NEET MDS Lessons
General Pathology
ADRENOCORTICAL TUMORS
Functional adenomas are commonly associated with hyperaldosteronism and with Cushing syndrome, whereas a virilizing neoplasm is more likely to be a carcinoma. Determination of of the functional status of a tumor is based on clinical evaluation and measurement of the hormone or its metabolites. In other words, functional and nonfunctional adrenocortical neoplasms cannot be distinguished on the basis of morphologic features.
Patholgical features
Adrenocortical adenomas
- They are generally small, 1 to 2 cm in diameter.
- On cut surface, adenomas are usually yellow to yellow-brown due to presence of lipid within the neoplastic cells
- Microscopically, adenomas are composed of cells similar to those populating the normal adrenal cortex. The nuclei tend to be small, although some degree of pleomorphism may be encountered even in benign lesions ("endocrine atypia"). The cytoplasm ranges from eosinophilic to vacuolated, depending on their lipid content.
Adrenocortical carcinomas
These are rare and may occur at any age, including in childhood.
- Carcinomas are generally large, invasive lesions.
- The cut surface is typically variegated and poorly demarcated with areas of necrosis, hemorrhage, and cystic change.
- Microscopically, they are composed of well-differentiated cells resembling those of cortical adenomas or bizarre, pleomorphic cells, which may be difficult to distinguish from those of an undifferentiated carcinoma metastatic to the adrenal.
Parathyroid hormone
Parathyroid hormone (PTH) is a polypeptide (84 amino acid residues) secreted by the chief cells of the parathyroid glands (four glands: two in each of the superior and inferior lobes of the thyroid; total weight 120 mg).
The main action of PTH is to increase serum calcium and decrease serum phosphate.
Its actions are mediated by the bones and kidneys -
In bone, PTH stimulates osteoclastic bone resorption and inhibits osteoblastic bone deposition. The net effect is the release of calcium from bone.
In the kidney, PTH has the following effects:
- Increases calcium reabsorption.
- Decreases phosphate reabsorption.
- Increases 1-hydroxylation of 25-hydroxyvitamin D (i.e. activates vitamin D).
PTH also increases gastrointestinal calcium absorption.
Hypoparathyroidism
Hypoparathyroidism is a condition of reduced or absent PTH secretion, resulting in hypocalcaemia and hyperphosphataemia. It is far less common than hyperparathyroidism.
The causes of hypoparathyroidism are:
- Removal or damage of the parathyroid glands during thyroidectomy—most common cause of hypoparathyroidism resulting from inadvertent damage or removal.
- Autoimmune parathyroid disease—usually occurs in patients who have another autoimmune endocrine disease, e.g. Addison’s disease (autoimmune endocrine syndrome type 1).
- Congenital deficiency (DiGeorge syndrome)— rare, congenital disorder caused by arrested development of the third and fourth branchial arches, resulting in an almost complete absence of the thymus and parathyroid gland.
The effects of hypoparathyroidism are:
- ↓ release of Ca2+ from bones.
- ↓ Ca2+ reabsorption but ↑ PO 43− re absorption by the kidneys
- ↓ 1-hydroxylation of 25-hydroxyvitamin D by kidney.
Most symptoms of hypoparathyroidism are those of hypocalcaemia:
- Tetany—muscular spasm provoked by lowered plasma Ca 2+
- Convulsions.
- Paraesthesiae.
- Psychiatric disturbances, e.g. depression, confusional state and even psychosis.
- Rarely—cataracts, parkinsonian-like movement disorders, alopecia, brittle nails.
Management is by treatment with large doses of oral vitamin D; the acute phase requires intravenous calcium and calcitriol (1,25-dihydroxycholecalciferol, i.e. activated vitamin D).
Leukaemias
Uncontrolled proliferation of leukocyte precursors (may be with associated red cell and platelet series proliferation).
Factors which may playa causal role are.
- Viral
- Radiation.
- Genetic.
Classification
1. Acule leukaemia:
a. Lymphocytic (lymphoblastic).
b. Myelocytic and promyelocytic (myeloblastic).
c. Monocytic.
d. Myelomonocytic.
e. Undifferentiated (Stem cell).
2. Chronic leukaemia:
a. Lymphocytic
b. Myelocytic
3. Miscellaneous:
a. Erythroleukaemia (De Guglielmo's disease).
b. Eosinophilic leukaemia.
c. Megakaryocytic leukaemia.
Bullous and Vesicular Disease
1. There are many diseases characterized by the presence of vesicles and bullae filled fluid.
2. In pemphigus vulgaris, large, flaccid bullae filled with fluid occur on the skin and within the oral mucosa.
- immunologic disease with IgG antibodies against the intercellular attachment sites between keratinocytes (type II hypersensitivity).
- the vesicle in pemphigus vulgaris has a suprabasal location (just above the basal cell layer and resembling "tombstones")
- scattered keratinocytes in the fluid as a result of acantholysis.
- Nikolsky's sign is where the epidermis slips when touched with the finger.
- fatal disease if left untreated (systemic corticosteroids)
3. Bullous pemphigoid is an immunologic vesicular disease whose vesicle are in a subepidermal location.
- circulating IgG antibody against antigens in the basement membrane (type II hypersensitivity).
4. Dermatitis herpetiformis is an immunologic vesicular lesion characterized by the presence of IgA immune complexes (type III hypersensitivity) at the tips of the dermal papilla at the dermal/epidermal junction producing a subepidermal vesicle filled with neutrophils.
- strong association with gluten-sensitive enteropathy, or celiac disease.