My Clinical Notes

 

• Small amount of intracellular enzymes are present in the blood as a result of normal cell turnover. When damage to cells occurs, increased amounts of enzymes will be released and their concentrations will rise
• However, as well as tissue damage, increased can also be due to;
  • Increased cell turnover
  • Cellular proliferation e.g. neoplasia
  • Increased enzyme synthesis (enzyme induction)
  • Obstruction to secretion
  • Decreased clearance

 

Enzyme activity

• Enzyme assays generally depend on the activity of an enzyme rather than its concentration
• It is important that the conditions of assays are optimised and standardised to give reliable results
• Reference ranges are dependant on assay conditions e.g. temperature

 

Disadvantages of enzyme assays

• Lack of specificity to a particular tissue type as many enzymes are common to more than one tissue
• This may be over come in different ways;
• Different tissues may contain and therefore release two or more enzymes in different proportions e.g. alanine and aspartate transaminase are both present in cardiac muscle and hepatocytes but there is relatively more alanine transaminase in the liver
• Some enzymes exist in different isoforms, often characteristic of a particular tissue. Although they have similar catalytic properties they may differ in some other measurable property such as heat stability and sensitivity to inhibitors
• Following tissue damage the level of intracellular enzyme rises and then falls as it is cleared therefore it is important to consider the time at which the sample is taken in relation to the insult – if too soon, there may be insufficient time for the enzyme to reach the blood stream and if too late it may have been cleared

 

Alkaline phosphatase (ALP)

• Enzyme is present in high concentrations in the liver, bone (osteoblasts), placenta and intestinal epithelium each with specific isoforms
• Causes of increased ALP
  • Pysiological
    • Pregnancy (last trimester)
    • Childhood – due to bone growth
  • Pathological
    • Often > 5 times the upper limit of normal
      • Paget’s disease of the bone
      • Osteomalacia
      • Rickets
      • Cholestasis (intra and extra hepatic)
      • Cirrhosis
    • Usually < 5 times the upper limit of normal
      • Bone tumours
      • Renal bone disease
      • Primary hyperparathyroidism with bone involvement
      • Healing fractures
      • Osteomyelitis
      • Hepatic space occupying lesions
      • Infiltrative hepatic disease
      • Hepatitis
      • IBD

 

• Plasma ALP activity might be slightly elevated in the healthy elderly possibly due to subclinical Paget’s disease
• ALP is not increased in osteoporosis unless there is a fracture

 

Aminotransferases

• Two aminotransferases are clinically important; aspartate aminotrasnferase and alanine aminotransferase
• There are no tissue specific isoforms of AST
• Causes of increased aspartate aminotransferase
  • >10 upper limits of normal
    • Acute hepatitis and liver necrosis
    • Major crush injuries
    • Severe tissue hypoxia
  • 5-10 x ULN
    • MI – plasma ASt begins to rise 12hr after infarct reaching a peak at 24-36hr and then declining over 2-3 days
    • Following surgery or trauma
    • Skeletal muscle disease
    • Cholestasis
    • Chronic hepatitis
  • <5 x ULN
    • Neonates
    • Other liver diseases
    • Pancreatitis
    • Haemolysis
• In most conditions when AST rises, there is a concurrent although smaller rise in ALT
• In hepatitis however the levels of ALT may exceed those of AST

 

Γ-Glutamyl transferase (GGT)

Present in high concentrations in the liver, pancreas and kidneys

• Causes of increased GGT
  • >10 x ULN
    • Cholestasis
    • Alcoholic liver disease
  • 5-10 x ULN
    • Hepatitis (acute or chronic)
    • Cirrhosis
    • Pancreatitis
  • <5 x ULN
    • Excessive alcohol ingestion
    • Enzyme inducing drugs – phenytoin, phenobarbitone and rifampicin (increased enzyme induction)
    • Congestive cardiac failure

 

Lactate dehydrogenase (LD)

• Exists as a tetramer – different combinations of H and M monomers combine to form 5 different isoforms
• Total LD is rarely measured as it lacks tissue specificity
• Increases due to acute damage to the liver, skeletal muscle and kidneys
• Is also increase in megaloblastic and haemolytic anaemias and in lymphoma (correlation between activity and tumour bulk)

 

Creatine Kinase

• Active CK is a dimer, produced by the monomers M and B
• BB is confined to brain
• MM is the isoenzyme normally present in the plasma
• Skeletal muscle is almost entirely MM
• Cardiac muscle up to 30% of CK is MB
• When plasma CK is elevated, if more than 5% or the total is MB, these suggests a cardiac origin
• Causes of increased plasma CK
  • >10 x UNL
    • Polymyositis
    • Rhabdomyolysis
    • Duchenne muscular dystrophy
    • MI
  • 5-10 x UNL
    • Following surgery
    • Skeletal muscle trauma
    • Severe exercise
    • Grand mal convulsions
    • Myositis
    • Carriers of Duchenne dystrophy
  • <5 x UNL
    • Physiological (Afro-Caribbeans)
    • Hypothyroidism

 

Amylase

• Enzyme is found in the salivary glands and exocrine pancreas
• Tissue specific isoenzymes
• Causes of increased plasma amylase
  • >10 x ULN
    • Acute pancreatitis
  • 5 x ULN
    • Perforated duodenal ulcer
    • Intestinal obstruction
    • Cute oligouric renal failure
    • Diabetic ketoacidosis
  • <5 x ULN
    • Salivary gland disorders e.g. calculi or inflammation
    • Chronic renal failure
    • Morphine administration – spasm of the sphincter of Oddi
    • Macroamylasaemia – amylase complexes with another protein leading to a greater molecular weight and reduced clearance

 

MI

• The first enzyme to increase is MB-CK, followed by total CK, aspartate aminotransferase and hydroxybutyrate dehydrogenase (the cardiac isoenzyme of LDH)
• CK-MB rise is the gold standard, yet an increase may not be seen until 4-8 hr after the onset of chest pain
• If the patient presents lat HBD may be helpful as it remains elevated for several days following the MI
• Troponin I and T are components of the contractile apparatus of myocardial muscle cells. Cardiac isoforms for both have been identified
• Both are highly specific and sensitive for MI, I more than T as T can also increase in unstable angina
• However neither rise early enough to inform the use of thrombolysis
• Myoglobin is also a sensitive indicator of cardiac damage (and can rise before CK-MB) but is non specific being present in skeletal muscle too
• If thrombolytic therapy is successful, then there may be a rapid rise in plasma markers of myocardial damage due to wash out phenomenon. The rise is slower if perfusion remains compromised

 

Bone disease

• Alkaline phosphatase is a marker of bone disease
• It rises in osteomalacia, Paget’s disease, renal osteodystrophy and secondary tumour deposits
• It can also rise in primary hyperparathyroidism but not in osteoporosis

 

Muscle disease

• Creatine kinase is a marker of muscle damage
• 95% of muscle creatine kinase is CK-MM, the rest is CK-MB, the proportion of which is greater in the Type I aerobic slow twitch fibres
• Other markers are aldolase and LDH but Ck has better sensitivity
• Myoglobin is also released following muscle damage

 

Pancreatic disease

• The major disorders of the exocrine pancreas are acute pancreatitis, chronic pancreatitis, pancreatic cancer and cystic fibrosis
• Acute pancreatitis leads to high levels of serum amylase (rapidly cleared by the kidneys)
• Pancreatic specific amylase can be measured
• Measurement of serum lipase activity has been reported as a more specific test than amylase but is rarely used
• An early elevation of serum aspartate transaminase activity is characteristic of pancreatitis caused by gallstones
• In chronic pancreatitis levels of serum amylase and lipase activity are normal
• CA 199 is a tumour marker for carcinoma of the pancreas

 

Cholinesterase deficiency

• Produced by the liver and hydrolyses the muscle relaxant drug succinylcholine
• The abnormal cholinesterase variants may be classified by measuring the percentage inhibition of the enzyme activity by dibucaine or by fluoride
• Homozygotes for dibucaine resistance or those that produce inactive enzymes are at risk of succinylcholine apnoea

This entry was posted on Sunday, February 3rd, 2008 at 1:32 pm and is filed under Chemical Pathology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.