NEET MDS Lessons
General Pathology
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.
Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
- due to Pitysporium species
- can be seen in AIDS as an opportunistic infection
Growth and spread of tumours
Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.
Modes of spread of malignant tumours
- local, invasion. This is a feature of all malignant tumors and takes place along tissue spaces and facial planes
o Lymphatic spread. Most often seen in carcinomas. This can be in the form of
o Lymphatic permeation: Where the cells extend along the lymphatics as a solid core
o Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode
-Vascular spread : This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.
Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.
Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.
-Body cavities and natural passages
o Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.
Autoimmune(acquired) Haemolytic anaemia
Auto antibodies are usually Ig g type (may be Ig M or Ig A). They may or may not bind complement and may be active in warm or cold temperature They may be complete (agggIutinating) or incomplete. Haemolysis s may be intravascular due to destruction of the antibody coated cells by RE system.
Causes:
a. Idiopathic
b. Secondary to
o Drugs - Methyldopa, Mefanamic acid
o Disease like
-> Infections especially viral.
-> Autoimmune disease especially SLE.
-> Lymphomas and chronic lymphatic leukaemia.
-> Tumours.
Diagnosis : is based on
• Evidences of haemolytic anaemia.
• Demonstration of antibodies
- On red cell surface by direct Coomb’s test
- In serum by indirect Coomb’s test.
Liver cirrhosis
It is a chronic, progressive diffuse process characterized by
a. Hepatocellular necrosis
b. Replacement by fibrosis and inflammation
c. Hyperplasia of surviving liver cells forming regenerating nodules
d. Vascular derangement.
All these changes lead to loss of the normal liver architecture.
Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight.
Consistency- Firm.
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment).
Morphologically According to the size of these nodules, cirrhosis can be classified
Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
Mixed cirrhosis is the end stage of all types of cirrhosis
Microscopic picture
1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids. Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated
2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular b -perisinusoidal c -pericellular and d -in relation to portal tracts.
- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.
-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates
3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.
4- Inflammatory cells:- Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules
Etiological classification of cirrhosis
Congenital Occurs at childhood
- congenital syphilis
Hereditary diseases:-
a. Primary idiopathic haemochromatosis b. Thalassemia c. Wilson’s disease d.α 1-antitrypsin deficien e. glycogen storage disease
Acquired
-Cryptogenic (10-50%).
-Alcoholic (30-70%)
-Post viral (15-20%)
- Biliary cirrhosis (16%) primary or secondary.
Acne vulgaris is a chronic inflammatory disorder usually present in the late teenage years characterized by comedones, papules, nodules, and cysts.
- subdivided into obstructive type with closed comedones (whiteheads) and open comedones (blackheads) and the inflammatory type consisting of papules, pustules, nodules, cysts and scars.
- pathogenesis of inflammatory acne relates to blockage of the hair follicle with keratin and sebaceous secretions, which are acted upon by Propionibacterium acnes (anaerobe) that causes the release of irritating fatty acids resulting in an inflammatory response.
- pathogenesis of the obstructive type (comedones) is related to plugging of the outlet of a hair follicle by keratin debris.
- chocolate, shellfish, nuts iodized salt do not aggravate acne.
- obstructive type is best treated with benzoyl peroxide and triretnoin (vitamin A acid)
- treatment of inflammatory type is the above plus antibiotics (topical and/or systemic; erythromycin, tetracycline, clindamycin).