Psoriasis
1. Characterized by skin lesions that appear as scaly, white plaques.
2. Caused by rapid proliferation of the epidermis.
3. Autoimmune pathogenesis; exact mechanism is unclear.

HEALING

Definition. Replacement of damages tissue by healthy tissue. It is an attempt to restore the tissue to structural and functional normalcy.

Healing may be of 2 types

A. Regeneration.

B. Repair by granulation tissue.

A. Regeneration

Where the replacement is by proliferation of parenchymatous cells of type destroyed. This depends upon:

(1) Regenerative capacity of cells. Cells may be :

(a) Labile cells which are constantly proliferating to replace cells continuously shed off or destroyed

Epithelial cells of skin and lining surfaces.

Lymphoid and haemopoietic tissue.

(b) Stable cell. Cells mostly in resting-phase, but capable of dividing when necessary e.g.

• Liver and other parenchymatous and glandular cells.
• Connective tissue cells.
• Muscle cells have a limited capacity to divide.

(c) Permanent cell. These cells, once differentiated are not capable. of  dividing e.g.-nerve

(2) The extent of tissue loss. If  there is extensive destruction including disruption of the framework, complete.regeneration is not possible. even with labile an stable cell

B. Repair by granulation tissue

Granulation tissue is formed by proliferation of surrounding connective tissue elements. which migrate into the site to be repaired.

Granulation tissue formation  seen in :

• Wound healing.
• Organisation of exudates.
• Thrombi.
• Infarcts.
• Haematomas.

The process of repair can be best studied in clean incised wounds, where there is .no or minimal tjssue loss or the_edges or the  edges of the wound are approximated closely as in a surgical wound. This is called Primary union (healing by first intention).

1. The blood in the incised area clots and the fibrin binds the edges together.

2. During the first 24 hours, an acute  inflammation sets in to .bring protein and phagocyte rich exudates to the site.

3. The superficial part of the clot get dry and dehydrated{scab). The surface epithelium proliferates just beyond the cut edges and the cells migrate-deep to dry scab. Epithelialisation is usually complete by 24- 48 hours.

4 Granulation tissue, with actively growing fibroblasts and capillary buds invades the clot (stage of vascularisation). These fibroblasts 'posses contractile myofibrils & hence are termed as myofibroblasts'.

5. Simultaneously, demolition of the debris and clot components takes place.

6 The granulation tissue initially lays down a mucopolysacharide rich ground substance

7.Reticulin and later collagen fibrils are formed by the fibroblasts (with 5 days)

8 with progressive maturation of collagen, some of the capiliary buds develop into arterioles and venules and majority of them are obliterated (stage of devascularisation).

9. With time (weeks to months) the tensile strength of the scar increases and it shrinks.

Secondary union (excised wound-healing by secondary intention).

1. Coagulum forms and fills the gap.

2. Inflammatory reaction is seen as in primary union but is more intense, as a lot more debris has to be removed. .

3. Epithelial proliferation starts covering the surface from the periphery by proliferation beyond the edges and migration under scab.

4.Debridement starts and simultaneously granulation tissue grows into the coagulum from the sides and base of the wound. This is much more exuberant than in primary union. The surface now looks red and granular.

5. Wound contraction. This is early contraction (starts after 3 days and is complete in 2 weeks) and  must be differentiated from contraction after scar formation Wounds can contract by up to 80% of original size of that the gap to be filled is much reduced, resulting in faster healing with a smaller scar.

Wound contraction is probably caused by:

• Dehydration
• Collagen contraction.
• Granulation tissue contraction .(myofibroblasts).

The exact mechanism is not known.

6. Laying down of collagen.

7 Maturation to form a scar which later shrinks and devascularises.

Factors affecting wound healing

Wound healing is delayed by :

A. Local  factors

1. Poor blood supply.

2. Adhesion to bony surfaces (e.g. over the tibia).

3. Persistent injurious agents (infective or particulate) results in chronicity of  inflammation and ineffective healing. .

4. Constant movement (especially in fracture healing).

5. ionizing radiation (in contrast, ultraviolet rays hasten healing).

6. Neoplasia.

B. General factors

I. Nutritional deficiency, especially of.

(i) Protein

(ii) Ascorbic acid (Vitamin C).

(iii) Zinc

2. Corticoids adversely affect wound contraction and granulation tissue formation

(anabolic steroids have a favorable effect).

3. Low temperature.

4. Defects (qualitative or quantitative) in polymorphs and macrophages

.Complication of wound healing

1. Wound dehiscence

2.  Infection

3. Epidermal inclusion (implantation) cysts.

4. Keloid formation

5. Cicatrisation resulting in contract Ires and obstruction(in hollow viscera).

6. Calcification and ossification.

7. Weak scar which could be a site for incisional hernia

8. Painful scar if it involves a nerve twig.

9. Rarely neoplasia (especially in burn scars).

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). 

Hepatitis

Hepatitis viruses—this group of viruses causes hepatitis, a disease affecting the liver.
1. General characteristics of hepatitis.
a. The general presentation of hepatitis is the same regardless of the infecting virus; however, the time and severity of symptoms may differ.
b. Symptoms of hepatitis include fever, anorexia, malaise, nausea, jaundice, and brown-colored urine.
c. Complications of a hepatitis infection include cirrhosis, liver failure, and hepatorenal failure.

Avitaminoses -  Vitamin deficiencies are more commonly secondary disorders associated with malabsorption conditions and chronic alcoholism.

A. Vitamin A - (retinoids, fat soluble compounds derived from ß-carotene) The best-known effect of deficiency is an inability to see in weak light (night blindness due to decreased rhodopsin).
-> The pathology is also characterized by skin lesions (rash on the extremities with punctate erythematous lesions). In malnourished children, vitamin A supplements reduce the incidence of infections such as measles, even in children without signs of preexisting deficiency.

B. Vitamin D - (1, 25 OH2 D3) Deficiency produces osteomalacia (called rickets in children). Many of the effects of osteomalacia overlap with the more common osteoporosis, but the two disordersare significantly different.
-> The specific alteration in osteomalacia and rickets is a failure of mineralization of the osteoid matrix resulting in decreased appositional bone growth. 

C. Vitamin E - Very rare. Occurs as a secondary disorder in conditions associated with fat maladsorption such as cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction).
-> Vitamin E deficiency causes a neurological disorder characterized by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage.

D. Vitamin K - (phylloquinone) Present in most leafy plants and also synthesized by intestinal bacteria. Vitamin K is required for the production of specific clotting factors and a deficiency is characterized by impaired coagulation (elevated clotting times). Although this can occur in newborns that are given breast milk low in vitamin K, the deficiency is almost always secondarily associated with the use of certain anti-coagulants or disorders such as obstructive jaundice, celiac, or pancreatic disease.

 E. Thiamine - (B1) The deficiency is known as beriberi. Thiamine deficiency is characterized by a peripheral neuropathy that affects sensation particularly in the legs (associated with demyelination of peripheral nerves), in more severe cases Korsakoff syndrome (neuropathy characterized by impaired ocular motility, ataxia, and mental confusion) and cardiomyopathy can occur.

F. Nicotinamide (niacin) - The deficiency is known as pellagra. Primary deficiencies are associated with diets that consist primarily of a single low quality protein source (i.e. corn). It results most commonly as a complication of alcoholism.

-> The pathology is characterized by hyperkeratosis and vesiculation of skin, atrophy of the tongue epithelium, and a neuropathy that can affect cortex and peripheral neurons.

- Initial symptoms include a smooth, red tongue, a sore mouth, and ulceration of the inside of the cheeks.

- The skin on the neck, chest, and back of the hands may become brown and scaly. 

- Often there is nausea, vomiting, and diarrhea. There may also be insomnia, depression, confusion, and rapid changes of mood. Long-standing pellagra can result in dementia and death.

G. Vitamin B12 - (cobalamin) Because cobalamin is synthesized by intestinal bacteria and is widely available in many foods, deficiencies are almost always secondary disorders associated with gastric atrophy (and decreased uptake via intrinsic factor), microbial proliferation (AIDS), long-term antacids, chronic alcoholism, idiopathic (age-related).

In addition to anemia, the primary clinical symptoms include a sensory neuropathy (polyneuropathy), sclerosis of the spinal cord and atrophy of some mucous tissues.

H. Vitamin C - (ascorbic acid) The classic deficiency is known as scurvy. The essential pathology involves an inability to produce mature collagen and hence affects connective tissue.

This is characterized by an inability to synthesize osteoid and dentin (and results in decreased wound healing) and a loss of integrity of blood vessel walls.

Oral lesions are only a feature of the advanced form of the disease; early signs include fatigue, dermatitis, and purpura. There can be abnormalities in the growing bones of infants. 

I. Vitamin B6 - (Pyridoxine) A deficiency can lead to peripheral neuropathy, most commonly associated with multivitamin B deficiencies in malnutrition and alcoholism. 

V. Major Minerals - Sodium, potassium, chlorine, and magnesium are required for life but dietary deficiencies do not develop.
A. Iodine - Essential for the synthesis of thyroid hormones, and severe iodine deficiency is  associated with hypothyroidism. The compensatory activity of the thyroid gland causes a  characteristic enlargement called goiter.

B. Calcium - Required for bone mineralization, the RDA for adults is 800 mg/day. Clinical trials have shown that 1000-2000 mg/day can delay the bone loss observed in the elderly and decrease the risk of osteoporosis. See also section IV B.

VI. Trace Elements - At least 10 elements (examples: Co, Mn, Si) are required in minute amounts for normal development and metabolism.

A. Zinc - A deficiency can result from inadequate amounts given during total parenteral nutrition or as a secondary effect of acrodermatitis enteropathica (autosomal recessive trait characterized by alopecia, dermatitis, and diarrhea - the disease responds to administration of zinc).

B. Copper - Deficiencies are rare and primarily associated with malabsorption syndromes and total parenteral nutrition. Copper is required for normal hematopoiesis and bone growth. A deficiency resembles iron deficiency anemia and osteoporosis.

C. Fluoride - Levels in drinking water greater than 1 ppm cause mottling of teeth and in areas with chronic naturally induced fluorosis there is abnormal calcification of ligaments and tendons.

Clinical genetics (cytogenetics),

This is a method in which inherited chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology.