LARGE INTESTINE (COLON) 

Congenital anomalies 

1. Hirschsprung's disease produces a markedly distended colon, usually proximal to the rectum. Caused by a section of aganglionic colon, which failed to develop normally due to the absence of ganglion cells).
This results in bowel obstruction and distention of the bowel proximal to the affected area.

2. Imperforate anus is due to a failure of perforation of the membrane that separates the endodermal hindgut from the ectodermal anal dimple. 

Benign conditions

1. Diverticular disease refers to multiple outpouchings of the colon.
Incidence. Diverticular disease is present in 30%-50%  adult autopsies in the United States. There is a higher dence with increasing age. 
Pathogenesis. Herniation of mucosa and submucoq through weak areas of the gut wall where arterial vasa recta perforate the muscularis is a characteristic pathological finding of the disease. 

Clinical features

- Diverticulosis is often asymptomatic, but may present with pain and/or rectal bleeding.
- In contrast, diverticulitis presents with pain and fever.  It is distinguished from diverticulosis by the presence of inflammation, which may or may not cause symptom. 

When symptomatic, the patlent experiences colicky left lower abdominal pain, change in bowel habits, and melena, so-called " left-sided appendicitis." 

Pathology 
Grossly, diverticula are seen most frequently in the sigmoid colon. 

Inflammatory diseases 

1. Crohn's disease, or regional enteritis, causes a segmental, recurrent, granulomatous inflammatory disease of the bowel. It most commonly involves the terminal ileum and colon but may involve any part of the gastrointestinal tract. There is a familial disposition. 
Etiology.

There is probably a similar etiology for both Crohn's disease and ulcerative colitis, which together are called inflammatory bowel disease. The following possible etiologies have been considered: infectious; immunologic (both antibody-mediated and cell-mediated); deficiencies of suppressor cells; and nutritional, hormonal, vascular, and traumatic factors. 

Clinical features.

Crohn's disease usually begins in early adulthood and is common in Ashkenazic Jews. Patients present with colicky pain, diarrhea, weight loss, malaise, malabsorption, low-grade fever, and melena. There is typically a remitting and relapsing course. If the involved bowel is resected, lesions frequently develop in previously uninvolved regions of the bowel. 

Pathology. Crohn's disease has a very characteristic pathology. 
Grossly, there are segmental areas (skip lesions) of involvement, most commonly in the terminal ileum. 

3. Ulcerative colitis is a chronic relapsing disease characterized by ulcerations, predominantly of the rectum and left colon, but which may affect the entire colon and occasionally the terminal ileum.

Incidence is higher in Caucasians than in Blacks, and is also more frequent in women than in men. The typical age of onset ranges from 12-35 years of age. There is a definite familial predisposition. 

Etiology. Etiologic theories are similar to those for Crohn's disease. Some inflammatory bowel disease has microscopic  features of both ulcerative colitis and Crohn's disease. 

Clinical course is characterized by relapsing bloody mucus diarrhea, which may lead to dehydration and electrolyte  imbalances, lower abdominal pain, and cramps. There is an  increased incidence of carcinoma of the colon, up to 50% after 25 years with the disease. 

Pathology 

Grossly, the disease almost always involves the rectum. It may extend proximally to involve part of the colon or its entirety. There are superficial mucosal ulcers, shortening of the bowel, narrowing of the lumen, pseudopolyps, and backwash ileitis. 

In contrast to Crohn's disease, the inflammation is usually confined to the mucosa and submucosa. 

Pseudomembranous colitis is an inflammatory process characterized by a pseudomembranous exudate coating the colonic mucosa 

Pathogenesis. The syndrome is associated with antibiotic  use (especially clindamycin), allowing proliferation of Clostridium difficile, which produces an exotoxin.

Clinical features include diarrhea that is often bloody, fever, and leukocytosis.
Diagnosis is made by identification of C. difficile and toxin  in stool.
Treatment includes stopping the original antibiotic and starting oral vancomycin or metronidazole. This disease is often a terminal complication in immunosuppressed patients. 

Vascular lesions 
Hemorrhoids are variceal dilatations of the anal and perianal venous plexus. They are caused by elevated intra-abdominal venous pressure, often from constipation and pregnancy and are occasionally due to portal hypertension, where they are associated with esophageal varices. Hemorrhoids may under thrombosis, inflammation, and recanalization. External hemorrhoids are due to dilatation of the inferior hemorrhoidal
plexus, while internal hemorrhoids are due to dilatation of the superior hemorrhoidal plexus. 

Polyps are mucosal protrusions. 

1. Hyperplastic polyps comprise 90% of all polyps. They are no neoplastic and occur mostly in the rectosigmoid colon. 
Grossly, they form smooth, discrete, round elevations.

2. Adenomatous polyps are true neoplasms. There is a higher incidence of cancer in larger polyps and in those containing a greater proportion of villous growth.

a. Tubular adenomas (pedunculated polyps) make up 75% of adenomatous polyps. They may be sporadic or familial 

For sporadic polyps, the ratlo of men to women is 2:1. The average age of onset is 60. 
Grossly, most occur in the left colon. Cancerous transformation (i.e., invasion of the lamina propria or the stalk) occurs in approximately 4% of patients.

b. Villous adenomas are the largest, least common polyps, and are usually sessile. About one-third are cancerous. Most are within view of the colonoscope. 
(1) Grossly, they form "cauliflower-like" sessile growth 1-10 cm in diameter, which are broad-based and have no stalks. 

3. Familial polyposis is due to deletion of a gene located on chromosome 5q. 

Familial multiple polyposis (adenomatous polyposis coli) shows autosomal dominant inheritance and the appearance of polyps during adolescence; polyps start in the rectosigmoid area and spread to cover the entire colon. The polyps are indistinguishable from sporadic adenomatous polyps. Virtually all patients develop cancers. When diagnosed, total colectomy is recommended. 

Gardner's syndrome refers to colonic polyps associated with other neoplasms (e.g., in skin, subcutaneous tissue, bone) and desmoid tumors. The risk of colon cancer is nearly 100%. 

Peutz-Jeghers syndrome presents with polyps on the entire gastrointestinal tract (especially the small intestine) associ-
ated with melanin pigmentation of the buccal mucosa, lips, palms, and soles. The polyps are hamartomas and are not premalignant. Peutz-Jeghers syndrome shows autosomal dominant inheritance. 

Turcot's syndrome is characterized by colonic polyps associated with brain tumors (i.e., gliomas, medulloblastomas). 

Malignant tumors 

Adenocarcinoma is the histologic type of 98% of all colonic cancers. Both environmental and genetic factors have been
identified.

Incidence is very high in urban, Western societies. It is the  third most common tumor in both women and men. The peak incidence
is in the seventh decade of life. 

Pathogenesis is associated with villous adenomas, ulcerative colitis, Crohn's disease, familial polyposis, and Gardner's syndrome. lncidence is possibly related to high meat intake, low-fiber diet, and deficient vitamin intake. A number of chromosomal abnormalities hme been associated with the development of colon cancer. 

Clinical features include rectal bleeding, change in bow habits, weakness, malaise, and weight loss in high-stage disease. The tumor spread by direct metastasis to nodes, liver, lung, and bones. carcinoembryonic antigen (CEA) is a tumor marker that helps to monitor tumor recurrence after surgery or tumor progression in  some patients.

Pathology 
(1) Grossly, 75% of tumors occur in the rectum and sigmoid colon.
(2) Microscopically, these tumors are typical mucin-producing adenocarcinomas. 
2. Squamous cell carcinoma forms in the anal region. It is often associated with papilloma viruses and its incidence is rising in homosexual males with AIDS. 

Pathology

The branch of medicine dealing with the essential nature of disease, especially changes in body tissues aorgans that cause or are caused by disease. Pathology is the structural and functional manifestations of disease.

Anatomic pathology  the anatomical study of changes in the function, structure, or appearance of organs or tissues,including postmortem examinations and the study of biopsy specimens.

Cellular pathology  - Cytopathology is a diagnostic technique that examines cells from various body sites to determine the cause or the nature of disease.

Clinical pathology  pathology applied to the solution of clinical problems, especially the use of laboratory 

methods inclinical diagnosis.

Comparative pathology  that which considers human disease processes in comparison with those of other 

animals.

Oral pathology  that treating of conditions causing or resulting from morbid anatomic or functional changes in thestructures of the mouth.

Surgical pathology  the pathology of disease processes that are surgically accessible for diagnosis or treatment.

DYSPLASIA
 It is disturbed growth or  cells in regard to their size, shape arrangement. In its mild degrees it represents a reversible reaction to chronic inflammation whereas the most severe degrees warrant a labelling of intraepithelial neoplasia. Hence it includes a wide spectrum of changes ranging from a reversible disorientation to 'carcinoma-in-situ'.

Histologically it is characterized by:

o    Basal cell hyperplasia.
o    Variation in size and shape of cells.
o    Disorderly maturation.
o    Increased mitotic activity.
o    Disorientation of arrangement of cells (loss of polarity)

Dysplasia is commonly seen in:

o    Squamous epithelium of cervix.
o    Bronchial epithelium in habitual smokers.
o    Gastric and colonic mucosa in long standing inflammation
o    Oral and vulval leucoplakia
 

EMBOLISM

Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.

Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour

Thromboembolism 
This is the commonest type of embolus and may be formed of the primary thrombus  or more often of propagated clot region which is loosely attached.

Emboli from venous thrombi can result In impaction in the pulmonary  arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.

Gaseous
This occurs when gas is introduced into the circulation:
•    Accidental opening of large veins during surgery.
•    Mismanaged transfusion. .
As air is  readily absorbed into blood only  sudden introduction or large quantities of air produces effects
Caisson’s Disease  bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.

Fat Embolism
Causes
•    Fractures especially of long bones and multiple
•    Crush injuries.

Sites of impaction:

o    Lungs.
o    Systemic: causing -
    →    petechial skin haemorrhages.
    →    Embolism to brain leading to coma and death.
    →     Conjunctival and retinal haemorrhages
    
Tumor Embolism.

Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
•    Metastatic deposits,
•    DlC
 

Lysosomal (lipid) storage diseases
- Genetic transmission: autosomal recessive.
- This group of diseases is characterized by a deficiency of a particular lysosomal enzyme. This results in an accumulation of the metabolite, which would have otherwise been degraded by the presence of normal levels of this specific enzyme.

Diseases include:
Gaucher’s disease
(1) Deficient enzyme: glucocerebrosidase.
(2) Metabolite that accumulates: glucocerebroside.
(3) Important cells affected: macrophages.

Tay-Sachs disease
(1) Deficient enzyme: hexosaminidase A.
(2) Metabolite that accumulates: GM2 ganglioside.
(3) Important cells affected: neurons.
(4) Symptoms include motor and mental deterioration, blindness, and dementia.
(5) Common in the Ashkenazi Jews.

Niemann-Pick disease
(1) Deficient enzyme: sphingomyelinase.
(2) Metabolite that accumulates: sphingomyelin.
(3) Important cells affected: neurons.

HERPES SIMPLEX

An infection with herpes simplex virus characterized by one or many clusters of small vesicles filled with clear fluid on slightly raised inflammatory bases.

The two types of herpes simplex virus (HSV) are HSV-1 and HSV-2. HSV-1 commonly causes herpes labialis, herpetic stomatitis, and keratitis; HSV-2 usually causes genital herpes, is transmitted primarily by direct (usually sexual) contact with lesions, and results in skin lesions

Primary infection of HSV-1 typically causes a gingivostomatitis, which is most common in infants and young children. Symptoms include irritability, anorexia, fever, gingival inflammation, and painful ulcers of the mouth.

Primary infection of HSV-2 typically occurs on the vulva and vagina or penis in young adults

Herpetic whitlow, a swollen, painful, and erythematous lesion of the distal phalanx, results from inoculation of HSV through a cutaneous break or abrasion and is most common in health care workers.