PATHOLOGY – Page 2

CAUSES OF PROTEINURIA (PROTEIN IN URINE)

– Glomerular or tubular urinary disease.
Proteinuria accompanies acute glomerulonephritis and is due to increased permeability of the glomerular basement
membrane. The degree of proteinuria reflects the severity of the condition and helps in assessing prognosis and
response to treatment.

– HIV associated renal disease and treatment with nephrotoxic antiretroviral drugs.

– Pyogenic or tuberculous pyelonephritis.

– Severe lower urinary tract infection.

– Nephrotic syndrome which is a condition characterized by heavy proteinuria and oedema. The oedema is caused by a reduction in the colloid osmotic pressure due to a fall in the level of plasma albumin brought about when proteinuria
rises to 5 or 10 g/l per day.

– Eclampsia when there is moderate to marked proteinuria.

– Urinary schistosomiasis which is usually accompanied by both proteinuria and haematuria.

– Severe febrile illnesses including malaria.

– Occasionally in diabetes . Diabetic nephropathy sometimes causes a nephrotic syndrome

THROMBOCYTOSIS

Occurs when platelet count rises above the normal range of 150–400 10^9 per litre of blood

What causes Thrombocytosis

● Chronic myeloproliferative diseases, e.g. essential thrombocythemia, polycythaemia vera, chronic myeloid leukaemia, myelofibrosis.
● Carcinoma (disseminated)
● Chronic inflammatory disease, e.g. tuberculosis
● Haemorrhage
● Sickle cell disease associated with a nonfunctioning spleen or after splenectomy.
● Iron deficiency anaemia, associated with active bleeding.

CHRONIC LYMPHOID LEUKEMIA

Marked lymphocytosis
Smugde cells are present
CD 19+ and weak IgM & IgD expression
Normochromic normocytic anaemia Reduced concentration of serum immunoglobulins
Neutropenia and red cell aplasia
Nodullar diffuse bone marrow, high concentration of lymphocytes
White pulp in the skin

Clinical Features

Lymphadenopathy
Splenomegaly (less common)
Hepatomegaly( late stages)
Bruising
Immunosupression

Staging

Lymphocytosis >5×10^9/L
1 + enlarged lymph
2 + enlarged liver and spleen
3 +anemia and splenomegaly
4 + thrombocytopenia

CHRONIC MYELOID LEUKEMIA

Arises due to Philadelphia chromosome t(22;9) The BCL- ADR oncogene

Marked leukocytosis with left shift (<200×10^9)
Normocytic normochromic anaemia
Increase in basophils and platelets
Hypercellular bone marrow (granulopoietic predominant)
High serum uric acid

Clinical Features

Hypermetabolism
Splenomegaly
Features of anaemia
Abnormal platelet count
Renal diseases
Rare visual disturbance, priapism

Staging

Chronic phase: more than 10% blasts
Accelerated phase: 15-30% blasts, 20% basophils and thrombocytopenia
Blasts phase: more than 20% blasts, it is acute and respond poorly to treatment

TYPES OF ANAEMIA

Anemia classified as follows based mechanisms described here

Iron deficiency
Microcytic hypochromic RBCs
● MCHC: ↓ Below 320 g/l
● MCV: ↓ Below 78 fl
● Reticulocytes: Normal or Low
– cells with ‘pencil’ appearance

Macrocytic anaemia
Folate deficiency(megaloblastic)
-MCV: ↑ More than 100 fl
– Macrocytes mostly oval, occasional megaloblast, pancytopenia
– Reticulocytes: Normal or ↓
-(late stages), hypersegmented neutrophils. -WBC and platelets: ↓
-MCHC: Normal
Liver disease: Non-megaloblastic Macrocytes (mainly round with target cells)

Sickle cell disease – Sickle cells, polychromasia,
● HbS: Positive
poikilocytosis, nucleated red cells,
● Reticulocytes: ↑ (blue stippling in
HbS thalassaemia target cells. Macrocytes due to folate background of thick film)
deficiency (when patient not receiving
folate)
Further test: Hb electrophoresis.

MECHANISM OF ANEMIA

BLOOD LOSS
● Acute bleeding, e.g. from wounds, surgical, ectopic pregnancy, placenta praevia
● Chronic blood loss, e.g. hookworm infection, schistosomiasis, gastrointestinal bleeding, menorrhagia

DECREASED RED CELL PRODUCTION
● Lack of essential nutrients, e.g. deficiencies of iron,
folate, vitamin B12, protein
● Depressed bone marrow activity, e.g. anaemias associated with chronic disease such as tuberculosis, HIV disease, chronic nephritis, chronic hepatitis,
connective tissue disorders, malignant disease, leukaemias
● Due to drugs, chemicals, ionizing radiation, some viruses
● Thalassaemia syndromes

INCREASED RED CELL DESTRUCTION
(HAEMOLYSIS)
● Inherited haemolytic anaemias:
– Haemoglobinopathies, e.g. sickle cell diseases,
thalassaemia syndromes
– Red cell enzyme deficiencies, e.g. G6PD
deficiency, pyruvate kinase deficiency
– Red cell membrane defects e.g. hereditary
spherocytosis
● Non-immune acquired haemolytic anaemias:
– Infections, e.g. malaria, African trypanosomiasis, meningococcal septicaemia, C. perfringens
infection, bartonellosis
– Pre-eclampsia and HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count)
– Conditions which cause disseminated intravascular coagulation (DIC)
– Haemolytic uraemic syndrome
– Hypersplenism and splenomegaly, e.g. visceral
leishmaniasis, hyper-reactive malaria, splenomegaly, myelofibrosis
– Burns
– Venomous snake and spider bites
– Chemicals, oxidant drugs, local herbal remedies
– Paroxysmal nocturnal haemoglobinuria
● Immune acquired haemolytic anaemias (DAT positive):
– Haemolytic disease of the newborn
– Haemolytic blood transfusion reaction
– Warm reactive autoantibody, e.g. drug-induced chronic lymphatic leukaemia, lymphoma, systemic lupus erythematosus
– Cold reactive autoantibody, e.g. M. pneumonia infection, lymphoma
– Paroxysmal cold haemoglobinuria

HAEMOGLOBIN MEASUREMENT

Haemoglobin is measured to detect Anaemia and its severity and to monitor an patient’s response to treatment. Monitoring the haemoglobin level (or PCV) is also required when patients with HIV disease are being treated with drugs such as AZT. The test is also performed to check the haemoglobin level of a blood donor prior to donating blood.

What are normal ranges for Haemoglobin?

Children at birth . . . . . . . . . 135–195 g/l
Children 2 y–5 y . . .. . . . . . 110–140 g/l
Children 6 y–12 y . . . . . . . .. . . 115–155 g/l
Adult men. . . . . . . . . . . . . . . 130–180 g/l
Adult women . . . . . . . . . . . 120–150 g/l
(Pregnant women) . . . . . . . . . . 110–138 g/l

As stated, Hb measurement along with other parameters can be used to identify different types of anaemia as described here

Hb 12 g/dl Not anaemic
Hb 10–11 g/dl Mild anaemia
Hb 8–9 g/dl Moderate anaemia
Hb 6–7 g/dl Marked anaemia
Hb 4–5 g/dl Severe anaemia
Hb 4 g/dl Critical

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.

MEGALOBLASTIC ANEMIA

Hypersegmented nuclei
Macroovalocytes
Erythroid hyperplasia in bone marrow
Giant metamyelocytes
Hight bilirubin and Lactate dehydrogenase
Presence of Howell jolly bodies
Anisopoikilocytosis
Lack of polychromasia
High MCV
Pancytopenia

Clinical Features

Evidence of ineffective erythropoiesis
Neuropathy
Cognitive impairment
Loss of position
Atrophic glossitis