W5: Clinically Important Proteins

Question 1

plasma vs serum

Answer 1

fluid component in blood
fluid obtained from blood that has clotted

Question 2

most common protein in plasma?

Answer 2

albumin

Question 3

where are proteins prod?

Answer 3

liver - albumin & most others
Ig - B lymphocytes
polypeptide hormones - endocrine glands

Question 4

factors affecting protein conc

Answer 4

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.

Question 5

albumin

Answer 5

Binds wide range of other proteins/hormones/drugs & Ca
Major contributor to oncotic colloidal pressure (80%)

Question 6

colloid oncotic pressure

Answer 6

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

Question 7

what happens aar of decr albumin/protein

Answer 7

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

Question 8

causes of low plasma albumin levels

Answer 8

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

Question 9

causes of raised plasma levles

Answer 9

main: secondary to dehydration
drugs (e.g. steroids, insulin)

Question 10

5 functions of plasma proteins

Answer 10

maintenance of colloid oncotic pressure
transport purposes
enzymes & enzyme inhibitors
defence mechanisms (CRP & procalcitonin & Igs)
buffer capacity
sources of aas

Question 11

4 transport purposes of plasma proteins

Answer 11

Hormonese.gthyroxine by albumin and thyroxine bindingglobulin
Metalse.giron by transferrin, copper by caeruloplasmin
Drugsegaspirin, phenytoin
Excretory productseghydrogen ions

Question 12

transferrin

Answer 12

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

Question 13

transferrin & ferritin

Answer 13

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

Question 14

caeruloplasmin

Answer 14

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.

Question 15

enzymes and enzyme inhibitors - name some

Answer 15

• Amylase & lipase
  ALT, CK, ALP
  -α1-antitrypsin

Question 16

amylase & lipase

Answer 16

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

Question 17

alanine aminotransferase

Answer 17

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’

Question 18

creatine kinase

Answer 18

(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

Question 19

α1-Antitrypsin deficiency

Answer 19

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.

Question 19

α1-antitrypsin

Answer 19

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

Question 19

isoenzymes

Answer 19

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

Question 19

C-reactive protein

Answer 19

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

Question 19

alkaline phosphatase

Answer 19

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’

Question 20

rheumatoid arthritis & CRP

Answer 20

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

Question 21

procalcitonin

Answer 21

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

Question 22

proteins in urine

Answer 22

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)

Question 23

Microalbumin or albumin creatinine ratio (ACR)

Answer 23

Low levels of albumin in urine called ‘microalbumin’ <300 mg/day
Yearly screening for people with diabetes mellitus

Screening in CKD
Hypertension

Question 24

Urine albumin creatinine ratio (ACR)

Answer 24

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

Question 25

proteinuria

Answer 25

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

Question 26

Bence Jones protein

Answer 26

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