W5: Clinically Important Proteins Flashcards
plasma vs serum
fluid component in blood
fluid obtained from blood that has clotted
most common protein in plasma?
albumin
where are proteins prod?
liver - albumin & most others
Ig - B lymphocytes
polypeptide hormones - endocrine glands
factors affecting protein conc
Rate of formation and entry to circulation
Rate of removal
Vol of fluid for distribution: changes in pregnancy and dehydration
Transcapillary escape rate – ‘leakiness’: increased in inflammation and sepsis.
albumin
Binds wide range of other proteins/hormones/drugs & Ca
Major contributor to oncotic colloidal pressure (80%)
colloid oncotic pressure
Proteins (colloids) cannot diffuse through capillary mems
Trapped in the vascular system & provides an osmotic pressure which helps maintain normal blood vol
Maintains normal water load in ISF and tissues
what happens aar of decr albumin/protein
increases water movement to interstitial fluid as albumin is major contributor to oncotic pressure
Can cause oedema - mmt of ISF into surrounding tissues can result from low albumin and inflammation
causes of low plasma albumin levels
Liver disease – decr formation of albumin
Shift of fluid – dilutional e.g pregnancy
Nutrition – decr synthesis due to poor protein intake or malabsorption conditions
Acute phase response (inflammatory state) -decreases plasma levels
Incr renal loss – nephrotic syndrome
causes of raised plasma levles
main: secondary to dehydration
drugs (e.g. steroids, insulin)
5 functions of plasma proteins
maintenance of colloid oncotic pressure
transport purposes
enzymes & enzyme inhibitors
defence mechanisms (CRP & procalcitonin & Igs)
buffer capacity
sources of aas
4 transport purposes of plasma proteins
Hormonese.gthyroxine by albumin and thyroxine bindingglobulin
Metalse.giron by transferrin, copper by caeruloplasmin
Drugsegaspirin, phenytoin
Excretory productseghydrogen ions
transferrin
Synthesised by the liver and is related to body iron stores
Transports iron in plasma as ferric ions (Fe3+)
Protects body against toxic effects of free iron
Normally 30% saturated w Fe3+ - incr or decr saturation indicative of iron overload or def, respectively
transferrin & ferritin
Clinical use: measure serum/plasma iron & transferrin & calculate transferrin saturation%
Used w ferritin levels as first line test- main store of body iron in the liver.
Iron overload is seen in liver disease and multiple transfusions
Genetic cause of iron overload - Hereditary Haemochromatosis (HH)
Causes iron overload and iron deposition in tissues
Treated with regular venesection
caeruloplasmin
Specific carrier protein for copper
Transports copper in plasma
Wilson’s disease – autosomal recessive disorder with low caeruloplasmin.
Copper then deposited in liver, brain & eye leading to liver disease or neurologic symptoms.
enzymes and enzyme inhibitors - name some
- Amylase & lipase
ALT, CK, ALP
-α1-antitrypsin
amylase & lipase
Amylase : present in pancreas and salivary glands
Raised in pancreatitis due to release from damaged tissue
Used to screen for acute abdominal pain
Excreted in urine so levels raised in renal disease
Lipase also used. Better marker for pancreatitis bc more sensitive than amylase
alanine aminotransferase
ALT: present in hepatocytes
Raised in liver disease. Small increase in early liver problems – fatty liver
Very high levels in hepatitis/paracetamol overdose due to release from damaged tissue
Part of ‘liver function test’
creatine kinase
(CK): present in muscle
Raised in skeletal muscle damage & cardiac muscle damage
CK tends to be higher in men as depends on muscle mass
Incr in exercise and by some drugs eg statins
α1-Antitrypsin deficiency
Def can cause lung disease in adults and liver disease in adults and children.
earliest symptoms: SoB following mild activity, reduced ability to exercise, and wheezing
10% of infants &15% of adults w α1-antitrypsin deficiency have liver damage.
α1-antitrypsin
a protease inhibitor
Prevents damage to tissue from enzymes which leak into blood
α1-antitrypsin levels are reduced in α1-antitrypsin deficiency – autosomal recessive genetic
Important in lung where it neutralises elastase – this digests damaged cells, foreign bodies & bacteria
isoenzymes
Alkaline phosphatase: diff isoforms in diff tissue- same function
ALP Isoenzymes can be used if not clear clinically why ↑ALP - liver disease or bone disease
Can also be of placental & intestinal origin
Can be useful in pts with metastases or multiple pathologies
C-reactive protein
Mediates binding of foreign polysaccharides, phospholipids and complex polyanions,
Once bound, it is able to activate the classical complement pathway
incr by bacterial infections and generally less elevated in viral infections.
Major marker of the acute phase response – occurs in response to tissue injury
Slightly elevated levels indicative of chronic, low-grade inflammation and have been correlated with an increased risk of CVD
used clinically to monitor infection and its treatment.
Used in hospital and by GPs to monitor chronic inflammatory diseases e.g rheumatoid arthritis
alkaline phosphatase
present in liver, bone, intestine, placenta
Raised in cholestatic liver disease as enzyme present in cells of the biliary tract
Part of ‘liver function test’ and ‘bone profile’
rheumatoid arthritis & CRP
Swelling is confined to the area of the joint capsule
Damage occurs early
CRP levels incr when disease is active
Used to monitortreatment – detectflare up
procalcitonin
Healthy individuals blood contains v low levels of PCT.
prod by numerous cell types and levels increase dramatically irt bacterial infection
greatest use may be for guiding early antibiotic discontinuation in patients with community-acquired pneumonia
proteins in urine
Kidneys filter blood and glomerulus allows only small amounts of protein into urine
Normal urine has very low levels of protein <130 mg/day (mostly albumin)
Microalbumin or albumin creatinine ratio (ACR)
Low levels of albumin in urine called ‘microalbumin’ <300 mg/day
Yearly screening for people with diabetes mellitus
Screening in CKD
Hypertension
Urine albumin creatinine ratio (ACR)
Microalbuminuria develops early in diabetic nephropathy
Increased escape of albumin due to early glomerular damage
Chronic kidney disease – helps classification (along w/ eGFR)
Hypertension – a raised ACR is associated w incr risk of CVD
Helps predict risk of disease progression – higher risk if ACR >30mg/mmol. Patients prescribed ACE inhibitors to protect kidney function
proteinuria
High levels of albumin/protein in urine in nephrotic syndrome >3 g/day
Use protein:creatinine ratio or 24h urine protein
Also get glomerular proteinuria in other diseases causing glomerular damage eg infections, lupus (SLE), amyloidosis
Bence Jones protein
Abnormal immunoglobulin in urine
Myeloma – over prod of intact or free light chains of Igs
Overwhelm kidney and are excreted in urine called overflow proteinuria
Measure using protein electrophoresis
