NEET MDS Lessons
General Pathology
Hyperparathyroidism
Hyperparathyroidism is defined as an elevated secretion of PTH, of which there are three main types:
1. Primary—hypersecretion of PTH by adenoma or hyperplasia of the gland.
2. Secondary—physiological increase in PTH secretions in response to hypocalcaemia of any cause.
3. Tertiary—supervention of an autonomous hypersecreting adenoma in long-standing secondary hyperparathyroidism.
Primary hyperparathyroidism
This is the most common of the parathyroid disorders, with a prevalence of about 1 per 800
It is an important cause of hypercalcaemia.
More than 90% of patients are over 50 years of age and the condition affects females more than males by nearly 3 : 1.
Aetiology
Adenoma 75% -> Orange−brown, well-encapsulated tumour of various size but seldom > 1 cm diameter Tumours are usually solitary, affecting only one of the parathyroids, the others often showing atrophy; they are deep seated and rarely palpable.
Primary hyperplasia 20% -> Diffuse enlargement of all the parathyroid glands
Parathyroid carcinoma 5% -> Usually resembles adenoma but is poorly encapsulated and invasive locally.
Effects of hyperparathyroidism
The clinical effects are the result of hypercalcaemia and bone resorption.
Effects of hypercalcaemia:
- Renal stones due to hypercalcuria.
- Excessive calcification of blood vessels.
- Corneal calcification.
- General muscle weakness and tiredness.
- Exacerbation of hypertension and potential shortening of the QT interval.
- Thirst and polyuria (may be dehydrated due to impaired concentrating ability of kidney).
- Anorexia and constipation
Effects of bone resorption:
- Osteitis fibrosa—increased bone resorption with fibrous replacement in the lacunae.
- ‘Brown tumours’—haemorrhagic and cystic tumour-like areas in the bone, containing large masses of giant osteoclastic cells.
- Osteitis fibrosa cystica (von Recklinghausen disease of bone)—multiple brown tumours combined with osteitis fibrosa.
- Changes may present clinically as bone pain, fracture or deformity.
about 50% of patients with biochemical evidence of primary hyperparathyroidism are asymptomatic.
Investigations are:
- Biochemical—increased PTH and Ca2+ , and decreased PO43- .
- Radiological—90% normal; 10% show evidence of bone resorption, particularly phalangeal erosions.
Management is by rehydration, medical reduction in plasma calcium using bisphosphonates and eventual surgical removal of abnormal parathyroid glands.
Secondary hyperparathyroidism
This is compensatory hyperplasia of the parathyroid glands, occurring in response to diseases of chronic low serum calcium or increased serum phosphate.
Its causes are:
- Chronic renal failure and some renal tubular disorders (most common cause).
- Steatorrhoea and other malabsorption syndromes.
- Osteomalacia and rickets.
- Pregnancy and lactation.
Morphological changes of the parathyroid glands are:
- Hyperplastic enlargement of all parathyroid glands, but to a lesser degree than in primary hyperplasia.
- Increase in ‘water clear’ cells and chief cells of the parathyroid glands, with loss of stromal fat cells.
Clinical manifestations—symptoms of bone resorption are dominant.
Renal osteodystrophy
Skeletal abnormalities, arising as a result of raised PTH secondary to chronic renal disease, are known as renal osteodystrophy.
Pathogenesis
renal Disease + ↓ vit. D activation , ↓ Ca 2+ reabsorption → ↓ serum Ca 2+ → ↑ PTH → ↓ bone absorption
Abnormalities vary widely according to the nature of the renal lesion, its duration and the age of the patient, but include:
- Osteitis fibrosa .
- Rickets or osteomalacia due to reduced activation of vitamin D.
- Osteosclerosis—increased radiodensity of certain bones, particularly the parts of vertebrae adjacent to the intervertebral discs.
The investigations are both biochemical (raised PTH and normal or lowered Ca 2+ ) and radiological (bone changes).
Management is by treatment of the underlying disease and oral calcium supplements to correct hypocalcaemia.
Tertiary hyperparathyroidism
This condition, resulting from chronic overstimulation of the parathyroid glands in renal failure, causes one or more of the glands to become an autonomous hypersecreting adenoma with resultant hypercalcaemia.
Pyelonephritis
- A bacterial infection that affects the renal tubules, interstitium, and renal pelvis.
- One of the most common renal diseases.
- Usually caused by gram-negative, rod-shaped bacteria that are part of the normal flora of the enteric tract. Most commonly caused by Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter.
- The infecting bacteria are usually from the patient’s own enteric flora an example of an endogenous infection.
- Usually associated with a urinary tract infection (acute pyelonephritis) or involved with another precipitating condition, such as obstruction (chronic pyelonephritis).
Hypopituitarism
Hypopituitarism is caused by
1. Loss of the anterior pituitary parenchyma
a. congenital
b. acquired
2. Disorders of the hypothalamus e.g. tumors; these interfere with the delivery of pituitary hormone-releasing factors from the hypothalamus.
Most cases of anterior pituitary hypofunction are caused by the following:
1. Nonfunctioning pituitary adenomas
2. Ischemic necrosis of the anterior pituitary is an important cause of pituitary insufficiency. This requires destruction of 75% of the anterior pituitary.
Causes include
a. Sheehan syndrome, refers to postpartum necrosis of the anterior pituitary, and is the most cause. During pregnancy the anterior pituitary enlarges considerably because of an increase in the size and number of prolactin-secreting cells. However, this physiologic enlargement of the gland is not accompanied by an increase in blood supply. The enlarged gland is therefore vulnerable to ischemic injury, especially in women who develop significant hemorrhage and hypotension during the peripartum period. The posterior pituitary is usually not affected.
b. Disseminated intravascular coagulation
c. Sickle cell anemia
d. Elevated intracranial pressure
e. Traumatic injury
f. Shock states
3. Iatrogenic i.e. surgical removal or radiation-induced destruction
4. Inflammatory lesions such as sarcoidosis or tuberculosis
5. Metastatic neoplasms involving the pituitary.
6. Mutations affecting the pituitary transcription factor Pit-1
Children can develop growth failure (pituitary dwarfism) as a result of growth hormone deficiency.
Gonadotropin or gonadotropin-releasing hormone (GnRH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men. TSH and ACTH deficiencies result in symptoms of hypothyroidism and hypoadrenalism. Prolactin deficiency results in failure of postpartum lactation.
INFLUENZA
An acute viral respiratory infection with influenza, a virus causing fever, coryza, cough, headache, malaise, and inflamed respiratory mucous membranes.
Influenza B viruses typically cause mild respiratory disease
Symptoms and Signs
mild cases:
Chills and fever up to 39 to 39.5° C
Prostration and generalized aches and pains, Headache, photophobia and retrobulbar aching
Respiratory tract symptoms may be mild at first, with scratchy sore throat, substernal burning, nonproductive cough, and sometimes coryza. Later, the lower respiratory illness becomes dominant; cough can be persistent and productive.
severe cases
sputum may be bloody. Skin is warm and flushed. Soft palate, posterior hard palate, tonsillar pillars, and posterior pharyngeal wall may be reddened, but no exudate appears. Eyes water easily, and the conjunctiva may be mildly inflamed
Encephalitis, myocarditis, and myoglobinuria are infrequent complications of influenza and, if present, usually occur during convalescence
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.
Nephritic syndrome
Characterized by inflammatory rupture of the glomerular capillaries, leaking blood into the urinary space.
Classic presentation: poststreptococcal glomerulonephritis. It occurs after a group A, β–hemolytic Streptococcus infection (e.g., strep throat.)
Caused by autoantibodies forming immune complexes in the glomerulus.
Clinical manifestations:
oliguria, hematuria, hypertension, edema, and azotemia (increased concentrations of serum urea nitrogen
and creatine).
Chemical Mediators In Inflammation
Can be classified as :
A. Neurogenic
Also called the Triple Response of Lewis. It involves neurogenic vasodilatation of arterioles due to antidromic axon reflex arc. The constituents of the response are:
1. arteriolar vasoconstriction followed by
2. arteriolar vasodilatation
3. swelling
B. Chemical
1. Amines: Histamine and 5 hydroxytryptamine. Released from platelets and mast cells.
Actions: Immediate and short lived.
Dilatation of arterioles.
Increased capillary premeability.
Kinins: Bradykinin and kallidin These are present in inactive from and are activated by kinin forming proteases
Actions:
Arteriolar dilatation.
Increased vascular permeability
Pain
Kinin forming proteases Plasmin and Kallikrein. Present as inactive precursors.
Cleavage products of complement C3a und C5a are called anaphylatoxins
Actions:
Histamine release from mast cells
Chemotaxis (also C567 )
Enhance phagocytosis.
Polymorph components
Cationic: proteins which cause
Increased permeability
Histamine release.
Chemotaxis of monocytes
Neutral proteases which:
Cleave C3 and C5 to active form
Convert Kininogen to Kinin
Increase permeability.
Acid proteases which liberate leucokinins
Slow reacting. substance of anaphylaxis: (SRS-A) is a lipid released from mast cell.
Action --Increases vascular permeability
Prostaglandins: E1 + E2 .
Platelets are rich source
Action:
Platelets are a rich source.
Vasodilatation.
Increased permeability.
Pain.
VIII. Miscellaneous: like
Tissue lactic acid.
Bacterial toxins.