SMALL INTESTINE 

Congenital anomalies 

1. Meckel's diverticulum (a true diverticulum) is due to persistence of the omphalomesenteric vitelline duct. 
2. Atresia is a congenital absence of a region of bowel, leaving a blind pouch or solid fibrous cord. 
3. Stenosis refers to a narrowing of any region of the gastrointestinal tract, which may cause obstruction. 
4. Duodenal diverticula are areas of congenital weakness permitting saccular enlargement. The duodenum is the most common region of the small bowel to contain diverticula. 
5. Diverticula of jejunum and ileum are herniations of mucosa and submucosa at points where the mesenteric vessels and nerves enter. 

Infections

1. Bacterial enterocolitis may be caused by the ingestion of preformed bacterial toxins, producing symptoms ranging from severe but transient nausea, vomiting, and diarrhea (Staphylococcus aureus toxin) to lethal paralysis (Clostridium botulinum toxin). Ingestion of toxigenic bacteria with colonization of the gut (e.g., Vibrio cholera, toxigenic E. coli, various species of Campylobacter jejuni, Shigella, salmonel
Yersinia, and many others) is another potential cause. 

2. Nonbacterial gastroenterocolitis
a. Viral 
(1) Rotavirus (children)
(2) Parvovirus (adults) 
b. Fungal-Candida 
c. Parasitic 
(1 ) Entamoeba histolytica 
(2) Giardia lamblia 

3. In HIV patients. Causes of infectious diarrhea in HIV patients include Cryptosporidium, Microsporidia, isospora belli, CMV, and M. avium-intracellulare. 

C. Malabsorption is defined as impaired intestinal absorption of dietary constituents. 
Clinical features include diarrhea,steatorrhea, weakness, lassitude, and weight loss. Steatorrhea results in deficiency of fat-soluble vitamins (A, D, E, K) and calcium. 

1. Celiac sprue
a. Etiology. Celiac sprue (nontropical sprue or gluten enteropathy) is caused by an allergic, immunologic, or toxic reaction to the gliadin component of gluten. There is a genetic predisposition. 

Symptoms:
– Steatorrhea, abdominal distention, flatulence, fatigue, and weight loss

Complications:
– Iron and vitamin deficiency
– Risk of lymphoma (T-cell type)

Extraintestinal manifestation:
– Dermatitis herpetiformis (a pruritic papulovesicular rash with IgA deposits at the dermoepidermal junction) 

2. Tropical sprue

Etiology. Tropical sprue is of unknown etiology, but may be  caused by enterotoxigenic E. coli. 

3. Disaccharidase deficiency is due to a deficiency of brush border enzymes. Lactase deficiency is most common. 

4. Diverticulosis Coli

- Acquired colonic diverticula are present in nearly half of the population over the age of 50
- Diverticula are associated with low-fiber, low-residue diets
- Etiology is most likely high intraluminal pressure required for propulsion of hard, small stools
- Complications include hemorrhage, acute diverticulitis, perforation, fistula formation 

Obstructive lesions

Hernias cause 15% of small intestinal obstruction. They are due to a protrusion of a serosa-lined sac through a weakness in the wall of the peritoneal cavity. They occur most commonly at the inguinal and femoral canals, at the umbilicus, and with scars. They may lead to entrapment, incarceration, and strangulation of the bowel. 

Tumors of the small bowel account for only 5% of gastrointestinal tumors. 

Benign tumors in descending order of frequency include:
leiomyomas, lipomas, adenomas (polyps), angiomas, and fibromas. Adenomatous polyps are most common in the stomach and duodenum and may be single or multiple, sessile or pedunculated. The larger the polyp, the greater the incidence of malignant transformation. 

Malignant tumors, in descending order of frequency, include: endocrine cell tumors, lymphomas, adenocarcinomas, and leiomyosarcomas. 

Idiopathic Inflammatory Bowel Disease (IBD)

- Chronic, relapsing, idiopathic inflamamtory disease of the GI tract
Crohn’s Disease
– Transmural granulomatous disease affecting any portion of the GI tract
Ulcerative Colitis
– Superficial, non-granulomatous inflammatory disease restricted to the colon

Ulcerative Colitis
- Bloody mucoid diarrhea, rarely toxic megacolon
- Can begin at any age, peaks at 20-25 years
- Annual incidence of ~10 per 100,000 in US
- Negligible risk of cancer in the first 10 years, but 1% per year risk of cancer thereafter
- Good response to total colectomy if medical therapy fails

Macroscopic
- Normal serosa
- Bowel normal thickness
- Continuous disease
- Confluent mucosal ulceration
- Pseudopolyp formation

Microscopic
- Crypt distortion + shortening
- Paneth cell metaplasia
- Diffuse mucosal inflammation
- Crypt abscesses
- Mucin depletion
- Mucosal ulceration

Crohn’s Disease

- Variable and elusive clinical presentation with diarrhea, pain, weight loss, anorexia, fever
- Can begin at any age, peaks at 15-25 years
- Annual incidence of ~3 per 100,000 in US
- Many GI complications and extracolonic manifestations
- Risk of cancer less than in UC
- Poor response to surgery 

Macroscopic
Fat wrapping
Thickened bowel wall
Skip Lesions
Stricture formation
Cobblestoned mucosa
Ulceration

Microscopic
- Cryptitis and crypt abscesses
- Transmural inflammation
- Lymphoid aggregates +/- granulomas
- “Crohn’s rosary”
- Fissuring
- Neuromuscular hyperplasia

Pernicious anaemia 

The special features are:

• Due to intrinsic factor deficiency
• Gastric atrophy with histamine fast achlorhydria
• Genetic basis (racial distribution and blood group A).
• Seen with auto immune disorders.
• Antibodies to parietal cells and to intrinsic factors are seen

Cushing’s syndrome

The symptoms and signs of Cushing’s syndrome are associated with prolonged inappropriate elevation of free corticosteroid levels.

Clinical features

- Central obesity and moon face.
- Plethora and acne.
- Menstrual irregularity.
- Hirsutism and hair thinning.
- Hypertension.
- Diabetes.
- Osteoporosis—may cause collapse of vertebrae, rib fractures.
- Muscle wasting and weakness.
- Atrophy of skin and dermis—paper thin skin with bruising tendency, purple striae.

Aetiopathogenesis — patients with Cushing’s syndrome can be classified into two groups on the basis of whether the aetiology of the condition is ACTH dependent or independent. 

Classification of Cushing's syndrome

ACTH dependent- Iatrogenic (ACTH therapy) Pituitary hypersecretion of ACTH Ectopic ACTH syndrome (benign or malignant non-endocrine tumour)

Non-ACTH dependent - Iatrogenic, e.g. prednisolone Adrenal cortical adenoma , Adrenal cortical carcinoma

ACTH-dependent aetiology:

- Pituitary hypersecretion of ACTH (Cushing’s disease)—bilateral adrenal hyperplasia secondary to excessive secretion of ACTH by a corticotroph adenoma of the pituitary gland.
- Production of ectopic ACTH or corticotrophin- releasing hormone (CRH) by non-endocrine neoplasm, e.g. small cell lung cancer and some carcinoid tumours. In cases of malignant bronchial tumour, the patient rarely survives long enough to develop any physical features of Cushing’s syndrome.

Non-ACTH-dependent aetiology

Iatrogenic steroid therapy—most common cause of Cushing’s syndrome.
Adrenal cortical adenoma—well-circumscribed yellow tumour usually 2–5 cm in diameter.
Extremely common as an incidental finding in up to 30% of all post-mortem examinations. The yellow colour is due to stored lipid (mainly cholesterol) from which the hormones are synthesised. The vast majority have no clinical effects (i.e. they are non-functioning adenomas), with only a small percentage producing Cushing’s syndrome.

Adrenal cortical carcinoma—rare and almost always associated with the overproduction of hormones, usually glucocorticoids and sex steroids. 

Cushing’s syndrome mixed with androgenic effects which are particularly noticeable in women. Tumours are usually large and yellowish white in colour. Local invasion and metastatic spread are common.

Irrespective of the aetiology, the diagnosis is based on clinical features and the demonstration of a raised plasma cortisol level.
The aetiology of the disorder is elucidated through:
- Raised urinary cortisol in the first instance, but further testing is required.
- Low-dose dexamethasone suppression test (suppression of cortisol levels in Cushing’s disease due to suppression of pituitary ACTH secretion, but a lack of suppression suggests ACTH-independent Cushing’s syndrome).
- MRI and CT scan visualisation of pituitary and adrenal glands.
- Analysis of blood ACTH (high = pituitary adenoma or ectopic ACTH source; low = primary adrenal tumour due to feedback suppression).
- Treatment of the underlying cause is essential as untreated Cushing’s syndrome has a 50% 5-year mortality rate.

The therapeutic administration of glucocorticosteroids (e.g. prednisolone) is a common cause of the features of Cushing’s syndrome. 

Histopathological techniques

Histopathological examination studies tissues under the microscope. During this study, the pathologist looks for abnormal structures in the tissue. Tissues for histopathological examination are obtained by biopsy. Biopsy is a tissue sample from a living person to identify the disease. Biopsy can be either incisional or excisional.

Once the tissue is removed from the patient, it has to be immediately fixed by putting it into adequate amount of 10% Formaldehyde (10% formalin) before sending it to the pathologist.

The purpose of fixation is:

1. to prevent autolysis and bacterial decomposition and putrefaction

2. to coagulate the tissue to prevent loss of easily diffusible substances

3. to fortify the tissue against the deleterious effects of the various stages in the preparation of sections and tissue processing.

 4. to leave the tissues in a condition which facilitates differential staining with dyes and other reagents.

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. 

INFARCTION

Definition : a localized area of ischaemic necrosis in an organ infarcts may be:
Pale :as in
    →    Arterial obstruction.
    →    solid organs.
Red as in
    →    Venous occlusion
    →    Loose tissue.

Morphology
Gross: infarcts are usually wedge shaped the apex towards the occluded vessel They are
separated from the surrounding tissue by an hyperemic inflammatory zone

Microscopic:
- An area of coagulative necrosis with a rim of congested vessels and acute inflammatory infiltration of the tissue .
- The polymorphs ale later replaced by mononuclear cells and granulation tissue.
- With time, scar tissue replaces necrosed tissue.