Glycogen storage diseases (glycogenoses)

1. Genetic transmission: autosomal recessive.

2. This group of diseases is characterized by a deficiency of a particular enzyme involved in either glycogen production or degradative pathways.

Diseases include:
on Gierke disease (type I)
(a) Deficient enzyme: glucose-6-phosphatase.
(b) Major organ affected by the buildup of glycogen: liver.

Pompe disease (type II)

(1) Deficient enzyme: α-glucosidase(acid maltase).
(2) Major organ affected by the buildup of glycogen: heart.

Cori disease (type III)
(1) Deficient enzyme: debranching enzyme (amylo-1,6-glucosidase).
(2) Organs affected by the buildup of glycogen: varies between the heart, liver, or skeletal muscle.

Brancher glycogenosis (type IV)
(1) Deficient enzyme: branching enzyme.
(2) Organs affected by the buildup of glycogen: liver, heart, skeletal muscle, and brain.

McArdle syndrome (type V)
(1) Deficient enzyme: muscle phosphorylase.
(2) Major organ affected by the buildup of glycogen: skeletal muscle.

Mycobacterium leprae 

- tuberculoid type has intact cellular immunity
 - forms granulomas and kill the organisms (very few present).
 - evokes a positive lepromin skin test
 - localized skin lesions that lack symmetry
 - nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
 - lepromatous leprosy patients lack cellular immunity
 - no granulomas
 - organisms readily identified
 - negative lepromin skin test
 - Bacteremia disseminates to cooler areas like the digits.
 - symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
 - neural involvement is a late feature of the disease.
 - lepromin skin test is to determine host immunity; not a diagnostic test.
 - treatment: dapsone + rifampin

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

Lichen planus is an itchy, violaceous, flat-topped papule highlighted by white dots or lines called Wickham's striae.
 - lichen planus may occur in the oral mucosa, where it has a fine white net-like appearance.
 - increased epidermal proliferation; ? immunologic; initiated by epidermal injury from drugs, viruses, or topical agents.
 - characteristic histologic features include:
 - hyperkeratosis
 - absence of parakeratosis
 - prominent stratum granulosum
 - an irregular "saw toothed" accentuation of the rete pegs. 

 - dermal-epidermal junction obscured by a band-like infiltrate of lymphocytes.
 - It is generally self-limiting and resolves spontaneously 1 to 2 years after onset; however, the oral lesions may persist for years.

Biochemical examination

This is a method by which the metabolic disturbances of disease are investigated by assay of various normal and abnormal compounds in the blood, urine, etc.

Blastomycosis (North American Blastomycosis; Gilchrist's Disease)

A disease caused by inhalation of mold conidia (spores) of Blastomyces dermatitidis, which convert to yeasts and invade the lungs, occasionally spreading hematogenously to the skin or focal sites in other tissues.

Pulmonary blastomycosis tends to occur as individual cases of progressive infection

Symptoms are nonspecific and may include a productive or dry hacking cough, chest pain, dyspnea, fever, chills, and drenching sweats. Pleural effusion occurs occasionally. Some patients have rapidly progressive infections, and adult respiratory distress syndrome may develop.