Lecture24 Flashcards
Use of serum proteins (3)
- Detecting disease
- monitor progress of disease
- Response to therapy
Difference between specificity and sensitivity
Specificity : higher specificity means less false result
Sensitivity : higher sensitivity means detection no matter how low or slight damage is with no false negative results
In terms of releasing enzymes what is difference between necrotic and inflamed tissue?
necrotic tissue release all its enzyme contents while inflamed tissue release soluble enzymes due to changes in membrane permeability
Possible causes for elevated enzyme levels in serum (4)
`1. Increased cellular turnover (normal or cell necrosis)
- Cellular proliferation (neoplasia)
- Increased enzyme synthesis (induction)
- Obstruction to secretion (pancreatic duct)
Gamma glutamyl transpeptidase (GGT) (for diagnosis)
Liver damage
Aspartate aminotransferase (AST) (for diagnosis)
Heart and liver damage
Alanine aminotransferase (ALT) (for diagnosis)
Liver damage
Alkaline phosphatase (ALP) (for diagnosis)
Obstructive liver disorder and bone disease
Acid phosphatase (for diagnosis)
Metastatic carcinoma of prostate gland
Alpha amylase (for diagnosis)
pancreatitis or obstruction of pancreatic duct
What is isoenzyme?
Catalyze same reaction, but differ in primary structure or subunit composition
(eg. glucokinase/hexokinase)
What is infarction?
necrosis of tissue / organ due to disruption of its blood supply
3 criteria for MI Diagnosis
- Severe chest pain
- ECG change
- Increased in activity of cardiac biomarkers
3 enzymes for myocardial infarction
- Creatine kinase (CK)
- LDH (also occur in liver)
- Aspartate aminotransferase (AST) (nonspecific since it is for both heart and liver)
3 Isoforms of CK
- CK1 = BB= Brain & lungs
- CK2 = MB = Myocardium
- CK3 = MM = Myocardium & skeletal muscle
CK1
BB = Brain & lung
CK2
MB = Myocardium
CK3
MM = Myocardium & skeletal muscle
Which isozyme of CK have most electrophoretic mobility?
CK1 BB > CK2 BM > CK3 MM(least negatively charged)
What is difference between use of total CKs and CKMB?
Total CKs are indicative of the size of infarction whereas the amount of serum CKMB indicates whether MI occurred or not.
What does increase in infarction size mean?
it means there is an increased development of cardiac arrhythmia which causes death
Half life of CKMB
24hours
Which LDH isoform indicate myocardial infarction?
LDH-1
What happens to LDH level following myocardial infarction?
sharply increase causing 1,2-flip, but 1,2-flip also found in erythrocytes(anemia, renal damage, hymolysis)
indicative level of CK-MB / total CK for myocardial infarction
> 3%
Peak of LDH
40-50 Post Myocardial infarction
Non enzymic cardiac biomarker for myocardial infarction
- Myoglobin 1-3hours post MI (but not specific to cardiac, its for all muscles)
- Troponin isoforms
Advantage and disadvantage of using myoglobin as MI biomarker
ADV : Highly sensitive of MI, if levels do not increase within first 3/6h it indicates no MI
DISADV : Not specific, associated with other causes too
3 isoforms of troponin
Tn T
Tn I
Tn c
difference between troponin T and I
I is specific for myocardial tissue, indicative of MI
T is less specific and in can be caused by angina attack
Earliest indicator of Acute MI (2)
Myoglobin and CK-2
Long diagnostic tool for MI
Troponin I
What diseases does liver function test (LFT) differentiate?
acute liver damage,
chronic liver damage,
cholestatic disease (reduced bile flow)
Hepatocyte function test measure decrease in capacity to synthesize which substance? (3) and increase in which (1)
- serum albumin
- prothrombin
- fibrinogen
- serum ammonia (increased)
Liver disease(hepatocyte integrity) is diagnosed by which enzymes elevated activities ? (3)
Serum aspartate aminotransferase (More sensitive)
Serum alanine aminotransferase (More specific)
Serum LDH-5
Role of ALT biochemically (2)
converse rebersibly alanine to pyruvate
also used to form glutamate (urea cycle)
Role of AST biochemically
Reversibl converrsion of aspartate to OAA
Ratio of AST:ALT for fatty liver disease (Alcoholic)
AST:ALT >2
Ratio of AST:ALT for hepatitis and NAFLD (nonalcoholic fatty liver disease)
High ALT:AST
What indicates abnormality in biliary excretion function of liver? (3)
- elevated serum and urine bilirubin
- serum bile acid
- membrane bound enzymes such as serum ALP, GGT and serum 5’nucleotidase
Isozymes of alkaline phosphatase (ALP)
- ALPI - Intestinal
- ALPL - liver/bone/kidney
- ALPP - Placental
How is alkaline phosphatase related to obstructive disorder/
ALPL is specifically synthesized in cells lining hepatic biliary ducts, thus related with obstructive disorders.
When are there increased alkaline phosphatase (ALP)? (4)
Bone disease
Liver (esp obstructive bile disorder)
pregnancy or childhood
Growth
Paget’s disease
excessive and disorganised resoprtion and bone formation
High plasma ALP indicated
Biomarkers for liver bile duct obstruction (3)
ALP-L, GGT, Conjugated bilirubin
How can we differentiate bile disorder from other bone and liver disorders?
For bile, elevated serum level of both ALPL and GGT should be shown. ALPL alone is liver or bone disorder.
Role of GGT biochemically
A cell surface glycoprotein that cleaves gamma glutamyl amide bond in the cells lining the bile ducts
What is cholestasis
When substance normally secreted in bile are retained
Bile duct obstruction
Biomarker for pancreatitis
Alpha amylase activity
Serum lipase : amylase ratio to diagnose ethanol-induced pancreatitis
ratio >2
