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97 Cards in this Set
- Front
- Back
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The Pancreas
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-made up of parenchyma and duct system
-dorsal and ventral segment fuse in embryo to form the gland -ventral duct (duct of Wirsung) provides the main drainage route by linking the body and the greater duodenal papilla -lack of continuity in duct and major papilla leads to pancreas divisum leading to the major drainage coming from the acessory duct (duct of Santorini) draining into the lesser papilla -islets of langerhans (endocrine cells producing insulin and glucagon) and acini (produce digestive enzymes) both drain into ducts lined by columnar cells that secrete 2.5 L of bicarb rich fluid every day -main secretory regulators: Cholecystokinin (CCK) is produced in response to fatty acid and amino acids in the duodenum; Secretin stimulates water and bicarb secretion from ductal cells mainly in response to duodenal acid loads and luminal fatty acids |
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What is acute pancreatitis?
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-inflammation of the pancreas usually with one etiologic agent (ex. gallstone, alcohol, etc)
-the pancreas doesn't autodigest because: 1)membrane attacking enzymes are made as zymogens; 2) enzymes are segregated in membrane-bound compartments; 3) pancreas has trypsin inhibitor intracellularly; 4) activating enzyme (enterokinase ) is located separately from the pancreas |
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Pancreatic enzymes
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INACTIVE PROENZYME: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidases A and B, prophosholipase
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What is the etiology of acute pancreatitis?
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-gallstones and alcohol: major cause (80%)
-trauma and iatrogenic: accidents, gun/knife wounds, opperative trauma and post-ERCP -drug induced: azathioprine, valproic acid, thiazides -others: hypercalcemia, hyperlipidemia, infections, ischemic/shock induced, anatomic predisposition, neoplastic or malignant -idiopathic: biliary sludge and genetics |
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What is the pathogenesis of gall stone pancreatitis?
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-pancreatic duct obstruction of ampulla of Vater (where common bile duct joins) with stone or edema
-intra-pancreatic enzyme activation (due to fusion with lysosomes in the acinar cells) and accumulation of trypsinogen in interstitial space -the acinar cells are autodigested and leakage of the activated enzymes infiltrate the surrounding parenchyma -neutrophils may also be recruited by cytokines |
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What is the pathogenesis of alcoholic pancreatitis?
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-dutular stricturing and dilation
-combination of stimulation of the pancreatic juice production leading to pugging the ducts/possibly a spasm in the sphincter of Oddi leading to increased pressure and back up -the more the retention of pancreatic enzymes, the more the liklihood of activation and autodigestion |
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What are the genetic factors of pancreatitis?
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-hereditary pancreatitis (HP) is an autosomal dominant familial form linked to mutation of the cationic trypsinogen gene (gain of function)
-1/2 patients may develop chronic pancreatitis -SPINK1 and PST1 mutations occuring in the trypsin inhibitor also have been found |
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What are the harmful effects that can be caused by trypsin?
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-cleaves several of the pancreatic enzymes for activation
-bradykinin: capillary permeability, vasodilation, hypertension -kallikriens: pain -thrombin: clots -plasminogen: clot lysis -inactivates hormones leading to Calcium disturbances |
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How is the diagnosis of acute pancreatitis made?
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SYMPTOMS: upper abd. pain radiating to the back, nausea/vomiting are common, tachycardia, tachypnea, HTN, abdominal distention and tenderness with decreased bowel sounds
LABS: increased serum amylase, serum lipase, urinary trypsinogen (rapid diagnosis and good for staging severity) RADIOLOGY: abnormal series (excludes bowel obstruction and perforation) calcifications suggest alcoholic; pancreatic and biliary ultrasound (can see presence of gall stones or edema; CT scan (best resolution of the pancreas, can see enlargement, fat necrosis, and inflammation) |
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How is acute pancreatitis medically managed?
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PREVENTION: correctable causes need to be identified, need to rule out biliary sludge, mutations for trypsinogen
ANALGESIA: demerol prefered to morphine as it causes less sphincter of Oddi spasm FLUID/ELECT REPLACEMENT: IV volume depletion secondary to splanchnic pooling, retroperitoneal losses and vomiting NUTRITION: NPO until pain has subsided and patient is hungry, TPN should be done for severe cases, enteral nutrition is associated with fewer pancreatic infections and multiorgan system failure |
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What is the typical course and prognostic signs of acute pancreatitis?
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-mild episode: pain for 3-6 days, hypoactive bowel sounds for 3-4 days; need to have NPO status until discharge 7-10 days
-severe/protracted episode: recurrent n/v and pain following PO intake, associated with psuedocyst or sterile necrosis -prognosis is evaluated on scoring systems (Ranson's criteria, APACHE II score and end organ dysfunction); elevated levels of PMN elastase, CRP and IL-6 PAP predict severity |
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What are the invasive procedures and surgeries in acute pancreatitis?
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-gallstone pancreatitis: cholecystectomy within 4 weeks with endoscopic retrograde cholangiography (ERC)
-acute pseudocyst: compicated by infection need surgical drainage, should try to obtain aspirate with fine needle to examine for organisms -clincally detriorating patients: CT scan with bolus contrast to look for areas of nonperfusion as it indicates necrosis; possibly IV antibiotics, endoscopic stenting and/or immediate surgery |
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What is chronic pancreatitis?
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-increase in CT and lobar atrophy with minimal acute inflammation
-four distinct clinical syndromes: chronic relapsing with episodes of acute pancreatitis and chronic histology; chronic abd. pain; pancreatic acinar insufficiency with malabsorption and steatorrhea; pancreatic islet failure (diabetes) etiology: Toxic-metabolic (alcohol, hypercalcemia), Idiopathic, Genetic, Autoimmune, Recurrent, Obstructive |
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What is the pathogenesis of chronic alcoholic pancreatitis?
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-precipitation of protein plugs composed of normal pancreatic enzymes in duct due to a higher concentration of enzymes produced
-plugs undergo calcification -smoking is an independent risk factor -fibrosis from pancreatic response to acetaldehyde -extensive fibrosis leads to interference of the blood supply and ischemia leading to atrophy of the islets --> secondary diabetes mellitus |
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What are the clinical patterns of chronic pancreatitis?
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-replasping acute episodes: very self limited to recovery withing 3-5 days
-chronic pain: punctuated acute attack associated with alcohol that usually diminishes with time -exocrine pancreatic insufficiency: pancreatic failure manifested by weight loss, steatorrhea and fat vitamin soluble deficiencies -pancreatic diabetes: occurs in 70% of patients with chronic pancreatitis with calcifications -problems: jaudice (stricturing of the intrapancreatic common bile duct, elevation of alkaline phosphatase or GGT) GI bleed (thrombosis of splenic vein leading to gastric varicies, pseudocysts can erode into blood vessels or intestinal tract) |
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How is chronic pancreatitis diagnosed?
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-pancreatic biopsy: gold standard, shows fibrosis and inflammation
-plain film of abdomen: calcifications -pancreatic function testing: secretin or secretin +CCK stimulation and collection of the secretions; ET-PABA administration requiring chymotrypsin cleavage; fecal tests for elastase -Endoscopic Retrograde Pancreatography: can show focal strictures and/or dilations but has risk of causing chronic pancreatitis -Endoscopic ultrasound (EUS) less invasive than ERCP with no risk of pancreatitis |
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What is the managment of pancreatitis?
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-abstinence from alcohol
-treatment of acute episodes -chronic pain: enzyme replacement, narcotic analgesics, celiac plexus neurolysis -pancreatic exocrine and endocrine insufficiency: low fat diet with enzyme preparations, treat dm -surgical: psuedocysts should get drainage or resected if indicated |
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What are the complications of acute pancreatitis?
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-abscess formation: necrotic tissue can be secondarily affected with gram neg. organisms
-psuedocyst: cavity filled with debris of necrotic tissue, degregaded blood, and enzymes that is walled off by granulation tissue; rupture is a serious complication and can lead to spillage leading to chemical peritonitis, widespread autodigestion, massive hemorrhage and shock; can also be septic and lead to septic peritonitis |
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What is the incidence and etiology of pancreatic ductal carcinoma?
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-tumor has a grim prognosis with death in almost all patients
-appears lat in life with greatest incidence over age 60 ETIOLOGY: heavy smokers have 2-3 times higher risk than nonsmokers; long-standing diabetes and chronic pancreatitis can be risks; obesity with a diet rich in fat also shows higher risk |
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What are the clinical features of pancreatic carcinoma?
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-insidious onset
-carcinoma of head can lead to jaundice (leads to earlier detection than those seen in the body or tail) -pain presents in most patients with body/tail involement; they tend to be large and invading retroperitoneal plexi (advancedc and usually inoperable) -weight loss due to TNF alpha and other cytokines released -migratory thrombophlebitis (trousseau syndrome) thrombi in multiple veins like subclavian, iliac and portal and IVC -dismal prognosis: deep in the retroperitoneum leads to large growth before detection, rich lyphatics and venous drainage leads to easy metastasis, 10-15% are operable but still carry a high mortality rate with surgery, median survival is 5 months, 5 year survival is 5% if located in the head (lowest of all cancers) |
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What is the pathology of pancreatic carcinoma?
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-can occur anywhere but is most frequent at the head (60%) followed by the tail (15%) and body (10%)
-most are mucin-producing ductal adenocarcinomas -SPREAD - head: usually invades common bile duct, ampulla of Vater, etc. leading to obstruction that can lead to atrophy of the body and tail; body and tail: invades retroperitoneum, stomach, colon, small bowel and spleen; distant spread: occurs through regional lymph nodes though the portal vein to the liver, lungs and other organs |
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What are the common complications of pancreatic carcinoma?
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-body and tail: widespread venous thrombosis and pulmonary embolism (Trousseau syndrome) and DIC
-head: biliary obstruction can lead to cholangitis and sepsis; can also lose the ability to absorb vitK leading to a bleeding tendency that counteracts the tendency to thrombose (why presenting Trousseau syndrome is characteristic of body/tail carcinoma) |
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What are the molecular genetics of pancreatic cancer?
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-multistep developing over several years
-initial mutation creates a lesion that is neoplastic but minimally dysplastic -pre-invasive lesions are termed "pancreatic intraepithelial neoplasias" (PanIns) -early stages have telomere shortenings of K-RAS oncogenes; next is inactivation of p15 tumor suppressor gene; loss of p53, SMAD4 and BRCA2 happen in hte late stages |
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What are the rules of studying pancreatic islet cell tumors pathologically?
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-not alsway possible to predict on histologic grounds whether benign or malignant, need to look for metastasis
-all look alike on H&E stain, need to do immunohistochem to determine hormone secreted -clinical presentation is based on hormone that is secreted the most -tumors can arise from duodenum, peripancreatic soft tissue or stomach -tumor can be part of a syndrome MEN |
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What is MEN1?
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-familial disorder of the tumor suppressor gene MEN1
-features are: 1) ademoma/hyperplasia of parathyroids (hypercalcemia: leading to kidney stones, pancreatitis by prolonged increase of enzyme secretion due to calcium) 2) adenoma/carcinoma/ hyperplasia of pancreatic islets: leading cause of morbidity and mortality, usually metastasized by diagnosis, gastinomas and insulinomas are most commmon 3)Adenoma of pituitary: usually a prolactinoma |
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What are the tumors of the pancreatic islet?
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INSULINOMA: B cell, hypoglycemia, 10% malignant
GLUCAGONOMA: A cell, mild diabetes, >75% malignant GASTRINOMA (Zollinger Ellison): G cell, g. acid hypersecretion, ulcers, diarrhea, malabsorbtion, >70% malignant VIPoma: D1 cell, watery diarrhea, hypokalemia, hypovolemia, 60% malignant SOMATISTATINOMA: D cell, diabetes, hypochlorhydria, steatorrhea, gallstones, 70% malignant PANCREATIC CARCINOID: EC cell, serotonin, carcinoid syndome 100% malignant |
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Epithelial Tumors of small and large intestine: Adenomas
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-benign, neoplastic growth
-precursor lesions of adenocarcinoma -have geographic variations related to diet (common in areas with high fat, low fiber) -high fat increases conc. of bile acids in stool (cacinogenic); low fiber means an increased bowel transit time; more contact time with bacteria to produce carcinogens -2 major growth patterns: pedunculated or sessile -histo features: tubular (closely packed with epithelial lining and intervening normal lamina propria); vilous (finger like projections, usually larger and sessile with a higher incidence of harboring carcinoma); tubulovillous (combination of the two) |
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What is Familial Adenomatous Polyposis?
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-mutation in APC tumor suppressor gene on chromosome 5
-APC: binds microtuble bundles and promotes cell adhesion and migration; also binds B catenin in a complex that also binds E-cadherin; mutation leads to reduction of affinity to B catenin leading to an enhancement of cell proliferation with a predisposition to adenomas and later carcinoma -see huge numbers of polyps in patients -100% risk of developing colon carcinoma, patients undergo prophylactic cholectomy -associated with several other extracolonic manifestations: osteomas, fibroma, lipomas, breast cancer, desmoid tumors (Gardener's syndrome) etc. |
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What is Hereditary Non-Polyposis Colon Cancer Syndrome (HNPCC)?
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-also known as Lynch Syndrome
-patients have germline mutation in DNA mismatch repair genes and they display genetic instability with a higher mutation rate than gen. public (microsatallite instability in DCC gene and cyclin D1 gene) -don't have large numbers of polyps -are also at risk for endometiral, breast, ovarian, stomach and urinary tract carcinoma -typically develop multiple colonic polyps but not as many as in FAP; are usually found on right side; are usually mucinous and poorly differentiated |
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What is Hyperplastic Polyposis?
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-diagnostic criteria: at least five histologically confirmed hyperplastic (serrated) polyps proximal to sigmoid colon, 2 > 1cm; first-degree relative with hyperplastic polyposis; more than 30 polyps distributed throughout the colon
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What are hyperplastic polyps? traditional serrated adenoma? and sessile serrated adenoma?
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HYPERPLASTIC POLYPS: frequently in left colon, show glandular serration, deeper crypts show expansion in proliferative zone with no dilation, surface epithelium is usuallyl thickened
TRADITIONAL SERRATED ADENOMA: tall, columnar cells with eosinophillic cytoplasm with hyperchromatic nuclei, can see ectopic crypts (shortened with no contact with the muscularis mucosa) SESSILE SERRATED ADENOMA: right sided, large, sessile and poorly circumscribed, see dilation of crypt bases with L or T shaped crypts |
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Colon Cancer
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-small carcinomas are usually sharply circumscribed button-like lesions
-as lesion grows it has deeper penetration and desmoplasia becoming firm and pale -right sided are usually bulky but rarely cause obstruction -left sided are usually ulcerated and ifiltrating -are adenocarcinomas with neoplastic glands w/in the submucosa -can be mucinous (>50%, has a poorer pronosis than normal adenocarcinoma); signet ring (large mucin vacuole displacing the nucleus, has a poor prognosis); small cell (neuroendo. differentiation w/o gland formation, very poor prognosis) |
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Small Intestinal Adenocarcinoma
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-frequently arise in ampulla of Vater
-Chron's patients and colonic polyposis syndrome pts. have higher incidence of ileal tumors -see symptoms of cramping pain, nausea, weight loss, anemia, and sometimes jaundice -at time of presentation most tumors are advanced with presence of mets to the liver of LN -w/ surgery the 5 year survival is 70% -carcinoids: more frequent distally, higher incidence of metastasis (commonly to the liver), high cure rate with if all is resected, flushing is the hallmark, can see a carcinoid crisis with anesthesia |
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Gastric Cancer: Risk Factors and Types
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-risk factors: diet (nitrites in food and water, salted and smoked food, pickled veges, and lack of fresh fruit/veges); host factors (chronic atrophic gastritis, H. pylori, gastrectomy, adenomas); genetics (racial groups and cancer syndromes)
-two types: diffuse (de novo, 50% of cancer in the US, earlier age of onset, signet ring cells) and intestinal (comes from areas of intestinal metaplasia, common in high risk areas, later onset, associated with chronic gastritis, goble cells not normally seen in the stomach are seen) |
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Gastric Cancer: Growth Patterns and Histo Features
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-usual location is in the antrum, lesser curvature and cardia
-patterns: exophytic: tumor projects into gastric lumen; flat or depressed: not visibly obvious, diffuse involvement of the wall leading to thickened stomach (Linitis Plastica); excavated: deeply ulcerated crater, differentiation from a benign ulcer is important -early cancer is confined to the mucosa of submucosa and status of LN, good prognosis at early stage -advanced: invasion into muscularis propria or serosa w/ or w/o LN mets |
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Hereditary Diffuse Gastric Cancer
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-patients inherit a defective copy of E-Cadherin gene
-develop diffuse gastric cancers usually advanced at time of diagnosis -metastasis: usually to regional LNs (sentinal, Virchow's node is common), peritoneal seeding and mets to the liver and lungs can be seen, also ovaries less frequently -prognosis: depends on depth of invasion and extent of nodal/distant mets; 5 yr for early is >95% but <10% for advanced |
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Gastric Epithelial Polyps
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-hyperplastic: most common, can be found at any location, are rarely malignant
-adenomatous: 2nd most common, located more in the antrum, "true neoplasm -syndromes: Gardner's, peutz-Jeghers, Cronkhite-Canada, Cowden's, FAP |
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Gastric Leiomyomas
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-most common benign tumor of the stomach, usually asymptomatic
-symptomatic polyps show bleeding and pain -surgical resection leads to lack of recurrance |
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Psuedotumors - Pseudolymphoma
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-lymphoid hyperplasia
-reactive lymphoreticular hyperplasia -reclassified as "low-grade MALT lymphoma" -stomach doesn't normally have lymphoid tissue, but tissue is present due to concurrent H. pylori infection |
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Gastric Carcinomas
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-malignant tumors (adenocarcinomas ~95%, lymphomas ~5%)
-risk decreases with migration to western countries, very common in Asia -role of nitrates: nitrates are converted to nitrites --> become notros-amines and -amides --> increased achlorhydria -foods that reduce risk: vitC, fresh veges, whole milk, refrigeration -H.Pylori: leads to irritation/inflammation, epithelial metaplasia and dysplasia -other high risk groups: postgastrectomy, pernicious anemia, hypertrophic gastropathy -symptoms and exam: abd. pain, weight loss, obstruction, dysphagia, Fe anemia, GI bleed; PE: normal, cachexia, abd. mass, hepatomegaly/acites, Virchow's node |
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Cystic Fibrosis
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-defect of absorption due to luminal phase defect
-more common in caucasian (1/2500 births) -see clinical triad of sweat gland, respiratory epithelium, and exocrine pancreas dysfunction, usually occurs by 2 yrs -defective CFTR gene (cAMP-activated chloride channel): luminal chloride ion secretion is prevented; chloride, bicarb, sodium and water are all unable to be drawn into the lumen; decreased luminal hydration is seen -chronic autodigestion of the exocrine pancreas leading to exocrine pancreatic insufficiency (can be treated with administration of exogenous enzymes) |
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Celiac Disease "Sprue": mechanism and etiology
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-defect in absorption due to surface area defect
-"gluten-sensitive": component of wheat and grains -mechanism: immune mediated with IgA and/or IgG Abs to gliadin; anti-endomysium antibodies (specific marker); tissue transglutaminase (tTG) is an antigen in the endomysium, anti-tTG can also be assayed -epidemiology: familial clustering, strong HLA-DQw2 genetic association, presentationis from infancy to mid-adulthood |
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Celiac Disease "Sprue": pathology and treatment
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-pathology: flattened small bowel mucosa, intraepithelial lymphocyte and plasma cell infiltrate, crypt hyperplasia, proximal dz worse than distal
-treatment: eliminate gluten, morphology of bowel goes back to normal, increased risk of intestinal lymphoma -refractory sprue: pts. redevelop flattened mucosa and malabsorption never responding to the gluten free diet; poor prognosis |
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Bacterial overgrowth
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-usually a combo of anatomic abnormality (Meckel's diverticulum, blind loop), abnl bowel motility, diminished host defense
-excessive accumulation of bacterial species not usually seen in the small bowel results -pathology: variable degree of vilous atrophy and crypt hyperplasia; reduction in absorptive surface area |
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Lactase Deficiency
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-defect in microvillus function
-inherited form leads to breast milk intolerance and severe failure to thrive -usually acquired that is most common in African Americans -mechanism: insufficient lactase, luminal lactose accumulation with no existence of lactose transporters, osmotic diarrhea occurs as water flows into the lumen -treatment: limit of dairy, "lactaid" |
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Giardia Lamblia Infection
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-defect in microvillus function
-protozoan infects the upper small bowel -damages enterocytes but doesn't invade, mucosa looks completely normal with mild villous blunting and mild inflammatory cell infiltrate -have common hypogammaglobulinemia: plasma cells absent from lamina propria, protective abs not produced, mucosa is entirely flat but can recover with antibiotic therapy -malabsorption due to damage of brush border enterocytes |
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Cryptosporidium
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-can infect any part of GI tract
-attatches to brush border of enterocytes -immunocompetent hosts: self limited course, normal villous length and inflamm. reaction -immunocompromised: villous blunting, organism can be invasive, severe watery diarrhea, no known effective treatment |
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Whipple's Disease
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-defect in absorption due to lymphatic flow defects
-rare disorder caused by Trophyrema whippelii -~85% are male, avg. 50 yrs, nearly all are caucasian -see mesenteric lymphadenopathy, lamina propria infiltration by macrophages, villus blunting, can see macrophages in brain, synovium, and elsewhere -all lead to vitamin deficiencies, malnutrition and wasting -usually responds to antibiotics |
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Mycobacteruium Avium Intracellulare (MAI)
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-usually occurs in severely immunosuppressed (AIDS)
-massive infiltration of macrophages with acid fast bacteria -similar pathology to Whipple's -malabsorption is due to distortion of mucosa and obstructed lymphatic flow |
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Lymphangectasia
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-congenital malformation in childhood or acquired in adults
-dilation of mucosal lymphatics usually affecting the small bowel -abnl lymphatics are prone to rupture and obstruction -protein (albumin), immunoglobulin and lymphocytes are all lost -secondary (acquired) cases usually due to mesenteric mass, tumor, radiation induced fibrosis leading to an obstruction |
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Abetalipoproteinemia
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-defect in absorption due to metabolic function defect
-very rare defect in apoB synthesis (apoB is responsible for synthesis and transport of LDL and chylomicrons) -apo gene is not affected, rather defect is in microsomal transport protein -lipid accumulates in epithelial cell, normal villi but enterocytes are filled wwith intracytoplasmic fat vacuoles -failure to thrive, diarrhea, steatorrhea, deficiency of essential fatty acids and vitamin E -progressive neuro and hematologic dysfunction |
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Drugs and Diarrhea
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-defect in absorption due to epithelial insufficiency
-colchicine, vincristine and other drugs interfering with cell replication -small bowel mucosa shows blunting of villi, shortened crypts, cellular atypia -mucosa recovers with cessation of the drug -malabsorption due to loss of enterocytes and absorptive surface area |
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What is the normal physiology or intestinal water and electrolyte transport?
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-fluid enters the lumen: 9L daily (2L from diet, 7L from exogenous excretions
-fluid is resorbed: 7.5L in the small bowel, 1.4L from the colon and 100mL are lost in stool -permeability: intestine can't dilute or concentrate beyond the plasma osmolality; duodenum and jejunum have high permeability relative to colon -geography: Cl secreted throughout intestine; HCO3 absorbed in jejunum and secreted in duodenum, illeum and colon; villus cells absorb Na and crypt cells secrete Cl -elec. composition of the stool: small bowel is similar to plasma, colon has lower Na and Cl and higher K conc. relative to plasma |
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What are the hormone/neurotransmitter effects on intestinal ion transport?
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NOREPI: dec. cAMP, diabetic diarrhea
SOMATOSTATIN and NEUROPEPTIDE Y: dec. cAMP GUANALINE: cGMP, toxigenic E.Coli infect goblet cells VIP: cAMP, tumors secreting VIP |
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What is diarrhea?
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-increased stool frequency or liquidity, stool weight > 200-250g/24 hrs
-can be acute (<2-3 weeks, usually self limited, drug or infection) or chronic (>6-8 weeks, with braod differential -can be due to: decreased absorbtion of fluid/elec.; increased secretion; occurs when amount of fluid leaving small intestine overwhelms reabsorptive capacity of the colon |
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What are the catagories of diarrhea?
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OSMOTIC: low volume < 1L, resolves with fasting, excess stool osmotic gap, stool pH<5-6 with carb malabsorption; caused by ingestion of poorly absorbed solute (Mg, PO4, lactulose sorbitol) or mucosal disease (acq. lactase def., celiac)
PURE SECRETORY: large stool volumes > 1L a day, persists with fasting, absence of fever, lack of stool osmotic gap; causes: 1)enterotoxigenic (inhibits small bowel Na and Cl absorption and stimulate Cl secretion, no damage to epithelium, glucose based rehydration solns are effective) examples include cholera (adenylate cyclase stimulating G-protein pathway is elevated) and toxigenic E.Coli (LT and ST toxin); 2)bile acid diarrhea from a decreased or resected illeum, colonic bacteria deconjugate wasted bile salts and inster themselves in coloncyte membrane increasing cAMP and Ca; 3) Tumor Hormones: VIP secreting tumors(pancreatic islets and ganglioneuromas), Carcinoid syndrome (intestinal/lung tumor metastasizes to liver and secretes serotonin, bradykinin, or substance P), Gastrinoma (high gastric output can overwhelm absorptive capacity of intestine), and Medullary Carcinoma of thyroid (calcitonin stimlates intestinal fluid secretion) |
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What are the catagories of diarrhea (cont.)?
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INFLAMMATORY: damage of intestinal epithelium; exudation of protein, blood and pus into lumen; urgency and frequency; low serum protein and albumin levels
-causes: ulcerative colitis, invasive bacterial infections (shigella, campylobacter, E.Coli) that invade intestinal epithelium resulting in damage also release of inflamm. mediators to inhibit Na and CL absorption, and cytotoxins (C. Diff, Shiga, hemorrhagic E.Coli) that cause damage with destruction and can cause severe diarrhea, pseudomembranous colitis or toxic megacolon ABNORMAL MOTILITY: hypermotility (thyrotixicosis, carcinoid) and hypomotility (scleroderma, amyloidosis, radiation, autonomic neuropathy) |
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What are the viral infections causing diarrhea?
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-usually cause short-term disease
CMV: immunocompromised, found commonly in colon but can be found anywhere, predominant in stroma and endothelial cells (also in glandular) |
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What causes acute self-limited colitis?
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-Salmonella, Shigella, E.coli, Yersinia and Aeromonas
-see the same histo regardless of organism, most important changes start 4 days after onset of clinical disease -cryptitis occurs more than crypt abscesses -colonic mucosa is regenerative |
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C. Diff (psuedomem. colitis)
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-increased amt in hospitalized pts.
-symptoms range from asymptomatic to full blown psuedomem. colitis -usually occurs after antibiotic use -"erupting volcano" |
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E.Coli O157:H7
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-outbreaks happen through three diff. ways 1) contaminated food 2) person to person 3) animal contact
-present with abd. cramps and watery diarrhea leading to bloody diarrhea in 2-3days -marked hemorrhagic mucosal necrosis with congestion, erythema and ulceration |
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Entamoeba histolytica
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-more prevalent in the tropics, in places where human feces is used as fertilizer
-high risk ppl are those people who travel to or immigrate from indemic areas; also in immunocompromised and institutionalized -resists gastric digestion giving rise to trophozoites who colonize in the colon -symptoms vary from mild diarrhea to deep flask shaped ulcers |
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Necrotizing Enterocolitis
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-progressive acute ischemic condition of premature infants at the time of enteral feeding
-usually also have RDS or sepsis that is thought to contribute to mesenteric ischemia and ischemia of the intestine -histologically see severe ischemia with hemorrhage and variable necrosis -need to perform surgery to remove gangrenous portions of the bowel |
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Graft vs. Host Disease
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-commonly follows bone marrow transplant
-usually occurs within 100 days of trasplant -principal targes are skin, GI tract, biliary tree, bm and lymphoid tissue -T cell mediated -symptoms include: skin rash, nausea, anorexia, diarrhea, intestinal hemorrhage, pain and jaundice -see APOPTOTIC BODIES collecting at the crypt bases and neck of the gastric glands -mucosal architecture is progressively lost with ulceration and submucosal edema |
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Diversion Colitis
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-happens in segments of bowel that are diverted from fecal stream
-commonly Hartmann's pouches following resection of sigmoid colon in patients with diverticular disease -disease goes away when bowel is restored |
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Microscopic Colitis
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LYMPHOCYTIC:
-middle aged, elderly patient with female proponderance -find autoantibodies (ANA and RF) can be found; also have associated autoimmune conditions -patients also have greater chance of celiac -see increased presence of lymphocytes in crypt and surface epithelium COLLAGENOUS COLITIS: -marked female proponderance, median age of 58-68 -have history of NSAID use -also thought to have an autoimmune etiology -symptoms are porlonged non-bloody diarrhea -collagen band forms around surface epithelium |
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Conditions impairing micelle formation
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-1)ZE syndrome, 2)decreased bile salt delivery due to cholestatic liver diseases like PBC
-3)blind loop syndrome: causes local statis/recirculation of luminal contents following gastrojejunostomy, jejunal diverticula, stricture, or enterocolonic fistula -bile salts are deconjugated in jejunum and rapidly diffuse across epithelium resulting in fat malabsorption -4)bile salt malabsorption: ileal disease or resection, cholesterol and fat-soluble vitamins require micelle formation for uptake |
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Aquired Lactase Deficiency
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-common cause of selective carb malabsorption beginning at 5 years old
-complain of diarrhea, gas and bloating after injesting milk products -lactase deficiency is normally due to decreased synthesis of the enzyme associated with the C/C13910 genotype CONGENITAL LACTASE DEFICIENCY: see diarrhea at birth, diagnosis is made by breath test after administration of lactose |
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Congenital Enteropeptidase Deficiency
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-enteropeptidase is a pancreatic protease or brush border oligopeptidase responsible for activating trypsinogen to trypsin
-rare cause of malabsorption in infants -see diarrhea, growth retardation and hypoproteniemic edema |
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Abetalipoproteinemia
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-rare autosomal disease due to failure to secrete cylomicrons by intestine
-see low plasma ApoB, triglyceride, and cholesterol levels -mutation of MTP gene responsible for assembly and secretion of apoB -treatment is a low fat diet with medium chain triglycerides (bypass the micelle problem) and high doses of fat souluble vitamins |
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Celiac Disease
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-gluten sensitive enteropathy, inflammatory disease percipitated by ingestion of dietary wheat, barley or rye
-people with type I DM, autoimmune thyroid dz, PBC, Down's and Turner's have increased risk -alcohol-soluble fraction of gluten (glandins) are most toxic -strong association with HLA class II DQ2 molecules, numerous CD4+ are present in the gut -other antibodies are directed toward smooth muscle (EMA) or tissue transglutaminase (tTG) - good for screening of high risk ppl -see villous blunting with lengthening of crypts, disorder of increased cell turnover -most commonly presents in early childhood; ppl with milder disease have select vitamin/mineral deficiency in absence of diarrhea -see decreased uptake and transport of nutrients secondary to loss of absorptive area -treatment is a gluten-free diet leading to the return of normal mucosa -patients have a higher incidence of malignancies |
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Tropical Sprue
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-seen in residents of the tropics or travelers
-patients present with MEGALOBLASTIC ANEMIA ONLY in abscence of intestinal symptoms -mucosal damage varies -typically patients respond to antibiotic treatment but a causative organism has not been found |
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What are the causes of cobalamnin deficiency?
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PERNICIOUS ANEMIA: inflammatory dz of stomach (chronic atrophic gastritis), can occur in association with autoimmune disease of endocrine organs particularly of thyroid; IF is decreased; found in 10% of elderly people
PARTIAL GASTRECTOMY/BYPASS SURGERY: lack gastric acid and pepsin to liberate dietary cobalamins from proteins BACTERIAL OVERGROWTH: bacteria take up vitB12 preventing intestinal absorption |
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Ulcerative Colitis
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-only affects the colon (shortened, normal serosal surface, colonic wall not thickened); can get dilation; no skip lesions
-can have areas of inactive disease that are flat and inflammatory polyps -inflammation normally in mucosa and submucosa, diffuse disease until abrupt transition, "backwash ileitis"; can see mucin depletion |
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Crohn's Disease
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-can affect any part of the GI tract, transmural; fibrous thickening, serosal inflammation and mesenteric creeping fat; long or short strictures can be present; skip areas or normal bowel are seen
-deep linear ulcers can be seen along with a cobblestone appearance; also see inflammatory polyps of various sizes and shapes -non-caseating granulomas are seen in mesenteric lymph nodes |
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Infectious (bacterial) colitis
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-clinically similar to UC, intraepithelial and lamina propria neutrophils and crypt abscesses can be present
-stool cultures are helpfuls in confiming diagnosis but are negative most of the time -clinical course is self-limited |
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Tuberculous Colitis
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-can mimic Crohn's clinically; causes inflammatoryh masses (usually right sided/cecal)
-see granulomas and acid fast bacteria |
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Dysplasia and Adenocarcinoma in UC
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-risk factors have to do with extent and duration of colitis (increases 1-2% every 10 years)
-detection of high grade dysplasia is associated with occult carcinoma -see abnl architecture of cribriforming and villiform surface projections; increased nuclear size |
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Dysplasia and Adenocarcinoma in UC
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-risk factors have to do with extent and duration of colitis (increases 1-2% every 10 years)
-detection of high grade dysplasia is associated with occult carcinoma -see abnl architecture of cribriforming and villiform surface projections; increased nuclear size |
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Ischemic Colitis
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-can mimic UC clinically
-older patients with atherosclerosis are at higher risk -diffuse hemorrhagic mucosal necrosis due to hairpin stricture of intestinal vasculature -distribution of disease is usually: rectum spared (dual supply), rectosigmoid involved along with splenic flexure (watershed zones) |
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Diverticulosis and Diverticulitis
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-lack complete muscularis propria
-have higher intraluminal than intraabdominal pressure, weak point of bowel at site of mesenteric vessel perforation; diverticula are usually present in rows along these sites; diverticula also more common in sigmoid colon -diverticulitis: acute inflammation, can be due to neck obstruction, can also rupture or perforate; presents as abdominal pain with change in bowel habits, bleeding or symptoms of abd. infection |
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Environmental and Genetic Factors in IBD
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-UC found in non-smokers and ex-smokers (worse in ex)
-CD more common in smokers, non-smokers have a worse course -IBD found in colder climates and more industrialized nations -there is an increased prevalence in first and second generation relatives also in Ashkenizi Jews and twins |
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What are the allelic variants associated with Chron's disease?
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NOD2-intracellular pattern recognition molecules
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What are the indications for surgery in UC and Chron's?
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UC: failure to control severe attacks/toxic megacolon, acute complications, sypmtoms despite med therapy, dysplasia/cancer
CROHN'S: obstructing strictures, complicating fistula, peri-anal abscess, toxic megacolon, localized/unresponsive disease |
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What are some causes of dysphagia?
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MECHANICAL: lower esophageal ring, peptic stricture, carcinoma, diverticulum, benign tumor, Plummer-Vinson, extrinsic mass
MOTOR: achalasia, diffuse esophageal spasm, CT disorders, Myesthenia Gravis |
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What are the causes of gastroesophageal reflux?
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-decreased lower esophageal sphincter tone: can be spontaneous, due to foods (peppermin, chocolate, caffeine, alcohol, etc), medication (Ca channel blockers, nitroglycerin) or a hiatal hernia
-delayed gastric emptying -increased acid secretion (rare) -inability to clear esophageal secretions |
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What is the treatment of GERD?
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-behavioral modification: avoid foods high in fat, smoking, alcohol; encourage wt. loss; avoid tight fitting cloths and meds affecting LES tone
-acid suppression: antacid; H2 blockade (blocks histamine-induced acid release by parietal cells, less effective than PPIs); proton pump inhibitors (inhibit H/K dependent ATPase proton pump controlling H secretion from parietal cell -Prokinetic agents (metoclopramide and domperidone) work as adjuvants to PPIs and H2 blockers; they improve gastric emptying, and increase lower esophageal sphincter tone |
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Barrett's Esophagus, Esophageal Adenocarcinoma, and Esophageal Squamous cell carcinoma
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BARRETT'S: specialized columnar epithelium, chronic acid exposure, increased adenocarcinoma risk, need to have surveillence with endoscopy
ESOPHAGEAL ADENOCARCINOMA: risks include: caucasian, middle aged, male, barrett's, chronic acid exposure, tobacco and alcohol use; often has spread by time of diagnosis and is associated with a poor prognosis SQUAMOUS CELL: AA, male, lower socioeconomic class, alcohol, tobacco, lye stricture, Plummer-Vinson, Tylosis; often presents with dysphagia and is advanced at time of diagnosis |
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Achalasia
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-motor disorder leading to the inability of the LES to relax along with aperistalsis
-there is damage to the dorsal motor nucleus of the vagus or loss of post-ganglionic nerve plexi in the esoph. wall -can be caused by Chaga's disease also from varicella -symptoms include: chest pain, dysphagia, regurgitation and weight loss -diagnosis: history, "rosette" on endoscopy, and "bird's beak esophagus" on esophagram -treatment: dilation, myomectomy, botox injection |
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Peptic Ulcer Disease
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-excoriation through the muscle layer of the stomach or duodenum
-etiology: weakness of mucosal barrier, acid hypersecretion, H. Pylori, NSAIDS, tobacco, alcohol, ZE Syndrome (gastrinoma) -symptoms: depends on location (can be better or worse with food), "gnawing" epigastric pain -complications are from hemorrhage and perforation -treatment: antibiotics plus PPIs or H2 blockers, use of prostagladins if indicated; also withdrawl of NSAID use |
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H. Pylori
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-host factors have: genetic predisposition and a mucosal immune response that paradoxically creates ulcers
-bacteria: has CagA virulence factor -is associated wtih gastritis, gastric cancer, and gastric lymphoma -treatment: dual therapy for 14 days, triple therapy for 7-14 days, or quadruple therapy; use clarithromycin, amoxicillin, metronidazole or tetracycline; use bismuth with quad therapy |
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Drugs for Acid Suppression
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MISOPROSTOL: PGE1 analog, COX1 enzyme, used to heal and prevent NSAID damage, SE(s) are diarrhea and cramping
SUCRALFATE: aluminum polymer that binds to ulcer base, has antacid activity and increases blood flow, mucus, PG, bicarb secretion, and decreases pepsin activity, SE: constipation BISMUTH CHELATE: binds ulcer base, does same stuff as sucralfate |
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Gastritis and ZE Syndrome
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GASTRITIS: inflammation of gastric mucosa; usually caused by H. Pylori and stress (ischemia in critically ill patients); symptoms are nonspecific n/v and epigastric pain, often are symptom free; treatment is symptomatic and eradication of H. Pylori
ZE SYNDROME: complicated PUD, usually in the duodenum, extreme gastic acid secretion, 80% isolated gastrinoma, 20% associated with MEN1, non beta cell islet tumors of pancreas |
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What are causes of esophagitis?
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-trauma: foreign bodies, intubation,
-chemicals: drugs (pill esophagitis), lye, acid, sclerotherapy, persistent vomiting -systemic dz: Crohn's, sarcoidosis, eosinophillic gastroenteritis, scleroderma, derm dz (pemphigus vulgaris), GVHD -infection: bacteria (rare), viruses (CMV and HSV) and fungus (Candida) |
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Classifications of Gastritis
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EROSIVE: stress erosions, associated with extreme stress (burns, trauma, multi-organ system failure), see erosions with marked hemorrhage, surrounding mucosa is usually normal, doesn't lead to chronic gastritis
EROSIVE (NSAID, aspirin, or ethanol): multiple randomly scattered erosions with marked epithelial changes, can lead to mucosa inflammation DIFFUSE ATROPHIC: usually in older patients, loss of parietal cells leading to atrophic gastritis, see decrease acid production, IF, presence of autoantibodies to parietal cells and IF, G cell hyperplasia; see areas of intestinal neoplasia and statistically increased risk of adenocarcinoma |
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Classification of Gastritis (cont.)
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H. PYLORI: antral gastritis pattern, present within mucus later over gastric surface but don't invade the cells; can lead to antral mucosa atrophy and intestinal metaplasia
-produces urease that converts urea to ammonium and buffers a microenvironment around itself (can do Hydrogen breath test to check) MULTIFOCAL ATROPHIC GASTRITIS: most common form in the world and rare in US; associated with dietary factors; see mostly in transitional zone between fundus and antrum (see focal loss of parietal cells) |
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Peptic Ulcers
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-gastric: usually hypochorhydric but not achohydric; H. Pylori present in most patients or use of NSAIDS; usually solitary and located along lesser curvature, sharply circumscribed with radiating folds of mucosa
-duodenal: much more common than gastric, increased parietal cell mass, abnlly rapid gastric emptying, almost all patients have H.Pylori, look similar to gastric ulcers |
