Flashcards in GI Deck (235):
What activities are carried out in Zone 1 vs Zone 3 of hepatic lopules?
Zone 1: adjacent to triad, O2 rich. gluconeogenesis, B-oxidation, AA metabolism, formation of urea
Zone 3: adjacent to central vein, O2 poor. P450 reactions, lipid synthesis, glycolysis
What are stellate cells?
Reside w/in Space of Disse
Store lipid and vitam A
Produce reticular fibers
Cirrhosis: multiply and produce large amounts of ECM
3 classifications of liver disease
1. Hepatocellular: acute, fulminant, chronic
2. Cholestatic: intrahepatic, extrahepatic
What viruses are associated with hepatocellular injury?
Hepatotropic: Hepatitis A,B,C,D,E
Systemic: EBV, CMV, HSV, enterovirus
What are microscopic features of acute hepatitis?
lobular disarray - disruption of architecture
apoptotic bodies (Councilman bodies)
inflammatory infiltrates, activated Kupffer cells
regeneration (with resolution)
What is fulminant hepatitis?
Rare variant of acute hepatitis. Rapid onset of liver failure over period of days - weeks.
*Heralded by AMS and coagulopathy*
Causes of fulminant hepatitis
Drugs (acetaminophen overdose, antimycobacterial (rifampin, isoniazid), antidepressants (MAOi), halothane, mushroom poisoning)
Virus (HAV, HBV + HDV)
What is chronic hepatitis?
Evidence of ongoing liver injury for >6mos
May be viral (HBV, HDV, HCV), autoimmune or metabolic
What is the predominant microscopic feature of chronic hepatitis?
inflammatory infiltrate surrounding portal tracts
What is "bridging" necrosis?
Seen in chronic hepatitis
fibrosis / necrosis stretching between portal tracts or from portal tract to central vein
What are microscopic indicators of HBV, HCV, and autoimmune hepatitis?
HBV: ground-glass cytoplasm
HCV: microvessicular fatty change and portal tract lymphoid aggregates
autoimmune: plasma cell infiltrates of portal triad
What is choledocholithiasis?
gall stones w/in the common bile duct
What are the characteristic lab findings assoc. with cholestasis?
Elevated alkaline phosphatase
elevated gamma-glutamyl transferase (GGT)
elevated 5' nucleotidase
What hepatic condition presents with the highest aminotrasnferase elevations?
ALT/AST elevation hallmark of hepatocellular necrosis:
Acute Hepatitis 10-30x
Biliary obstruction 1-5x
Hepatic metastases 1-2x
What defines acute liver failure?
Rapid onset of hepatic dysfunction with no underlying liver disease progressing to encephalopathy w/in 8-12 weeks
What are symptoms of acute liver failure?
Mental status changes
Jaundice, dark urine, light stool
How is cholestasis diagnosed?
Elevated alkaline phosphatase
Elevated GGT, 5' nucleosidase
Prolonged prothrombin time (Vit K deficiency)
Anti-mitochondrial Ab (primary)
What are the physical signs of portal hypertension?
3. Abdominal vasculature accentuation
3 classifications of portal HTN
What does TIPS stand for?
Transjugular Intrahepatic Portosystemic Shunt
Performed by interventional radiologist - treatment for portal HTN
How do acute and chronic hepatic encephalopathy differ?
Acute: Type A: assoc. w/ acute disease. Delirium and convulsions progressing to coma. BBB and cerebral edema are common.
Chronic: Types B and C: chronic disease: pathogenesis unclear. Asterixis, Hyperreflexia, Mental disturbances, EEG changes
Production of toxic substances by gut bacteria implicated
What is therapy for chronic hepatic encephalitis?
Treat precipitating factor
Abx: Rifaximin, neomycin
What does protein content of ascites fluid indicate?
Etiology of ascites
Serum albumin - ascites albumin
if > 1.1, portal HTN likely
Elevated ascites albumin: tumor or chronic infection
What are complications of ascites
Spontaneous Bacterial Peritonitis - esp. low protein fluid
Flood's syndrome: ruptured umbilical hernia
Drug dilution in "3rd space"
What is hepatorenal syndrome?
Renal failure w/ accompanying advanced severe liver disease
No ATN (tubules intact - low urine Na+), but severe oliguria
How is hepatorenal syndrome diagnosed and treated?
Diagnosis: rule out pre-renal azotemia via trial of fluid expansion
Treatment: Often liver transplant. Dialysis.
Primary cause of unconjugated bilirubinemia
Hemolytic jaundice: production of bilirubin in excess of liver's ability to process it.
What are the 2 leading causes for liver transplant?
Hep C (45%)
Alcoholic cirrhosis (15%)
At what pressure within the hepatic portal vein is variceal bleeding likely?
5 factors that contribute to chronic ascites
1. Portal HTN -> systemic vasodilation, decreased effective bv, SNS activation
2. RAAS activation -> increased Na+
3. ADH -> increased H2O
4. Increased transsinusoidal filtration
5. hypoalbuminemia -> decreased osm
What microscopic feature is associated with alcoholic hepatitis?
Mallory bodies or alcoholic hyalin: eosinophilic cytoplasmic inclusions
What are transaminase levels in alcoholic hepatitis?
Mild to moderate increase with AST > ALT
vs. viral where ALT > AST
Is alcoholic cirrhosis micro or macronodular?
In what setting does Non-alcoholic Fatty Liver Disease typically present?
Obesity and Insulin resistance.
4 metabolic liver diseases
Non-alcoholic fatty liver disease
a1 antitrypsin deficiency
What mutation is often seen in hemochromatosis?
HFE gene (6p) mutation
What organs are affected by hemochromatosis?
Liver - micronodular cirrhosis, hepatocellular carcinoma
Myocardium - dysfunction
Pancreas - fibrosis, cell loss -> diabetes mellitus
Joints - synovial tissue damage -> arthropathy
Endocrine glands - hypopituitarism -> hypogonadism
What is another name for Wilson disease?
Lenticular = putamen and caudate = basal ganglia
What is Wilson's disease?
Autosomal recessive defect in copper ATPase
defective transport in liver -> decreased incorporation into ceruloplasmin and decreased excretion in bile
Symptoms of Wilson's disease
Hepatitis / cirrhosis
CNS injury (tremor, rigidity, dysarthria, depression, anxiety, psychosis)
Kaiser-Fleischer rings, sunflower cataracts
What gene is involved in a1-antitrypsin deficiency?
chromosome 16: Pi locus: normal = MM, severe = ZZ
who should be screened for a1-antitrypsin deficiency?
All people w/ COPD, unexplained liver disease, and 1st degree family members of probands
How does a1-antitrypsin deficiency disease cause liver damage?
Accumulation of misfolded, polymerized a1-AT proteins in hepatocyte ER
Manifestations of a1-AT deficiency
Panlobular emphysema (esp. basilar)
Hepatitis (neonatal hepatitis), cholestatic jaundice, cirrhosis, hepatocellular carcinoma
Eosinophilic inclusion bodies in hepatocytes
Pathology of primary biliary cirrhosis
Autoimmune, Tcell mediated destruction of small - medium bile ducts
Granulomatous destruction of bile ducts w/ chronic inflammatory infiltrate
Lab findings in Primary Biliary Cirrhosis
elevated hepatic alkaline phosphatase, GGT, cholesterol, conjugated bilirubin
elevated IgM, antimitochondrial Ab and lipoprotein X
What is treatment for PBC?
Symptomatic treatment (pruritis, osteoporosis, portal HTN)
What is Primary Sclerosing Cholangitis?
progressive destruction of large intra and extrahepatic bile ducts
autoimmune, ANCA assoc., close assoc. with ulcerative colitis
Mostly men <40
Produces alternating stricture and dilation in ducts
What are complications of Primary Sclerosing Colangitis?
Progressive biliary obstruction and portal fibrosis
Increased risk of cholangeosarcoma
What is DILI?
Drug Induced Liver Injury
Most common reason for FDA removal of approved drugs
What part of the liver is initially affected by acetaminophen toxicity?
Zone 3 (P450 activity)
2 ways in which ETOH contribute to acetaminophen toxicity
Induction of P450 pathway
Depletion of GSH stores
First line treatment for acetaminophen OD?
Describe unpredictable / idiosyncratic DILI
Usually latent "sensitization" period before symptoms, more rapid on re-challenge
Associated fever, rash, eosinophilia
2 theories to explain unpredictable DILI
1. Hypersensitivity: drug + carrier = macromolecule = neo-antigen -> Immune response -> hepatotoxicity
2. Metabolic + genetic: drug + genetics -> novel metabolite -> liver injury
What drugs are associated w/ cholestasis?
Oral Contraceptives (estrogens)
Amoxicillin / Clavulanate (augmentin)
What effect does Chlorpromazine (thorazine) have on the liver?
Assoc. with cholestasis + inflammation via unknown mechanism
3-5 weeks after initiation of therapy
Resolves w/ discontinuation
What effect does Methotrexate have on the liver?
Fatty change related to cumulative dose
Toxicity lower in RA, higher in psoriasis
Liver biopsy in follow up
Name some drugs assoc. w/ chronic hepatitis
Name some drugs associated with granuloma formation
3 drugs associated with "predictable" hepatotoxicity
What is the cause of dental carries?
Dissolution of inorganic component of tooth by organic acids via microbial metabolism of carbohydrates
What microbes are primarily involved in the formation of dental carries?
S. mutans - crown
Lactobacillus - root
What is oral tori?
bony overgrowth of palate or lingual side of mandible.
No need for removal unless impedence of function or speech
What causes amalgam tattooing?
insoluble silver salt (from silver amalgam filling) deposited in collagen fibers of lamina propria
What are Fordyce Spots?
Occurrences of sebaceous glands in oral cavity
not apparent in children, activated at puberty
No clinical significance, found in 82% of population
"denture injury tumor" due to mechanical irritation of ill-fitting denture
Usually no pain or tenderness unless infection is involved
found on soft tissue of vault of hard palate
numerous papillary projections due to mechanical irritation and ill-fitting denture, food debris
Is oral papilloma cancerous?
NO - benign w/ stratified squamous epithelium
What is an aphthous ulcer?
Recurrent, superficial ulcer of non-keratinized epithelium
Persist 8-14 days
Causes: psychic, autoimmune, microbial, traumatic endocrine, hereditary
Treatment: tetracycline mouthwash, kenalog in orabase, analgesics
What is treatment for oral herpes?
Systemic acyclovir for immunocompromised patients.
What oral ulcers should be considered for biopsy?
Highly suspicious, slow healing ulcers in patients who are poor historians.
What is Moniliasis? Culture? treatment?
Oral thrush - Candida albicans
Culture: Sabouraud's agar
Treatment: Nystatin, Ketoconazole, Fluconazole, saline baking soda rinse
Oral manifestation of Addison's disease and treatment
Hyperpigmented spots due to pituitary stimulation of melanotrophic activity
treated w/ corticosteroids
What are oral manifestations of leukemia?
gingival hyperplasia, gingivitis, hemorrhage, petechia, mucosal ulceration
What is Paget's disease, oral manifestations, treatment
Abnormal bone resorption and deposition
Oral: enlargement of maxilla / mandible, spacing of teeth
Treatment: NSAID, ASA, calcitoinin, diphosphonates, mithramycin
Oral presentation of Lichen Planus
Pruritic, Purple, Polygonal, Planar, Papules and Plaques
Oral: Wickham Striae: white, lace-like patterns on top of papules
may be erosive - low, but increased risk for malignancy
Yeast infection common
Treat with corticosteroids
Oral manifestations of HIV / AIDS
Kaposi's sarcoma - most frequent malignancy of AIDS
What is the organism involved in cat scratch disease?
Children w/ cervical lymphadenopathy referred for dental exam to exclude oral infection
In VZV outbreak, when should anti-virals be started?
w/in 72 hours of onset
What is leukoplakia?
white patch or plaque on oral mucosa that does not scrape off and cannot be otherwise classified.
Homogenous or Erythroleukoplakia (4-5x increased risk of malignant transformation)
Infrequent agents of viral hepatitis
CMV: children, anicteric, no chronicity. May be lethal in immunocompromised
EBV: self-limited mono. 40% have elevated transaminase. no chronicity
HSV: immunocompromised, high mortality. Liver biopsy shows viral inclusion bodies
How is HAV transmitted?
fecal-oral route - contaminated food and water
How is Hep A diagnosed?
IgM antibody: current infection
IgG antibody: previous infection
Infection spontaneously clears - no carrier state
How does Hep B result in death?
Cirrhosis w/ liver failure
What is vertical transmission?
Mother to child
What is the gold standard for diagnosis of HBV?
Serum HBV DNA by PCR
If acute HBV infection is suspected, what test should be ordered to confirm?
What marker is seen in patients immunized against HBV?
What is the earliest detectable Ab in HBV infection?
What does the presence of anti-HBcAg indicate?
Exposure to virus. will be positive for life.
What ethnicity has the highest rate of HBV carriage in USA?
Most commonly used HBV medications
entecavir (guanosine analog)
tenofovir (adenosine analog)
both inhibit HBV RT
Post-exposure treatment for HBV
By age, what % of HBV infected patients will become chronic carriers?
1-5 yrs: 30%
What does HDV require for replication?
Which has a worse prognosis HBV + HDV co-infection of superinfection
superinfection: 90% develop chronic liver disease, 80% cirrhosis w/in 5 years
co-infection: 2% develop chronic disease. Co-infection is typically self-limited and resembles acute Hep B
What is treatment of HDV?
In HCV infection, what is assumed with symptoms of chronic liver disease?
End Stage Liver Disease has occurred.
Acute Hepatitis rare, usually asymptomatic until late in course
What is Von Meyenberg Complex?
Bile duct hamartomas - non neoplastic - persistence of embryonic structure
Collection of small, irregular bile ducts in fibrous tissue
Multiple small, pale spots on liver
3 non-neoplastic tumors of liver
1. Von Meyenberg Complex
2. Nodular Hyperplasia (oral contraceptives, anabolic steroids)
3. Nodular Regenerative Hyperplasia: regenerative nodules w/o fibrosis
Complication of Nodular regenerative hyperplasia of liver
What is the most common benign hepatic tumor?
What is hepatic cell adenoma associated with? appearance?
Young women taking contraceptives (long-term)
Solitary, well circumscribed, soft green mass lacking portal tracts
Complication of hepatic adenoma?
Hemorrhage - acute onset of RUQ pain
What is the risk of malignant transformation in hepatic adenoma?
Very small risk
B-catenin gene: elevated risk if present
Malignancies that most frequently metastasize to the liver
Lung, GI (colon), pancreas, breast
What lab abnormalities are found in tumors that have metastasized to the liver?
early: alkaline phosphatase and lactate dehydrogenase
Late: serum bilirubin and ALT / AST levels
3 major risk factors for hepatocellular carcinoma
HBV carrier state (incorporation into cellular DNA -> oncogene activation and HBV X-protein expression)
Cirrhosis (repetitive regenerative cycles -> mutations (RAS, p53, etc))
Exposure to aflatoxin (p53 mutation)
What is Budd-Chiari?
Occlusion of IVC or hepatic veins w/ centrilobular congestion and necrosis
Sudden liver enlargement, pain, and ascites
May occur w/ hepatocellular carcinoma
What lab abnormalities may be seen in hepatocellular carcinoma?
a-fetoprotein: neither sensitive nor specific
ALP and LD elevation
Late: bilirubin and ALT/AST elevation
What is an important variant of hepatocellular carcinoma?
young adults, no predisposing factors, otherwise normal liver
well differentiated tumor cells in dense fibrous stroma w/ parallel collagen lamellae
Risk factors for cholangiocarcinoma
Primary sclerosing cholangitis
Congenital biliary tract structural abnormalities
Chronic parasitic biliary tract infection (Opisthorchis sinensis)
What is angiosarcoma?
Endothelial tumor - hemorrhagic nodules and blood filled cysts
In liver associated with vinyl chloride, thorotrast, arsenic exposure
What is hepatoblastoma?
tumor of young children
large, soft, hemorrhagic, necrotic mass
microscopic: small, round blue cells. epithelial mesenchymal differentiation
What marker is elevated in hepatoblastoma?
2 functions of bile
absorption of fat via formation of micelles
rid body of cholesterol via bile salts and bilirubin
What is a choledocal cyst?
Dilation or outpouching of common bile duct
2 causes of biliary atresia
1. Hypoplasia or aplasia (rare)
2. Idiopathic neonatal bile duct destruction (several weeks after birth)
What is the most common type of gallstone in US?
How are cholesterol gallstones formed?
supersaturation of bile with cholesterol + bile stasis -> crystal nucleation
Risk factors for cholesterol gallstones
Due to excess cholesterol secretion (+/- decreased bile salt secretion)
-Estrogens (contraceptive use)
-Obesity / rapid weight loss
-Inherited metabolic disorders
How do cholesterol gallstones appear on xray?
2 types of pigment gallstones and causes.
1. black stones: chronic hemolysis. Unconjugated bilirubin precipitates with Ca++
2. brown stones: assoc. with biliary tract infections (Flukes)
2 causes of acute cholecystitis
1. calculus: stone obstructs neck of gallbladder or cystic duct -> distention and vascular compression
2. acalculus: critically ill patients - biliary sludge obstructs cystic duct -> poor biliary perfusion, possibility of infection
What is seen on CBC in acute cholecystitis?
elevated WBC, esp. neutrophils
What are Rokitansky-Aschoff sinuses?
Feature of chronic cholecystitis
mucosal diverticula w/in gallbladder wall
What is a significant risk factor for cancer of the gallbladder?
Porcelain gallbladder : dystrophic calcification
Prognosis for carcinoma of the gallbladder?
very poor - diagnosis frequently incidental
Frequent local invasion of liver, and adjacent viscera
Metastasis to lymph nodes, peritoneum, lungs
What is a Klatskin tumor?
tumor at origin of common bile duct- slowly progressive
Subtype of carcinoma of extrahepatic bile duct
3 regulators of pancreatic exocrine function
CCK: HCO3- secretion
Secretin: zymogen secretion
How is trypsin activated?
Trypsin (from pancreas) activated by enterokinase on brush border of duodenum
Systemic and local complications of acute pancreatitis
-ARF (shock -> ATN -> ARF)
-metabolic hypocalcemia, hypoalbuminemia, hyperglycemia, acidosis)
-pseudocyst, abscess, biliary / duodenal obstruction
What defines chronic pancreatitis and what are symptoms?
Frequently relapsing inflammation -> progressive pancreatic injury
Usually alcohol related
May be CF, obstruction, idiopathic
Symptoms: pain, loss of function (malabsorption, DM), biliary / duodenal obstruction
Differentiate true pancreatic cysts from pseudocysts
true cysts: lined with epithelium, associated with ADPKD, VHL
pseudocysts: complications of pancreatitis - no epithelial lining
What are risk factors for pancreatic adenocarcinoma?
Smoker, male, black, Native American, high fat diet, nitrosamine exposure, diabetes mellitus
What part of the pancreas is most frequently involved in adenocarcinoma?
Head > body > tail
How does pancreatic cancer usually spread?
Head: duodenum, common bile duct
Body and Tail: vertebrae, retroperitoneal and abdominal organs
lymph nodes, liver
What causes hereditary pancreatitis?
Mutation of trypsinogen on chromosome 7
Trypsin is resistant to lysis -> prolonged activity
What are lab findings in acute pancreatitis?
Lipase and amylase 3x normal (lipase more specific for pancreas)
AST 2x (gallstone)
What imaging studies are preferred in diagnosis of acute pancreatitis?
Prognosis: CT - specific and indicates extent of necrosis -> complication / mortality risk
According to Ranson's criteria, what features on admission are suggestive of gallstone pancreatitis?
Glucose (blood) >220
What organisms are most frequently involved in necrotizing pancreatisis?
How is infected pancreatic necrosis treated?
Abx use is controversial
Should pancreatic pseudocysts be treated?
Only if symptomatic
What is a Bentiromide test?
Test of pancreatic function. Oral dose given (Bentiromide has PABA linked) chymotrypsin cleaves, frees PABA for absorption and renal excretion.
Low PABA in urine indicates decreased pancreatic function
How is a secretin stimulation test performed?
IV secretin given
Tube placed in pancreatic duct, timed periodic collections measuring for HCO3- levels: low indicates chronic pancreatitis
Cumbersome, unpleasant, rarely done
What is the role of the Schilling test in pancreatitis diagnosis / treatment?
Pancreatitis -> reduced absorption of fat soluble vitamins (B)
Schilling test will be abnormal
Administration of pancreatic enzymes will normalize Schilling test, suggesting chronic pancreatitis
At what point in pancreatic disease is steatorrhea usually apparent? How is it treated?
90% loss of lipase activity
Supplement pancreatic enzymes w/ 30,000 IU lipase activity at each meal
Acid suppression and low-fat diet
Pancreatic adenocarcinoma 5 year survival rate
What are some indications for cholecystectomy?
Symptomatic gallstones, hemolytic anemia, gastric bypass, porcelain bladder, gallbladder adenoma >1-2cm
What is a drug that can be used to treat cholesterol gallstones
Inhibits HMG coA reductase -> reduced cholesterol production
Reduces hepatic cholesterol secretion in bile
What is cholangitis?
Infection of the common bile duct
Usually gram neg organisms. can spread to liver and blood.
Charcot's triad: pain, fever, jaundice
3 risk factors for carcinoma of the extrahepatic biliary ducts
In Asia: parasites - Chloronorchis sinensis, infections, IBD, sclerosing cholangitis
What is sudan black staining used for?
Sudan black stain of stool: shows excess fat in stool (steatorrhea) chronic pancreatitis
Describe venous drainage of esophagus
Upper 1/3: SVC
Mid 1/3: Azygos
Lower 1/3: Hepatic portal vein via L. gastric (coronary) vein
What is the muscular distribution of the esophagus?
Upper 1/3: Skeletal
Mid 1/3: Mixed
Lower 1/3: Smooth
What are Auerbach and Meisner's plexuses?
What is EGD used for?
Esophagogastroduodenoscopy: used to visualized epithelium of esophagus, stomach, duodenum. Allows biopsy capability.
3 components of swallowing (esophageal phase
Tertiary: uncoordinated, non-propulsive
What factors can trigger diffuse esophageal spasm?
Stress, very hot or very cold liquids
What happens with the lower esophageal sphincter in Diffuse Esophageal Spasm?
Normal function is preserved.
How does scleroderma affect the esophagus?
Collagen deposition in smooth muscle -> aperistalsis in distal esophagus
How are strictures and obstructive ring lesions of the esophagus usually treated?
Dilation - usually balloon or bougie
Surgery - uncommon
What are possible pharmacological treatments for GERD
Acid suppressors (H2RA, PPI, antacid)
Prokinetics (metoclopramide, domperidone, cisapride)
Where are Meissner and Auerbach plexuses located in esophagus?
Meissner: within the submucosa
Auerbach: between layers of muscularis propria
What are pulsion diverticula and 2 examples
Outpouchings of esophagus due to high pressure
1. Zenker: hypopharynx: between inferior pharyngeal constrictor and cricopharyngeus
2. Epiphrenic: just above LES: associated w/ motility disorders (achalasia, hiatal hernia)
What causes an esophageal traction diverticulum?
Continuous external traction - mediastinal inflammation / fibrosis
Who is most at risk for esophageal webs?
Middle aged women
Esophageal webs, iron-deficiency anemia, glossitis, cheilosis, koilonchia (spoon nails)
Increased risk for pharyngeal and esophageal carcinoma
2 examples of esophageal rings
A ring: proximal to GE junction
B ring: located at squamo-columnar GE junction. Almost always associated w/ hiatal hernia
2 subtypes of hiatal hernias
1. Sliding: GE junction and portion of stomach slide through esophageal hiatus
2. Paraesophageal: "rolling" portion of fundus prolapses into thorax adjacent to esophagus. GE junction stays in abdomen.
2 esophageal lacerations
1. Mallory-Weiss: after prolonged vomiting / retching as w/ ETOH intox. superficial longitudinal tears at GE junction
2. Boerhaave: distal esophageal rupture -> mediastinitis - catastrophic event
3 types of esophagitis
1. Iatrogenic: (radiation, GVHD)
2. Infectious: immunocompromise: candida, HSV
3. Reflux: GERD
Complications of Barret's Esophagus
How many layers of muscle surround the stomach?
3 layers of smooth muscle: innermost oblique, inner circular, outer longitudinal
Note: Auerbach's plexus between circular and longitudinal
3 etiologies of gastric ulceration
1. NSAID use
2. Intracranial trauma: vagal stimulus -> increased gastric H+ secretion
3. Physiologic stress (shock, sepsis, burns): decreased perfusion of gastric mucosa, systemic acidosis (-> decreased HCO3-)
What are Cushing and Curling ulcers?
Cushing: gastric ulceration due to intracranial injury
Curling: gastric ulceration assoc. with burns
What is the most common cause of chronic gastritis?
H. pylori infection (90% of cases)
H.pylori virulence factors
urease (urea -> NH3 -> neutralization of acid)
Lewis antigens: allow adherence to gastric foveolar epithelium
3 diagnostic tests for H.pylori
1. H. pylori fecal Ag test
2. Carbon labeled Urea breath test (detects exhaled labeled CO2)
3. H. pylori serology: not helpful for post-treatment follow up
What happens in autoimmune gastritis?
CD4+ cells lose tolerance for parietal cell antigens -> anti parietal cell and anti-IF antibodies
Hyperplasia of G cells -> increased gastrin production
How is the spinal cord affected by autoimmune gastritis?
B12 deficiency -> demyelination of neurons
Posterior and lateral columns most effected -> loss of position and vibratory sensation (leg > arms) w/ sensory ataxia
What are the most common locations for gastric ulcers
proximal duodenum > antrum > elsewhere
Clinical presentation of gastric ulcer
Recurrent epigastric pain - worse at night and few hours post-meal
-relieved w/ food and alkalai
Describe Menetrier disease
Excessive productin of TNF-a -> hyperplasia of foveolar mucous epithelium and atrophy of parietal and chief cells
increased risk of gastric adenocarcinoma
What is Zollinger-Ellison Syndrome?
Gastrin secreting tumor -> intractible peptic ulcer disease and mucosal hyperplasia (esp. parietal cells)
How is peptic ulcer disease diagnosed?
History and physical
Upper GI series (75% sensitivity)
What patients can be tested and treated for H. pylori w/o undergoing endoscopy?
Patient <45 w/ ulcer symptoms and no alarm signs or complications
What NSAIDS are "high risk" for Ulcer development?
Who is a candidate for co-administration of NSAID and acid suppressive agent?
Patient requiring chronic NSAID use and having at least 1 risk factor for development of gastric ulcer (>60 yoa, multiple NSAID, corticosteroid or anticoagulant use, Hx of PUD or GI complications)
2 prokinetic agents that can be used to treat gastroparesis
1. Dopamine antagonist: DA has anti-motility action on GI
2. 5-HT agonist: Serotonin stimulates motility
What is the preferred drug for hospitalized patients w/ gastroparesis?
Eythromycin: motilin receptor agonist
What is the MOA of Metoclopramide?
Accelerates gastric emptying in treatment of gastroparesis
What is the treatment of choice for variceal bleeding?
Endoscopic ligation is also acceptable
In a patient with an active GI bleed, when should PPI be given?
Post-endoscopy. No value to Pre-endoscopy admin.
Drugs used to treat ulcerative colitis
5-aminosalicylates: oral - active management, maintain remission
rectal - most effective for patients w/ proctitis
corticosteroids: suppress migration of PMNs. Used for management of acute / extensive disease.
Immunomodulators (6MP, Azathioprine): if corticosteroid unresponsive
What receptors are found in high density in the emesis center of the medulla?
Treatment for hypertrophic pyloric stenosis
What is Meckel diverticulum? complication?
Failure of embryonic vitelline duct to involute
Often contains heterotropic foci (gastric mucosa) -> gastric acid production -> GI bleeding, pain, perforation
What serology can be used to diagnose Celiac Disease?
Anti-tissue transglutaminase Ab
What is the dermatologic presentation of celiac sprue? Cause?
Dermatitis Herpetiformis: Pruritic vessicles that form on back and extensor surfaces of extremities
Caused by anti-gliadin IgA
What is Abetalipoproteinemia?
Deficient apoprotein B -> defective lipid transport -> lipid accumulation in enterocytes
Vacuolization of enterocytes, acanthocytes
Is celiac sprue associates w/ malignancy risk?
Sm. intestinal adenocarcinoma
Sq. cell carcinoma of esophagus
What is Whipple Disease?
bacterial infection affecting middle-aged white men
PAS+ macrophages (foamy) fill lamina propria of sm. intestine
also affects joints, brain, heart valves
-> chronic malabsorption, arthropathy, lymphadenopathy, hyperpigmentation, psychiatric complaints, cardiac dysfunction
Where are GI carcinoid tumors usually found?
Appendix, ileum, rectum
Where do MALT lymphomas generally develop? What is a common associated disorder?
stomach > sm. intestine > colon
Very often associated w/ H. pylori infection
What are important factors that go with Burkitt's Lymphoma?
c-myc gene translocation (t[8;14])
latent EBV infection
What is GIST and what is it associated with (origin, genetics)?
Gastrointestinal stromal tumor - from interstitial cells of Cajal
Varying malignant potential
mutations: c-KIT, PDGFRA: tyrosine kinase receptors
How does steatorrhea -> renal stones?
Malabsorbed FAs bind Ca++ which would normally bind oxalate in the colon
Oxalate is then available for colonic reabsorption -> renal oxalate stones
How does smoking effect the risk of developing either of the 2 forms of IBD?
Crohn's: current and former smokers - increased risk of developing
Ulcerative Colitis: former and non-smokers have increased risk
What serum markers are found in Crohn's and UC?
Ulcerative Colitis: p-ANCA (60-80%)
Crohn's: ASCA: (70%)
What is recommended for colon cancer surveillance in UC and Crohn's?
Colonoscopy every 2 years w/ multiple biopsy after 8-10 yrs. of diagnosis
What are some causes of sm. bowel obstruction?
#1: adhesions from prior surgery
Other: hernia, crohn's, volvulus, neoplasm, foreign body
What is open loop vs. closed loop bowel obstruction?
Open loop: Intestinal flow blocked, but decompression possible via vomiting
Closed loop: Inflow and outflow blocked -> gas and secretion accumulation w/ no means of decompression
what is obstipation?
inability to pass flatus or feces
sign of obstruction along w/ pain, vomiting and distension
What organisms tend to flourish in sm. bowel obstrution?
Normally sm. intestine is nearly sterile
Outline treatment for intestinal obstruction
IV fluids (NaCl, lactated ringer's) - monitor electrolytes
Add KCl if needed after adequate urine formed
NG tube - decompression, avoid aspiration of stomach contents
Imaging - monitor - surgery if no resolution
What cancers are associated with Peutz-Jeghers?
colon, pancreas, breast, testicular, ovarian, cervical
What ovarian cells do LH and FSH work on respectively and what is the effect?
Rising FSH (folicular phase) induces increase in LH receptors in Theca
LH works on Theca cells -> androgen production (Prog, Androstenedione, T) Theca lacks aromatase
FSH works on granulosa cells -> Estradiol from androgens Granulosa cells lack 17a-hydroxylase
What causes the LH surge and what is its effect?
increasing estradiol levels -> pos. feedback @ hypothalamus -> LH surge -> ovulation
**Ovulation 36 hrs. after surge**
What genes are involved in migration of GnRH secreting neurons? What is the route of migration?
Genes: Kal-1 (encodes for Anosmin), Kal-2, Prox-2
Migration from olfactory placode to Arcuate Nucleus of medial basal hypothalamus
Absence of menses by 16 regardless of growth / pubertal dev
Absence of menses by 13 w/o dev. of 2ndary sex characteristics
lack of menses for 3 cycles
What is idiopathic hypogonadotrophic hypogonadism? subtype?
Functional congenital absence of GnRH secretion
Kallman: defective migration of GnRH cells and formation of olfactory bulb: IHH + anosmia and other defects
What is the cause of Functional Hypothalamic Amenorrhea? How is it diagnosed?
No pathologic disease found
Eating disorders, weight loss, exercise, stress
Low leptin levels believed to be involved - neg. impact on GnRH secretion
Diagnosis: Estrogen <50pg/mL; no withdrawal bleeding on Progesterone challenge
Female Athletic Triad
What are treatments for hyperprolactinemia?
DA agonists: bromocriptine, cabergoline
Surgery if adenoma
What is the most common cause of gonadal dysgenesis in women?
Turner syndrome (X0)
Accelerated postnatal follicular atresia -> primary amenorrhea
High LH and FSH, but low estrogen
With what disease is Premature Ovarian Failure associated?
Fragile X Syndrome: CGG repeat amplification (usually >500)
Also: autoimmune oophoritis (polyglandular autoimmune disease)
Describe the pathogenesis of Polycystic Ovary Syndrome
Elevated LH production -> excess androgen production by theca cells
Depressed FSH production -> low estrogen level, depressed follicle maturation
Insulin intolerance contributes to androgen production by theca cells
Obesity -> increased adipose -> aromatization of androgen -> estrone -> promotes high LH, low FSH