ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

PRIMARY LYMPHEDEMA  
can occur as:
1- A congenital defect, resulting from lymphatic agenesis or hypoplasia.  

2- Secondary or obstructive lymphedema  
- blockage of a previously normal lymphatic; e.g. Malignant tumors 
- Surgical procedures that remove lymph nodes 
- Postirradiation  
- Fibrosis 
- Filariasis 
- Postinflammatory thrombosis and scarring 

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. 

Adrenocortical Hyperfunction (Hyperadrenalism)

Hypercortisolism (Cushing Syndrome) is caused by any condition that produces an elevation in glucocorticoid levels. The causes of this syndrome are 
A. Exogenous through administration of exogenous glucocorticoids; the most common causeB. Endogenous 
1. Hypothalamic-pituitary diseases causing hypersecretion of ACTH (Cushing disease)
2. Adrenocortical hyperplasia or neoplasia 
3. Ectopic ACTH secretion by nonendocrine neoplasms (paraneoplastic)

Pathological features 

- The main lesions of Cushing syndrome are found in the pituitary and adrenal glands. 
- The most common change in the pituitary, results from high levels of endogenous or exogenous  glucocorticoids, is termed Crooke hyaline change. In this condition, the normal granular, basophilic cytoplasm of the ACTH-producing cells in the anterior pituitary is replaced by homogeneous, lightly basophilic material. This is due to accumulation of intermediate keratin filaments in the cytoplasm. 
- There is one of four changes in the adrenal glands, which depends on the cause.
1. Cortical atrophy 
2. Diffuse hyperplasia
3. Nodular hyperplasia 
4. Adenoma, rarely a carcinoma 

1. In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in bilateral cortical atrophy, due to a lack of stimulation of the cortex by ACTH. In cases of endogenous hypercortisolism, in contrast, the adrenals either are hyperplastic or contain a cortical neoplasm. 
2. In Diffuse hyperplasia the adrenal cortex is diffusely thickened and yellow, as a result of an increase in the size and number of lipid-rich cells in the zonae fasciculata and reticularis. 
3. Nodular hyperplasia, which takes the form of bilateral, up to 2.0-cm, yellow nodules scattered throughout the cortex. 

4. Primary adrenocortical neoplasms causing Cushing syndrome may be benign or malignant. The  adrenocortical adenomas are yellow tumors surrounded by capsules, and most weigh < 30 gm .

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:

1. Heart failure
2. Tachy- or bradyarrhythmias
3. Severe heart attack
4. Hypertensive crisis
5. Excess body fluids, e.g. from kidney failure
6. Pericardial effusion with tamponade

Non-cardiogenic causes, or ARDS (acute respiratory distress syndrome):

1. Inhalation of toxic gases
2. Multiple blood transfusions
3. Severe infection
4. Pulmonary contusion, i.e. high-energy trauma
5. Multitrauma, i.e. severe car accident
6. Neurogenic, i.e. cerebrovascular accident (CVA)
7. Aspiration, i.e. gastric fluid or in case of drowning
8. Certain types of medication
9. Upper airway obstruction
10. Reexpansion, i.e. postpneumonectomy or large volume thoracentesis
11. Reperfusion injury, i.e. postpulmonary thromboendartectomy or lung transplantation
12. 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.

Enterococci

Most common are E. fecalis and E. fecium.  Cause inflammation at site of colonization.

Serious resistance to antibiotics.  E. fecium is now a vancomycin resistant enterococcus (VRE)