ESOPHAGUS Pathology

Congenital malformations 
1. A tracheoesophageal fistula (the most prevalent esophageal anomaly) occurs most commonly as an upper esophageal blind pouch with a fistula between the lower segment of the esophagus and the trachea. It is associated with hydramnios, congenital heart disease, and other gastrointestinal malformation. 

2. Esophageal atresia is associated with VATER syndrome (vertebra1 defects, anal atresia, tracheoesophageal fistula, and renal dysplasia)

3. Stenosis refers to a narrowed esophagus with a small lumen.  lt may be congenital or acquired, e.g., through trauma or inflammation. 

Inflammatory disorders 

Esophagitis 

most often involves the lower half of the esophagus.  Caused by the reflux of gastric contents (juices) into the lower esophagus. One of the most common GI disorders.

Clinical features. 

Patients experience substernal burning  associated with regurgitation, mild anemia, dysphagia,  hematemesis, and melena. Esophagitis may predispose to esophageal cancer. 

Etiology

- Reflux esophagitis is due to an incompetent lower esophageal sphincter that permits reflux of gastric juice into the lower esophagus. 
- Irritants such as citric acid, hot liquids, alcohol, smoking, corrosive chemicals, and certain drugs, such as tetracycline, may provoke inflammation. 
- Infectious etiologies include herpes, CMV, and C. albicans. The immunocompromised host is particularly susceptible to infectious esophagitis. 
Although chronic or severe reflux disease is uncommon, consequences of these conditions can lead to Barrett’s esophagus, development of a stricture, or hemorrhage.

Pathology

-Grossly, there is hyperemia, edema, inflammation, and superficial necrosis. 

Complications include ulceration, bleeding, stenosis, and squamous carcinoma. 

Treatment: diet control, antacids, and medications that decrease the production of gastric acid (e.g., H blockers).

Barrett's esophagus, 

gastric or intestinal columnar epithelium replaces normal squamous epithelium in response to  chronic reflux.- A complication of chronic gastroesophageal reflux disease.
- Histologic findings include the replacement of squamous epithelium with metaplastic columnar epithelium.
- Complications include increased incidence of esophageal adenocarcinoma, stricture formation, or hemorrhage (ulceration).

 Motor disorders. 

Normal motor function requires effective peristalsis and relaxation of the lower esophageal sphincter. 

Achalasia is a lack of relaxation of the lower esophageal sphincter (LES), which may be associated with aperistalsis of the esophagus and increased basal tone of the LES. 

Clinical features. Achalasia occurs most commonly between the ages of 30 and 50. Typical symptoms are dysphagia, regurgitation, aspiration, and chest pain. The lack of motility promotes stagnation and predisposes to carcinoma. 

Hiatal hernia is the herniation of the abdominal esophagus, the stomach, or both, through the esophageal hiatus in the  diaphragm.

Scleroderma is a collagen vascular disease, seen primarily in women, that causes subcutaneous fibrosis and widespread  degenerative changes. (A mild variant is known as CREST syndrome which stands for calcinosis. raynaud's phenomenon , esophageal dysfunction, sclerodactyly and telengectseia. esophagus is the most frequently involved region of the gastrointestinal tract.

Clinical features are mainly dysphagia and heartburn due to reflux oesophagitis caused by aperlistalsis and incompetent LES. 

Rings and webs 

1. Webs are mucosal folds in the upper esophagus above the aortic arch. 
2. Schatzki rings are mucosal rings at the squamocolumnarjunction below the aortic arch.
3. Plummer Vinson Syndrome consist of triad of dysphagia, atrophic glossitis, and anemia. Webs are found in the upper esophagus. The syndrome is associated specifically with iron deficiency anemia and sometimes hypochlorhydria. Patients are at increased risk for carcinoma of the pharynx or esophagus. 

Mallory-Weiss syndrome
Mallory-Weiss tears refers to small mucosal tears at the gastroesophageal junction secondary to recurrent forceful vomiting. The tears occur along the long axis an result in hematemesis (sometimes massive).

- Characterized by lacerations (tears) in the esophagus.
- Most commonly occurs from vomiting (alcoholics).
- A related condition, known as Boerhaave syndrome, occurs when the esophagus ruptures, causing massive upper GI hemorrhage.

Esophageal varices
- The formation of varices (collateral channels) occurs from portal hypertension.
Causes of portal hypertension include blockage of the portal vein or liver disease (cirrhosis).
- Rupture of esophageal varices results in massive hemorrhage into the esophagus and hematemesis.
- Common in patients with liver cirrhosis.

Diverticula 
are sac-like protrusions of one or more layers of  pharyngeal or esophageal wall. 

Tumors 
- Benign tumors are rare. 
- Carcinoma of the esophagus most commonly occurs after 50 and has a male:female ratio of 4.1. 

Etiology: alcohal ingestion, smoking, nitrosamines in food, achalasia , web ring, Barrettes esophagus, and deficiencies of vitamins A and C , riboflavin, and some trace minerals

Clinical features include dysphagia (first to solids), retrosternal pain, anorexia, weight loss, melena, and symptoms secondary to metastases. 

Pathology 

- 50% occur in the middle third of the esophagus, 30% in the lower third, and 20% in the upper third. Most esophageal cancers are squamous cell carcinomas. 
Adenocarcinomas arise mostly out of Barrett's esophagus.

Prognosis

is poor. Fewer than 10% of patients survive 5 years, usually because diagnosis is made at a late stage. The  most common sites of metastasis are the liver and lung. The combination of cigarette smoking and alcohol is particularly causative for esophageal cancer (over l00%  risk compared to nondrinkers/nonsmokers). 

Vitiligo is an autoimmune destruction of melanocytes resulting in areas of depigmentation.
 - commonly associated with other autoimmune diseases such as pernicious anemia, Addison's disease, and thyroid disease.
 - common in the Black population

Rickets and Osteomalacia 

Rickets in growing children and osteomalacia in adults are skeletal diseases with worldwide distribution. They may result from
1. Diets deficient in calcium and vitamin D
2. Limited exposure to sunlight (in heavily veiled women, and inhabitants of northern climates with scant sunlight)
3. Renal disorders causing decreased synthesis of 1,25 (OH)2-D or phosphate depletion 
4. Malabsorption disorders.

Although rickets and osteomalacia rarely occur outside high-risk groups, milder forms of vitamin D deficiency (also called vitamin D insufficiency) leading to bone loss and hip fractures are quite common in the elderly.

Whatever the basis, a deficiency of vitamin D tends to cause hypocalcemia. When hypocalcemia occurs, PTH production is increased, that ultimately leads to restoration of the serum level of calcium to near normal levels (through mobilization of Ca from bone & decrease in its tubular reabsorption) with persistent hypophosphatemia (through increase renal exretion of phosphate); so mineralization of bone is impaired or there is high bone turnover.

The basic derangement in both rickets and osteomalacia is an excess of unmineralized matrix. This complicated in rickets by derangement of endochondral bone growth.

The following sequence ensues in rickets:
1. Overgrowth of epiphyseal cartilage with distorted, irregular masses of cartilage
2. Deposition of osteoid matrix on inadequately mineralized cartilage
3. Disruption of the orderly replacement of cartilage by osteoid matrix, with enlargement and lateral expansion of the osteochondral junction
4. Microfractures and stresses of the inadequately mineralized, weak, poorly formed bone
5. Deformation of the skeleton due to the loss of structural rigidity of the developing bones 

Gross features
• The gross skeletal changes depend on the severity of the disease; its duration, & the stresses to which individual bones are subjected.
• During the nonambulatory stage of infancy, the head and chest sustain the greatest stresses. The softened occipital bones may become flattened. An excess of osteoid produces frontal bossing. Deformation of the chest results from overgrowth of cartilage or osteoid tissue at the costochondral junction, producing the "rachitic rosary." The weakened metaphyseal areas of the ribs are subject to the pull of the respiratory muscles and thus bend inward, creating anterior protrusion of the sternum (pigeon breast deformity). The pelvis may become deformed.
• When an ambulating child develops rickets, deformities are likely to affect the spine, pelvis, and long bones (e.g., tibia), causing, most notably, lumbar lordosis and bowing of the legs .
• In adults the lack of vitamin D deranges the normal bone remodeling that occurs throughout life. The newly formed osteoid matrix laid down by osteoblasts is inadequately mineralized, thus producing the excess of persistent osteoid that is characteristic of osteomalacia. Although the contours of the bone are not affected, the bone is weak and vulnerable to gross fractures or microfractures, which are most likely to affect vertebral bodies and femoral necks.

Microscopic features

• The unmineralized osteoid can be visualized as a thickened layer of matrix (which stains pink in hematoxylin and eosin preparations) arranged about the more basophilic, normally mineralized trabeculae.

Pemphigoid
1. Ulcerative lesions on the skin and oral mucosa.
2. An autoimmune disease in which patients have autoantibodies against basal cells (desmosome attachment to the basement membrane).
3. Histologically, the entire epithelium appears to separate from the connective tissue. There is no acantholysis.
4. A positive Nikolsky sign is observed.
5. Complications include blindness, due to ocular lesions present in some patients.
6. Treatment: corticosteroids.

Myocardial infarction (MI)—heart attack

A. Ischemia versus MI: Ischemia is a reversible mismatch between the supply and demand of oxygen. Infarction
is an irreversible mismatch that results in cell death caused by the lack of blood flow (oxygenation). For instance, chest pain caused by ischemia can be relieved by administering nitroglycerin (a vasodilator) to the patient. If the patient has an MI, the pain will not be relieved with nitroglycerin.

1. MIs most commonly occur when a coronary artery is occluded by a thrombus generated in an atherosclerotic artery.

2. Symptoms include:
a. Chest pain, shortness of breath.
b. Diaphoresis (sweating), clammy hands.
c. Nausea, vomiting.

3. Consequences:
a. Death (one third of patients).
b. Arrhythmias (most common immediate cause of death).
c. Congestive heart failure.
d. Myocardial rupture, which may result in death from cardiac tamponade.
e. Thrombus formation on infarcted tissue; may result in systemic embolism.
 

Polycystic kidney disease

Characterized by the formation of cysts and partial replacement of renal parenchyma.
Genetic transmission: autosomal dominant.
Clinical manifestations:

 hypertension, hematuria, palpable renal masses, and progression to renal failure. Commonly associated with berry
aneurysms.