Principles of clinical chemistry Flashcards
Why are clinical labs important?
Disease diagnosis, severity. Diagnosis is achieved via physical examination and then confirmed by lab diagnostic tests
What are the most requested samples?
Biological sample for urine and faces, venous blood
What is a qualitative sample?
What is a quantitative sample?
Number of something such as concentration or amount of metabolite.
What is plasma?
Blood with all cells removed.
What is serum?
Blood with all cells and coagulation proteins removed.
What is used to prevent coagulation?
EDTA
What colour is serum when RBC have ruptured?
Yellow due to haemolysis with the release of haem.
Orange/brown serum
Bilirubin present in blood, indication of jaundice
What is measured in a biological sample?
1) Concentrations/levels of metabolites
2) Presence of particular proteins
3) Enzyme activity
What should be considered in biological sample?
Ease of obtaining sample and location of target analyte.
What allows accurate interpretation of results?
Patient characteristics such as age, sex, menstrual cycle stage
What happens in sample transport failure?
Sample deterioration and may be a biohazard
What are the groups of laboratory tests?
Selective requesting: based on individual patient’s clinical situation
Screening test: searches for disease
What are the selective tests?
One-off tests: asks specific questions to support diagnosis
Biochemical profiles: plasma electrolyte and liver function test
Dynamic function test: measures response to external stimulus
What is a dynamic function test?
Measures response to external stimulus.
What is a biochemical profile?
Measures plasma electrolyte and liver function test.
What is arterial blood sampling?
Determines arterial blood gases; this is performed via heparinised syringe. The require rapid transport on ice.
What is the role of selective testing?
Confirm diagnosis and differential diagnosis, assess severity of disease, monitor progress of disease and see side effects.
How are test results interpreted?
Analytical variation: limitation of the test
Sensitivity: Detection limit
Specificity: How good the assay is at discriminating between analyte
What is biological variation?
Results are affected by physiological factors. It is compared to reference range.
What is analytical variation?
Limitations of the test, considering precision and accracy. Includudes sensitivity and specificity
What is sensitivity in analytical variation?
Detection limit
What is specificity in analytical variation?
How good the analyte is at discriminating between analyte and any contamination.
What are the core biochemical test?
Na+, K+, Cl– these are produced in hospitals and clinics.
What is the role of aminotransferase enzymes?
Synthesis of amino acids. Examples include aspartate aminotransferase (AST) and alanine aminotransferase (ALT). They are sensitive markers for liver damage.
What is prothrombin time (PT) ?
Measures time of extrinsic pathway; prolonged time is an indicator of liver disease
What are the liver function tests?
Measures analytes in the blood for signs of jaundice, acute liver disease and chronic liver disease.
Types of jaundice?
Haemolytic
Cholestatic
Hepatocellular
What are the markers of jaundice?
Increased bilirubin, present in urine, Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), normal prothrombin time
What is acute liver disease?
Posioning or hepatic failure.
What are the markers for biliary disease?
Increased levels of ALP (alkaline phosphatase) and GGT
What are the markers for liver disease?
Increased levels of ALT (alanine transferase) and AST (aspartate transferase).
-> ALT is generally higher in liver disease than AST EXCEPT for alcoholic liver disease where AST is higher
What are the markers for pancreas disease?
Increased levels of amylase and lipase
-> Lipase is a more sensitive marker because amylase is produced in the salivary gland
What is aspartate aminotransferase? (AST)
It is produced in the liver and raised in liver damage. It is located in the muscle, heart and liver.
What are the markers of acute liver disease?
Increased bilirubin, ALP
Normal AST
Increased prothrombin time
Decreased albumin
Why does chronic liver disease occur?
Excess alcohol intake
Primary biliary cirrhosis: autoimmune disease
Chronic acute hepatitis
What are the markers of chronic liver disease?
Cirrhosis
Increased prothrombin time
Biopsy
Coagulation markers
Hypoalbuminaemia
What is bilirubin?
Derived from haem breakdown which is excreted into bile. Blockages in bile duct lead to rise on bilirubin in serum and jaundice.
What are aminotransferases?
Non specific markers of general liver damage. AST (aspartate aminotransferase) and ALT (alanine transferase) is sensitive.
What is alkaline phosphatase? (ALP)
Involved in generating phosphate for bone mineralisation, found in liver and bone. It is synthesised in the canaliculi bile in response to cholestasis.
It is a very specific marker for liver damage. Elevated levels indicate liver disease (shock, toxic injury/hepatitis) or
What is Gamma-glutamyl transpeptidase? (GGP)
Transport molecule produced in the gall bladder which is found in the liver and renal tubules. It is responsible for carrying drugs but activity is raised in cholestasis.
What are the plasma proteins?
Albumin is a major plasma protein and slow decline in concentration is indicative of liver disease.
Hypoalbuminemia
What is prothrombin time?
Measures of coagulation protein which are synthesised in the liver.
Short half life and increased prothrombin time is an early indicator of liver disease.
What are lipoprotein disorders?
High levels of proteins in the blood due to abnormal synthesis, storage or catabolism of plasma lipoprotein particles This may be due to genetic defect or underlying condition. Difficult to detect because of heterogenous nature such as LDL vs VLDL.
What are the characteristics of hyperlipoproteinaemia?
Transparent serum which becomes milky after a meal.
What are the causes of secondary hyperlipoproteineimia?
Alcohol
Renal dysfunction due to nephrotic syndrome or chronic renal failure
Pregnancy: increases VLDL, LDL and HDL
Pancreatitis: impairs lipase production
Diabetes, obesity and glycogen storage disease
What are the lipoprotein metabolism tests?
Measure of plasma lipoprotein concentration. Accurate measurement is via LDL and HDL
How are lipoproteins measured?
Ultracentrifugation to isolate substance
Electrophoresis
What is used to estimate plasma triglyceride levels?
VLDL
What is used to estimate LDL?
Cholesterol and vice versa
What are screening tests?
Identifying people who appear healthy but have increased risk of disease.
What are newborn screening?
Screening for conditions at 5 days old of:
Sickle cell disease
Cystic fibrosis
Congenital hypothyroidism
What are the inherited metabolic conditions?
Phenylketonuria
Medium chain Acyl co-A dehydrogenase deficiency
Maple syrup uterine disease
Isovaleric acidaemia
Glutaric aciduria type 1
Homocysturia
What is point of care testing?
Urgent tests for immediate management of patient. More expensive
What is the role of phenylalanine?
Component for synthesis of important amino acids such as conversion of phenylalanine -> tyrosine for production of dopamine
What is phenylketonuria?
Condition where there is an inability to break down phenylalanine due to deficiency in phenylalanine hydroxylase. Maintaining a low-protein diet is essential to prevent build up in the brain.
What inhibits phenylalanine hydroxylase?
Beta-2-thieyalanine
Troponin elevated
Indicates myocardial infarction
What is an aspirate?
Fluid drawn by suction
Distributed evenly between cells in a sample
Glucose
What is an important consideration when administering contrast dyes?
They are nephrotoxic
-> It is important to measure urea and electrolyte levels before administering
Which liver disease is AST higher than ALT?
Alcoholic fatty disease
Which liver enzymes are raised in biliary disease?
ALP and GGT- this is also raised in hepatocellular carcinoma.
Which enzymes indicate pancreatic issues?
Amylase and lipase.
Why would ALP be higher than GGT?
Extrahepatic issue such as increased osteoblast activity.
What does a sudden increase in GGT?
GGT
What is the transport for unconjugated bilirubin?
Albumin
