Chemical Pathology 2

Question 1

Albumin - Definition and Role

Answer 1

Major plasma protein synthesised in the liver. Contributes to oncotic pressure so low levels result in oedema.

Question 2

Causes of Low Albumin

Answer 2

• Decreased synthesis - malnutrition, malabsorption or in chronic liver disease.
• Abnormal distribution - enters interstitial space if increased vascular permeability e.g. sepsis.
• Excess excretion - nephrotic syndrome, protein losing enteropathy, burns or haemorrhage.

Question 3

Creatinine Kinase

Answer 3

• 3 forms - CK-MM in skeletal muscle, CK-BB in brain and CK-MB in cardiac muscle.
• No longer routinely used to detect MI.
• Raised CK - statin related myopathy, muscle damage from any cause e.g. strenuous exercise, myopathy e.g. muscular dystrophy or can be physiological in Afro-Caribbean’s.

Question 4

Alkaline phosphatase

Answer 4

• Present in liver, bone, intestine and placenta but pathological rises usually due to liver or bone disease.
• Causes of raised ALP (<5 times normal) - fracture, tumour, osteomyelitis or hepatitis.
• Causes of raised ALP (>5 times normal) - physiological in 3rd trimester or during a growth spurt, Pagets, osteomalacia, cholestasis or cirrhosis.

Question 5

Troponin

Answer 5

• A structural protein complex (troponin I, T and C) in the actin-myosin contractile apparatus.
• Troponin I and T measured in suspected MI.
• Levels rise at 4-6 hours post MI.
• Levels peak at 12-24 hours.
• Levels remain raised for 3-10 days.

Question 6

LFTs - Obstructive Picture

Answer 6

Raised serum bilirubin and ALP

Question 7

Bilirubin

Answer 7

• Derived from haem in red blood cells.
• Transported almost completely bound to albumin.
• Taken up by the liver and conjugated to form mono and di-glucuronides.
• Conjugated bilirubin is broken down by bacteria to form stercobilinogens - excreted in faeces.
• Also enters enterohepatic circulation and is excreted as urobilinogen in urine.

Question 8

LFTs - Acute Hepatocellular Damage

Answer 8

• Raised serum aminotransferase activity - AST and ALT are non-specific indicators of acute damage to hepatocytes.
• Causes - hepatitis, toxic injury, drug overdose, hypoxia or secondary to right heart failure.

Question 9

LFTs - Chronic Liver Disease

Answer 9

Serum albumin concentration and prothrombin time can be used to measure synthetic capacity.

Question 10

Gamma-glutamyl Transpeptidase

Answer 10

A microsomal enzyme that is raised with cholestasis, acute hepatocellular damage and ingestion of alcohol and some drugs e.g. phenytoin.

Question 11

Alpha-fetoprotein

Answer 11

• Synthesised by the fetal liver and present in low concentrations in healthy adults.
• Increases by 80-90% in hepatocellular carcinoma.

Question 12

Causes of Jaundice

Answer 12

• Pre-hepatic - haemolysis.
• Hepatic - viral hepatitis, drugs, alcoholic hepatitis, cirrhosis, pregnancy and cholestasis.
• Post-hepatic - common bile duct stones, malignancy e.g. bile duct, head of pancreas, biliary stricture, sclerosing cholangitis or pancreatic pseudocyst.

Question 13

Insulin - Definition

Answer 13

• A protein synthesised in Beta cells in the islets of Langerhans in the pancreas.
• Main targets - liver, muscle and adipose tissue.

Question 14

Insulin - Actions

Answer 14

• Lower blood glucose levels
• Promotes - glucose uptake in muscle and adipose tissue, glycolysis (glucose degradation), glycogen synthesis, protein synthesis and the uptake of potassium and phosphate.
• Inhibits - gluconeogenesis, glycogenolysis, lipolysis, ketogenesis and proteolysis.

Question 15

Calcium Homeostasis

Answer 15

• Parathyroid hormone is released in response to low levels of circulating unbound calcium.
• PTH causes bone reabsorption.
• PTH causes increased renal Ca reabsorption.
• PTH causes hydroxylation of vitamin D in the liver and kidneys which leads to production of 1,25-DHCC which promotes intestinal reabsorption of Calcium.

Question 16

Adjusted Calcium

Answer 16

• Both bound (to albumin) and unbound calcium are routinely measured in laboratories.
• However only unbound calcium in active.
• So labs also give an adjusted calcium = total measure calcium + 0.02 (47 - albumin).

Question 17

Hypocalcaemia - Causes

Answer 17

• Hypoparathyroidism.
• Renal disease - 1,25-DHCC no longer synthesised.
• Vitamin D deficiency - due to malabsorption or dietary insufficiency.
• Magnesium deficiency

Question 18

Hypocalcaemia - Clinical Features

Answer 18

CAT numb - convulsions, arrhythmia’s, tetany and numbness in hands, feet and around mouth.

Question 19

Hypocalcaemia - Management

Answer 19

• Treat the underlying cause.
• Oral calcium supplements often prescribed.
• In addition 1,25-DHCC or synthetic vitamin D can also be given depending on the cause.

Question 20

Hypercalcaemia - Causes

Answer 20

• Common causes include hyperparathyroidism or malignancy.
• Rarer causes - excess vitamin D replacement, excess 1,25-DHCC found in granulomatous disease or lymphoma, thyrotoxicosis due to increased bone turnover.

Question 21

Hypercalcaemia - Clinical Features

Answer 21

Stones ( renal or biliary), Bones (bone pain), Groans (abdominal pain, constipation, N+V), Thrones (polyuria) and Psychiatric Overtones (depression, anxiety, cognitive impairment.

Question 22

Hypercalcaemia - Management

Answer 22

• Urgent IV saline should be given for concentrations >3.5mmol to promote diuresis.
• Bisphosphonates are used in malignancy - inhibit the reabsorption of bone.
• Treat the underlying cause where possible e.g. removal of a parathyroid adenoma.