Category Archives: PATHOLOGY

HYPERGLYCEMIA


A raised blood glucose level is called hyperglycaemia. When definite it is diagnostic of diabetes mellitus. In an adult with symptoms of diabetes mellitus, a random venous plasma glucose of 11.1 mmol/l or more on two occasions or a fasting value of 7.0 mmol/l or more on two
occasions is diagnostic.

  • Hyperglycemia occurs in pancreatic disease and some endocrine disorders such as thyrotoxicosis
  • 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.

These are essentially forms of transient diabetes (e.g. “stress diabetes”, “steroid diabetes”). However, it is now recognized that a number of these patients
may have pre-existing type 2 diabetes, therefore it is important to check that hyperglycaemia does resolve when the intercurrent illness resolve.

See also:

GLUCOSE

Glucose provides the energy for life processes. It is the main end product of carbohydrate digestion.

Oxidation of glucose by the glycolytic and tricarboxylic acid pathways provides the chemical energy needed for cellular activity.

When not required for the body’s immediate energy needs, glucose
is converted to glycogen and stored in the liver and muscles (glycogenesis).

When required to maintain the blood glucose level, liver glycogen is converted back to glucose (glycogenolysis).

Muscle glycogen provides the glucose for muscular activity. Excess glucose is oxidized to fatty acids and stored as fat in the tissues. If needed, glucose can also be formed from fats and protein (gluconeogenesis).

An increase in the breakdown of fats to provide energy, results in an increase in the
production of ketones.

Insulin is the most important hormone that regulates the amount of glucose in the blood, the rate at which glucose is
taken up by the tissues, and the conversion of glucose to glycogen. It is made and secreted by the beta-islet cells of the
pancreas. Only insulin is capable of reducing the concentration of glucose in the blood.

See also:

D-DIMER AND FIBRINOLYTIC SYSTEM


Fibrinolysis is the enzymatic process used by the body to remove a fibrin thrombus to restore normal blood flow once damaged endothelium is repaired.
During the clotting process, tissue plasminogen activator (t-PA) released from the blood vessel wall and the plasma proenzyme plasminogen bind to the fibrin thrombus. When activated, plasminogen is converted to plasmin which degrades the
fibrin network, causing the clot to dissolve. During this process, fibrin degradation products (FDPs), i.e. fragments called D-Dimers are produced.

Raised FDP levels in DIC

In Disseminated intravascular coagulation (DIC), activated procoagulants are released into the circulation. Platelets and coagulation factors are consumed and fibrin is deposited in small vessels, activating the fibrinolytic system. The plasmin formed degrades the fibrin (also some fibrinogen), resulting in a build-up of FDPs in the circulation. The FDPs act as anticoagulants interfering with platelet function and fibrin stabilization.
Laboratory tests are available to semi-quantify D-DIMER in plasma.

DISORDERS OF BLOOD COAGULATION

Can result in uncontrolled haemorrhaging into joints, muscles and deep tissues with the formation of haematoma. Coagulation disorders may be:

Hereditary

  • haemophilia A due to a deficiency of clotting factor VIII (commonest hereditary coagulation disorder),
  • haemophilia B (Christmas disease) due to a deficiency of factor IX
  • Von Willebrand’s disease caused by a deficiency or abnormality of the von Willebrand factor resulting in a defect in platelet adhesion. Haemophilia is carried by the female and affects males.

Acquired

  • Vitamin K deficiency
  • Severe liver disease, and disseminated intravascular haemolysis (DIC) associated with infections.
  • Obstetric complications (septic abortion, eclampsia, fetal retention, ruptured uterus).
  • Haemorrhagic disease of the newborn.
  • Snake envenomation.
  • Malignancies.
  • Overdose of anticoagulant drugs, e.g. warfarin.

Laboratory investigations

TYPES OF JAUNDICE

Haemolytic jaundice

In haemolytic (prehepatic) jaundice, more bilirubin is produced than the liver can metabolize, e.g. in severe haemolysis
(breakdown of red cells). The excess bilirubin which builds up in the plasma is mostly of the unconjugated type and is therefore not found in the urine.

Hepatocellular jaundice

In hepatocellular (hepatic) jaundice, there is a build up of bilirubin in the plasma because it is not transported, conjugated, or excreted by the liver cells because they are damaged, e.g. in viral hepatitis. The excess bilirubin is usually of both the unconjugated and conjugated types with bilirubin being found in the urine.

Obstructive jaundice

In obstructive (post-hepatic) jaundice, bilirubin builds up in the plasma because its flow is obstructed in the small bile
channels or in the main bile duct. This can be caused by gallstones or a tumour obstructing or closing the biliary tract. The
excess bilirubin is mostly of the conjugated type and is therefore found in the urine. The term cholestasis is used to describe a failure of bile flow.

See also

Bilirubin test

FORMS OF DIABETES MELLITUS BASED ON WHO CLASSIFICATION

Type 1 diabetes : formerly known as insulin-dependent diabetes (IDDM):

Insulin treatment is required to sustain life. There is an absolute insulin deficiency due to the immune destruction of pancreatic beta-cells possibly triggered in genetically
susceptible persons by a viral infection (e.g. congenital rubella), consumption of cows milk early in life, or possibly by chemical toxins. The onset of type 1 diabetes is
abrupt with severe symptoms, often including ketosis.
Type 1 diabetes is the commonest form of diabetes among children and young adults in European countries but has a low prevalence in tropical countries.

Type 2 diabetes : formerly known as non-insulin dependent diabetes (NIDDM):

Individual or ethnic genetic factors lead to susceptibility.
There is some secretion of insulin but a decrease in insulin action (insulin resistance). Several factors are associated
with the development of type 2 diabetes in susceptible individuals. These include dietary changes, overnutrition
with increased intake of saturated fats and decreased intake of dietary fibre, obesity, physical inactivity, and ageing. There is often arterial hypertension and
dyslipidaemia. Some drugs and hormones can also cause glucose intolerance and diabetes.

Malnutrition-related diabetes mellitus (MRDM):

MRDM is a controversial entity, and current WHO classifications of diabetes does not include MRDM. It is also known as ‘tropical pancreatic diabetes’, and is seen in
localized areas throughout tropical countries. It is related to pancreatic damage and is characterized by young age of
onset and past or present malnutrition. Steatorrhoea may occur due to exocrine pancreatic deficiency. Pancreatic
calcification can occur in some cases. The cause is unknown; toxicity from the cyanide content of the root crop cassava has been suggested but not definitely
substantiated.

Gestational diabetes mellitus (GDM):

This is defined as diabetes first recognized in pregnancy. Glucose values often return to normal postpartum but glucose intolerance and type 2 diabetes may occur later in life.

Other forms of diabetes:

These rarer forms can be found with pancreatic disease, some hormonal diseases and genetic syndromes, abnormalities of insulin or its receptors, and as a result of treatment with certain drugs or exposure to certain chemical
toxins.

See also blood glucose for diabetes diagnosis

SOURCES OF ERROR ASSOCIATED WITH THE HbS SOLUBILITY


● Using a reagent that has deteriorated. If after adding blood to the working reagent, a pale orange colour develops, this indicates reagent deterioration. A fresh reagent must be prepared.

● Using blood with too few red cells. Either the volume of blood used should be increased or preferably the test performed on a plasma reduced blood sample.

● Testing the blood of a transfused patient. The test should be performed at a later date to obtain a reliable test result.

THROMBOCYTOPENIA

It occurs when platelets fall below the normal range of 150–400×10^9 per litre of blood

REDUCED PRODUCTION OF PLATELETS

● Infections, e.g. typhoid, brucellosis
● Deficiency of folate or vitamin B12
● Aplastic anaemia
● Drugs (e.g. cytotoxic, quinine, aspirin), chemicals
(e.g. benzene), some herbal remedies, alcoholism
● Leukemias, lymphoma, myeloma, myelofibrosis, carcinoma
● Hereditary thrombocytopenia (rare condition).

INCREASED DESTRUCTION OR CONSUMPTION OF
PLATELETS

● Infections, e.g. acute falciparum malaria, dengue, trypanosomiasis, visceral leishmaniasis
● Disseminated intravascular coagulation (DIC)
● Hypersplenism
● Immune destruction of platelets, e.g. idiopathic thrombocytopenic purpura (ITP), systemic lupus erythematosus (SLE), other connective tissue disorders, chronic lymphatic leukaemia, lymphomas and HIV/AIDS. Also, exposure to drugs, e.g. quinine, mefloquine, penicillin, and some herbal remedies.

ABNORMAL SPECIMEN APPEARANCE

● A dark coloured urine may be positive for bilirubin or haemoglobin.

● A urine that contains whole blood may contain S. haematobium eggs.

● A black faecal specimen may contain occult blood due to gastrointestinal bleeding.

● A dark brown serum may indicate intravascular haemolysis due to sickle cell disease, severe malaria, or an incompatible blood transfusion.

● A lipaemic (fatty) serum is associated with raised triglycerides (above 3.4 mmol/l).

● A deep yellow (icteric) serum indicates that a patient is jaundiced.

● A serum sample that is abnormally viscous (thick) or turbid may contain paraproteins.

● A serum that becomes markedly turbid after being refrigerated may contain cryoglobulins or cold agglutinins.

● A blood sample that contains a high concentration of red cells from which little serum or plasma can be obtained indicates severe dehydration or a blood disorder.

WHAT ARE ABNORMAL CHEMICAL CONSTITUENTS OF URINE


● Protein which can be found in the urine of persons with urinary schistosomiasis, urinary tract infections, nephrotic syndrome, renal diseases such as It may also be found in urine from pregnant women and sometimes from healthy young individuals.

● Glucose which may be found in the urine of diabetic patients and occasionally in some healthy individuals.

● Ketones which can be found in the urine of untreated diabetic patients or persons suffering from starvation.

● Bilirubin which can be found in the urine of persons with hepatocellular jaundice or cholestatic (obstructive) jaundice.

● Urobilinogen (in increased amounts), which can be found in the urine of those with conditions causing abnormal haemolysis.

● Nitrite which can be found in the urine of
patients with urinary tract infection caused by nitrate-reducing bacteria.

● Blood which can be found in the urine in urinary schistosomiasis, bacterial infections, acute glomerulonephritis (inflammation of the glomeruli of the kidneys), sickle cell disease, leptospirosis, infective endocarditis, calculi (stones) in the urinary tract, malignancy of the
urinary tract, and haemorrhagic conditions.
Free haemoglobin in urine can be found in
malaria haemoglobinuria and other conditions that cause intravascular haemolysis