Pathology Final - Gen. Disorders, GI, Liver

• Fetal alcohol syndrome: Growth retardation, Facial abnormalities ( maxillary hypoplasia, etc.), Mental retardation
• Rubella: Microcephaly, Microphthalmia, Cardiac defects
• Thalidomide
• Radiation exposure

• 47, XXY - Tall male, infertile, testicular atrophy
• Genetic chromosomal abnormality

45, X - Short female, web neck, infertility, streak gonads

Trisomy 21; Congenital heart disease (40%), 15x increase in risk for leukemia; male infertility; Early Alzheimer changes in CNS

• defective fibrillin protein—think of Abe Lincoln Floppy valve syndrome; dissecting aortic, aneurysms; Eye disorders (cataracts, detached retina)
• Autosomal dominant

• Think rubber man—hypermobility and hyper-elasticity; Defect in collagen gene; fragility of blood vessels
• Autosomal dominant

• Defect in collagen type 1; bones break easily; Can have blue sclerae; dentinogenesis imperfecta
• Autosomal dominant

• dwarfism (short limbs); defect in endochondral ossification, affects long bones; mutation of gene encoding the receptor for fibroblast growth factor
• Autosomal dominant

• gene on chromosome 16; progressive cystic dilation of renal tubules which become non-functional—renal failure in 3rd or 4th decade.
• Autosomal dominant

• Expanded CAG nucleotide repeat chromosome 4; Progressive dementia, chorea (involuntary movements), and affective outbursts.
• Autosomal dominant

Low density lipoprotein cannot be removed from circulation leading to accelerated atherosclerosis and deposits of cholesterol in tissues (xanthomas)

most common lethal autosomal recessive disorder of humans; almost exclusively affects Caucasians; involves the lack of transport of chloride across the cell membrane; affects bronchial glands (mucus buildup) and pancreas (dilation of ducts with thick mucus leading to pancreatic fibrosis), decreased function, and malabsorption of nutrients due to deficiency of digestive enzymes)

high serum phenylalanine; mental deterioration

• Tay Sachs---hexosaminidase deficiency
• Gauchers---Glucocerebrosidase deficiency
• Nieman Pick—Sphingomyelinase deficiency
• Hurlers—alpha-L-Iduronidase deficiency

• Reflux of stomach acid (GERD)
• Over-eating
• Smoking-alcohol
• Autoimmune diseases with epithelial sloughing

• Peptic ulcers
• Esophageal strictures (causes difficulty swallowing)
• Barrett’s esophagus - Metaplasia of squamous epithelium to columnar glandular epithelium; predisposes to development of adenocarcinoma

Squamous cell--upper 2/3rds--most common worldwide Adenocarcinoma-lower 1/3 --about 50% of cases in US Prognosis: 5% five year survival

• Lack of neural ganglion cells
• Symptoms: difficulty swallowing; esophageal spasms; regurgitation

Causes difficulty swallowing

• most common--stomach herniates through diaphragm into esophagus
• Complication of portal hypertension/ liver cirrhosis (often due to Hepatitis C)
• Rupture causes life-threatening bleeding

• herniates alongside the esophagus varices
• Complication of portal hypertension/ liver cirrhosis (often due to Hepatitis C)
• Rupture causes life-threatening bleeding

Esophageal laceration due to vomiting; seen in alcoholics

blind pouch in esophagus just above esophageal sphincter; dysphagia (difficulty swallowing)

• Congenital or acquired; 1 in 1000 births;
• Causes difficulty in passage of food; projectile vomiting

• Superficial inflammation of stomach
• Due to NSAIDS, alcohol, aaspirin
• Can be erosive may vomit up blood (Hematemesis)

• More common with age
• 3 causes: Infectious--Helicobacter, Autoimmune---causes pernicious anemia-antibodies or intrinsic factor or parietal cells; achlorhydria (lack of gastric acid secretion), Reactive--post partial gastrectomy

• Mucin layer depletion
• Atrophy of gastric glands
• Mixed inflammatory infiltrates
• Intestinal metaplasia

• Ulcers of esophagus, stomach, and/or duodenum
• Multifactorial etiology: Helicobacter; stress, NSAIDs, radiation, vascular insufficiency, smoking, primary hyperparathyroidism
• Complications: hemorrhage, adhesions, perforation, strictures
• NOT a precursor to carcinoma
• Zollinger-Ellison syndrome: peptic ulcers secondary to Gastrin secreating pancreatic tumor

• Not common in US---more common in Asia, Scandinavian countries; more frequent with Blood type A
• Aggressive: tends to spread to adjacent organs
• Risk factors: smoked foods, chronic gastritis, H pylori
• Bilateral involvement of the ovaries by metastatic stomach cancer is called a Krukenberg tumor

• MALT (mucous-associated lymphoid tissue)
• Originates from B cells in the marginal zone of the MALT

Most common anomaly of small intestine; Rules of twos; can be complicated with ulceration

• Chronic inflammatory condition of any part of GI tract;
• Skip lesions of involvement
• Young people 2nd and 3rd decades
• Symptoms: pain diarrhea, fever
• Transmural inflammation
• Strictures; fistulae, non-caseating granulomas
• Linear ulcerations; cobblestone appearance

• Limited to large bowel; continuous progression from rectal area
• Crypt abscess; pseudopolyps; red granular appearance to colon mucosa involved
• Not Transmural-shallow ulceration; can have extra-intestinal manifestation also such as polyarthritis
• Chronic diarrhea with passage of blood and mucus; cramping
• Complications: Colon cancer risk increased; perforation

malabsorption syndrome resulting in fatty stools

• gluten (gliadin) sensitivity; villous atrophy, flat mucosa; chronic inflammation; growth retardation--failure to thrive
• Malabsorption syndrome

• small intestine; Tropheryma whippeli bacillus in PAS positive macrophages; arthralgias, cardiac, neurologic symptoms
• Malabsorption syndrome

Dilation of colon (megacolon) and absence of ganglion cells; always involves the rectal area; constipation/ blockage

flask shaped ulcers in colon; liver abscesses

Villous adenomas (they are also the least common type of polyp)

• Gardner syndrome
• Familial polyposis
• Turcot syndrome
• (all have very high malignant potential)

• Adenomatous polyps
• Inherited polyposis syndrome
• Longstanding ulcerative colitis
• Genetic factors
• Low fiber, high animal fat diet

twisting of the bowel

telescoping of the bowel; mostly occurs in kids <4

protrusion of bowel from its normal position through a defect in the abdominal cavity wall

Blind pouches in colonic wall; can be due to lack of fiber

Inflammation of diverticula; colicky pain; rectal bleeding

ballooning degeration; hepatocytes necrosis (Councilman bodies); Piecemeal necrosis in chronic hepatitis; Ground glass hepatocytes-Hepatits B;

fatty change, focal liver cell necrosis, neutrophil infiltrates; Mallory bodies

no carrier state; no relation to cancer; oral fecal transmission

most infectious of the bloodborne Hepatitis virus

85% proceed to chronic infection

Requires Hep B presence to infect

transmitted oral fecal like Hep A

HBsAg in serum more than 6 months

• Associated with higher incidence of hepatocellular carcinoma
• Many types of cirrhosis
• Primary biliary cirrhosis due to autoimmune origin; anti-mitochondrial antibodies; middle aged women; severe obstructive jaundice, itching, elevated cholesterol
• Secondary biliary cirrhosis due to extrahepatic biliary obstruction; bile stasis
• Alcoholic cirrhosis: starts with fatty change (steatosis); can proceed to inflammation with necrosis and Mallory bodies; can finally proceed to cirrhosis

• excess iron absorption and severe iron overload;
• autosomal recessive; increased serum iron and transferrin
• Can cause cirrhosis
• Bronze diabetes=triad of diabetes mellitus, cirrhosis, and increased skin pigmentation

local or systemic deposition of hemosiderin without organ damage

• Autosomal recessive disorder of copper metabolism
• Decreased serum ceruloplasmin
• Kayser Fleischer rings in cornea
• Liver disease ranging from chronic hepatitis to cirrhosis
• Involvement of basal ganglia---motor signs

• One of the most common causes of childhood cirrhosis
• Inability to inhibit protease enzymes
• Can have effects on lungs and liver
• Increased risk for hepatocellular carcinoma

• Benign tumor
• Related to oral contraceptive use
• Rupture can result in severe hemorrhage

• Most common Primary malignancy of liver
• Associated with cirrhosis (especially HBV and HepC)
• Aflatoxin B exposure
• Increased serum alpha fetoprotein

associated with thorotrast dye, arsenic, or polyvinyl chloride

Metastatic malignancy

• Predisposed by alcohol intake and gallstones
• Increased serum amylase
• Severe abdominal pain
• Hypocalcemia
• 20% mortality

• Progressive parenchymal fibrosis
• Associated with alcoholism/cholecystitis
• Can have calcifications
• May have pseudocysts

• Most often in the head of pancreas
• Causes obstructive jaundice
• Abdominal pain radiating to the back
• Poor prognosis; early metastases

• Five F’s (female, fertile, fat, over age forty, flatulent)
• Most are cholesterol/ calcium stones in U.S.
• Attacks often precipitated by a fatty meal

• Also called juvenile diabetes—begins early in life usually before age 30; sudden onset
• Due to a failure in insulin synthesis by Beta cells of pancreatic islets
• May be caused by a genetic predisposition complicated by autoimmune inflammation (destroys Beta cells) triggered by a viral infection or environmental factors
• Unless insulin is replaced: Carbohydrate intolerance with hyperglycemia; polyuria, polydipsia, weight loss despite increased appetite
• Can lead to ketoacidosis, coma, and death
• TYPE 1:Usually before age 30
• Sudden onset
• Normal body weight
• HLA associations; familial history < 20%)
• Antibodies to beta cells
• Inflammation (insulitis), loss of Beta cells, fibrosis
• Reduced serum insulin levels
• 90% exhibit complication of diabetes with 20 years

• Characteristically begins in middle age
• Due to increased insulin resistance
• Gradual onset
• Etiologic factors: Positive family history, High concordance among twins, Mild to moderate obesity
• Clinical/LAB: Normal to increased serum insulin, Mild carbohydrate intolerance, Ketoacidosis is unusual —precipitated by infection or surgery
• Usually after age 30
• Gradual onset
• Obese
• No HLA assoc.; familial history more common (60%)
• No antibodies
• Non-specific islet changes and amyloidosis
• Normal to elevated serum insulin
• Less common to have complications than type 1 diabetes

• Increased thickness of GBM/ more permeable
• Diffuse glomerulosclerosis/ Kimmelsteil Wilson disease
• Arteriolar lesions
• Pyelonephritis/ papillary necrosis

• Increased atherosclerosis
• Myocardial infarctions more common
• Peripheral vascular insufficiency
• Gangrene of extremities

• Cataracts more common
• Diabetic (proliferative) retinopathy-exudates, microaneurysms

Peripheral neuropathy—numb toes and other woes

Fatty changes

• Xanthomas
• Abscesses/ fungal lesions - increased tendency toward infection