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. 

Pyelonephritis

- A bacterial infection that affects the renal tubules, interstitium, and renal pelvis.
- One of the most common renal diseases. 
- Usually caused by gram-negative, rod-shaped bacteria that are part of the normal flora of the enteric tract. Most commonly caused by Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter.
- The infecting bacteria are usually from the patient’s own enteric flora an example of an endogenous infection.
- Usually associated with a urinary tract infection (acute pyelonephritis) or involved with another precipitating condition, such as obstruction (chronic pyelonephritis).

Causes of disease

The causes of disease Diseases can be caused by either environmental factors, genetic factors or a combination of the two.

A. Environmental factors

Environmental causes of disease are many and are classified into:

 1. Physical agents

 2. Chemicals

 3. Nutritional deficiencies & excesses

 4. Infections & infestations

 5. Immunological factors

 6. Psychogenic factors

 1. Physical agents

These include trauma, radiation, extremes of temperature, and electric power. These agents

apply excess physical energy, in any form, to the body.

2. Chemicals

With the use of an ever-increasing number of chemical agents such as drugs,

3. Nutritional deficiencies and excesses

Nutritional deficiencies may arise as a result of poor supply, interference with absorption, inefficient transport within the body, or defective utilization. It may take the form of deficiency.

4. Infections and infestations

Viruses, bacteria, fungi, protozoa, and metazoa all cause diseases. They may do so by causing cell destruction directly as in virus infections (for example poliomyelitis) or protozoal infections (for example malaria).

5. Immunological factors

A. Hypersensitivity reaction

This is exaggerated immune response to an antigen. For example, bronchial asthma can occur due to exaggerated immune response to the harmless pollen.

B. Immunodeficiency

This is due to deficiency of a component of the immune system which leads to increased susceptibility to different diseases. An example is AIDS.

C. Autoimmunity

This is an abnormal (exaggerated) immune reaction against the self antigens of the host. Therefore, autoimmunity is a hypersensitivity reaction against the self antigens. 4

6. Psychogenic factors

The mental stresses imposed by conditions of life, particularly in technologically advanced

communities, are probably contributory factors in some groups of diseases.

B. Genetic Factors

These are hereditary factors that are inherited genetically from parents.

Respiratory Pathology

A. Pulmonary infections

1. Bacterial pneumonia

a. Is an inflammatory process of infectious origin affecting the pulmonary parenchyma.

2. Bacterial infections include:

a. Streptococcus pneumoniae (most common).

b. Staphylococcus aureus.

c. Haemophilus influenzae.

d. Klebsiella pneumoniae.

e. Anaerobic bacteria from the mouth

(aspiration of oral secretions).

3. Viral infections include:

a. Influenza.

b. Parainfluenza.

c. Adenoviruses.

d. Respiratory syncytial virus.

Note: viruses can also cause pneumonia. Infection of the interstitial tissues, or interstitial pneumonia, is commonly associated with these types of infections.

Common symptoms include fever, dyspnea, and a productive cough

Two types:

(1) Lobar pneumonia

(a) Infection may spread through entire lobe(s) of lung. Intraalveolar exudates result in dense consolidations.

(b) Typical of S. pneumoniae infections.

(2) Bronchopneumonia

(a) Infection and inflammation spread through distal airways, extending from the bronchioles and alveoli. A patch distribution involving one or more lobes is observed.

(b) Typical of S. aureus, H. influenzae,and K.pneumoniae infection

Diseases that Produce a Productive Cough

Pneumonia

Lung abscess

Tuberculosis

Chronic bronchitis

Bronchiectasis

Bronchogenic carcinoma

Classification

Diseases of the respiratory system can be classified into four general areas:

• Obstructive Diseases (e.g., Emphysema, Bronchitis, Asthma)
• Restrictive Diseases (e.g., Fibrosis, Sarcoidosis, Alveolar Damage, Pleural Effusion)
• Vascular Diseases (e.g., Pulmonary Edema, Pulmonary Embolism, Pulmonary Hypertension)
• Infectious, Environmental and Other Diseases (e.g., Pneumonia, Tuberculosis, Asbestosis, Particulate Pollutants)

Parasitic
1. Leishmania produce 3 kinds of disease in man

- visceral leishmaniasis (kala azar) due to Leishmania donovani complex, 
- cutaneous leishmaniasis due to Leishmania tropica complex, and 
- mucocutaneous leishmaniasis due to Leishmania braziliensis. 
 
 - cutaneous (Oriental sore) and mucocutansous leishmaniasis limit themselves to the skinalone (ulcers) in the former disease and skin plus mucous membranes in the latter variant. 

 - the diagnosis of cutaneous or mucocutaneous leishmaniasis is made by biopsy, culture, skin test, or serologic tests
 
 - the laboratory diagnosis of visceral leishmaniasis is made by performing a bone marrow aspirate and finding the leishmanial forms in macrophages, by culture, by hamster inoculation, or by serology. 
 - recovery from the cutaneous form incurs immunity.
 - treatment: stibogluconate 

Herpes simplex is subdivided into type 1 and 2, the former usually developing lesions around the lips and mouth and the latter producing vesicular lesions in the genital region 
 - contracted by physical contact; incubation 2-10 days.
 - primary HSV I usually is accompanied by systemic signs of fever and Lymphadenopathy, while recurrent herpes is not associate with systemic signs.
 - dentists often become infected by contact with patient saliva and often develop extremely painful infections on the fingers (herpetic whitlow).
 - Herpes viruses remain dormant in sensory ganglia and are reactivated by stress, sunlight, menses, etc. 

 - Herpes gingivostomatitis is MC primary HSV 1 infectionÆpainful, vesicular eruptions that may extend for the tongue to the retropharynx.
 - Herpes keratoconjunctivitis (HSV 1)
 - Kaposi's varicelliform eruption refers to an HSV 1 infection superimposed on a previous dermatitis, usually in an immunodeficient person.
 - laboratory: culture; ELISA test on vesicle fluid; intranuclear inclusions within multinucleated squamous cells in scrapings (Tzanck preps) of vesicular lesions.