NEET MDS Lessons
General Pathology
Adrenocortical Hyperfunction (Hyperadrenalism)
Hypercortisolism (Cushing Syndrome) is caused by any condition that produces an elevation in glucocorticoid levels. The causes of this syndrome are
A. Exogenous through administration of exogenous glucocorticoids; the most common causeB. Endogenous
1. Hypothalamic-pituitary diseases causing hypersecretion of ACTH (Cushing disease)
2. Adrenocortical hyperplasia or neoplasia
3. Ectopic ACTH secretion by nonendocrine neoplasms (paraneoplastic)
Pathological features
- The main lesions of Cushing syndrome are found in the pituitary and adrenal glands.
- The most common change in the pituitary, results from high levels of endogenous or exogenous glucocorticoids, is termed Crooke hyaline change. In this condition, the normal granular, basophilic cytoplasm of the ACTH-producing cells in the anterior pituitary is replaced by homogeneous, lightly basophilic material. This is due to accumulation of intermediate keratin filaments in the cytoplasm.
- There is one of four changes in the adrenal glands, which depends on the cause.
1. Cortical atrophy
2. Diffuse hyperplasia
3. Nodular hyperplasia
4. Adenoma, rarely a carcinoma
1. In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in bilateral cortical atrophy, due to a lack of stimulation of the cortex by ACTH. In cases of endogenous hypercortisolism, in contrast, the adrenals either are hyperplastic or contain a cortical neoplasm.
2. In Diffuse hyperplasia the adrenal cortex is diffusely thickened and yellow, as a result of an increase in the size and number of lipid-rich cells in the zonae fasciculata and reticularis.
3. Nodular hyperplasia, which takes the form of bilateral, up to 2.0-cm, yellow nodules scattered throughout the cortex.
4. Primary adrenocortical neoplasms causing Cushing syndrome may be benign or malignant. The adrenocortical adenomas are yellow tumors surrounded by capsules, and most weigh < 30 gm .
Cryptococcosis
An infection acquired by inhalation of soil contaminated with the encapsulated yeast Cryptococcus neoformans, which may cause a self-limited pulmonary infection or disseminate, especially to the meninges, but sometimes to the skin, bones, viscera, or other sites.
Cryptococcosis is a defining opportunistic infection for AIDS, although patients with Hodgkin's or other lymphomas or sarcoidosis or those receiving long-term corticosteroid therapy are also at increased risk.
AIDS-associated cryptococcal infection may present with severe, progressive pneumonia with acute dyspnea and an x-ray pattern suggestive of Pneumocystis infection.
Primary lesions in the lungs are usually asymptomatic and self-limited
Pneumonia usually causes cough and other nonspecific respiratory symptoms. Rarely, pyelonephritis occurs with renal papillary necrosis development.
Most symptoms of cryptococcal meningitis are attributable to brain swelling and are usually nonspecific, including headache, blurred vision, confusion, depression, agitation, or other behavioral changes. Except for ocular or facial palsies, focal signs are rare until relatively late in the course of infections. Blindness may develop due to brain swelling or direct involvement of the optic tracts. Fever is usually low-grade and frequently absent.
Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus
- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.
N. meningiditis
Major cause of fulminant bacteremia and meningitis. Has a unique polysaccharide capsule. It is spread person to person by the respiratory route. Frequently carried in nasopharynx, and carriage rates increased by close quarters. Special risk in closed populations (college dorms) and in people lacking complement. Sub-saharan Africa has a “meningitis belt.”
Pathogenesis is caused by adherence factors that attach to non-ciliated nasopharyngeal epithelium. These factors include pili which promote the intial epithelial (and erythrocyte) attachment, and Opa/Opc surface binding proteins.
Adherence stimulates engulfment of bacteria by epithelial cells. Transported to basolateral surface.
The polysaccharide capsule is a major virulence factor that prevents phagocytosis and lysis.
A lipo-oligosaccharide endotoxin also contributes to sepsis.
Posterior Pituitary Syndromes
The posterior pituitary, or neurohypophysis, is composed of modified glial cells (termed pituicytes) and axonal processes extending from nerve cell bodies in the hypothalamus. The hypothalamic neurons produce two peptides: antidiuretic hormone (ADH) and oxytocin that are stored in axon terminals in the neurohypophysis.
The clinically important posterior pituitary syndromes involve ADH production and include
1. Diabetes insipidus and
2. Inappropriate secretion of high levels of ADH.
- ADH is released into the general circulation in response to increased plasma oncotic pressure & left atrial distention.
- It acts on the renal collecting tubules to increase the resorption of free water.
- ADH deficiency causes diabetes insipidus, a condition characterized by polyuria. If the cause is related to ADH Diabetes insipidus from - - ADH deficiency is designated as central, to differentiate it from nephrogenic diabetes insipidus due to renal tubular unresponsiveness to circulating ADH.
- The clinical manifestations of both diseases are similar and include the excretion of large volumes of dilute urine with low specific gravity. Serum sodium and osmolality are increased as a result of excessive renal loss of free water, resulting in thirst and polydipsia.
- ADH excess causes resorption of excessive amounts of free water, with resultant hyponatremia.
- The most common causes of the syndrome include the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinomas of the lung), and local injury to the hypothalamus and/or neurohypophysis.
- The clinical manifestations are dominated by hyponatremia, cerebral edema, and resultant neurologic dysfunction.
Varicose Veins
- are abnormally dilated, tortuous veins produced by prolonged increase in intraluminal pressure and loss of vessel wall support.
- The superficial veins of the leg are typically involved
-venous pressures in these sites can be markedly elevated -> venous stasis and pedal edema (simple orthostatic edema)
-Some 10% to 20% of adult males and 25% to 33% of adult females develop lower extremity varicose veins
RISK FACTORS
-> obesity
-> Female gender
-> pregnancy.
-> familial tendency (premature varicosities results from imperfect venous wall development)
Morphology
- wall thinning
- intimal fibrosis in adjacent segments
- spotty medial calcifications (phlebosclerosis)
- Focal intraluminal thrombosis
- venous valve deformities (rolling and shortening)
COMPLICATIONS
- stasis, congestion, edema, pain, and thrombosis
- chronic varicose ulcers
- embolism is very rare.
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).