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.

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
 

Immunodeficiency

This may be :- 
- Congenital (Primary)
- Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

T Cell Defects :

- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.

STOMACH 
Congenital malformations

1. Pyloric stenosis 

Clinical features. Projectile vomiting 3-4 weeks after birth associated with a palpable "olive" mass in the epigastric region is observed. 
Pathology shows hypertrophy of the muscularis of the pylorus and failure to relax. 

2. Diaphragmatic hernias are due to weakness in or absence of parts of the diaphragm, allowing herniation of the abdominal contents into the thorax. 

Inflammation 

1. Acute gastritis (erosive)

Etiology. Alcohol, aspirin and other NSAIDs, smoking,  shock, steroids, and uremia may all cause disruption of the mucosal barrier, leading to inflammation. 
Clinical features. Patients experience heartburn, epigastric pain, nausea, vomiting, hematemesis, and even melena. 

2. Chronic gastritis (nonerosive) may lead to atrophic mucosa with lymphocytic infiltration. 

Types 

(1) Fundal (Type A) gastritis is often autoimmune in origin.  It is the type associated with pernicious anemia and, therefore, achlorhydria and intrinsic factor deficiency. 
(2) Antral (Type B) gastritis is most commonly caused by Helicobacter pylori and is the most common form of chronic gastritis in the U.S. H. pylori is also responsible for proximal duodenitis in regions of gastric metaplasia.

Clinical features. The patient may be asymptomatic or suffer epigastric pain, nausea, vomiting, and bleeding. Gastritis may predispose to peptic ulcer disease, probably related to  H. pylori infection.

3. Peptic ulcers

Peptic ulcers are usually chronic, isolated ulcers observed in  areas bathed by pepsin and HCI; they are the result of mucosal breakdown

Common locations are the proximal duodenum, the stomach, and the esophagus, often in areas of Barrett's esophagus. 

Etiology. There are several important etiologic factors. 
Duodenal ulcers occur predominantly in patients with excess acid secretion, while gastric ulcers usually occur in patients with lower than average acid secretion. 

Other predisposing conditions include smoking, cirrhosis, pancreatitis, hyperparathyroidism, and H. pylori infection. Aspirin, steroids, and NSAlDs are known to be assoicated with peptic ulcer disease. Next to H. pylori colonization, aspirin or NSAID ingestion is the most common cause of peptic ulcer. 

Clinical features. Patients experience episodic epigastric pain. Duodenal and most gastric ulcers are relieved by food or antacids. Approximately one-fifth of gastric ulcer patients get no relief from eating or experience pain again  within 30 minutes.

Pathology. Benign peptic ulcers are well-circumscribed  lesions with a loss of the mucosa, underlying scarring, and sharp walls. 

Complications include hemorrhage, perforation, obstruction, and pain. Duodenal ulcers do not become malignant .Gastric ulcers do so only rarely; those found to be ma1ignant likely originated as a cancer that ulcerated.

Diagnosis is made by upper gastrointestinal Series , endoscopy, and biopsy to rule out malignancy or to demonstrate the presence of H. pylori. 

4. Stress ulcers 

are superficial mucosal ulcers of the stomach or duodenum or both. Stress may be induced by burns, sepsis shock, trauma, or increased intracranial pressure. 

Tumors 
1. Benign 

a. Leiomyoma, often multiple, is the most common benign neoplasm of the stomach. Clinical features include bleeding, pain, and iron deficiency anemia. 

b. Gastric polyps are due to proliferation of the mucosal epithelium. 

2. Malignant tumors 

a. Carcinoma 

Etiology. Primary factors include genetic predisposition and diet; other factors include hypochlorhydria, pernicious anemia, atrophic gastritis, adenomatous polyps, and exposure to nitrosamines. H. pylori are also implicated. 

Clinical features. Stomach cancer is usually asymptomatic until late, then presents with anorexia, weight loss, anemia, epigastric pain, and melena. Virchow's node is a common site of metastasis. 

Pathology. Symptomatic late gastric carcinoma may be expanding or infiltrative. In both cases the prognosis is poor (approximately 10% 5-year survival), and metastases are frequently present at the time of diagnosis. 
Adenocarcinomas are most common. 

b. Gastrointestinal lymphomas may be primary In the gastrointestinal tract as solitary masses. 

c. Sarcoma is a rare, large, ulcerating mass that extends into the lumen. 

d. Metastatic carcinoma. Krukenberg's tumor is an ovaria metastasis from a gastric carcinoma. 

e. Kaposi's sarcoma. The stomach is the most commonly involved GI organ in Kaposi's sarcoma. It primarily occurs in homosexual men, appearing as hemorrhagic polypoid, umbilicated nodular lesions, typically in a submucosal location. It rarely causes symptoms

Graves disease 

Graves disease is an organ-specific autoimmune disorder that results in thyrotoxicosis due to overstimulation of the thyroid gland by autoantibodies. 
- It is the most common form of thyrotoxicosis, females being affected more than males by 8: 1. 
- It is usually associated with a diffuse enlargement of the thyroid.

Pathogenesis
 
IgG-type immunoglobulins bind to TSH membrane receptors and cause prolonged stimulation of the thyroid, lasting for as long as 12 hours 
(cf. 1 hour for TSH). The autoantibody binds at a site different to the hormone-binding locus and is termed the TSH-receptor autoantibody (TRAb); 95% of Graves’ disease patients are positive for TRAbs

Gross features 
- The thyroid gland is diffusely and moderately enlarged
- It is usually smooth, soft, and congested  

Histologically
- the gland shows diffuse hypertrophy and hyperplasia of acinar epithelium, reduction of stored colloid and local accumulations of lymphocytes with lymphoid follicle formation.

Clinical features

- Exophthalmos (protrusion of the eyeballs in their sockets)—due to the infiltration of orbital tissues by fat, mucopolysaccharides and lymphocytes. May cause compression of the optic nerve, hence blindness. However, only about 5% of Graves’ patients show signs of exophthalmos.
- Thyroid acropachy—enlargement of fingernails. 
- Pretibial myxoedema—accumulation of mucoproteins in the deep dermis of the skin.

Treatment is as for thyrotoxicosis.

Pathology

The branch of medicine dealing with the essential nature of disease, especially changes in body tissues aorgans that cause or are caused by disease. Pathology is the structural and functional manifestations of disease.

Anatomic pathology  the anatomical study of changes in the function, structure, or appearance of organs or tissues,including postmortem examinations and the study of biopsy specimens.

Cellular pathology  - Cytopathology is a diagnostic technique that examines cells from various body sites to determine the cause or the nature of disease.

Clinical pathology  pathology applied to the solution of clinical problems, especially the use of laboratory 

methods inclinical diagnosis.

Comparative pathology  that which considers human disease processes in comparison with those of other 

animals.

Oral pathology  that treating of conditions causing or resulting from morbid anatomic or functional changes in thestructures of the mouth.

Surgical pathology  the pathology of disease processes that are surgically accessible for diagnosis or treatment.