Pheochromocytoma

Pheochromocytomas are neoplasms composed of chromaffin cells, which as their normal counterparts synthesize and release catecholamines. 

1. Arise in association with one of several familial syndromes such as MEN syndromes, type 1 neurofibromatosis, von Hippel-Lindau disease, and Sturge-Weber syndrome. 
2. Are extra-adrenal, occurring in sites such as the organ of Zuckerkandl and the carotid body, where they are usually called paragangliomas rather than pheochromocytomas. 
3. Are bilateral; but in association with familial syndromes, this figure may rise to 50%. 
4. Are malignant; frank malignancy, however, is more common in extra-adrenal tumors.  

Gross features

- The size of these tumors is quite variable ranging from small to huge masses. 
- Sectioning shows yellow-tan, well-defined tumor that compress the adjacent adrenal. Large lesions display areas of hemorrhage, necrosis, and cystic degeneration.  
- Incubation of the fresh tissue with potassium dichromate solutions converts the tumor a dark brown color.

Microscopic features
- These tumors are composed of polygonal to spindle-shaped chromaffin cells and their supporting sustentacular cells, arranged in well-defined small nests (Zellballen)," rimmed by a rich vascular network.
- The cytoplasm is often finely granular (catecholamine-containing granules) 
- The nuclei are often quite pleomorphic. 
- Both capsular and vascular invasion may be encountered in benign lesions, and the presence of mitotic figures per se does not imply malignancy. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone. 

The laboratory diagnosis of pheochromocytoma is based on demonstration of increased urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid (VMA)&  metanephrines.

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

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

Wuchereria bancrofti, Brugia malayi (Filariasis)
 - the microfilaria of Wuchereria bancrofti or Brugia malayi (nematodes) are transmitted to man by the bite of infected mosquitoes (Anophele, Aedes, Culex).
 - microfilaria characteristically circulate in the bloodstream at night and enter into the lymphatics, where they mature and produce an inflammatory reaction resulting in lymphedema (elephantiasis) of the legs, scrotum, etc. 

Fungal
 
Superficial mycoses

1. Superficial mycoses→outermost layers of the skin or its appendages; skin, nails and/or hair.
2. Dermatophytoses transmitted by contact with man (anthropophilic; weak inflammatory response), animals (zoophilic; brisk inflammatory response), or contact with soil (geophilic; strongest inflammatory response).
3. Trichophyton→hair, skin, or nails; Microsporum → hair and skin; and Epidermophyton→skin alone.
4. The diagnosis is best made by culture of skin scrapings secured from the leading edge of the lesion.
 - use Wood's light to check for fluorescing metabolites.
 - direct KOH preparations of the scraped material
 
 Subcutaneous Mycoses
 
1. Subcutaneous mycoses are usually related to traumatic implantation into the skin.
2. Chromoblastomycosis, or verrucous (wart-like) dermatitis, is a chronic skin lesion associated with several pigmented fungi (Fonsecaea, Phialophora, and Cladosporium).
 - granulomatous reaction in subcutaneous tissue are pigmented, thick walled bodies are visible in tissue section.
3. Mycetomas (maduromycosis) are characterized by a localized, tumorous nodule (usually foot) that occurs in response to chronic progressive destruction of skin, subcutaneous tissue, fascia, muscle and bone 

4. Sporotrichosis is caused by the dimorphous fungus, Sporothrix schenckii.
 - traumatic implantation of the fungus growing in soil, thus the association with "rose gardeners disease".
 - MC lymphocutaneous disease → painless nodule at inoculation site → chain of suppurating subcutaneous nodules that drain to the skin surface along the course of the lymphatics.

- cigar shaped yeast forms are seen in the suppurative nodules and asteroid bodies (Splendore-Hoeppi phenomenon) are noted within granulomatous microabscesses.
 - treatment: oral potassium iodide

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.