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.
The Specific Immune Response
Definition
The immune response comprises all the phenomenon resulting from specific interaction of cells of the immune-system with antigen. As a consequence of this interaction cells appear that mediate cellular immune response as well cells that synthesis and secrete immunoglobulins
Hence the immune response has 2 components.
1. Cell mediated immunity (CMI).
2:. Humoral immunity (antibodies)
(I) Macrophages. Constituent of the M. P. S. These engulf the antigenic material.
(i) Most of the engulfed antigen is destroyed to' prevent a high dose paralysis of the Immune competent cells.
(ii) Some of it persists in the macrophage, retaining immunogenecity for continued stimulus to the immune system.
(iii)The antigenic information is passed on to effectors cells. There are two proposed mechanisms for this:
(a) As messenger RNA with code for the specific antibody.
(b) As antigen-RNA complexes.
(2) Lymphocytes. There are 2 main classes recognized by surface characteristics.
(A) T-Lymyhocytes (thymus dependant) :- These are responsible for cellular immunity . On exposure to antigen
- They transform to immunoblasts which divide to form the effectors cells.
- They secrete lymphokines These are
- Monocyte migration inhibition factor
- Macrophage activation factor
- Chemotactic factor
- Mitogenic factor
- Transfer factor
- Lymphotoxin which kills target cell
- Interferon.
- Inflammatory factor which increases permeability. .
- Some remain as 1onglived memory cell for a quicker recognition on re-exposure
- They also modify immune response by other lymphocytes in the form of “T – helper cells “ and “T-suppressor” cells
- They are responsible for graft rejection
(B) B-Lymphocytes (Bursa dependent). In birds the Bursa of Fabricious controls
these cells. In man, its role is taken up by," gut associated lymphoid tissue)
(i) They are responsible for antibody synthesis. On stimulation they undergo blastic transformation and then differentiation to plasma cells, the site of immunoglobulin synthesis.
(ii) They also form memory cells. But these are probably short lived.
(C) In addition to T & B lymphocytes, there are some lymphocytes without the surface markers of either of them. These are 'null' cells-the-natural Killer (N,K.) cells and cells responsible for antibody dependent cellular-cytotoxicity.
(3) Plasma cells. These are the effectors cells of humoral immunity. They produce the immunoglobins, which are the effector molecules.
Pulmonary edema
Pulmonary edema is swelling and/or fluid accumulation in the lungs. It leads to impaired gas exchange and may cause respiratory failure.
Signs and symptoms
Symptoms of pulmonary edema include difficulty breathing, coughing up blood, excessive sweating, anxiety and pale skin. If left untreated, it can lead to death, generally due to its main complication of acute respiratory distress syndrome.
Diagnosis
physical examination: end-inspiratory crackles during auscultation (listening to the breathing through a stethoscope) can be due to pulmonary edema. The diagnosis is confirmed on X-ray of the lungs, which shows increased vascular filling and fluid in the alveolar walls.
Low oxygen saturation and disturbed arterial blood gas readings may strengthen the diagnosis
Causes
Cardiogenic causes:
- Heart failure
- Tachy- or bradyarrhythmias
- Severe heart attack
- Hypertensive crisis
- Excess body fluids, e.g. from kidney failure
- Pericardial effusion with tamponade
Non-cardiogenic causes, or ARDS (acute respiratory distress syndrome):
- Inhalation of toxic gases
- Multiple blood transfusions
- Severe infection
- Pulmonary contusion, i.e. high-energy trauma
- Multitrauma, i.e. severe car accident
- Neurogenic, i.e. cerebrovascular accident (CVA)
- Aspiration, i.e. gastric fluid or in case of drowning
- Certain types of medication
- Upper airway obstruction
- Reexpansion, i.e. postpneumonectomy or large volume thoracentesis
- Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation
- Lack of proper altitude acclimatization.
Treatment
When circulatory causes have led to pulmonary edema, treatment with loop diuretics, such as furosemide or bumetanide, is the mainstay of therapy. Secondly, one can start with noninvasive ventilation. Other useful treatments include glyceryl trinitrate, CPAP and oxygen.
Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.
2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.
Osteonecrosis (Avascular Necrosis)
Ischemic necrosis with resultant bone infarction occurs mostly due to fracture or after corticosteroid use. Microscopically, dead bon trabevulae (characterized by empty lacunae) are interspersed with areas of fat necrosis.
The cortex is usually not affected because of collateral blood supply; in subchondral infarcts, the overlying articular cartilage also remains viable because the synovial fluid can provide nutritional support. With time, osteoclasts can resorb many of the necrotic bony trabeculae; any dead bone fragments that remain act as scaffolds for new bone formation, a process called creeping substitution.
Symptoms depend on the size and location of injury. Subchondral infarcts often collapse and can lead to severe osteoarthritis.
Strep viridans
Mixed species, all causing α-hemolysis. All are protective normal flora which block adherence of other pathogens. Low virulence, but can cause some diseases:
Sub-acute endocarditis can damage heart valves.
Abscesses can form which are necrotizing. This is the primary cause of liver abscesses.
Dental caries are caused by Str. mutans. High virulence due to lactic acid production from glucose fermentation. This is why eating sugar rots teeth. Also have surface enzymes which deposit plaque.
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).