VIRAL DISEASES

RABIES (Hydrophobia)

An acute infectious disease of mammals, especially carnivores, characterized by CNS pathology leading to paralysis and death.

Etiology and Epidemiology

Rabies is caused by a neurotropic virus often present in the saliva of rabid animals

Pathology

The virus travels from the site of entry via peripheral nerves to the spinal cord and the brain, where it multiplies; it continues through efferent nerves to the salivary glands and into the saliva.

microscopic examination shows perivascular collections of lymphocytes but little destruction of nerve cells. Intracytoplasmic inclusion bodies (Negri bodies), usually in the cornu Ammonis, are pathognomonic of rabies, but these bodies are not always found.

Sign/Symptoms

In humans, the incubation period varies from 10 days to > 1 yr and averages 30 to 50 days.

Rabies commonly begins with a short period of depression, restlessness, malaise, and fever. Restlessness increases to uncontrollable excitement, with excessive salivation and excruciatingly painful spasms of the laryngeal and pharyngeal muscles. The spasms, which result from reflex irritability of the deglutition and respiration centers, are easily precipitated Hysteria due to fright

Prognosis and Treatment

Death from asphyxia, exhaustion, or general paralysis usually occurs within 3 to 10 days after onset of symptoms

Infections caused by gonorrhea

1.  Acute urethritis.  Mostly in males.  Generally self-limiting.  Dysuria and purulent discharge.

2.  Endocervical infection.  Purulent vaginal discharge, abnormal menses, pelvic pain.  Often co-infection with other STD’s.  Some women are asymptomatic.

3.  Pelvic Inflammatory Disease (PID).  Consequence of ascending endocervical infection.  Causes salpingitis, endometriosis, bilateral abdominal pain, discharge, fever.  May lead to sterility, chronic pain, and ectopic pregnancy because of loss of fallopian cilia.

4.  Anorectal inflammation.  Mostly in homosexual men.  Pain, itching, discharge from anus.

5.  Dermatitis/arthritis.  Occurs after bacteremia.  Skin will have papules on an erythematous base which develop into necrotic pustules.  Asymmetric joint pain.  These infections are susceptible to penicillin.

6.  Neonatal infections.  Ophthalmia neonatorum is a conjunctival infection from going through infected vagina.  After one year of age, suspect child abuse.

Staphylococcal Infection

Staphylococci, including pathogenic strains, are normal inhabitants of the nose and skin of most healthy people
Virulence factors include coagulase (which clots blood), hemolysin, and protein A (which ties up Fc portions of antibodies). Although we have antibodies against staphylococci, they are of limited usefulness. 

Staphylococci (and certain other microbes) also produce catalase, which breaks down H2O2, rendering phagocytes relatively helpless against them. 

The coagulase-positive staphylococcus (Staphylococcus pyogenes var. aureus) is a potent pathogen. It tends to produce localized infection
It is the chief cause of bacterial skin abscesses. Infection spreads from a single infected hair (folliculitis) or splinter to involve the surrounding skin and subcutaneous tissues

Furuncles are single pimples
carbuncles are pimple clusters linked by tracks of tissue necrosis which involve the fascia.

Impetigo is a pediatric infection limited to the stratum corneum of the skin -- look for honey-colored crusts

Staphylococcal infections of the nail-bed (paronychia) and palmar fingertips (felons) are especially painful and destructive

These staph are common causes of wound infections (including surgical wounds) and of a severe, necrotizing pneumonia. Both are serious infections in the hospitalized patient.

Staph is the most common cause of synthetic vascular graft infections. Certain sticky strains grow as a biofilm on the grafts

Staph aureus is pathogenic, β-hemolytic, and makes coagulase.
Staph epidermidis are non-pathogenic strains that don’t make coagulase.  Often Antibiotics resistant, and     can become opportunistic infections in hospitals.

Staph aureus is normal flora in the nose and on skin, but can also colonize moist areas such as perineum.  Causes the minor infections after cuts.  Major infections occur with lacerations or immune compromise, where large number of cocci are introduced.

While Staph aureus can invade the gut directly (invasive staphylococcal enterocolitis), it is much more common to encounter food poisoning due to strains which have produced enterotoxin B, a pre-formed toxin in un-refrigerated meat or milk products

Staph epidermidis (Coagulase-negative staphylococci)
Universal normal flora but few virulence factors.  Often antibiotic resistant.
Major cause of foreign body infections such as prosthetic valve endocarditis and IV line sepsis.

Staph saprophyticus
Common cause of UTI in women.

Pathogenicity
Dominant features of S. aureus infections are pus, necrosis, scarring.  The infections are patchy.  Serious disease is rare because we are generally immune.  However, foreign bodies or necrotic tissue can start an infection.  Staph infections include wound infections, foreign body sepsis, pneumonia, meningitis.
Occassionally, S. aureus can persist within cells.

Major disease presentations include:
    --Endocarditis
    --Abscesses (due to coagulase activity)
    --Toxic Shock
    --Wound infections
    --Nosocomial pneumonia

Prevention of Staph aureus infections
S. aureus only lives on people, so touching is the main mode of transmission.  Infected patients     should be isolated, but containment is easy with intense hand washing.
 

Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
 - genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
 - the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
 - the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
 - the characteristic histologic features of psoriasis include:
 - hyperkeratosis
 - absence of the granulosa cells (present in lichen planus).
 - parakeratosis
 - regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
 - characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
 - 7% develop HLA B27 positive psoriatic arthritis

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.

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.