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.
Myocardial infarction (MI)—heart attack
A. Ischemia versus MI: Ischemia is a reversible mismatch between the supply and demand of oxygen. Infarction
is an irreversible mismatch that results in cell death caused by the lack of blood flow (oxygenation). For instance, chest pain caused by ischemia can be relieved by administering nitroglycerin (a vasodilator) to the patient. If the patient has an MI, the pain will not be relieved with nitroglycerin.
1. MIs most commonly occur when a coronary artery is occluded by a thrombus generated in an atherosclerotic artery.
2. Symptoms include:
a. Chest pain, shortness of breath.
b. Diaphoresis (sweating), clammy hands.
c. Nausea, vomiting.
3. Consequences:
a. Death (one third of patients).
b. Arrhythmias (most common immediate cause of death).
c. Congestive heart failure.
d. Myocardial rupture, which may result in death from cardiac tamponade.
e. Thrombus formation on infarcted tissue; may result in systemic embolism.
Keloids
1. Characterized by a progressively enlarging scar.
2. Caused by an abnormal accumulation of collagen at the site of injury.
3. More common in African-Americans.
Blastomycosis (North American Blastomycosis; Gilchrist's Disease)
A disease caused by inhalation of mold conidia (spores) of Blastomyces dermatitidis, which convert to yeasts and invade the lungs, occasionally spreading hematogenously to the skin or focal sites in other tissues.
Pulmonary blastomycosis tends to occur as individual cases of progressive infection
Symptoms are nonspecific and may include a productive or dry hacking cough, chest pain, dyspnea, fever, chills, and drenching sweats. Pleural effusion occurs occasionally. Some patients have rapidly progressive infections, and adult respiratory distress syndrome may develop.
Lymphocytosis:
Causes
-Infections in children and the neutropenic infections in adults.
-Lymphocytic leukaemia.
-Infectious mononucleosis.
-Toxdplasmosis.
-Myast'henia gravis.
INFARCTION
Definition : a localized area of ischaemic necrosis in an organ infarcts may be:
Pale :as in
→ Arterial obstruction.
→ solid organs.
Red as in
→ Venous occlusion
→ Loose tissue.
Morphology
Gross: infarcts are usually wedge shaped the apex towards the occluded vessel They are
separated from the surrounding tissue by an hyperemic inflammatory zone
Microscopic:
- An area of coagulative necrosis with a rim of congested vessels and acute inflammatory infiltration of the tissue .
- The polymorphs ale later replaced by mononuclear cells and granulation tissue.
- With time, scar tissue replaces necrosed tissue.
Autopsy
Autopsy is examination of the dead body to identify the cause of death. This can be for forensic or clinical purposes.