4/1/99

Pathology II

 

Idiopathic inflammatory Bowel Disease

·        Crohn's disease—granulomatous disease that can affect any part of the alimentary tract but most often involves the small intestine and colon

·        Ulcerative colitis—non-granulomatous

 

Crohn's

·        Terminal ileitis, regional enteritis

·        Systemic accompanied by extraintestinal immune complications

·        Migratory polyarthritis

·        Erythema nodosum

·        Sacroilities

·        Irits and uveitis

·        Prevelant in US, Great Britian, Scandinavia

·        Rare in Asian and Africa

·        US incidence is 1-3/100,000—rising

·        Peaks b/w 2^nd-3^rd decade

·        Slightly more in females

·        Whites 2-5 times more than non-whites

·        Jews 3-5 times more than non-Jews

·        Distributions of lesions

·        40%--small intestine only

·        30%--small intestine and colon

·        30%--colon only

·        noncaseating granulomas in 40-60%

·        skip lesions—sharply delimited transmural segments of bowel

·        creeping fat—mesentric fat wraps around bowel surfaces

·        string sign—thin stream of barium through narrowed lumen of diseased segments of bowel

·        fissures—may penetrate through bowel wall and develop adhesions w/adjacent loops

·        fistulas or sinus tracts—may extend into organs, skin or blind cavities and form abscesses

·        highly variable and unpredictable presentation

·        recurrent diarrhea, crampy abdominal pain and fever lasting days to wks

·        50% will have melena

·        toxic dilation of the colon

·        massive bleeding

·        carcinoma of colon/small intestine

·        fistula formation to loops of bowel, urinary bladder, vagina, or perianal skin

·        abdominal abscesses or peritonitis

·        intestinal stricture or obstruction

 

Ulcerative Colitis

·        inflammatory disease of colon, ulcerations are limited to the mucosa and submucosa.  Begins in rectum, extends proximally in a continuous manner.  May affect entire colon

·        systemic disorder—also associated w/migratory polyarthiritis, sacroilitis, ankylosing spondylitis

 

Primary Differences w/Crohn's Disease

1.      no granulomas

2.      no skip lesions

3.      mucosal ulcers are superficial w/little fibrosis

4.      no mural thickening and serosal surface is normal

5.      do have greater risk for carcinoma

 

·        more common than Crohn's:  4-6 per 100,000—incidence is rising

·        more common in whites, no sex prediliction

·        peak incidence b/w 20 and 25 yrs

·        UC and ankylosing spondylitis-- + HLA-B27 (related to As not UC)

·        80% involve rectum or rectosgmoid

·        10% have pancolitis (entire colon)

·        pseudopolyps—islands of regenerating mucosa, surrounds by areas of ulceration—give impression of polyps

·        toxic megacolon—rare—extensive erosin and exposure of neural plexus to fecal material—neuromuscular function shuts down, colon progressively swells and becomes gangrenous

·        most serious complication is colon carcinoma.  Duration of the disease and extent increase the risk

·        chronic relapsing disease w/attacks of bloody mucoid diarrhea—may persists for days, wks, or months

·        asymptomatic intervals may last months, yrs, decades

·        presentation:  insidious w/cramps, tenesmus, and colicky lower abdominal pain relieved by defecation

·        bloody stools

·        blood loss is significant

·        migratory polyarthritis is more common than w/CD

 

Colonic Diverticulosis

·        diverticulum is a blind pouch off the alimentary tract.  It is lined by mucosa and communicates w/the gut lumen

·        acquired diverticula are most common in the colon—divertiuclosis

·        areas of herniation are where taenia coli (3 bands of longitudinal muscle penetrate inner circular muscle coat)

·        Western societies—low fiber diets produce low bulk in stools.  Spasitc colon contractions to move contents.  High intraluminal pressure w/herniation through anatomic weak poinst

·        Prevalence:  50% of adults over age 60

 

Bowel Obstruction

1.      hernia—weakness in wall of peritoneal cavity w/protrusion.  Segments

2.      intestinal adhesions—surgical procedures, infections endometriosis or peritonitis can form fibrous bridges than may create loops and trap viscera

3.      intussuception—telescoping of proximal segment of bowel into the immediate distal segment.  In children, may occur spontaneously.  Adults usually have a point of attachment (tumor) that "sling-shots" the proximal bowel forward

4.      volvulus—twisting of bowel loop or ovary blocking venous outflow and arterial supply.  Infarction and obstruction may follow

 

Tumors of the Small and Large Intestines

·        colon and rectum host more 1° neoplasms than any other organ

·        polyps—tumorous mass protruding into the gut lumen

·        pedunculated polyp—growth has a stalk

·        sessile polyp—no stalk—flat against wall

·        non-neoplastic polyps—due to abnormal mucosal maturation, inflammation or architecture.  No malignant potential

·        Adenomatous polyps (adenomas)—true neoplasms—result of epithelial proliferation and dysplasia

 

Colorectal Carcinoma

·        98% are adenocarcinomas

·        dietary practices

·        low intake vegetable fiber

·        high intake of refined carbohydrates

·        high intake of fat

·        low intake of protective micronutrients (vit A, C, E)

·        reduced fiber and low bulk causes slow transit time and altered bacterial flora of gut

·        potentially toxic oxidative byproducts of CHO degradation by bacteria are in higher [] for longer periods of time

·        high fat enhances synthesis of cholesterol and bile acids, which may be converted into potential carcinogens by bacteria

·        refined diets contain less vit A,C,E which may act as oxygen radical scavengers

·        genetic alteration are present in virtually all colon carcinomas

·        K-ras gene is most frequently observed activated onocgene

·        Well-defined shift toward right colon—esp in elderly

·        25% are in cecum or ascending colon

·        25% in rectum and distal sigmoid

·        25% descending colon and proximal sigmoid

·        proximal colon—polypoid, fungating masses extending along one wall—obstruction uncommon

·        distal colon—annular, encircling lesions—"napkin ring" constriction of the lumen

·        asymptomatic for yrs—symptoms develop insidiously and may be present for months/yrs before dx

·        cecal and right colon—fatigue, weakness, iron deficiency anemia

·        left-sided lesions—occult bleeding, changes in bowel habit, or crampy LLQ discomfort

·        iron deficiency anemia in an older male means GI cancer until proven otherwise

·        tumors spread by direct extension into adjacent structures and metastasize via lymphatics and blood vessels

·        favorite metastatic sites:  regional lymph nodes, liver, lungs and bone

·        25%-30% of cases are beyond surgical cure at dx

·        detection—DRE, fecal occult bleeding, changes in bowel habit or crampy LLQ discomfort

·        iron deficiency anemia in an older male means

 

Chapter 16

·        vulnerable to variety of metabolic, toxic, microbial, circulatory and neoplastic insults

·        functional reserve of liver masks the clinical impact of early disease

·        Table 16-2  Clinical Consequences of Liver Diseases

Characteristic Signs	Hepatitisatic dysfxn
	Jaundics and cholestasis
	Hypoalbuminemia
	Hyperammonemia
	Fetor hepatitisaticus
	Palmar erythema
	Spider angiomas
	Hypogonadism
	Gynecomastia
	Weight loss and muscle wasting
	Portal hypertension form cirrhosis:
	Ascites
	Splenomegaly
	Hemorrhoids
	Caput medusa
Life-threatening Complications	Hepatitisatic failure
	Multiple organ failure
	Coagulopathy
	Hepatitisatic encephalopathy
	Hepatitisatorenal syndrome

 

Cirrhosis

·        Progressive fibrosis w/development of diffuse parenchymal injury (nodules).  Entire liver is affected

·        Among the top 10 causes of death in Western world

·        Etiological Classification

·        Alcoholic liver disease—60-70%

·        Viral hepatitisatitis—10%

·        Billary diseases—5-10%

·        Genetic hemochromatosis

·        Many are clinically silent

·        Symptoms—anorexia, weight loss, weakness

·        Mechanisms of death:

·        Progressive liver failure

·        Complication of portal hypertension

·        Hepatitisatocellular carcinoma

 

Portal Hypertension

·        Increased resistance to portal blood flow, most often due to cirrhosis

·        Clinical consequences

·        Ascites

·        Venous shunts—esophageal varices, hemorrhoids, abdominal wall collateral (caput medusae)

·        Congestive splenomegaly

·        Hepatitisatic encephalopathy

 

Hepatitisatitis A—infectious hepatitisatitis

·        Benign, self-limiting disease w/incubation period of 2-6 wks

·        Does not cause chronic hepatitisatitis or a carrier state and rarely causes fulminant hepatitisatitis.  Fatality rate is 0.1%

·        HAV is shed in stools for 2-3 wks before and 1 wk after onset of jaundice

·        Spread by ingestion of contaminated water and foods—most cases are due to close personal contact or fecal-oral contamination

·        Consumption of raw or steamed shellfish (oysters, mussels, clams) which concentrate HAV from sea water contaminated w/human sewage

·        Damage to liver is from immunologically mediated injury

·        IgG anti-HAV appearance following infection provides life-long immunity

 

Hepatitisatits B—serum hepatitisatitis

·        More serious infection and may cause all of the following

·        Acute hepatitis

·        Chronci nonprogressive hepatitis

·        Progressive chronic disease leading to cirrhosis

·        Fluminant hepatitis w/massive liver necrosis

·        Asymptomatic carrier state (w/ or w/o progressive subclinical disease

·        Hepatitisatocellular carcinoma

·        Transmitted by blood and bodily fluids—semen, saliva, sweat, tears, breast milk, and pathologic effusions

·        1° risk

·        transfusion

·        blood products

·        dialysis

·        needle-stick accidents

·        intravenous drug use

·        male-to-male sexual activity

·        Long asymptomatic incubation period (4-26 wks, average is 6-8 wks) Acute disease may