CAUSE:

-Hepatocellular disease such as viral hepatitis A

-Intra/Extra hepatic biliary obstruction so can’t enter the gut

-Genetic defects of bilirubin excretion- Rotor syndromes

SYMPTOMS: Dark brown, black urine, no neurotoxicity

Measurement of bilirubin

-Measured by forming a coloured product on reaction with diazo reagent

-Conjugated, water soluable bilirubin reacts directly- measures DIRECT bilirubin

-Unconjugated, lipophilic bilirubin is dissolved by the addition of polar solvent such as methanol- measures INDIRECT bilirubin

-Normal concentrations < 20 micromoles/litre, Jaundice is not apparent until bilirubin concentration is > 50 micromoles/litre

Treatment of small excess of unconjugated bilirubin

-Bilirubin is light sensitive and breaks down to more polar soluable derivatives which can be excreted without further metabolism

-occurs in the skin- basis of phototherapy for jaundice in newborn babies – irradiate with blue green light

3) Fe Homeostasis

-Total body Fe is 3/4g- mostly found in Haemoglobin (RBC), myoglobin (muscle) and cytochromes (ETC)

-Remainder is stored in cells as soluable/mobile form FERRITIN or insoluable aggregates HAEMOSIDERIN

-Stored iron depends on overall iron nutrition and ranges from 0-1g- evenly distributed between liver, bone marrow and muscle

i) Fe transport

-Fe is carried in plasma on TRANSFERRIN in form of Fe 3+, 2 binding sites on the protein

-Total iron binding capacity is 60micromolar/litre but as transferrin is 30% saturated and plasma iron concentration is 20 micromolar/litre

-The transferrin with bound Fe 3+ binds to specific receptors on the cell surface membrane this leads to invagination of the...

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