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

 IMMUNO PATHOLOGY

Abnormalities of immune reactions are of 3 main groups

• Hypersensitivity,
• Immuno deficiency,
• Auto immunity.

Hypersensitivity (ALLERGY)

This is an exaggerated or altered immune response resulting in adverse effects

They are classified into 4 main types.

I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.

Clinical  situations

I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.

2. Local (atopic) allergy.

• Allergic rhinitis (hay fever)
• Asthma
• Urticaria.
• Food allergies.

2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.

The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell.

Clinical situations

• Haemolytic anemia.
• Transfusion reaction
• Auto immune haemolytic anemia.
• Haemolysis due to some drugs like Alpha methyl dopa

Drug induced thrombocytopenia (especially sedormid).

Agranulocytosis due to sensitivity to some drugs.

Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.

3. Type III. (Immune complex disease). Circulating immune complexes especially

small soluble complexes tend to deposit in tissues especially kidney, joints, heart and

arteries.

These then cause clumping of platelets with subsequent release of histamine. and

serotonin resulting in increased permeability. Also, complement activation occurs which

being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to

release of lysosmal enzymes

Clinical situations

• Serum sickness.
• Immune complex glomerulonephritis.
• Systemic lupus erythematosus.
• Allergic alveolitis.
• Immune based vasculitis like
  • Drug induced vasculitis.
  • Henoch – Schonlein purpura

4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by

cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.

Clinical situations

I. Caseation necrosis in tuberculosis.

2. Contact dermatitis to

• Metals.
• Rubber.
• Drugs (topical).
• Dinitrochlorbenzene (DNCB).

5. Type V. (stimulatory) This is classed by some workers separately and by other with

cytotoxic type (Type II) with a stimulatory instead of toxic effect

Clinical Situations :

LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)

Varicose Veins  
- are abnormally dilated, tortuous veins produced by prolonged increase in intraluminal pressure and loss of vessel wall support. 

- The superficial veins of the leg are typically involved  

-venous pressures in these sites can be markedly elevated -> venous stasis and pedal edema (simple orthostatic edema)

-Some 10% to 20% of adult males and 25% to 33% of adult females develop lower extremity varicose  veins  

RISK FACTORS 
-> obesity  
-> Female gender  
-> pregnancy.  
-> familial tendency (premature varicosities results from imperfect venous wall development) 

 Morphology
 
- wall thinning  
- intimal fibrosis in adjacent segments 
- spotty medial calcifications (phlebosclerosis) 
- Focal intraluminal thrombosis 
- venous valve deformities (rolling and shortening) 

COMPLICATIONS
 
- stasis, congestion, edema, pain, and thrombosis 
- chronic varicose ulcers 
- embolism is very rare. 

Miscellaneous Bone Tumors 

1. Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET) are primary malignant small round-cell tumors of bone and soft tissue. They are viewed as the same tumor because they share an identical chromosome translocation; they differ only in degree of differentiation. PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated. After osteosarcomas, they are the second most common pediatric bone sarcomas. Most patients are 10 to 15 years old. The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. The resulting hybrid protein functions as an active transcription factor to stimulate cell proliferation. These translocations are of diagnostic importance since almost all patients with Ewing tumor have t(11;22).

Pathological features

• Ewing sarcoma and PNETs arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass.
• The tumor is tan-white, frequently with foci of hemorrhage and necrosis.

Microscopic features

• There are sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma.
• The cells have scant glycogen-rich cytoplasm.
• The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET. 

Ewing sarcoma and PNETs typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. The tumor may be confused with osteomyelitis because of its association with systemic signs & symptoms of infection. X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion. 

2. Giant-Cell Tumor of Bone (GCT) is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma. GCT is benign but locally aggressive, usually arising in individuals in their 20s to 40s. Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic. Tumors are large and red-brown with frequent cystic degeneration. They are composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei.

The majority of GCTs arise in the epiphysis of long bones around the knee (distal femur and proximal tibia).
Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed, producing a bulging soft tissue mass with a thin shell of reactive bone. Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs 

PERTUSSIS (Whooping Cough)

An acute, highly communicable bacterial disease caused by Bordetella pertussis and characterized by a paroxysmal or spasmodic cough that usually ends in a prolonged, high-pitched, crowing inspiration (the whoop).

Transmission is by aspiration of B. pertussis

Symptoms and Signs

The incubation period averages 7 to 14 days (maximum, 3 wk). B. pertussis invades the mucosa of the nasopharynx, trachea, bronchi, and bronchioles, increasing the secretion of mucus, which is initially thin and later viscid and tenacious. The uncomplicated disease lasts about 6 to 10 wk and consists of three stages: catarrhal, paroxysmal, and convalescent.

Agranulocytosis. Severe neutropenia with symptoms of infective lesions.

Drugs. are an important cause and the effect may be due to .
-Direct toxic effect.
-Hypersensitivity.

Some of the 'high risk drugs are.
-Amidopyrine.
-Antithyroid drugs.
-Chlorpromazine, mapazine.
-Antimetabolites and other drugs causing pancytopenia.

Bloodpicture:  Neutropenia with toxic granules in neutrophils. Marrow shows decrease in granulocyte precursors with toxic granules in them.