Hyperparathyroidism 

Abnormally high levels of parathyroid hormone (PTH) cause hypercalcemia. This can result from either primary or secondary causes. Primary hyperparathyroidism is caused usually by a parathyroid adenoma, which is associated with autonomous PTH secretion. Secondary  hyperparathyroidism, on the other hand, can occur in the setting of chronic renal failure. In either situation, the presence of excessive amounts of this hormone leads to significant skeletal changes related to a persistently exuberant osteoclast activity that is associated with increased bone resorption and calcium mobilization. The entire skeleton is affected. PTH is directly responsible for the bone changes seen in primary hyperparathyroidism, but in secondary hyperparathyroidism additional influences also contribute. In chronic renal failure there is inadequate 1,25- (OH)2-D synthesis that ultimately affects gastrointestinal calcium absorption. The hyperphosphatemia of renal
failure also suppresses renal α1-hydroxylase, which further impair vitamin D synthesis; all these eventuate in hypocalcemia, which stimulates excessive secretion of PTH by the parathyroid glands, & hence elevation in PTH serum levels. 

Gross features
• There is increased osteoclastic activity, with bone resorption. Cortical and trabecular bone are lost and replaced by loose connective tissue. 
• Bone resorption is especially pronounced in the subperiosteal regions and produces characteristic radiographic changes, best seen along the radial aspect of the middle phalanges of the second and third fingers.

Microscopical features

• There is increased numbers of osteoclasts and accompanying erosion of bone surfaces.
• The marrow space contains increased amounts of loose fibrovascular tissue.
• Hemosiderin deposits are present, reflecting episodes of hemorrhage resulting from microfractures of the weakened bone.
• In some instances, collections of osteoclasts, reactive giant cells, and hemorrhagic debris form a distinct mass, termed "brown tumor of hyperparathyroidism". Cystic change is common in such lesions (hence the name osteitis fibrosa cystica). Patients with hyperparathyroidism have reduced bone mass, and hence are increasingly susceptible to fractures and bone deformities.

Bronchitis

Bronchitis is an obstructive pulmonary disease characterized by inflammation of the bronchi of the lungs

Signs and symptoms

persistent cough that produces sputum

shortness of breath (dyspnea) on exertion

hypercapnia

insufficient oxygenation of the blood hypoxemia leading to cynosis

Severe chronic bronchitis will commonly lead to cor pulmonale and heart failure.

Pathology

an increase in the number of goblet cells with mucus blocking the airway clusters of pigmented alveolar macrophages

the presence of inflammatory cells (e.g. neutrophils) scarring (fibrosis) of the walls of the bronchioles

Diagnosis

• decreased intensity of breath sounds (rhonchi) and extended expiration.
• a sputum culture has pathogenic microorganisms
• a chest x-ray that reveals hyperinflation and increased bronchovascular markings
• a pulmonary function test that shows an increase in the lung's residual volume and a decreased vital capacity

Pathophysiology

• The initiating event in developing bronchitis appears to be chronic irritation due to inhalation of certain chemicals
• earliest clinical feature of bronchitis is increased secretion of mucus by submucousal glands of the trachea and bronchi
• Damage caused by irritation of the airways leads to inflammation and infiltration of the lung tissue by neutrophils
• The neutrophils release substances that promote mucousal hypersecretion
• As bronchitis persists to become chronic bronchitis, a substantial increase in the number of goblet cells in the small airways is seen
• The role of infection in the pathogenesis of chronic bronchitis appears to be secondary.

Treatment

Quit smoking, Oxygen therapy, bronchodilator drugs

Prognosis

Pulmonary hypertension, cor pulmonale, and chronic respiratory failure are possible complications of chronic bronchitis

In severe chronic bronchitis is poor

AMYLOIDOSIS

Definition. Extra cellular  deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical  states.

Staining reactions

Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive  (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.

Amyloid is called typical if it given the above staining  reactions Other wise it is termed atypical or para-amyloid.

Classification 

1.    Systemic  amyloidosis associated with underlying disease (secondary),

(A) Chronic infections like 

- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.

(B) Chronic inflammations of varied etiology:

- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.

(C) Neoplastic proliferations:

- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.

II Systemic primary amyloidosis  with no underlying cause.

III Heredofamilial types.

- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy

IV. Localised amyloidosis:

- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.

Deposition sites
In relation to reticulin  and collagen fibres and to basement, membranes especially
subendothelial. 

Organs involved commonly are : 

Secondary amyloidosis

- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.

Primary amyloidosis

- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.

Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns

- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)

- In addition to these, extracts of crude amyloid contain  mucopolysacharides complement and gamma globulins.

- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response

The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.

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).

Cardiac tamponade
A. Caused by accumulation of fluid in the pericardium. This severe condition can quickly impair ventricular filling and rapidly lead to  decreased cardiac output and death.

1. Signs and symptoms include:
a. Hypotension.
b. Jugular venous distention.
c. Distant heart sounds.

Peutz-Jeghers syndrome
1. Lesions appear as small, melanotic, and freckle-like. They can be found on the skin, oral mucosa, lips, feet, and hands. 
2. May also present with intestinal polyps, which may develop into a gastrointestinal carcinoma. 
3. Genetic transmission: autosomal dominant.