Category Archives: CLINICAL CHEMISTRY

BLOOD GLUCOSE TEST

Mainly tested for diagnosis and management of diabetes mellitus

What are the Normal ranges for blood glucose?


Adults
– Fasting (plasma) 3.6–6.4 mmol/l
– Random (plasma) 3.3–7.4 mmol/l
Children
– Fasting (plasma) 2.4–5.3 mmol/l
Newborn values are slightly lower, i.e. 1.1–4.4

Causes of raised blood glucose levels

Hyperglycaemia (Raised blood glucose levels) may accompany pancreatic disease
and some endocrine disorders such as thyrotoxicosis and Cushings syndrome. Steroid therapy may also cause hyperglycaemia. Transient hyperglycaemia
often occurs following severe stress, e.g. after surgery, injury, shock, infections, or severe burns.

Causes of low blood glucose levels

A low blood glucose level is called hypoglycaemia.
Persistent occurrences of hypoglycaemia with glucose levels less than 2.2 mmol/l accompanied by symptoms such as fainting, fits, sweating, hunger, pallor, confusion, or violence, should be investigated.
Causes of hypoglycaemia include severe malnutrition, kwashiorkor, severe liver disease, alcoholic excess, insulin secreting tumours, Addison’s disease,
and certain drugs. Commonly, however, markedly reduced blood glucose levels occur following the overtreatment of diabetes.

Neonatal hypoglycaemia: Newborn infants may suffer hypoglycaemia when blood glucose levels fall below 1.1 mmol/l. Infants particularly at risk are
underweight poorly nourished babies, twins, premature infants, and babies born of diabetic mothers. It is important to detect hypoglycaemia of the newborn because without treatment brain damage may
occur.
Malaria associated hypoglycaemia: In severe malaria, hypoglycaemia is a common finding and can increase mortality particularly in young children.
Hypoglycaemia can also occur in those being treated with quinine and quinidine.

URINE APPEARANCE AND VOLUME

Urine changes in disease
Production and composition of urine depend on glomerular filtration, tubular reabsorption and tubular secretion.
Changes that can occur in the volume, appearance, constituents, and mass density (specific gravity) of
urine in disease are as follows:
Volume

What is the normal volume of urine in 24hrs?

The volume of urine excreted daily depends on fluid intake, diet, climate, and other physiological factors. It is usually between 1–2 litres per 24 hours.

What causes increase in urine volume?

An increase in the volume of urine is called
polyuria. It occurs in diabetes mellitus due to an increase in the osmolality of the filtrate preventing the normal reabsorption of water (osmotic diuresis).
Polyuria also occurs when the secretion of the antidiuretic hormone is reduced, e.g. in diabetes

What causes decrease in urine volume?

A decrease in the volume of urine excreted is called oliguria. It occurs when the renal blood flow and, or, glomerular filtration rate are reduced. One of the causes of a reduced renal blood flow is low
blood pressure (hypotension) caused for example by severe dehydration or cardiac failure. A fall in glomerular filtration rate occurs in acute glomerulonephritis (inflammation of the kidney glomeruli) and also in the early stages of acute tubular necrosis.

If severe, oliguria progresses to a complete cessation of urine flow, this is called anuria and is usually due to severe damage to the renal tubules (acute tubular necrosis). Acute tubular necrosis may
follow any of the conditions which cause severe hypotension or may be due to a direct toxic effect on
the tubules by drugs or following an incompatible
blood transfusion.

Interpretation of urine appearance


Normal freshly passed urine is clear and amber in colour. A dilute urine appears pale in colour and a concentrated one has a dark yellow appearance. The yellow colour is due to the pigments
urochrome, urobilin, and porphyrins.
When normal urine has been allowed to stand for some time, a white phosphate deposit may form
if the urine is alkaline (dissolved by adding a drop of acetic acid) or a pink uric acid deposit may form if the urine is highly acidic or concentrated (disappears
on warming). A ‘mucus’ cloud may also form if normal urine is left to stand.

Changes of urine appearance in difference condition

The appearance of urine may be altered in many
conditions including:
● Urinary tract infections in which the urine appears cloudy because it contains pus cells and bacteria.
● Urinary schistosomiasis in which the urine often appears red and cloudy because it contains blood (haematuria).
● Malaria haemoglobinuria (blackwater fever) and other conditions causing intravascular haemolysis in which the urine appears brown and cloudy
because it contains free haemoglobin (haemoglobinuria).
● Jaundice in which the urine may appear yellowbrown or green-brown because it contains bile pigments or increased amounts of urobilin (oxidized urobilinogen).
● Bancroftian filariasis in which the urine may appear milky-white because it contains chyle.

MEASURING C.S.F PROTEINS

Total protein in c.s.f. can be measured by the following methods:
Colorimetrically using a trichloroacetic acid method.
Visual comparative semiquantitative method when a colorimeter is not available

What are normal ranges for C.S.F proteins?

0.15–0.40 g/l

What Causes increase in C.S.F Proteins?


An increase in total protein and a positive
Pandy’s test occurs in all forms of meningitis, in amoebic and trypanosomiasis meningoencephalitis,
cerebral malaria, brain tumours, cerebral injury, spinal cord compression, poliomyelitis, the GuillainBarré syndrome (often the only abnormality), and polyneuritis.

Increases in c.s.f. protein also occur in diseases which cause changes in plasma proteins such as multiple myeloma.
When the total protein exceeds 2.0 g/l (200mg%), the fibrinogen level is usually increased sufficiently to cause the c.s.f. to clot. This may occur in severe pyogenic meningitis, spinal block, or following haemorrhage.

SERUM ELECTROLYTES TEST

The measurement of sodium, potassium, or both electrolytes is usually requested in the assessment of renal function, to assist in the management of a patient that is unconscious or confused or a diabetic
patient with ketoacidosis, to assess and monitor states of dehydration (particularly an infant losing fluid), to monitor diuretic therapy and to assist in fluid replacement therapy.

What are the Normal ranges for sodium and potassium?

Sodium:
134–146 mmol/l (134–146 mEq/l)
Potassium:
Adults: 3.6–5.0 mmol/l (3.6–5.0 mEq/l)
Newborns: 4.0–5.9 mmol/l (4.0–5.9 mEq/l)
Values are highest immediately after birth

What are causes of increase in Sodium levels?


An elevated sodium level is known as hypernatraemia. It is nearly always due to dehydration with the rise in sodium (also chloride and urea) being due
to a concentrating effect. It is usually brought about by a reduction of body water content by fluid loss without compensatory reduction in sodium content, rather than a dietary overload, although excessive IV saline is a potential factor.
Typical causes of hypernatraemia are:
– Severe vomiting
– Prolonged diarrhoea
– Profuse sweating, fever
– Polyuria, as in diabetes
– Hyperaldosteroidism
– Cushing’s syndrome
– Inadequate water intake
– Accidental ingestion of sea water.

Note: A high sodium level must be reported as soon as possible. Severe hypernatraemia (sodium level that has reached 155 mmol/ is a serious finding .

What are causes of low sodium levels?


A low sodium level is known as hyponatraemia. It is a common finding than hypernatraemia. A greatly
reduced level (as low as 125 mmol/l) indicates a dangerous condition and must be reported as soon as possible.
A low sodium level may accompany any severe illness including viral and bacterial infections, malaria, heart attacks, heart failure, strokes, and tumours of the brain and lung.

Other causes of hyponatraemia
– Surgery or severe accident.
– Treatment with diuretics.
– Side effect of some drugs.
– When loss of salt and water (e.g. by vomiting,
diarrhoea or excessive sweating) is replaced by
water only.
– Loss of sodium in the urine as in severe renal impairment and salt-losing nephritis.
– Hypoadrenalism (Addison’s disease). In tropical countries hypoadrenalism can be caused by tuberculosis of the adrenal glands.

What are causes of high Potassium levels?



A raised potassium level is known as hyperkalaemia.
Levels above 6.5 mmol/l are particularly dangerous and must be reported immediately because fatal
disorders of heart rhythm can occur suddenly.

Typical causes of hyperkalaemia are:
– Excessive IV infusion, or increased ingestion of
potassium.
– Reduced renal excretion, renal failure with oliguria, anuria, acidosis.
– Addison’s disease.
– Hypoaldosteronaemia.
– Leakage of cellular potassium following: acute starvation, gross haemolysis, diabetic ketoacidosis, dehydration, severe tissue injury.

Falsely high potassium result: This can occur if a blood sample is haemolyzed due to poor venepuncture technique, a sample is left for a long time (e.g.
overnight) without the plasma or serum being removed or if whole blood is refrigerated before it is centrifuged. Red cells contain a high concentration
of potassium.

What are causes of low Potassium levels?

A low potassium level is called hypokalemia. The depletion of potassium can be masked by topping up of the plasma levels from intracellular sources and clinical symptoms may present in the
face of apparently normal values. These include:
weakness, tetany, polyuria and ECG changes.
Causes of hypokalaemia include:
– Inadequate intake of potassium in the diet and long term starvation.
– Increased loss of potassium due to prolonged vomiting or diarrhoea, renal tubular failure, diuretics, hyperaldosteroidism.
– Redistribution from plasma into cells; insulin therapy, metabolic or respiratory alkalosis.

Note: In the management of patients with salt and water depletion a simple test for urine chloride may be of value when facilities are not available for measuring serum or plasma electrolytes.

ACUTE PANCREATITIS


Very high concentrations of serum or plasma amylase (over 1850 U/l) are virtually diagnostic of acute
pancreatitis or acute episodes of chronic relapsing pancreatitis.

When chronic pancreatitis has reached
the stage of scarring and calcification, the serum amylase level is usually normal.
With acute pancreatitis, the rise in serum or plasma amylase is often very brief with the enzyme reaching its highest level within 12–24 hours and returning to normal within 3–5 days.

Slight to moderate increases of serum amylase must be interpreted carefully. They are not diagnostic of acute pancreatitis unless the blood has been
collected too late to catch the peak level.

Other laboratory findings in pancreatitis
In acute pancreatitis the white cell count is raised. A serious condition is indicated if the serum or plasma albumin and calcium and blood haematocrit levels fall and the serum or plasma bilirubin and urea
levels rise.

Falsely elevated amylase levels may result if the serum is markedly turbid or the sample has been contaminated with amylase during analysis

Note: It is useful to measure amylase both in serum and in urine. Amylase is quickly filtered into the urine, therefore a person suffering from acute pancreatitis may have normal serum amylase levels but
high enzyme activity in the urine.

SERUM AMYLASE TEST

Measurement of serum or plasma amylase activity is usually requested to assist in the differentiation of acute pancreatitis from other acute abdominal disorders. It is an early indicator of acute pancreatitis.

What are the Normal ranges for Serum amylase test?

70-340 U/l

What causes high levels of serum amylase?

Acute pancreatitis
Very high concentrations of serum or plasma amylase (over 1850 U/l) are virtually diagnostic of acute pancreatitis or acute episodes of chronic relapsing
pancreatitis. Read more.

Other conditions giving raised amylase values
Serum or plasma amylase levels of approximately 740–1500 U/l may be due to:
– Renal failure
– Salivary gland obstruction or inflammation such as
with mumps
– Diabetic ketoacidosis
– Opiate drugs and some antiretroviral drugs
– Alcoholism
– Hypothermia
– Ectopic pregnancy
– Almost any acute abdominal emergency, and also cholecystitis, perforated peptic ulcer, or peritonitis.

Falsely raised amylase level
Falsely elevated amylase levels may result if the serum is markedly turbid or the sample has been contaminated with amylase during analysis.

SERUM ALANINE AMINOTRANSFERASE(ALT) TEST

Also referred to as to Glutamate Pyruvate Transaminase (GPT)

Measurement of ALT activity is mainly performed to investigate liver disease. Increasingly ALT is being measured to monitor patients receiving antiretroviral drugs associated with hepatotoxicity such
as nevirapine (NVP) and stavudine (d47).

While both ALT and AST are raised with hepatocellular injury, ALT is more specific for detecting liver cell damage.

What are the Normal ranges for Serum ALT ?

5–35 IU/l

Causes of high levels of serum ALT

Liver disease
The most important cause of raised ALT activity is hepatocellular injury. With acute hepatocellular injury, AST levels are usually higher than ALT levels. As damage continues, ALT activity becomes higher. In viral hepatitis, both enzymes are usually raised before the patient becomes jaundiced.

In Liver cirrhosis:
ALT levels fall below AST levels. Both ALT and AST are raised in hepatitis caused by hepatotoxic antiretroviral drugs.

Obstructive liver disease is usually accompanied by only small or moderate ALT and AST rises especially in the early stages. With complete obstruction, enzyme levels fall.

ALT and AST enzymes are artefactually increased when haemolysis is present or if the blood has been stored without separation of the serum or
plasma.

SERUM ASPARTATE AMINOTRANSFERASE TEST (AST)

What causes increase in Serum ALT?

It also referred to as Glutamate Oxaloacetate Transaminase (GOT)

Myocardial infarction
An important cause of elevated AST activity is myocardial infarction, i.e. destruction of an area of heart muscle because its blood supply has been cut off due to a blood clot in a coronary artery. The enzyme level rises soon after the coronary vessel becomes blocked, reaches its highest value 24–48 hours after the infarct and returns to normal usually within 3–5 days. In general, the more extensive the infarct, the higher the AST peak level.

Other causes of raised AST levels
Because AST is widely distributed in body tissues, many other diseases involving cellular injury may be accompanied by increases in AST levels:
– Severe bacterial infections, – -Malaria,pneumonia
– Infectious mononucleosis, Pulmonary infarcts, and tumours.
AST activity is also increased in some muscle disorders and following surgery, injury or blood transfusion.

ALT and AST enzymes are artefactually increased when haemolysis is present or if the blood
has been stored without separation of the serum or
plasma.

SERUM ALBUMIN TEST

Serum albumin is mainly measured to investigate liver diseases, protein energy malnutrition, disorders of water balance, nephrotic syndrome, and protein-losing gastrointestinal diseases.

What are the Normal ranges for Serum albumin Test?

30 – 40g/dl

What does test result mean?

Increases Serum albumin levels are rarely raised except in
diarrhoea or prolonged vomiting and artefactually by prolonged venous stasis.

Decreases
Hypoalbuminaemia occurs whenever there is increased plasma volume (e.g. in pregnancy).
Pathological causes include:
– Low protein intake as in protein energy malnutrition.
– Malabsorption as in chronic pancreatitis, coeliac disease, and sprue.

See also:

SERUM BILIRUBIN TEST

The measurement of serum or plasma bilirubin is usually performed to investigate the causes of liver disease and jaundice, and to monitor a patient’s progress, e.g. an infant with serious neonatal jaundice (high levels of unconjugated bilirubin).

Bilirubin is a product of erythrocytes breakdown and exists as conjugated or non- conjugated. These two combined gives the Total Bilirubin.

What are normal ranges for Total bilirubin?

Adults: 3–21 mol/l 0.2–1.3 mg/100 ml

Newborns: 8–67 mol/l 0.5–4.0 mg/100 ml

What does high serum Bilirubin indicate?

RISE in the level of bilirubin in the blood is called hyperbilirubinaemia. The main causes are as follows:

● Overproduction of bilirubin caused by an excessive breakdown of red cells (haemolytic jaundice). The bilirubin is of the unconjugated type.
In tropical countries haemolysis is due mainly to:
– Severe falciparum malaria.
– Sickle cell disease haemolytic crisis.
– Haemolysis associated with glucose-6-
phosphate dehydrogenase deficiency and
hereditary spherocytosis.
– Antigen antibody reactions as in haemolytic disease of the newborn, autoimmune haemolytic anaemias, or following an incompatible blood transfusion.
– Toxins from bacteria, snake venoms, drugs or herbs.

● Liver cell damage in which there is usually an increase in both conjugated and unconjugated bilirubin (hepatocellular jaundice). The commonest causes are:
– Hepatitis caused by hepatitis viruses and other viruses
– Leptospirosis
– Relapsing fever
– Brucellosis
– Typhoid
– Chemicals, plant toxins and drugs

● Metabolic disturbances in the liver involving defective conjugation, transport and, or, excretion
of bilirubin. Examples include:
– type of neonatal jaundice, often referred to as ‘ physiological jaundice’
– Rare inherited disorders of conjugation such as Gilbert’s and Crigler-Najjar syndromes.

● Partial or complete stoppage of the flow of bile through bile channels with a build up of conjugated bilirubin in the blood (obstructive
jaundice). Cholestasis can be due to:
– Obstruction of the extra-hepatic biliary ducts by gallstones, tumours (especially hepatomas and carcinoma of the pancreas), cholangitis
(inflammation of the biliary ducts), or by
helminths such as Opisthorchis and Fasciola species. Occasionally heavy Ascaris infections, especially in children, may result in blockage of the common bile duct.
– Pressure on the small bile ducts as may occur in hepatitis or as a side effect of drugs.

NB: Mild to moderate hyperbilirubinaemia may also be found in association with any serious condition such as a terminal illness, or following major trauma, surgery, or blood transfusion