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 PO₄^3- .
- 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. 

Hyperthyroidism 

Hyperthyroidism (Thyrotoxicosis) is a hypermetabolic state caused by elevated circulating levels of free T3 and T4 . This may primary (Graves disease) or rarely, secondary (due to pituitary or hypothalamic diseases).

- The diagnosis is based on clinical features and laboratory data. 

Lab Test

- The measurement of serum TSH concentration provides the most useful single screening test for hyperthyroidism, because TSH levels are decreased in primary cases, even when the disease is still be subclinical. 
- In secondary cases TSH levels are either normal or raised. 
- A low TSH value is usually associated with increased levels of free T4 . 
- Occasionally, hyperthyroidism results from increased levels of T3 .

FUNGAL INFECTION

Aspergillosis

Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.

Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.

Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.

Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.

 Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache

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.

IMMUNITY AND RESISTANCE TO INFECTION

Body's resistance to infection depends upon:

I. Defence mechanisms at surfaces and portals of entry.

II. Nonspecific or innate immunity

Ill. Specific immune response.

INFARCTION

 An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue 

 Nearly 99% of all infarcts result from thrombotic or embolic events 
 
other mechanisms include: local vasospasm, expansion of an atheroma, extrinsic compression of a vessel (e.g., by tumor); vessel twisting (e.g., in testicular torsion or bowel volvulus; and traumatic vessel rupture

MORPHOLOGY OF INFARCTS 

 infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or aseptic 

 All infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base 
 
 The margins of both types of infarcts tend to become better defined with time 
 
 The dominant histological characteristic of infarction is ischemic coagulative necrosis 
 
 most infarcts are ultimately replaced by scar. The brain is an exception, it results in liquefactive necrosis 
 
 RED INFARCTS:
occur in 
(1) venous occlusions (such as in ovarian torsion) 
(2) loose tissues (like lung) that allow blood to collect in the infarcted zone 
(3) tissues with dual circulations (lung and small intestine) 
(4) previously congested tissues because of sluggish venous outflow 
(5) when flow is re-established to a site of previous arterial occlusion and necrosis 

WHITE INFARCTS 

occur with: 
1) arterial occlusions 
2) solid organs (such as heart, spleen, and kidney).

Septic infarctions - occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. - the infarct is converted into an abscess, with a correspondingly greater inflammatory response

FACTORS THAT INFLUENCE DEVELOPMENT OF AN INFARCT
- nature of the vascular supply 
- rate of development of the occlusion (collateral circulation ) 
- vulnerability to hypoxia - Neurons undergo irreversible damage 
- 3 to 4 minutes of ischemia. - Myocardial cells die after only 20 to 30 minutes of ischemia 
- the oxygen content of blood