Q6 Gnmd Week 1 Lasku's Study Guide Pathologies

Front 1

GERD: M,SS,C

Back 1

Morphology: inflammatory epithelial cells, basal zone hyperplasia w/ 20% epithelial layer
Clinically:
• Heartburn
• Regurgitation
• Hematemesis, Melena
• Dysphagia
Complications: Barrett’s Esophagus

Front 2

Esophagitis: E, SS

Back 2

Etiology: alcohol, heavy smoking, candidiasis
Clinically: odynophagia, dysphagia, chest pain

Front 3

Eosinophilic Esophagitis

Back 3

Etiology: food allergies
Clinically: dysphagia, food impaction, heartburn

Front 4

Esophageal Varices: E, SS, C

Back 4

Etiology: 90% cirrhotic (chronic alcoholism)
Clinically: asymptomatic, rupture w/ massive hematemesis
Complications: hemorrhage, hepatic coma

Front 5

Acute Gastritis: E, M, SS

Back 5

Etiology: nSAIDs, alcohol, smoking, chemotherapy, uremia
Morphology: infiltration of neutrophils + erosions
Clinically:
• Asymptomatic
• Epigastric pain, N/V
• Hematemesis, Melena

Front 6

Peptic Ulcer: E, P, L, SS

Back 6

Epidemiology: middle-aged men
Pathogenesis:
• nSAIDs, ASA, corticosteroids, smoking
• H. Pylori secretes: Urease, Proteinase, Phospholipase, MPO, Bacterial PAF

Front 7

Duodenal Ulcer Morphology:

Back 7

• 100% H. Pylori
• Zollinger-Ellison Syndrome: ↑ gastric acid secretion or ↓ mucosal protection
• Pain w/ meals
• More benign
• Also occurs w/ COPD, alcoholic cirrhosis, chronic renal failure, hyperparathyroidism

Front 8

Gastric Ulcer (lesser curvature) Morphology

Back 8

• 70% H. Pylori
• ↓ mucosal protection against acid
• Pain relieved w/ meals
• “punched-out” appearance
• May be cancerous! Sharply demarcated (benign)
*All gastric ulcers should be biopsied!

Front 9

Gastric Carcinoma: E, SS, L, Met

Back 9

Epidemiology: most common cancer of stomach (usually adenocarcinomas)
Pathogenesis: H. Pylori, Barrett Esophagus, nitrates, smoked food, Blood Group A
Morphology:
• Location: Antrum/pylori (most common) → Lesser curvature (40%) → Cardia
• Depth of invasion:
o Early: mucosa + submucosa
o Advanced: transmural
• Growth patterns: excavated, exophytic, flat
o Excavated advanced: heaped-up, beaded margins, shaggy necrotic bases
• Linitus Plastica: “leather bottle” appearance, diffusely infiltrated + ulcerations of gastric wall.

Front 10

gastric carcinoma

Back 10

• Poorly differentiated: marked pleomorphism, vacuole of mucin, Ab to Cytokeratin
Metastatization: regional lymph nodes, Virchow Node (supraclavicular), liver, Krukenberg Tumor (ovaries)
Clinically:
• Abdominal pain, N/V
• Anorexia, Weight loss
• Altered bowel habits
• Anemia
• Dysphagia
• Hemorrhage

Front 11

Diffuse gastric carcinoma

Back 11

• Signet ring cells: tumor cells filled w/ mucin that push nucleus to one side; from pluripotent stem cells
• Stiffened stomach
• Short precancerous state
• High animal products, low veggies

Front 12

Intestinal gastric carcinoma

Back 12

• Penetrate gastric wall
• Chronic gastritis
• Discrete mass in stomach
• Long precancerous state
• High salt + nitrates, low veggies

Front 13

Malabsorption Tests
1) Celiac Sprue (transepithelial transport): E, SS, M

Back 13

a. Def: malabsorption of what gliadins and related grains
b. Pathogenesis: cell-mediated HR (type 2) → accumulation of Tc → cytokine release → damage to jejunum
i. HLA-DRw2 & HLA-B8
c. Morphology: diffuse enteritis in PROXIMAL small intestine, marked atrophy or total loss of villi, ↑ # of intraepithelial lymphocytes
d. Clinically:
i. Infants: diarrhea, FTT
ii. Adults: diarrhea, Fe deficiency anemia
e. Labs: IgG+IgA antigliadin antibodies, Antiendomysial antibodies
f. Complications: intestinal T lymphomas, GI, breast cancer

Front 14

IBD
1) Crohn’s: E, P, SS, C

Back 14

a. Def: transmural involvement of bowel and inflammation process w/ mucosal damage.
b. Incidence: affects any age, mainly teens-20s, white, female
c. Etiology: HLA-DR1/DQw5 combo (27%)
d. Morphology:
i. Bowel wall thickening in small intestine + terminal ileum
ii. “creeping fat”: ulcerations + edema → cobblestone appearance
iii. apthous ulcers → fistula formation
iv. Skip lesions: normal intestine among affected segments
v. Histology: infiltration of neutrophils, crypt abscess formation, lymphoid aggregates, noncaseating granulomas, fibrosis, strictures.
e. Clinically: intermittent attacks of mild diarrhea, abd pain (RLQ), fever
f. Complications: abscess, strictures, fistulas to other organs

Front 15

IBD

2) Ulcerative Colitis: E, P, SS, C

Back 15

a. Etiology: genetic predisposition, ulcerations of mucosa from inflammation.
b. Epidemiology: white, female, 20-25 y/o, non-smokers/ex-smokers
c. Pathogenesis: begins in rectum → entire colon w/out skip lesions, broad-based ulcers of mucosa
i. Large area of ulceration → giving appearance of pseudopolyps
ii. Crypt abscesses
d. Clinically:
i. Asymptomatic intervals w/ insidious or fulminant attacks of bloody, mucoid diarrhea, fever, urgency, cramping; lower abd pain and cramps relieved by defecation
ii. Anemia, hypoalbuminemia, severe weight loss, electrolyte imbalance, dehydration.
e. Complications: toxic megacolon, colorectal cancer

Front 16

Vascular Diseases
1) Ischemic Bowel Disease: E, P, SS

Back 16

a. Etiology: results from acute occlusion or hypoperfusion of a segment or several meters of bowel.
i. Severity ranges from mucosal → mural → transmural infarct
b. Pathogenesis:
i. Arterial thrombosis: atherosclerosis
ii. Arterial embolism: cardiac vegetations, angiographic procedures, aortic atheroembolism
iii. Venous thrombosis
iv. Non-occlusive ischemia
v. Miscellaneous
c. Morphology: infarctions
i. Mucosal + Mural: dark red or purple but hemorrhage/inflammatory exudate are absent from serosa
ii. Transmural: congested and purple-red, later hemorrhagic infarct
1. Arterial: sharply demarcated
2. Venous: not sharply defined
iii. Chronic: mucosal + submucosal; mimics acute enterocolitis or IBD
iv. Histology: edema, interstitial hemorrhage, necrosis of mucosa/submucosa, gangrene within 1-4 days by intestinal bacterial
d. Clinically:
i. Transmural infarct → (death d/t perforation) bloody, mucoid diarrhea, severe abd pain, N/V, shock

Front 17

Vascular Diseases
1) Colorectal Cancers: E, P, M, SS, L

Back 17

Carcinogeneisis
a. Adenoma-carcinoma sequence: colorectal carcinomas develop from adenomas
b. Molecular carcinogenesis: genes that are mutated are
i. APC: tumor-suppressor gene common in FAP/Gardner Syndrome
ii. K-ras: in 50% of colorectal carcinomas
iii. DCC: produces an adhesion molecule in 70-75% colon cancers
iv. P53: 70-80% of colon cancers
c. Multihit hypothesis: the 1st genes to mutate are APC → DNA repair genes → adenomas → P53, DCC etc contribute.
• Epidemiology: 60-79 y/o
• Etiology: Excess food, low fiber, red meat (high cholesterol)
• Pathogenesis:
a) Toxic oxidative products of carb degradation produced by bacteria may stay in colon longer or high cholesterol stimulates liver to prduce higher amount of primary bile acids → secondary bile acids by bacteria which irritate colonic mucosa → predisposing for colorectal carcinoma.
b) PGE2 binds to EP2; G protein and its subunit act through distinct pathways to converge to promote stabilization and nuclear translocation of beta-catenin (protein that promotes transcription of genes to increase proliferation of cancer cells).
• Explain why nSAIDs inhibit signaling of PGE2
• Morphology: cecum + ascending colon (38%), “apple core” lesion
a) Histology: adenocarcinomas
• Clinically:
a) Fatigue, weakness
b) Fe Deficiency Anemia (in older males, means GI cancer usually)
c) Melena
• Prognosis: extent of tumor at time of diagnosis; Astler-Coller used for staging ;;

Front 18

1. LabDX of intestinal malabsorption: D-xylose Test, Schilling Test, H+ Breath Test

Back 18

Fecal fat is INCREASED =
i. D-xylose absorption test: Abnormal – Intestinal Disease
ii. Perform:
1. Small bowel biopsy
2. Abnormal: Celiac’s, Whipple’s disease, hypogammaglobulinemia (IgA), lymphoma
3. Normal: bacterial overgrowth; perform Urinary Indican Test
iii. Other Tests
1. Hct, BUN & Creatinine, Na+ (dehydration); Eosino (parasites); Platelets (Ulcerative colitis, Whipple's disease, Celiac sprue), PT; LDH, AST (Decreased Vit. B12, death of megaloblasts); ALP (osteomalatia, Vit. D def).
iv. Other tests that are decreased with Intestinal Malabsorption:
1. Hct (blood loss); Lymphocytosis (leakage of lymph in the gut); Na+ & K+ (diarrhea); Ca+2 (Vit. D def., hypoalbuminemia); glucose & BUN (malabsorption of glucose and proteins); Mg+2, Albumin, Bilirubin (decreased albumin); Cholesterol, iron. ;;

Absorption Testing: Schilling Test =
v. Also identifies megaloblastic anemia due to B12 deficiency
vi. If the test indicates low excretion (and thus low absorption of B 12), then the test in repeated with intrinsic factor.
1. If the test again indicates low excretion, the test can be repeated a 3rd time with intrinsic factor after a therapeutic trial of antibiotics for bacterial overgrowth.
vii. In most cases, malabsorption is likely the cause and antibiotics are avoided. Further testing can be used to confirm the malabsorption (e.g. intestinal biopsy, stool analysis, D xylose test, breath hydrogen).
viii. Normal values
1. Normal - 9% of tagged B12 is excreted in first 24 hrs
ix. Clinical significance
1. Lack of intrinsic factor seen in pernicious anemia, malabsorption, celiac disease ;;
b. Intestinal Bacterial Overgrowth Tests: H+ Breath Test =
i. Measures hydrogen levels of exhaled breath. Hydrogen (H2) is produced by fermentation by intestinal bacteria. Overgrowth of intestinal bacteria results in increased breath hydrogen levels.
ii. Used for lactase deficiency, dysbiosis, malabsorption
iii. May be used with an oral dose of lactose (50 grams) similar to a Glucose tolerance test. Blood and breath samples are gathered at 15, 30, 60 and 120’.
iv. Lactose curve is flat – disease present.
1. Glucose increases < than 20 mg/dL (N increases more)
2. H2 increased 20 times
v. Clinical Significance
1. Elevated breath hydrogen seen in malabsorption, dysbiosis and lactase deficiency.
2. The levels of hydrogen are proportional to the amount of lactose not absorbed.

c. Steatorrhea
i. 72h stool collection for Quantitative fecal fat analysis
ii. Microscopic exam of stools & Sudan stain (80 - 90% sensitivity)
iii. Serum Vit. A & carotene (not reliable)
iv. 14C-triolein breath test (sensitivity 85-100%; specificity 93-96%)

d. Fecal fat is NOT increased – Lactose Intolerance
i. Perform:
1. Lactose Intolerance Test
2. H+ Breath Test (better) ;;

Front 19

2. LabDx of pancreatic malabsorption:

Back 19

a. Fecal fat is INCREASED
D-xylose absorption test: Normal - Biliary & pancreatic diseases
i. Perform
1. Secretin test (complicated but sensitive)
2. Bentiromide assay (Ingest 500 mg of bentiromide. Normal - 50% of bentiromide is secreted as PABA in urine within 6h)
3. Serum Trypsin-like immunoreactivity level test
4. Interpretation - Bentiromide test & STLI test are decreased with Chronic pancreatitis & pancreatic cancer
Tests
b. D-Xylose: normal levels found in pancreatic insufficiency
c. Pancreatic Function
i. Serum Amylase
ii. B. Serum Lipase
1. Digestive enzyme produced by the pancreas for the digestion of fat (assisted by bile)
2. Levels are measured in serum
3. Lipase levels rise (12h) slower than amylase and remain elevated longer (7-10d).
iii. Clinical Significance
1. Elevated levels are indicative of pancreatic disorders including pancreatitis and pancreatic cancer
2. Decreased levels associated with lipidemia (false decrease)
3. sAmylase+sLipase = 100% sensitivity for Acute pancreatitis
iv. Chymotrypsin (in Stools)
1. Chymotrypsin is a proteolytic enzyme produced by the pancreas
2. Chymotrypsin levels are measured in stool. Stool levels correlate well to duodenal levels.
3. Clinical Significance
a. Low levels indicate low production by pancreas, pancreatic insufficiency
b. b. High levels indicate rapid transit time.