Biochemistry Enzymes and Biomarkers Flashcards Preview

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Flashcards in Biochemistry Enzymes and Biomarkers Deck (63)
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1

Enzymes are:

1. Intracellular catalysts
2. Measured by activity (U/L) or concentration (ng/L)

2

Serum enzyme activity is a marker of

Tissue function or dysfunction

3

Isoenzymes:


Enzymes of similar catalytic activity but structural differences, pattern may be helpful to localize origin, e.g. CK, ALP

e.g. alkaline phosphatase isoenzymes

4

Clinical important enzymes:

• Liver enzymes
• Creatine kinase (CK)
• Amylase

5

LFT looks at

Bilirubin
ALk Phosphatase (cholestasis measurement)
ALT – hepatocullar function
Total Protein
Albumin
Globulin

6

Tranaminases types

ALT and AST (intracellular enzymes)

7

ALT location

Largely confined to hepatic cytoplasm
Use routinely to test liver function

8

AST location**

o Hepatic cytoplasm and mitochondria
o Skeletal and cardiac muscle (will rise post MI)
o Red blood cells (haemolysis causes increased0

9

Causes of increased transaminase
>10 x ULN (>400 U/L)

• Acute hepatitis and liver necrosis
• Paracetamol poisoning
• Major crush injuries (AST)
• Severe hypoxia

10

Increased Transaminase

5-10 x ULN (200-400 U/L)

• Chronic hepatitis
• Following surgery or liver trauma
• Myocardial infarction (AST)
• Skeletal muscle disease (AST)

11

Increased Transaminase Usually <5x ULN (40-200 U/L) – upper limit of normal

• Other liver disease (e.g. drug induced)
• Pancreatitis
• Haemolysis (in vivo and in vitro) (AST)

12

Haemolysis can cause

increased in AST

13

Necrosis of the liver cells e.g. fatty liver disease LF shows

– AST rises more than ALT
• Non-alcohol fatty liver disease

14

Tests of cholestasis:


Alkaline Bone phosphatase (ALP)
• Bone (osteoblasts) – can be seen in late childhood with finishing growing
• Liver (biliary tree and cell surface)

15

Minor Sources of ALP

• Intestine (some patients, postprandial)
• Placenta (third trimester, variable)
• Rare cancers (e.g. germ cell)

16

Causes of increased alkaline phosphatase
Physiological

• Pregnancy (third trimester) – usually use bile acids as test of choice for cholestasis
• Childhood – germ cell tumours

17

Causes of increased alkaline phosphatase:
Pathological
Often >5 x ULN

• Cholestasis (intra – and extra hepatic)
• Cirrhosis
• Paget’s disease of bone (metabolic)
• Osteomalacia, rickets

18

ALP - Usually <5 x ULN
Seen in

• Hepatitis
• Infiltrative liver disease
• IBD – ascending cholangitis
• Hepatic space-occupying lesions –obstruction drainage
• Bone tumours (primary and secondary) – Mets very common
• Renal bone disease (RARE)
• Primary hyperparathyroidism (longstanding)
• Healing fractures
• Osteomyelitis

19

Pregnancy (late) disease:

• HeLLPs syndrome
• Obstetric Cholestasis

20

Tests of cholestasis:

Not in liver function tests as very sensitive e.g. ptients with autumn virus (subclinical disease will cause a rise in γGT.

21

Gamma glytamyl trnasferase (γGT)
Source – very sensitive

Liver
Kidney
Pancreas
Seminal vesicles

22

γGT increased in

Cholestasis and hepatocellular damage
Also due to enzyme induction – alcohol, phenobarbitone, phenytoin, oestrogen

23

γGT clinical uses

Detection of alcohol – via hyper-lipid detection – not extremely specific
Identification of the source of ALP (.e. Liver or Bone) – of γGT is normal then ALP likely to be coming from bone.

24

γGT in alcohol abuse elevation due to

Enzyme induction
Structural damage – cholestasis e.g. alcoholic cirrhosis

25

γGT is elevated in

50-66% of subjects consuming >80g/day

26

γGT sensitivity in alcoholics

54-85%

27

Predictive value of a positive test for the diagnosis of alcoholism is approximately

20% (if prevalence is 1%)

28

AST/ALT elevated and normal alkaline phosphatase means that

Approx. 90% have hepatitis

29

AST/ALT normal and elevated alkaline phosphatase means that

Approx. 90% have obstructive jaundice

30

CK structurally

Two subunits: M and B
Three isoforms: MM, MB and BB

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