NEET MDS Lessons
General Pathology
Mycobacterium leprae
- tuberculoid type has intact cellular immunity
- forms granulomas and kill the organisms (very few present).
- evokes a positive lepromin skin test
- localized skin lesions that lack symmetry
- nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
- lepromatous leprosy patients lack cellular immunity
- no granulomas
- organisms readily identified
- negative lepromin skin test
- Bacteremia disseminates to cooler areas like the digits.
- symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
- neural involvement is a late feature of the disease.
- lepromin skin test is to determine host immunity; not a diagnostic test.
- treatment: dapsone + rifampin
Pleural effusion is a medical condition where fluid accumulates in the pleural cavity which surrounds the lungs, making it hard to breathe.
Four main types of fluids can accumulate in the pleural space:
Serous fluid (hydrothorax)
Blood (hemothorax)
Lipid (chylothorax)
Pus (pyothorax or empyema)
Causes:
Pleural effusion can result from reasons such as:
- Cancer, including lung cancer or breast cancer
- Infection such as pneumonia or tuberculosis
- Autoimmune disease such as lupus erythematosus
- Heart failure
- Bleeding, often due to chest trauma (hemothorax)
- Low oncotic pressure of the blood plasma
- lymphatic obstruction
- Accidental infusion of fluids
Congestive heart failure, bacterial pneumonia and lung cancer constitute the vast majority of causes in the developed countries, although tuberculosis is a common cause in the developing world.
Diagnosis:
- Gram stain and culture - identifies bacterial infections
- Cell count and differential - differentiates exudative from transudative effusions
- Cytology - identifies cancer cells, may also identify some infective organisms
- Chemical composition including protein, lactate dehydrogenase, amylase, pH and glucose - differentiates exudative from transudative effusions
- Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins
Cushing’s syndrome
The symptoms and signs of Cushing’s syndrome are associated with prolonged inappropriate elevation of free corticosteroid levels.
Clinical features
- Central obesity and moon face.
- Plethora and acne.
- Menstrual irregularity.
- Hirsutism and hair thinning.
- Hypertension.
- Diabetes.
- Osteoporosis—may cause collapse of vertebrae, rib fractures.
- Muscle wasting and weakness.
- Atrophy of skin and dermis—paper thin skin with bruising tendency, purple striae.
Aetiopathogenesis — patients with Cushing’s syndrome can be classified into two groups on the basis of whether the aetiology of the condition is ACTH dependent or independent.
Classification of Cushing's syndrome
ACTH dependent- Iatrogenic (ACTH therapy) Pituitary hypersecretion of ACTH Ectopic ACTH syndrome (benign or malignant non-endocrine tumour)
Non-ACTH dependent - Iatrogenic, e.g. prednisolone Adrenal cortical adenoma , Adrenal cortical carcinoma
ACTH-dependent aetiology:
- Pituitary hypersecretion of ACTH (Cushing’s disease)—bilateral adrenal hyperplasia secondary to excessive secretion of ACTH by a corticotroph adenoma of the pituitary gland.
- Production of ectopic ACTH or corticotrophin- releasing hormone (CRH) by non-endocrine neoplasm, e.g. small cell lung cancer and some carcinoid tumours. In cases of malignant bronchial tumour, the patient rarely survives long enough to develop any physical features of Cushing’s syndrome.
Non-ACTH-dependent aetiology
Iatrogenic steroid therapy—most common cause of Cushing’s syndrome.
Adrenal cortical adenoma—well-circumscribed yellow tumour usually 2–5 cm in diameter.
Extremely common as an incidental finding in up to 30% of all post-mortem examinations. The yellow colour is due to stored lipid (mainly cholesterol) from which the hormones are synthesised. The vast majority have no clinical effects (i.e. they are non-functioning adenomas), with only a small percentage producing Cushing’s syndrome.
Adrenal cortical carcinoma—rare and almost always associated with the overproduction of hormones, usually glucocorticoids and sex steroids.
Cushing’s syndrome mixed with androgenic effects which are particularly noticeable in women. Tumours are usually large and yellowish white in colour. Local invasion and metastatic spread are common.
Irrespective of the aetiology, the diagnosis is based on clinical features and the demonstration of a raised plasma cortisol level.
The aetiology of the disorder is elucidated through:
- Raised urinary cortisol in the first instance, but further testing is required.
- Low-dose dexamethasone suppression test (suppression of cortisol levels in Cushing’s disease due to suppression of pituitary ACTH secretion, but a lack of suppression suggests ACTH-independent Cushing’s syndrome).
- MRI and CT scan visualisation of pituitary and adrenal glands.
- Analysis of blood ACTH (high = pituitary adenoma or ectopic ACTH source; low = primary adrenal tumour due to feedback suppression).
- Treatment of the underlying cause is essential as untreated Cushing’s syndrome has a 50% 5-year mortality rate.
The therapeutic administration of glucocorticosteroids (e.g. prednisolone) is a common cause of the features of Cushing’s syndrome.
Thalassaemia. Genetic based defect in synthesis of one of the normal chains.
Beta thalassaemia ---> reduced Hb A and increased HbF (α2, Y2) HBA2(α2)
Alpha thalassaemia ---> reduced Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.
Features:
• Microcytic hypochromic RBC is in iron deficjency.
• Marked anisopoikilocytsis with prominent target cells.
• Reticulocytosis and nucleated RBC seen.
• Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
• Decreased osmotic. fragility.
• Increased marrow iron (important difference from iron deficiency anaemia).
• Haemosiderosis, especially with repeated transfusions.
Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).
Neutropenia: Neutropenia is an abnormally low number of neutrophils
Causes
-Typhoid, paratyphoid. .
-Viral and ricketseal infections.
-Malaria, Kala azar.
-Hypersplenism.
-Aplastic and megaloblastic anaemia.
-Marrow infiltration by malignancies, lymphomas etc.
-SLE.
Immunodeficiency
This may be :-
- Congenital (Primary)
- Acquired (Secondary)
Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.
B. T Cell Defects :
- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome
These lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.
C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.
Acquired deficiency
A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.
B. Neaplasia of lymphoid system :
- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).
c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.
CHRONIC INFLAMMATlON
When the inflammatory reaction instead of subsiding after the acute phase (or without entering an acute phase), persists as a smouldering lesion, it is called chronic inflammation. .
Characteristics
- Predominantly mononuclear response.
- Inflamation.and..repair going on simultaneously.
- Usually results in more prominent-scarring.
Causes:
Chronicity may be due to :
- Defective defence mechanisms.
- Persistence of injurious agent.
(a) Certain organisms resist phagocytosis and destruction e.g tubercle bacillus, fungi
(b) insoluble particulate matter e.g., crystals. fibres suture materials.
(c) Constants supply of causative agent as in autoimmune disease where body reacts against its own tissues.
- Defective healing.
Granulomatous inflammation
It is a type of chronic inflammation characterised by localised collections of histiocytes.
These cells are usually accompanied by lymphocytes, fibroblasts and giant cells also.
Granulomas are characteristically seen in diseases like tuberculosis. syphilis, leprosy, sarcoidosis, fungal infections etc. In some of these, the lesion is morphologically distinct enough to point to the type of underlying disease. These are sometimes called' specific' granulomas. Granulomas can also be elicited by particulate, insoluble foreign material e.g. granuloma, suture granuloma, cholesterol granuloma (organising haemorrhages).