344 terms

Step 1 GI


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Causes of acute acalculous cholecystitis (14)
Sepsis, immunosuppression, TPN, major trauma, burn, DM, infection, mechanical ventilation, opiates, coronary heart disease, cholesterol emboli, multiple transfusions, childbirth, nonbiliary surgery
Acute acalculous cholecystitis: pathogenesis, manifestations (5), labs (2), diagnosis, complications (3), treatment (3)
Pathogenesis: gallbladder stasis & ischemia cause inflammation & injury to gallbladder wall
Manifestations: fever, severe RUQ pain, positive Murphy's sign, jaundice, palpable RUQ mass
Labs: leukocytosis, abnormal LFTs
Diagnosis: ultrasound shows edematous & enlarged gallbladder but no gallstones
Complications: gangrene, perforation, emphysematous cholecystitis
Treatment: IV broad-spectrum abx + cholecystectomy + drainage of any abscess
Porcelain gallbladder: diagnosis
Diagnosis: AXR shows rim of calcium deposits outlining gallbladder
Choledochal cyst
Congenital dilations of common bile duct
Chronic cholecystitis: pathogenesis, diagnosis, sequela
Pathogenesis: repeated mild attacks of acute cholecystitis lead to thickening of gallbladder wall
Diagnosis: ultrasound shows a shrunken fibrosed gallbladder
Sequela: porcelain gallbladder
Most likely outcome of HCV infection?
Stable chronic hepatitis
Prognosis of HCV infection (4)
15-45% have complete resolution of acute infection
55-85% develop chronic infection
<50% develop cirrhosis
0-3% of patients with cirrhosis develop HCC
When should you discontinue statins?
HFE gene: definition, location of protein, function, regulation
Definition: encodes an HLA class I-like molecule that affects iron absorption from the GI tract; on chromosome 6
Location: expressed on the basolateral surface of epithelial cells of the small intestine crypts
Function; complexes with beta2-microglobulin --> binds transferrin receptor to regulate endocytosis of transferrin/iron complex into cells --> iron is released once inside the cell and is added to the iron regulatory pool
Regulation: iron regulatory pool determines intensity of apical iron uptake expression
Hemochromatosis: pathogenesis, inheritance, risk factor, time of presentation (2), manifestations (9), labs (4), complications (2)
Pathogenesis: cysteine-to-tyrosine missense mutation in HFE gene (C282Y) --> iron uptake protein is unable to detect circulating iron levels --> unregulated expression --> excessive iron absorption from GI tract --> iron deposits in heart, pancreas, liver, pituitary, adrenals
Inheritance: autosomal recessive
Risk factors: Northern European descent
Time of presentation: sx start in middle adulthood when >20g iron have accumulated; women present later due to menses + pregnancy
Manifestations: hepatomegaly, abdominal pain, skin hyperpigmentation, DM, hypogonadism, impotence, arthropathy, cardiomegaly, cardiac dysfunction
Labs: mildly elevated LFTs, elevated iron, transferrin saturation >50%, elevated ferritin
Complications: cirrhosis, HCC
Toxic megacolon: pathogenesis, manifestations (6), diagnosis, microscopic findings, complication, risk factors (2), treatment (4)
Pathogenesis: complete cessation of neuromuscular activity in intestinal wall --> rapid colonic distention --> thins the intestinal wall
Manifestations: abdominal pain & tenderness, marked abdominal distention, tympany on percussion, fever, diarrhea, signs of shock
Diagnosis: AXR shows colonic dilation (esp. transverse colon) with diameter >5.5cm and fluid levels
Microscopic: segmental necrosis
Complications: perforation
Risk factors: ulcerative colitis, Crohn's
Treatment: IV fluids, steroids, immunosuppressants, total colectomy with ileostomy if no improvement within 24-48hrs
What studies are contraindicated in toxic megacolon? Why?
Barium enema and colonoscopy. May cause perforation.
Pyogenic hepatic abscess: manifestations (6), diagnosis (2)
Manifestations: fever, chills, RUQ pain, anorexia, weight loss, n/v
Diagnosis: U/S or CT scan
How do organisms that cause hepatic abscess reach the liver? (6)
Penetrating injury: mixed aerobic & anaerobic flora
Ascending cholangitis: enteric gram-negative bacilli, enterococci
Seeding from portal vein: appendicitis, diverticulitis
Arterial supply: hematogenous seeding of Staph aureus
Direct invasion from an adjacent source: enteric gram-negative bacilli, enterococci
Parasitic infection in developing country: entamoeba, echinococcus
HNPCC (Lynch syndrome): defect, inheritance, manifestations (4)
Defect: mutation in one allele of a genes responsible for DNA mismatch repair (MLH1, MSH2, MSH6, PMS2); mutation of second allele occurs during adult life
Inheritance: autosomal dominant
Manifestations: colon cancer <50y/o, mainly right-sided, synchronous & metachronous (occur after resection of primary tumor) cancers common, cancer arises from macroscopically-normal areas of dysplastic mucosa
Lynch syndrome I vs. Lynch syndrome II
Lynch syndrome I: predisposition to colon adenocarcinoma
Lynch syndrome II: predisposition to colon cancer + increased incidence of extraintestinal cancers (endometrial, ovarian, gastric, pancreatic, urothelial)
Sporadic colon adenocarcinoma: most common locations (2), risk factors (6), labs, prevention (2), prognosis
Location: 1) rectosigmoid colon, 2) ascending colon
Risk factors: adenomatous polyps, low-fiber diet, diet high in cholesterol & carbohydrates, IBD, obesity, charred/fried foods
Labs: follow CEA
Prevention: regular colonoscopies after 50y/o, aspirin may reduce risk of adenomatous polyp formation
Prognosis: determined by lymph node involvement & distant mets
Biliary atresia: pathogenesis, manifestations (5), labs (3), liver biopsy (3)
Pathogenesis: congenital obstruction of extrahepatic bile ducts with total obstruction by 3rd week of life
Manifestations: jaundice beginning 3rd-4th week, acholic (light) stool, dark urine, firm enlarged liver, biliary cirrhosis by 6 months
Labs: increased direct bilirubin, alk phos, GGT
Liver biopsy: marked intrahepatic bile ductule proliferation, portal tract edema & fibrosis, parenchymal cholestasis
Hemolytic disease of the newborns: cause, manifestations, labs (3)
Cause: Rh+ infant born to Rh- mother
Manifestations: jaundice within 24hrs of birth
Labs: unconjugated hyperbilirubinemia, hemolytic anemia, positive Coombs test
Gilbert syndrome: pathogenesis, triggers (6), labs (5)
Pathogenesis: reduced UDP-glucuronyl transferase production --> mild unconjugated hyperbilirubinemia & jaundice during times of stress
Triggers: hemolysis, fasting, physical exertion, febrile illness, stress, fatigue
Labs: elevated indirect bilirubin; normal LFTs, CBC, blood smear, reticulocyte count
Alpha-1 antitrypsin deficiency: liver sx (6), pulmonary sx (2), liver biopsy (3), diagnosis (2), complications (2)
Liver symptoms: hepatomegaly, splenomegaly, cholestasis, elevated LFTs, neonatal hepatitis with cholestatic jaundice, childhood hepatitis that completely resolves or becomes chronic and silently progressive
Pulmonary symptoms: panacinar emphysema or chronic bronchitis <50y/o, COPD in nonsmokers
Liver biopsy: oval-to-round intracytoplasmic hepatocyte inclusions (globules of unsecreted A1AT) that are eosinophilic on H&E stain, strongly PAS-positive (stain red), and diastase-resistant
Diagnosis: measurement of A1AT level + genetic testing
Complications: cirrhosis, HCC
Physiologic jaundice of newborn: pathogenesis, timing
Pathogenesis: insufficient UDP-glucuronyl transferase --> mild unconjugated hyperbilirubinemia
Timing: occurs after first 24hrs, subsides by end of first week
Worst prognostic lab values in hepatic cirrhosis (2)
PT and albumin
What does a high AST level indicate
Hepatocellular injury and release of intracellular enzymes into the blood.
Why do patients with alcoholic cirrhosis have thrombocytopenia? (2)
1. direct toxic effects of EtOH on bone marrow
2. cirrhosis causes hypersplenism and sequestration of platelets
Diffuse esophageal spasm: physiology, manifestations 4), manometry, barium swallow, caution
Physiology: uncoordinated contractions of esophageal body --> prevents propagation of food bolus towards stomach
Manifestations: muscle contractions may be painful, intermittent dysphagia, crampy chest pain not associated with exertion, chest pain may mimic unstable angina in intensity & location
Manometry: multiple disorganized contractions in mid- to lower esophagus; periodic non-peristaltic esophageal muscle contractions
Barium swallow: corkscrew esophagus
Caution: rule out cardiac cause of chest pain
Describe the process of swallowing food (3)
1. Oral phase (voluntary): Food bolus is collected at back of mough and lifted up to posterior wall of pharynx.
2. Pharyngeal phase: Involuntary pharyngeal muscle contractions propel food bolus to esophagus.
3. Esophageal phase: Food bolus enters esophagus and stretches its walls. Peristaltic contractions start just above site of distention and propel food bolus down. LES relaxes to allow it to enter stomach.
Aflatoxin: source, geographic distribution (2), effects
Definition: produced by aspergillus flavus and aspergillus parasiticus, which grow on corn, soybeans, peanuts; B1 aflatoxin is most toxic
Geography: Asia, Africa
Effects: high levels of dietary aflatoxin intake are associated with G-to-T mutation in p53 gene --> increased risk of HCC especially if pt is infected with HBV
Transcription factor responsible for cytokine production (e.g. TNF-alpha) in immune response to infectious pathogens.
Crohn's disease: genetics, proposed pathogenesis, location, manifestations (7), complications (5)
Genetics: associated with HLA-DR1 & HLA-DQw5
Proposed pathogenesis: NOD2 mutation increases activity of NF-kappaB --> increased cytokine production in response to an unknown antigen --> increased Th1 cell activation --> activation of macrophages, granuloma formation, etc.
Location: any part of GI tract, most commonly ileocecal region
Manifestations: insidious presentation over years, abdominal pain, diarrhea +/- blood, malaise, fever, aphthous ulcers, perianal disease
Complications: fistulas (due to transmural inflammation), strictures (due to transmural inflammation), chronic intestinal obstruction (due to strictures), abscesses, colon adenocarcinoma
NOD2: source (2), function, mutation
Source: epithelial cells, leukocytes
Function: intracellular microbial receptor that triggers NF-kappaB --> induces cytokine production in immune response to infectious pathogens
Mutation: Crohn's disease
Ulcerative colitis: genetics, manifestations (5), macroscopic findings (3), microscopic findings (2)
Genetics: associated with HLA-DR2
Manifestations: bloody diarrhea +/- abdominal pain, low-grade fever, erythema nodosum, pyoderma gangrenosum
Macroscopic: rectum ALWAYS involved, continuous areas of erythematous friable granular mucosa, pseudopolyps
Microscopic: inflammation limited to mucosa & submucosa, collections of neutrophils within crypt lumina (crypt abscesses)
Complications: toxic megatcolon, colon cancer
Secretory diarrhea: causes (4), pathogenesis, manifestations (3), treatment (3)
Causes: Crohn's, carcinoid syndrome, VIPoma, bacterial toxins
Pathogenesis: excess secretions of fluid & electrolytes in gut
Manifestations: watery diarrhea with high electrolyte content, no blood or pus, orthostatic hypotension
Treatment: bismuth subsalicylate, probiotics, octreotide
VIP: source (2), function (4)
Source: pancreatic islet cells, neurons in GI mucosa
Function: relaxation of GI smooth muscle, inhibition of gastric acid secretion, stimulation of pancreatic HCO3 & Cl secretion, stimulation of intestinal water secretion
VIPoma: pathogenesis, manifestations (5), treatment
Pathogenesis: increased intestinal chloride loss in stool --> excess loss of H2O, Na and K
Manifestations: intractable watery diarrhea, metabolic acidosis, hypokalemia, achlorydria, hypotension due to dehydration & vasodilation
Treatment: somatostatin (octreotide)
Cholecystokinin (CCK): source, regulation (2), function (3)
Source: I cells of duodenum & jejunum mucosa
Regulation: stimulated by fatty acids & monoglycerides entering duodenum
Function: stimulates secretion of pancreatic enzymes & HCO3, stimulates gallbladder contraction, inhibits gastric emptying
Secretin: source, regulation (2), function (3)
Source: S cells of duodenum
Regulation: stimulated by release of gastric HCl into duodenum (pH <5) and fatty acids
Function: increases HCO3 secretion from pancreatic ductal epithelium, decreases gastric acid secretion, stimulates pyloric sphincter contraction
Gastrin: source, regulation, function (5)
Source: G cells in mucosa of gastric antrum
Regulation: stimulated by stomach distention, peptides, vagal stimulation
Function: stimulates parietal cells to produce HCl, stimulates ECL cells to produce histamine, stimulates growth of gastric mucosa, stimulates proliferation of parietal cells, stimulates gastric motility
Opiate-induced biliary colic: pathogenesis, manifestations (2), treatment (3)
Pathogenesis: mu opioid analgesics can cause contraction of smooth muscle cells in sphincter of Oddi --> constriction & spasm --> increased pressure in common bile duct and gallbladder
Manifestations: severe pain & cramping in RUQ, jaundice (rare)
Treatment: stop opiate, supportive care, pain control with NSAIDs (diclofenac, ketorolac)
Meperidine: MOA, AE
MOA: selective mu receptor agonist
AE: thought to cause less biliary colic than other opiates
Side effects of opiates (7)
Biliary colic (less in meperidine)
Decreased parietal cell acid secretion
Indirectly increases somatostatin secretion from pancreas
Duodenal ulcer: most common location, structure, cause (2), complications (3), epidemiology
Location: first part of duodenum (duodenal bulb, usually anterior)
Structure: breach of mucosa that extends through muscularis mucosae into submucosa (or beyond)
Cause: H. pylori (most), NSAIDs
Complications: perforation (anterior wall of duodenal bulb), hemorrhage (posterior wall erodes into gastroduodenal artery), NO increase in risk of cancer
Epidemiology: more common than gastric ulcers
Duodenal bulb: anatomy, significance
Anatomy: begins at pylorus and ends at neck of gallbladder; posterior to gallbladder & liver; anterior to gastroduodenal artery, common bile duct and portal vein; superior to head of pancreas
Significance: ulcer in posterior wall tends to erode into gastroduodenal artery
Gastroduodenal artery: source, anatomy, supply, branches (3)
Source: arises from common hepatic artery
Anatomy: courses inferiorly, posterior to first part of duodenum
Supply: pylorus and proximal part of duodenum
Branches: right gastroepiploic, supraduodenal and superior pancreaticoduodenal arteries
Common hepatic artery: source, supply (5), branches (2), anatomy
Source: arises from celiac trunk
Supply: liver, gallbladder, pylorus, duodenum, pancreas
Branches: proper hepatic & gastroduodenal
Anatomy: passes superior to duodenal bulb
Inferior pancreaticoduodenal artery: source, function
Source: arises from SMA
Function: supplised blood to lower duodenum and head of pancreas
How does HBV cause HCC? (5)
1. HBV DNA is incorporated into genome of hepatocytes that survive the immune response to infection
2. Host antiviral antibodies appear --> viral replication stops --> infectivity ceases and liver damage tapers off, but risk of HCC remains high
3. Integrated DNA causes chronic liver cell injury and regenerative hyperplasia --> increases number of hepatocytes susceptible to mutations
4. HBV DNA encodes HBx protein, which activates insulin-like growth factor II and receptors for insulin-like growth factor I --> stimulates cell proliveration
5. HBV gene products also suppress p53 activity --> disrupts growth control of infected cells
How does HCV cause HCC?
HCV causes chronic liver injury and inflammation followed by liver regeneration. Increased mitotic activity of infected hepatocytes residing within an altered environment (cirrhotic liver) leads to genetic instability.
Rapid urease test
Place gastric biopsy into urea-containing solution. When present, urease (product of H. pylori) degrades urea into CO2 and ammonia. This causes a pH increase and resultant color change in pH indicator. Alkaline pH (pink) persisting more than 5 minutes indicates H. pylori infection.
Barrett esophagus: pathogenesis, histology, complication
Pathogenesis: acidic gastric contents enter esophagus in patient with GERD --> irritate mucosa --> inflammation --> epithelial necrosis --> sustained epithelial demage promotes replacement of normal stratified squamous epithelium with intestinal-type columnar cells (more resistant to acid)
Histology: intestinal-type columnar epithelium with goblet cells in esophagus
Complication: increased risk of esophageal adenocarcinoma
Achalasia: pathogenesis, manifestations (4), diagnosis (2), complications
Pathogenesis: loss of ganglion cells in lower esophageal sphincter --> impaired esophageal peristalsis and decreased relaxation of LES during swallowing --> food retention and dilatation of esophageal body
Manifestations: intermittent nonprogressive dysphagia, chest pain, food regurgitation, aspiration
Diagnosis: manometry shows elevated resting pressure of LES; barium swallow shows dilated esophagus and 'bird's beak' deformity
Complications: increased risk of squamous cell carcinoma of esophagus
Squamous cell carcinoma of esophagus: risk factors (8), manifestations (3), macroscopic findings, microscopic findings (7)
Risk factors: smoking, alcohol, achalasia, Plummer-Vinson syndrome, consumption of nitrosamine-containing foods, corrosive strictures, betel nuts, consumption of exceedingly hot foods
Manifestations: progressive dysphagia (solids first), significant weight loss, iron deficiency anemia (due to chronic GI blood loss)
Macroscopic: plaque-like thickenings of mucosa that may become excavated and ulcerated
Microscopic: flattened polyhedral or ovoid epithelial cells, abundant eosinophilic cytoplasm, distinct borders, keratin nests of 'pearls' within or between cells, intercellular bridging, areas of keratinization if well-differentiated, large hyperchromatic cells with bizarre nuclei & atypical mitoses
Most common benign tumor of esophagus
Esophageal leiomyoma
Pathogenesis of acute interstitial pancreatitis & acute necrotic pancreatitis
1. Acute interstitial pancreatitis: Duct obstruction leads to stasis of pancreatic secretions and digestion of adipose cells by lipase. This leads to formation of fatty acids that bind Ca and precipitate as insoluble Ca salts. Areas of focal necrosis & Ca precipitation induce an inflammatory reaction.
2. Acute necrotic pancreatitis: If inflammatory process continues, edema reduces blood flow to pancreatic acini. Ischemia damages acinar cells, causing activation of trypsin inside acinar cells. Trypsin then activates other proteolytic enzymes, initiating autodigestion of pancreatic tissue. Destruction of blood vessel walls can cause hemorrhage into necrotic areas.
Acute interstitial pancreatitis: macroscopic finding, microscopic findings (3)
Macroscopic: pancreas looks edematous
Microscopic: interstitial edema, focal fat necrosis, Ca deposits
Acute necrotic pancreatitis: macroscopic findings (3), microscopic findings (2)
Macroscopic: areas of white chalky fat necrosis in pancreatic tissue; may spread to mesentery, omentum & other parts of abdominal cavity; black areas of hemorrhage
Microscopic: focal fat necrosis, Ca bound to free fatty acids deposits as soaps in areas of necrosis
Bacterial peritonitis: histology (2)
Histology: dull-appearing peritoneal surface, areas of viscous white-yellow suppurative exudate
Retroperitoneal structures (SAD PUCKER)
Suprarenal (adrenal) glands
Abdominal aorta & IVC
Duodenum (parts 2, 3, part of 4)
Pancreas (except tail)
Ureters & bladder
Colon (ascending, descending)
Osmotic laxatives: drugs (3), MOA
Drugs: magnesium citrate, magnesium hydroxide, polyethylene glycol
MOA: poorly absorbable substance that attracts water into intestinal lumen --> distends intestinal wall and increases peristalsis
Lactase deficiency: cause (4), pathogenesis, manifestations (3), diagnosis (5), histology, risk factors (4)
Cause: genetic mutation near lactase gene (rare), cessation of lactase production by mid-childhood (common), injury to GI mucosa, bacterial overgrowth
Pathogenesis: deficiency of lactase (disaccharidase) in intestinal brush border --> inability to break down lactose into glucose & galactose --> undigested lactose attracts water & electrolytes into intestinal lumen --> osmotic diarrhea
Manifestations: abdominal pain, distension, watery diarrhea
Diagnosis: lactose challenge causes symptoms, glucose increase <20mg/dL, high stool osmotic gap (>100), increased breath hydrogen content (>20ppm), decreased stool pH
Histology: normal intestinal mucosa
Risk factors: African American, Native American, Asian, Hispanic
Why do pts with lactase deficiency have abdominal distention? Why do they have low stool pH?
Normal gut flora metabolizes lactose via fermentation, producing gas and distention. Fermentation produces short-chain fatty acids and excess amounts of hydrogen.
IBS: manifestations (4)
Manifestations: diarrhea alternating with constipation, abdominal pain, distention, no organic cause
Rectal prolapse: description, causes (4)
Description: protrusion of rectal mucosa through anus
Causes: pregnancy, constipation, severe diarrhea, CF (esp. children)
Celiac disease: pathogenesis, manifestations (6), microscopic findings (4), labs (4), treatment
Pathogenesis: hypersensitivity to gluten
Manifestations: diarrhea, steatorrhea, sx of malabsorption, weight loss, iron deficiency anemia, dermatitis herpetiformis
Microscopic findings: flattening of intestinal mucosa, loss of villi, chronic inflammatory infiltration of lamina propria, esp. in duodenum & proximal jejunum
Labs: IgA to tissue transglutaminase, IgA to gliadin, anti-endomysial antibodies, anti-reticulin antibodies
Treatment: gluten-free diet (oats, rice; NOT wheat, rye, barley)
Whipple disease: etiology, pathogenesis, manifestations (8), microscopic findings (2), risk factor, treatment
Etiology: tropheryma whippelii (gram positive actinomycete)
Pathogenesis: actinomycete proliferates within macrophages of small intestine, joints and CNS without provoking inflammatory response
Manifestations: malabsorption, diarrhea, weight loss, arthropathy, polyarthritis, pyschiatric sx, cardiac sx, ocular sx
Microscopic findings: small intestine lamina propria contains enlarged foamy macrophages packed with rod-shaped bacilli and PAS-positive diastase-resistant granules (magenta color); granules consist of lysosome & partially digested bacteria
Risk factors: white male
Treatment: antibiotics
Splenic artery branches (3)
Pancreatic branches: run posterior to upper border of pancreas --> supply body & tail
Left gastroepiploic artery: supplies middle part of greater curvature of stomach; strong anastomosis with right gastroepiploic artery
Short gastric branches: supply upper part of greater curvature of stomach; very poor anastomoses, so tissue they supply is vulnerable to ischemic injury following splanic artery blockage
Right gastric artery: source, function
Source: proper hepatic artery
Function: supplies distal lesser curvature of stomach
Tissues supplied by what artery are most likely to be affected by compression of splenic artery?
Short gastrics
Primary biliary cirrhosis: pathogenesis, risk factors (8), manifestations (12), labs (5)
Pathogenesis: autoimmune destruction of intrahepatic bile ducts leading to cholestasis
Risk factors: female, middle-age, Sjogren's, Raynaud's, scleroderma, autoimmune thyroid disease, hypothyroidism, celiac disease
Manifestations: insidious onset, pruritus (first sx), fatigue, HSM, xanthelasma, pale stool, jaundice, steatorrhea, portal HTN, osteopenia, bone pain, other sx of fat malabsorption
Labs: elevated alk phos, cholesterol, direct bilirubin, serum IgM; positive anti-mitochondrial antibodies
Why do pts with Crohn's get gallstones?
Normally, bile acids are reabsorbed in the terminal ileum to be recycled back in the liever. When mucosa of terminal ileum is inflamed as in Crohn's, bile acids are not reabsorbed but are instead lost with feces. As a result, less bile acid is present in bile, increasing the ratio of cholesterol to bile acids. Cholesterol precipitates in the gallbladder and forms gallstones.
Acetaminophen: metabolism, mechanism of toxicity, treatment of toxicity
Metabolism: 90% metabolized in liver via sulfation & glucoronide conjugation; remainder is eliminated via oxidation by cytochrome p450 system and urinary excretion of unmetabolized drug; toxic metabolite of p450 pathway (NAPQI) is metabolized by hepatic glutathione into non-toxic compounds
Toxicity: sulfation & glucoronidation conjugation are saturated --> excess NAPQI production --> once glutathione is depleted, NAPQI interacts with hepatocytes causing hepatocellular injury & centrilobular necrosis
Treatment of toxicity: N-acetylcysteine acts as a glutathione substitute and binds NAPQI; also provides sulfhydryl groups to increase non-toxic sulfation of acetaminophen
Deferoxamine: MOA, indications (2)
MOA: binds iron in bloodstream --> facilitates urinary excretion
Indication: antidote for iron poisoning, hemochromatosis
Salicylate toxicity: treatment (4)
Treatment: gastric decontamination, decrease GI absorption, correct fluid & electrolyte imbalance, alkalinize urine
Barbiturate toxicity: treatment (5)
Treatment: supportive care, gastric decontamination, decrease GI absorption, alkalinize urine, diuresis
Dietary energy derived from each type of food: protein, carb, fat, ethanol
Protein: 4 calories per gram
Carbohydrate: 4 calories per gram
Fat: 9 calories per gram
Ethanol: 7 calories per gram
D-xylose: definition, test
Definition: monosaccharide that can be absorbed directly without the action of pancreatic enzymes (which are needed for degradation of polysaccharides into monosaccharides)
Test: measure absorption to determine brush border absorptive function independent of pancreatic function --> differentiate between pancreatic and intestinal causes of malabsorption
Conditions with decreased trypsinogen (3)
Chronic pancreatitis
Subtotal pancreatectomy
Hepatic encephalopathy: pathogenesis, precipitants (8), labs, treatment
Pathogenesis: ammonia & nitrogen absorption in the gut --> liver fails to metabolize waste products due to hepatocyte dysfunction +/- shunting of blood through collateral circulation --> increased levels of ammonia in circulation --> may cross BBB and stimulate GABA in CNS
Precipitants: GI bleed (increased NH3 absorption in gut) and any stressor that alters ammonia balance (hypovolemia, hypokalemia, metabolic alkalosis, hypoxia, sedatives, hypoglycemia, infection)
Labs: decreased BUN (less NH3 converted to urea)
Treatment: lactulose
Metabolism of ammonia (4)
1. Ammonia is created during the catabolism of glutamine in enterocytes and catabolism of dietary protein in colon
2. Enters circulation
3. Travels to liver via portal vein
4. Detoxified to urea in liver
Lactulose: MOA, indication
MOA: bacterial acts on lactulose (a disaccharide), leading to acidification of colonic contents --> converts absorbable NH3 into nonabsorbable NH4+ --> excretion of NH4+
Indication: hepatic encephalopathy
Alkaline phosphatase: locations (7)
Locations: 1) liver, bone; 2) intestine, kidney, placenta, WBC, some neoplasms
Gamma glutamyl transpeptidase (GGT): locations (8), use in lab
Locations: 1) hepatocytes, biliary epithelium; 2) kidney, spleen, pancreas, heart, lung, brain
Use in lab: helps determine whether an elevated alk phos is of hepatic or bony origin
Hindgut: structures (4), blood supply, venous drainage
Structures: distal 1/3 transverse colon, descending colon, sigmoid colon, rectum
Blood supply: IMA (L3)
Venous drainage: IMV (drains into splenic vein, which joins with SMV to form portal vein)
Foregut: structures (4), blood supply
Structures: all structures from mouth to 2nd part of duodenum, liver, pancreas, gallbladder
Blood supply: celiac artery from distal esophagus downward
Midgut: structures, blood supply
Structures: from 3rd part of duodenum to proximal 2/3 transverse colon
Blood supply: SMA
How long does it take for a colonic adenoma to become malignant?
About 10 years
Determination of malignant potential of adenomatous polyps (3)
Size: <1cm unlikely to undergo malignant transformation, >4cm has 40% risk of malignancy
Histology: villous adenomas are more likely to be malignant than tubular adenomas
Degree of dysplasia
Adenoma-to-carcinoma sequence of colon cancer (4)
1. APC mutation: decreased intercellular attachment and increased cell growth causes progression from normal mucosa to small adenomatous polyp (~1cm)
2. K-ras mutation: encoded can stimulate cell cycle but can no longer inhibit it, leading to uncontrolled cell proliferation and increase in size of polyps
3. p53 and DCC mutation: decreased apoptosis leads to malignant transformation
4. Some forms of colon adenocarcinoma and inherited polyposis syndrome have increased COX-2 activity and methylation abnormalities
How many half-lives until a drug is virtually totally eliminated?
5 half-life intervals (97%)
Mechanism of resistance of VRE
Alters vancomycin-binding site from D-alanyl-D-alanine terminus to D-alanine-D-lactate terminus.
Mechanisms for resistance to penicillin (2)
1. bacteria produce beta-lactamase (penicillinase) --> destroy beta-lactam ring of penicillins; does NOT affect cephalosporins, carbapenems, or penicillinase-resistant penicillins (e.g. nafcillin)
2. bacteria have modified penicillin-binding proteins in their peptidoglycan cell wall --> beta-lactam abx can't bind and interfere with cell wall synthesis; seen in MRSA
Cycloserine: MOA, AE
MOA: inhibits incorporation of D-alanine into UDP-MUrNAc-oligopeptide during bacterial cell wall synthesis
AE: high risk of ototoxicity (rarely used)
Polymyxin: MOA
MOA: abx that binds to, disrupts and interferes with permeability of cytoplasmic membrane
Wilson's disease: defect, pathogenesis, inheritance, manifestations (12), labs (3), gold standard dx, treatment (2)
Defect: mutation of ATP7B gene on chromosome 13
Pathogenesis: decreased production of ceruloplasmin --> excess non-ceruloplasmin-bound serum copper --> decreased secretion into biliary system --> accumulation in liver, CNS lenticular nucleus, cornea --> causes damage via generation of free radicals
Inheritance: autosomal recessive
Manifestations: chronic or fulminant hepatitis, portal HTN, cirrhosis, Parkinson-like tremor, rigidity, catatonia, ataxia, slurred speech, personality changes, depression, paranoia, Kayser-Fleischer rings (seen on slit-lamp)
Labs: elevated LFTs, ceruloplasmin <20mg/dL, increased urine copper
Diagnosis: liver bx demonstrates copper level >250mcg/g dry weight
Treament: copper chelators that remove excess copper in tissues (d-penicillamine, trientine)
INH metabolism
N-acetyl transferase metabolizes INH via acetylation to N-acetyl-isoniazid in the hepatic microsomal system. Slow acetylators metabolize INH much more slowly than normals (bimodal distribution), so they are at higher risk of adverse effects.
Drugs metabolized significantly more slowly by 'slow acetylators' (4)
Drugs that are methylated during metabolism (2)
Acute HBV: incubation period, prodromal sx, labs, histology (6)
Incubation period of 30-180 days
Prodrome: 'serum sickness-like', malaise, fever, skin rash, pruritus, LAD, joint pain --> later anorexia, nausea, jaundice, RUQ pain
Labs: significantly elevated ALE & AST after symptoms start to abate, followed by elevated bilirubin & alk phos
Histology: diffuse ballooning degeneration (hepatocyte swelling), mononuclear cell infiltrates, eosinophilic apoptotic hepatocytes (Councilman bodies), hepatocyte necrosis, portal inflammation, hepatocyte cytoplasm has a fingely granular eosinophilic ('ground glass') appearance due to accumulation of spheres & tubules of HBsAg
Pathogenesis of alcohol-induced hepatic steatosis (3)
1. Increased activitiy of alcohol dehydrogenase & aldehyde dehydrogenase --> excess NADH production --> decreased free fatty acid oxidation & gluconeogenesis
2. Impaired lipoprotein assembly and secretion
3. Increased peripheral fat catabolism & TG synthesis
HAV: manifestations (12), labs (4), epidemiology
Manifestations: may be asymptomatic ('anicteric') esp. in children; acute self-limited low-grade fever, jaundice, malaise, fatigue, anorexia, n/v, RUQ pain, hepatomegaly, dark urine, aversion to smoking; lasts 3-6 weeks
Labs: ALT & AST spike early, elevated bilirubin & alk phos later, positive anti-HAV IgM
Epidemiology: less common but more severe in adults
Histology of acute viral hepatitis (7)
Diffuse ballooning degeneration (hepatocyte swelling): cytoplasm appears empty with only occasional eosinophilic organelle remnants
Eosinophilic apoptotic hepatocytes (Councilman bodies)
Lobular architectural disruption
Bridging necrosis: confluent hepatocyte necrosis, regions of adjacent lobules are interconnected by swaths of dead hepatocytes
Mononuclear cell infiltration in portal tracts and sinusoids
Kupffer cells are hypertrophied and laden with lipofuscin pigment due to phagocytosis of hepatocellular debris
Formation of pseudoacini of dividing hepatocytes as liver attempts to regenerate cells lost to viral damage
Histology of cirrhosis: macroscopic (4)
Macroscopic: diffuse hepatic fibrosis; replacement of normal lobular architecture by fibrous-lined parenchymal nodules; micronodular if most nodules are <3mm; macronodular if most nodules are >3mm
Causes of cholestasis (9)
Intrahepatic: erythromycin, OCPs, primary biliary cirrhosis, cholestasis of pregnancy, primary sclerosing cholangitis (may be extrahepatic), cholangiocarcinoma
Extrahepatic: choledocholithiasis, pancreatic cancer, gallbladder cancer
Cholestasis: histology, sequelae
Histology: deposition of yellow-green bile pigment in hepatic parenchyma, green-brown plugs in dilated bile canaliculi
Sequelae: intestinal malabsorption, deficiency of fat-soluble vitamins
Seborrheic dermatitis (2)
Chronic inflammatory condition
Scaly greasy skin on scalp, face, ears, eylids, eyebrows
Chronic gastritis: causes (4), pathogenesis, histology (5), complication
Cause: autoimmune (type A in body), H. pylori (type B in antrum), radiation, granulomatous conditions
Pathogenesis: increased acid production --> increased risk of duodenal ulcer formation
Histology: gastric atrophy, intestinal metaplasia, loss of intrinsic factor-secreting parietal cells in upper glandular layer, marked lymphocytic & plasma cell infiltration, megaloblastic changes in mucosal cells
Complication: increased risk of gastric cancer
First-order kinetics
The quantity of metabolite formed is directly proportional to the dose administered --> a fixed PROPORTION of drug is converted to the metabolite. Represented graphically by a linear line with positive slope, indicating that an increase in drug dose leas to a proportional increase in metabolite conversion.
Zero-order (saturable) kinetics
The active sites of the metabolizing enzyme are fully saturated (Vmax), so a constant AMOUNT of drug is metabolized and eliminated per unit time, regardless of the concentration or dose of the drug. Further increases in drug dose are not accompanied by an increase in formation of metabolite. Represented graphically by a linear line with 0 slope.
Diphenoxylate: MOA, indication, AE (3)
MOA: binds mu opiate receptors in GI tract --> slows motility; combined with small doses of atropine to discourage abuse
Indications: anti-diarrheal at low dose
AE: high dose causes anticholinergic effecs (blurry vision, nausea), which discourages abuse & physical dependence; bloating, mild sedation
Pathogenesis of diarrhea in IBD
Inflammation of gut causes mucus, protein and bloody discharge, leading to diarrhea
GERD: pathogenesis, manifestations (5), macroscopic findings (2), microscopic findings (3), manometry
Pathogenesis: transient LES relaxations & hypotensive LES --> acidic gastric contents reflux back into esophagus and irritate esophageal mucosa --> inflammatory reaction & epithelial repair
Manifestations: heartburn, regurgitation, dysphagia, nocturnal cough, sore throat
Macroscopic: mucosal erythema or edema in distant esophagus; erosions or ulcuerations if severe
Microscopic: elongation of lamina propria papillae; basal cell hyperplasia; intraepithelial eosinophils, neutrophils, lymphocytes
Manometry: decreased LES pressure
Esophageal leiomyoma: definition, histology
Definition: slow growing benign tumor
Histology: fascicles of spindle cells, variable amounts of fibrosis
Hepatic metabolism of bilirubin (7)
1. Unconjugated bilirubin binds tightly to albumin and is highly insoluble in water
2. Carrier-mediated uptake of bilirubin at sinusoidal membrane
3. Storage within hepatocyte
4. Conjugation with glucuronic acid by UDP-glucuronyl transferase in endoplasmic reticulum
5. Biliary excretion of bilirubin glucuronides into bile canaliculi via biliary transport protein MRP2; conjugated bilirubin is water-soluble, loosely bound to albumin, nontoxic, and can be excreted in urine when present in excess
6. Bacterial enzymes reduce bilirubin into urobilinogens in colon --> most are excreted in feces as stercobilin
7. Small fraction of urobilinogens return to liver via enterohepatic circulation --> re-enter GI tract or get excreted in urine
Most likely cause of unexplained chronic hepatitis in a patient younger than 30?
Wilson's disease
Dubin-Johnson syndrome: defect, inheritance, manifestations (2), labs (2), histology (3)
Defect: absence of biliary transport protein MRP2 used in hepatocellular excretion of bilirubin glucuronides into bile canaliculi
Inheritance: autosomal recessive
Manifestations: jaundice that may only be triggered by illness, pregnancy or OCP use; otherwise asymptomatic
Labs: conjugated hyperbilirubinemia with direct bilirubin >50%, otherwise normal LFTs, elevated coproporphyrin I
Histology: abundant pigment inclusions in lysosomes of hepatocytes, pigment is composed of epinephrine metabolites, liver appears black
Histopathology of Crohn's: macroscopic (5), microscopic (6)
Macroscopic: affected bowel is hyperemic & edematous; narrowing of intestinal lumen due to edema & fibrosis (strictures); mesenteric fat extends along serosa ('creeping fat'); serosa is dull-gray, edematous, granular; mesentery is edematous & fibrotic
Microscopic: skip lesions, noncaseating granulomas, transmural inflammation, infiltration of monocytes & lymphocytes, linear ulcers, cobblestone appearance of mucosa
Budd-Chiari syndrome: pathogenesis, manifestations (3), macroscopic findings (3), microscopic findings (5)
Pathogenesis: occlusion of hepatic vein or intra/suprahepatic IVC --> decreased drainage of blood from liver and portal circulation into systemic circulation --> increased pressure in liver
Manifestations: portal HTN, ascites, HSM
Macroscopic: liver is swollen, reddish purple, tense capsule
Microscopic: centrilobular congestion, dilation of sinusoids, perivenular hemorrhage, fibrosis, necrosis
46y/o man with no PMH is found to have a palpable spleen, esophageal varices, and normal liver biopsy. What is the cause of his condition? Explain.
Portal vein thrombosis
Increased hydrostatic pressure in portal system caused blood to be shunted through portocaval anastomoses, forming esophageal varices. Normal liver biopsy indicates that the cause of portal HTN is PREsinusoidal.
Portal vein thrombosis: manifestations (4), histology
Manifestations: portal HTN, splenomegaly, varicosities at portocaval anastomoses, no ascites
Histology: normal hepatic parenchyma (problem is PREsinusoidal)
Acetaminophen toxicity: manifestations, histology
Manifestations: liver failure 24-48hrs after ingestion
Histology: centrilobular hepatic necrosis
Where does H. pylori live? How does it cause duodenal ulcers, gastric ulcers, gastric adenocarcinoma and gastric lymphoma?
Location: bug lives in mucus layer overlying epithelium of gastric antrum (esp. pre-pyloric area) & fundus, as well as any ectopic gastric tissue in duodenum or esophagus; protected from gastric acid by mucus layer & urease production
Duodenal ulcers: causes local inflammation of gastric mucosa --> decreases number of somatostatin-producing antral cells --> decreased inhibition of gastrin --> very low pH gastric fluid enters duodenum --> areas of gastric metaplasia that are then colonized by H. pylori --> produces ulcers if not adequately neutralized by HCO3; does NOT increase risk of duodenal cancer
Gastric ulcers: destroys local mucous layer and induces local inflammatory response --> normal levels gastric acid are sufficient to cause gastric ulcers
Gastric adenocarcinoma: maybe immune activation or local inflammation
Gastric lymphoma: maybe immune activation or local inflammation
Autoimmune gastritis: pathogenesis, manifestations (4)
Pathogenesis: autoantibodies against gastric parietal cells --> inflammation of gastric mucosa, parietal cell destruction, achlorhydria
Manifestations: chronic gastritis with antral sparing, pernicious anemia, fatigue, paresthesias
Zenker diverticulum: pathogenesis, manifestations (6), diagnosis
Pathogenesis: failure of cricopharyngeus to relax during swallowing --> more force is needed to move food bolus down --> more intense contractions of pharyngeal muscles increase oropharyngeal intraluminal pressure --> pharyngeal mucosa eventually herniates through muscle fibers in posterior hypopharynx, forming a false diverticulum
Manifestations: choking or 'food sticking' sensation with swallowing, odynophagia, coughing, regurgitation, recurrent aspiration, lateral neck mass
Diagnosis: video fluoroscopic swallowing study
Diverticulosis: pathogenesis, manifestations (2), location, histology, risk factors (3)
Pathogenesis: increased intraluminal pressure when straining during a bowel movement --> mucosa & submucosa herniate through weak spots in colonic mucosal layer ('pulsion' diverticula) --> may disrupt arterioles adjacent to diverticulum
Manifestation: painless lower GI bleeding, acute diverticulitis
Location: most often in sigmoid colon
Histology: contains only mucosa & submucosa layers ('false')
Risk factors: age >60y/o, constipation, low fiber diet
Traction diverticulum: cause, structure, example
Cause: inflammation and subsequent scarring
Structure: includes mucosa, submucosa, muscular layers ('true')
Example: midesophageal diverticulum occurring due to mediastinal lymphadenitis (TB, fungal infection) and periesophageal scarring
Peptic ulcer disease: structure, most common locations (3)
Structure: breach of mucosa that extends through muscularis mucosae into submucosa (or beyond) in areas exposed to acid and peptic juices
Locations: proximal duodenum, antral stomach, GE junction
Treatment: triple therapy if H. pylori is the cause, PPI, H2 blocker
Diffuse gastric adenocarcinoma: manifestations, macroscopic (4), microscopic (2), risk factors (8), prognosis (2)
Manifestations: anemia
Macroscopic: diffuse involvement of stomach wall, plaque-like appearance, ill-defined, may infiltrate large areas of stomach wall causing leather-bottle stomach (linitis plastica)
Microscopic: cells don't form glands, contain abundant mucin droplets that push nucleus to one side ('signet ring')
Risk factor: H. pylori, Barrett esophagus, chronic gastritis, frequent nitrate consumption, alcohol, smoking, diet lacking in fresh fruit & vegetables, smoking
Prognosis: depends on depth of invasion through gastric wall and whether LNs are involved
Esophageal adenocarcinoma: risk factors (4), histology
Risk factors: Barrett's esophagus, GERD, obesity, smoking
Histology: ulcerated exophytic lesion at GE junction
Histology of colon adenocarcinoma: macroscopic (3), microscopic
Macroscopic: usually a protuberant mass; annular lesion with 'napkin-ring' constriction of bowel; lesion may have heaped-up edges and ulcerated central region in distal colon
Microscopic: dysplastic mucosal cells with variable degree of gland formation
Gastric acid
Source: parietal cells in mucosal glands of fundus & body of stomach
Stimulation of gastric acid (3)
1. Histamine: binds H2 receptors --> increases cAMP
2. Parasympathetic system: ACh binds M3 receptors --> increases Ca
3. Gastrin: binds gastrin receptor on parietal cell, increasing Ca; stimulates enterochromaffin-like cells in stomach to secrete histamine
Increased intracellular cAMP and Ca activate protein kinases that lead to increased activity of the H/K/ATPase pump
Systemic mastocytosis: pathogenesis, manifestations (13)
Pathogenesis: mast cell proliferation in bone marrow & other organs --> increased histamine secretion
Manifestations: pruritus, urticaria, dermatographism, flushing, syncope, hypotension, tachyardia, bronchospasm, abdominal cramps, increased gastric acid secretion, diarrhea (due to inactivation of pancreatic & intestinal enzymes by gastric acid), nausea/vomiting, gastric ulcers
Gastroparesis: causes (3), manifestations (4)
Causes: DM, uremia, hypothyroidism
Manifestations: constipation, episodic diarrhea, early satiety, food stasis with subsequent vomiting
Treatment of H. pylori infection
2 antibiotics (metronidazole, tetracycline, amoxicillin, clarithromycin) + PPI +/- bismuth for 14 days to prevent recurrence of ulcer
Sucralfate: MOA, indication
MOA: binds base of mucosal ulcers --> physically protects against gastric acid
Indication: helps peptic ulcers heal
Metoclopramide: MOA, indications (2)
MOA: dopamine agonist with central & peripheral effects --> prokinetic & antiemetic properties
Indications: gasstroparesis, prevention of nausea & vomiting
Misoprostol: MOA, indication
MOA: prostaglandin E1 analog
Indication: prevent NSAID-induced ulcer disease
Allopurinol: MOA, indications (2)
MOA: inhibits xanthine oxidase --> decreased uric acid synthesis
Indications: gout, tumor lysis syndrome
AE: may precipitate acute gouty attack
Mallory-Weiss tear: cause, triggers (5), manifestations (3), histology, risk factors (2)
Cause: rapid increase in intraabdominal & intraluminal gastric pressure
Triggers: retching, vomiting, coughing, hiccupping, abdominal trauma
Manifestations: may be asymptomatic; hematemesis; not life-threatening
Histology: longitudinal mucosal tear at esophagogastric-squamocolumnar junction
Risk factor: hiatal hernia, alcoholism
Manifestations of cirrhosis (14)
Hyperestrogenism: gynecomastia, testicular atrophy, decreased body hair, spider angiomata
Palmar erythema
Hypoalbuminemia: pedal edema, ascites
Hyperammonemia: hepatic encephalopathy, asterixis, malodorous breath (fetor hepaticus)
Portal HTN: esophageal varices, hemorrhoids, caput medusae, splenomegaly
Why do pts with cirrhosis have hyperestrogenism?
1. Liver is unable to metabolize circulating androstenedione, leading to increased estradiol levels.
2. Concentration of sex hormone-binding globulin increases --> increased binding of testosterone --> decreased ratio of testosterone to estrogen, creating an estrogen-excess state
Spleen: embryonic origin, blood supply
Embryonic origin: mesoderm-derived, originates from dorsal mesentery
Blood supply: splenic artery (branch of celiac trunk)
Liver: embryonic origin, blood supply
Embryonic origin: endoderm-derived foregut structure that forms from a diverticulum of primitive gut tube within ventral mesentery
Blood supply: proper hepatic artery (branch of celiac trunk)
Pancreas: embryonic origin, blood supply
Embryonic origin: endoderm-derived structure of foregut & midgut
Blood supply: superior and inferior pancreaticoduodenal arteries from celiac and SMA respectively
Blood supply to transverse colon
Proximal 2/3: middle colic artery (branch of SMA)
Distal 1/3: left colic artery (branch of IMA)
Most likely outcome of HBV?
Complete resolution
Prognosis of HBV infection (4)
>95% acute hepatitis with mild or subclinical symptoms that completely resolve
4-5% develop chronic hepatitis; of these, 20-50% develop cirrhosis
10% of pts with cirrhosis develop HCC
<1% fulminant hepatitis with massive liver necrosis
How do cholesterol gallstones form?
Free cholesterol is converted into bile acids in the liver. These bile acids are then conjugated to glycine or taurine to create bile salts. The bile salts are secreted into bile canaliculi. As more water-insoluble cholesterol is secreted into bile, it is rendered soluble in small amounts by the detergent action of amphipathic bile salts and phospholipid phosphatidylcholine. This prevents cholesterol stones from forming. If gallbladder is hypomotile or there is more cholesterol than bile salts, cholesterol precipitates into insoluble crystals that form stones. High levels of bile acid and phosphatidylcholine reduce the risk of gallstone formation.
Pancreatic pseudocyst: cause, pathogenesis, histology (3), most common location
Cause: complication of pancreatitis
Pathogenesis: proteolytic enzymes disrupt walls of pancreatic ducts --> cause leakage of pancreatic secretions into peripancreatic space --> high pancreatic enzyme content of fluid induces inflammatory reaction in walls of surrounding organs --> granulation tissue forms, encapsulating the fluid collection & forming a pseudocyst
Histology: walls consist of granulation tissue; no epithelial lining; fibrosis, thickening and organization of walls occurs over 4-6 weeks
Location: lesser peritoneal sac, bordered by stomach, duodenum, transverse colon
Serous pancreatic neoplasm: histology
Histology: glycogen-rich cuboidal epithelium
Mucinous cystic neoplasm of pancreas: histology
Histology: columnar mucinous epithelium
Pancreatic adenocarcinoma: histology, serum markers (2), risk factors (9)
Histology: atypical cells forming papillary projections
Serum markers: CEA, CA 19-9
Risk factors: age 65-75y/o, smoking (most impt), diabetes mellitus, obesity, chronic pancreatitis (esp. after 20yrs), hereditary pancreatitis, MEN syndromes, HNPCC, FAP
Zollinger-Ellison syndrome: cause, pathogenesis, manifestations (3), histology (2)
Cause: gastrin-secreting tumor in pancreas (most), duodenum, or stomach; 67% malignant
Pathogenesis: increased gastrin production --> increased gastric acid secretion and parietal cell proliferation --> peptic ulcers in stomach, duodenum and atypical locations
Manifestations: diarrhea due to inactivation of pancreatic enzymes, abdominal pain, GERD
Histology: hyperplasia of gastric glands, thickening of gastric rugal folds
Factors that increase likelihood of gastrinoma as cause of ulcers (4)
Ulcer in distal duodenum
Multiple ulcers
Ulcers refractory to therapy
Recurrence of ulcers after acid-reducing surgery
Acute erosive gastritis: causes (9), pathogenesis, manifestations (4), histology (5), prognosis
Causes: surgery, intracranial injury (Cushing), burns (Curling), shock, sepsis, severe trauma, heavy NSAID use, smoking, alcohol
Pathogenesis: impaired oxygenation --> short-term severe mucosal injury --> inflammation & superficial mucosal destruction
Manifestations: epigastric pain, n/v, may be asymptomatic, may cause fatal GI hemorrhage
Histology: multiple shallow mucosal defects in stomach +/- duodenum, do not penetrate muscularis mucosa, measure <1cm, neutrophil infiltration, unremarkable adjacent mucosa
Prognosis: once causative stressors are resolved, healing with rull re-epithelialization of gastric mucosa occurs within days to weeks
Gastric ulcers: most common location, structure
Location: lesser curvature, at transition zone between acid-secreting epithelium of gastric corpus & gastrin-producing epithelium of antrum
Histology: breach of mucosa extends through muscularis mucosa into submucosa (or beyond)
Complication: may erode into left gastric artery
Pathogenesis of acute calculous cholecystitis (6)
1. ingestion of fatty foods stimulates contraction of gallbladder against obstructed gallbladder neck or cystic duct
2. obstructive stones disrupt protective mucus layer of gallbladder
3. epithelium becomes exposed to detergent action of bile salts
4. prostaglandins released in gallbladder wall further incite inflammation of mucosa & deeper tissues, leading to gallbladder hypomotility
5. increasing distention & internal pressure within gallbladder eventually lead to ischemia
6. bacteria invade injured & necrotic tissue, causing infection
Mesenteric adenitis: etiology, manifestations (3), epidemiology
Etiology: yersinia eterocolitica
Manifestations: RUQ pain, fever, n/v
Epidemiology: children 5-14y/o
Copper metabolism (5)
1. 60% ingested copper (0.6-3mg/d) is absorbed in stomach & duodenum --> loosely bound to albumin --> transported to liver
2. In liver, copper is incorporated into an alpha2-globulin to form ceruloplasmin
3. Ceruloplasmin is secreted into plasma, where it accounts for 90-95% of circulating copper
4. Senescent ceruloplasmin and remainder of ingested unabsorbed copper are secreted into bile & excreted in stool (85-95%).
5. 5-15% excreted in urine
Curling ulcer
Ulcers arising in proximal duodenum in association with severe trauma or burns.
Cushing ulcer: definition, pathogenesis
Definition: ulcers arising in esophagus, stomach or duodenum in pts with high ICP; particularly prone to perforation.
Pathogenesis: increased ICP stimulates vagus nerve, which stimulates hypersecretion of gastric acid
Granulomatous gastritis: cause, histology (2), prognosis
Cause: idiopathic
Histology: intramucosal epithelioid granulomas, transmural inflammation causing narrowing of antrum
Prognosis: benign
Intestinal-type gastric adenocarcinoma: pathogenesis, manifestations, macroscopic (3), microscopic (2), prognosis (2)
Pathogenesis: arisess from precursor lesions
Manifestations: upper GI bleeding
Diagnosis: biopsy to differentiate from peptic gastric ulcers
Macroscopic: nodular, polypoid, well-demarcated masses; can become ulcerated; may rapidly expand into gastric lumen
Microscopic: well-formed glands consisting of columnar or cuboidal cells, similar in appearance to colon adenocarcinoma
Prognosis: depends on depth of invasion through gastric wall and whether LNs are involved
Why is liver such a common site of metastatic spread? (4)
Large size
Dual blood supply
High perfusion rate
Filtration function of Kupffer cells
Presentation of liver metastases
Patients present with jaundice or abnormal hepatic enzymes only once majority of liver parenchyma is destroyed or major bile ducts are obstructed with tumor.
Hepatic adenoma: origin, location, risk factors (2), manifestations (2), complication, prognosis
Origin: epithelial tissue
Location: solitary mass in right hepatic lobe
Risk factors: young/middle-age, OCP use
Manifestations: usually asymptomatic; may have RUQ or epigastric pain
Complications: rupture & intraabdominal bleeding
Prognosis: may regress with discontinuation of OCPs
Hepatic angiosarcoma: risk factors (3), prognosis
Risk factors: vinyl chloride, arsenic, thorotrast
Prognosis: extremely aggressive, most pts die within 1yr
Cholangiocarcinoma: location, macroscopic findings, risk factors (4), prognosis
Location: intra- & extrahepatic bile ducts
Macroscopic: treelike mass, grows along intrahepatic portal system
Risk factors: primary sclerosing cholangitis, congenital fibropolycystic diseases of biliary system (Caroli disease, choledochal cysts), thorotrast exposure
Prognosis: very poor
Hepatoblastoma: epidemiology, types (2), prognosis
Epidemiology: most common liver neoplasm of children
Types: epithelial type, mixed epithelial/mesenchymal type
Prognosis: fatal within a few yrs if not resected
Most common hepatic neoplasm
Gallbladder hypomotility: description, risk factors (7), consequence
Description: slow or incomplete gallbladder emptying
Risk factors: pregnancy, rapid weight loss, prolonged use of TPN, octreotide, high spinal cord injuries, hypertriglyceridemia, older age
Consequence: bile precipitation, leading to formation of biliary sludge and acute cholecystitis
Biliary sludge: composition, complication
Composition: cholesterol monohydrate crystals, Ca bilirubinate, mucus
Complication: stone formation & acute cholecystitis
Brown pigment gallstones: cause, pathogenesis, risk factors (3)
Cause: biliary tract infection with e. coli, ascaris lumbricoides, or liver fluke opisthorchis sinensis
Pathogenesis: organisms in infected bile cause hepatocyte injury --> bacteria and injured hepatocytes release beta-glucuronidase, which deconjugates bilirubin --> free bilirubin complexes with calcium and precipitates in bile
Risk factor: rural Asian populations, women, elderly
Black pigment gallstones: pathogenesis, cause (3), risk factors (3), appearance (4)
Pathogenesis: increased unconjugated bilirubin precipitates in bile as calcium bilirubinate --> contain high amounts of Ca carbonate & phosphate
Cause: chronic extravascular hemolysis (e.g. sickle cell anemia, beta-thalassemia, hereditary spherocytosis)
Risk factor: rural Asian populations, women, elderly
Appearance: small, spiculated, crumbly, radioopaque on x-ray
Intestinal malabsorption: manifestations (4), causes (3), diagnosis (2)
Manifestations: diarrhea, steatorrhea (foul-smelling bulky floating greasy stools), weight loss, symptoms of nutritional deficiencies
Causes: pancreatic exocrine deficiency, intestinal mucosal defects, bacterial proliferation
Diagnosis: 1) Sudan III stool stain to identify presence of fat, 2) quantitative analysis of fecal fat (>7g/day is diagnostic)
Causes of intestinal malabsorption: pancreatic exocrine insufficiency (2), intestinal mucosal defects (4), bacterial proliferation (3)
Pancreatic exocrine insufficiency: leads to impaired hydrolysis of nutrients in small intestine; CF, chronic pancreatitis
Intestinal mucosal defects: structural defect or injury to intestinal epithelial cells hemapers nutrient transport from lumen and/or intestinal cells to peripheral organs; celiac, tropical sprue, Whipple's, Crohn's
Bacterial proliferation: bacteria compete for nutrients, causing relative nutrient deficiency; surgically created blind loops, small-bowel diverticulosis, diabetic neuropathy
Cavernous hemangioma: epidemiology (2), pathogenesis, manifestations (2), diagnosis, macroscopic findings (4), microscopic findings (3), treatment, prognosis
Epidemiology: most common benign liver tumor, usually 30-50y/o
Pathogenesis: congenital malformation that enlarges by ectasia (not hyperplasia or hypertrophy)
Manifestations: most asymptomatic, may have RUQ fullness
Diagnosis: do NOT biopsy --> can cause fatal hemorrhage
Macroscopic: may be single or multiple, well-circumscribed, spongy consistency, measures <5cm
Microscopic: cavernous blood-filled vascular spaces of variable size, lined by a single epithelial layer, collagenous scars or fibrous nodules may be seen in association with thrombosis
Treatment: resection if symptomatic or compressing adjacent structures
Prognosis: excellent
HCV infection: histology (2)
Histology: lymphoid aggregates within portal tracts, focal areas of macrovesicular steatosis
Congenital pyloric stenosis: pathogenesis, manifestations (4), treatment, epidemiology
Pathogenesis: hypertrophy of pyloric muscularis mucosae + localized edema & inflammation cause narrowing of the pyloric channel
Manifestations: recurrent projectile nonbilious vomiting, visible perstalsis on exam, olive-sized mass in distal stomach or pyloric region, presents within weeks of birth
Treatment: surgically split the muscle
Epidemiology: 3x more common in males, multifactorial pattern of inheritance
Features that differentiate IBD-associated colon cancer from sporadic colon cancer (6)
Affects younger patients
Progresses from flat and non-polypoid dysplasia
Histology is higher grade with mucinous and/or signet ring morphology, more likely to be anaplastic
Early p53 mutations and late APC mutations (opposite of sporadic)
Proximal colon (esp. Crohn's & primary sclerosing cholangitis)
Timing of IBD-associated colon cancer
After 10yrs of colitis
Compare left-sided (8) and right-sided (7) colon cancers
Left-sided: smaller; infiltrate wall of colon, encircling it and narrowing the lumen; presents with obstruction, change in stool caliber, constipation, cramping abdominal pain, abdominal distention, n/v
Right-sided: large bulky mass that protrudes into colonic lumen; no obstruction due to large caliber of ascending colon; more likely to bleed; presents with iron-deficiency anemia, anorexia, malaise, weight loss
M cells: location, function, disease
Location: base of mucosal villi within Peyer's patches of ileal mucosa
Function: sample contents of gut lumen and transfer antigens to basal lamina within endosomes; at the base of the cell within a special pocket (microfold), macrophages & lymphocytes await , ready to mount an immune response
Disease: specifically targeted by shigella
Epithelial absorptive cells: location, function, disease
Location: mucosa of small & large bowel
Function: absorb and secrete water and electrolytes
Disease: diarrhea
Goblet cells: function, disease (3)
Function: mucus secretion into gut lumen
Disease: mucus release is increased in inflammatory states --> stool has visible mucus in inflammatory diarrhea, giardiasis, Crohn's
Paneth cells: location, function (4)
Location: occur in small groups at base of intestinal crypts
Function: phagocytic, secrete lysozyme (dissolves cell wall of many bacteria), secretes defensins (antimicrobial & antiparasitic), first line of immune defense against intestinal microorganisms
Inflammatory diarrhea: etiology (5), manifestations, lab
Etiology: Shigella, EHEC, EIEC, C. difficile, C. jejuni
Manifestations: bloody diarrhea
Labs: WBC in stool
Parietal cells: location, histology (4), function, regulation (4)
Location: mucosal glands of body & fundus of stomach
Histology: oxyntic (pale pink) cytoplasm, round, platelike, abundant mitochondria, intracellular tubulovesicular system, in periphery of upper-layer glands of mucosa
Function: secrete HCl and intrinsic factor
Regulation: stimulated by histamine, ACh, gastrin; inhibited by PGE2
Cells in gastric mucosa from lumen down (5)
1. Simple columnar epithelial cells: secrete mucus to protect gastric lining from acid
2. Lamina propria: contains numerous gastric pits (invaginations) lined by simple columnar epithelium; base of each pit contains 2-4 gastric mucosal glands that contain parietal cells and chief cells
3. Superficial gastric glands + pale pink round parietal cells
4. Deep gastric glands + many small basophilic granular chief cells (secrete pepsinogen)
5. Muscularis mucosae
Chief cells: location, histology, function
Location: deeper region of gastric glands (deep to parietal cells)
Histology: small, basophilic, granular cells
Function: secrete pepsinogen
Why do pregnant women get gallstones?
Estrogen upregulates HMG-CoA reductase activity, which increases cholesterol and causes bile to become supersaturated with cholesterol. Progesterone reduces bile acid secretion and slows gallbladder emptying. Same pathogenesis for women on OCPs.
Atropine: MOA in stomach
MOA: blocks M3 ACh receptor in gastric parietal cell
MOA: cholinomimetic muscarinic agonist, esp. M2 receptors
Indication: ileus, urinary retention
AE: may increase gastric acid secretion
PPI: MOA, indications (3)
MOA: block primary active transport by H/K/ATPase pump at parietal cell apical membrane, the final common pathway for HCl secretion --> increase pH of gastric lumen
Indications: PUD, GERD, Zollinger-Ellison syndrome
Chronic alcoholism: labs (3), long-term sequelae (5)
Labs: AST:ALT >2, MCV >100 (even without folate or B12 deficiency), elevated GGT
Sequelae: head & neck cancer, squamous cell cancer of esophagus, cirrhosis, HCC, chronic pancreatitis
How does alcohol induce acute pancreatitis? (3)
1. Induces pancreatic secretions with a high protein concentration and low fluid content. These viscous secretions precipitate and form plugs that may obstruct the lumina of pancreatic ductules.
2. Causes spasms in sphincter of Oddi
3. Direct toxic effect on acinar cells
Acute pancreatitis: manifestations, labs
Manifestations: epigastric pain radiating to back, may have left pleural effusion
Labs: leukocytosis, hypocalcemia, hypernatremia (3rd space fluid loss + decreased fluid intake), hyperglycemia
Functions of stomach (3)
1. Protein digestion: Parietal cells produce HCl and chief cells produce pepsinogen. HCl provides low pH necessary for protein digestion and conversion of pepsinogen to pepsin. Pepsin cleaves polypeptides at sites of aromatic amino acids. These proteins are later degraded by pancreatic proteases.
2. B12 absorption: Parietal cells in body & fundus secrete intrinsic factor
3. Gastric reservoir: Acts as reservoir for ingested food.
Pepsin: source, function (2)
Source: secreted from chief cells as pepsinogen and converted to pepsin by HCl in stomach
Function: cleaves polypeptides at sites of aromatic amino acids; helpful but not required for protein digestion
Dumping syndrome: pathogenesis, manifestations (4), tx
Pathogenesis: after total gastrectomy, loss of gastric reservoir --> accelerated emptying of hyperosmolar food boluses into small bowel
Manifestations: nausea, diarrhea, sweating, dizziness
Treatment: avoid large meals, low intake of simple sugars
Gastrojejunostomy (Billroth II): description, indications (2), complications (5)
Description: gastric antrum is removed to decrease gastrin production --> side-to-side anastomosis between jejunum & gastric body --> creates a blind loop composed of duodenum & proximal jejunum
Indications: complicated PUD, ulcers refractory to medical management
Complications: iron deficiency anemia due to anatomy and decreased gastric acidity; malabsorption of vitamin B12, folate, fat-soluble vitamins, Ca
Where is iron absorbed? What vitamin increases its absorption?
Main in duodenum & proximal jejunum
Absorption increased by vitamin C
How is vitamin C absorbed?
In distal small bowel via active transport process
How is pyridoxine absorbed?
In jejunum and ileum via passive diffusion
How are biotin (B7) and pantothenic acid (B5) absorbed?
In small and large intestine via Na-dependent multivitamin transporter
Manifestations of pancreatic adenocarcinoma: head (3), body/tail
Head: palpable but nontender gallbladder (Courvoisier sign), weight loss, obstructive jaundice (compression of common bile duct)
Body/tail: usually doesn't produce sx until it invades splanchnic plexus and causes midepigastric abdominal pain
Ribavirin MOA (5)
1. Ribavirin is phosphorylated intracellularly by adenosine kinase to ribavirin mono-, di- and triphosphate metabolites. When it is incorporated into RNA, it pairs with uracil or cytosine --> causes hypermutation during RNA-dependent RNA replication --> lethal to RNA viruses.
2. Ribavirin triphosphate directly inhibits HCV RNA polymerase --> decreased viral replication
3. Ribavirin monophosphate inhibits IMP dehydrogenase --> decreased conversion of IMP to GMP --> depletion of intracellular pools of GTP
4. Inhibits viral RNA guanylyl transferase & methyltransferase, leading to defective 5'-cap formation on viral mRNA transcripts and inefficient viral translation.
5. Enhances Th1-mediated immunity and inhibits Th2 cytokine production, leading to a more effective immune response.
Acute HCV
Self-limited, rarely causes hepatic failure, usually leads to chronic infection
Treatment of HCV: indications, drugs
Indications: evidence of chronic infection --> HCV RNA detectable in serum + liver biopsy showing chronic inflammation with fibrosis
Indications for ribavirin (2)
Chronic HCV
Elevated AFP (4)
HCC (does NOT correlate with size, stage or prognosis)
Tumors of gonadal origin
Chronic liver disease
HCC: pathogenesis, manifestatiosn (6), diagnosis, prevention, risk factors (7)
Pathogenesis: often follows development of cirrhosis
Manifestations: RUQ pain, malaise, fatigue, weight loss, sensation of abdominal fullness, sudden decompensation of stable cirrhosis
Diagnosis: sudden increase in AFP above baseline, AFP >500 in high-risk patient
Prevention: monitor AFP
Risk factors: HBV, HCV, alcoholism, aflatoxin, hemochromatosis, A1AT deficiency, cirrhosis of any cause
CEA: source, elevated levels (8), use in medicine
Source: produced in embryonic pancreas, liver, intestine; detected in munte amounts in serum of healthy adults
Elevated levels: cancer of colon, pancreas, stomach, breast; IBD, cirrhosis, pancreatitis, smokers
Use: sensitive indicator of cancer recurrence
Acid phosphatase (2)
Secondary prostate tumor marker antigen
Elevated in pts undergoing active osteoclast-initiated bone resorption
Best site to biopsy to demonstrate presence of H. pylori?
Prepyloric area (colonization density is highest here)
Dysplasia in colon cancer: mild (2), moderate (5), severe (2)
Mild: elongated hyperchromatic cells, loss of mucin from cytoplasm
Moderate: increased variation in shape & size (pleomorphism), nuclei are enlarged & hyperchromatic, increased number & size of nucleoli, increased N:C ratio, increased number of mitotic figures
Severe: glands are branched, may have disordered cribiform appearance
Hydatid cyst: etiology (2), manifestations (4), histology (3), diagnosis (2), treatment, caution
Etiology: echinococcus granulosus (unilocular), echinococcus multilocularis (multilocular)
Manifestations: initial infection is asymptomatic; subsequent cyst formation causes hepatomegaly, RUQ pain, n/v
Histology: encapsulated & calcified cyst ('eggshell calcification'), contains fluid & budding cells (will become daughter cysts), outer wall composed of many layers of delicate gelatinous sheets surrounded by thick fibrous capsule
Diagnosis: imaging (U/S, CT or MRI) + serology
Treatment: surgery + mebendazole or albendazole
Caution: do NOT aspirate, as spilling of contents into peritoneum can cause anaphylactic shock!
Periodic acid-Schiff (PAS) reaction: description, use (3), addition of diastase
Description: periodic acid oxidizes carbon-carbon bonds --> forms aldehydes that produce magenta colon upon reacting with fuchsin-sulfurous acid
Use: stains polysaccharides of fungal cell wall, mucosubstances secreted by epithelia, basement membranes
Diastase: digests glycogen to form maltose & glucose, which are easily washed from sections --> can be added to demonstrate glycogen (negative reaction); tropheryma whippelii is diastase-resistant so it appears bright magenta
Best stain for iron?
Prussian blue --> appears blue
Best stain for Ca?
H&E --> appears dark purple
Best stain for neutral lipids?
Nile red or Sudan black
Dermatitis herpetiformis: pathogenesis, manifestations (4), common locations (4), histology (5), epidemiology (3)
Pathogenesis: IgA and IgG antibodies against gliadin cross-react with reticulin, a protein found in anchoring fibils of epidermal basement membrane
Manifestations: erythematous papules, vesicles and bullae; extensor surfaces, symmetric distribution, extremely pruritic
Locations: knees, elbows, buttocks, back
Histology: neutrophils & fibrin at tips of dermal papillae that form microabscesses; IgA deposits in tips of dermal papillae; overlying basal cells become vacuolated; blisters form at tips of involved papillae; older lesions may have eosinophilic infiltrates
Epidemiology: more common in men, 30-40y/o, strongly associated with celiac disease
Chronic pancreatitis: manifestations (6), risk factors (3), imaging
Pathogenesis: EtOH induces protein precipitation within pancreatic ducts --> proteins form ductal plugs that may calcify, forming calculi consisting in part of calcium carbonate
Manifestations: recurrent abdominal pain, weight loss, diarrhea, steatorrhea, pancreatic exocrine insufficiency, malabsorption
Risk factors: chronic alcoholism, CF, hypertriglyceridemia
Imaging: pancreatic calcifications
Abetalipoproteinemia: defect, inheritance, manifestations (8), labs, histology (2)
Defect: impaired synthesis of apoB --> inability to form chylomycrons --> accumulation of lipids in cells of intestinal absorptive epithelium
Inheritance: autosomal recessive
Manifestations: presents in 1st yr of life; abdominal distention, steatorrhea, malabsorption, FTT, progressive ataxia, retinitis pigmentosa, RBCs with thorny projections (acanthocytes) due to insufficient lipids for membrane formation
Labs: decreased levels of all lipids
Histology: normal intestinal mucosal structure, epithelial cells with clear or foamy cytoplasm esp. on tips of villi
Octreotide: MOA (3), indications (3)
MOA: synthetic analog of somatostatin with a longer half-life --> decreases gut motility and gut blood flow, and inhibits secretion of many hormones & hormone-like substances
Indications: VIPoma, secretory diarrhea, carcinoid syndrome,
Iron toxicity: stage 1 (6), stage 2 (2), stage 3 (3), stage 4
Stage 1: nausea, diarrhea, abdominal pain, hematemesis, melena, hypovolemia
Stage 2: GI sx resolve, pt appears better
Stage 3: metabolic acidosis, hepatic dysfunction, hypoglycemia
Stage 4: scarring of recovering GI tract
Methanol toxicity: toxic metabolites (2), manifestations (4), treatment
Toxic metabolites: formaldehyde, formic acid
Manifestations: metabolic acidosis; damage to eyes, GI tract, CNS
Treatment: fomepizole
Non-neoplastic polyps: hyperplastic, hamartomatous (4), inflammatory (3), lymphoid (2)
Hyperplastic: well-differentiated mucosal cells that form glands & crypts
Hamartomatous: consist of mucosal glands, smooth muscle, connective tissue; sporadic, Peutz-Jeghers, juvenile polyposis
Inflammatory: regenerating intestinal mucosa; Crohn's, ulcerative colitis
Lymphoid: intestinal mucosa infiltrated with lymphocytes; children
Carcinoid tumor: origin, most common locations (3), light microscopy (4), electron microscopy
Origin: enterochromaffin cells (endocrine) of intestinal mucosa
Most common location: ileum > appendix > rectum
Light microscopy: eosinophilic cytoplasm; oval-to-round stippled nuclei; minimal to no variation in shape & size of tumor cells; may form glands, nests, rows, sheets
EM: multiple dense-core granules in cytoplasm (contain secretory products of tumor cells)
Stimulation of acid secretion in stomach: cephalic phase, gastric phase, intestinal phase
Cephalic phase: thought, sight, smell and taste of food triggers cholinergic & vagal stimulation of parietal cells
Gastric phase: chemical stimulus of food and distention of stomach triggers release of gastrin
Intestinal phase: protein-containing food enters duodenum; plays a minor role in stimulating gastric acid secretion
Mechanisms of down-regulation of gastric acid secretion after a meal
1. Ileum and colon release peptide YY --> binds receptors on enterochromaffin-like cells --> inhibits gastrin-stimulated histamine release --> counteracts cephalic & gastric phases of acid secretion
2. Somatostatin
3. Prostaglandins
Receptive relaxation
Reflex that allows gastric fundus to dilate in anticipatio nof food passing through pharynx & esophagus.
Postprandial alkaline tide
Increase in plasma HCO3 and decrease in plasma Cl secondary to surge of acid within gastric lumen.
Chronic mesenteric ischemia: pathogenesis, manifestations (3), histology (2), diagnosis (2)
Pathogenesis: atherosclerosis in intestinal arteries (esp. celiac, IMA, SMA) --> arteries cannot dilate in response to increased blood flow requirements during digestion & absorption of food
Manifestations: epigastric or periumbilical pain 30-60mn after meal, weight loss, pain out of proportion to physical exam
Histology: hypoperfused areas of intestine show mucosal atrophy and loss of vili; atherosclerotic plaques in intestinal vessels
Diagnosis: angiography (gold standard), mesenteric duplex ultrasound
Candida esophagitis: endoscopy, microscopy
Endoscopy: patches of adherent grey/white pseudomembranes on erythematous mucosa
Microscopy: yeast cells and pseudohyphae invading mucosal cells, necrotic debris
HSV-1 esophagitis: endoscopy, microscopy
Endoscopy: small vesicles that evolve into 'punched-out' ulcers
Microscopy: eosinophilic intranuclear inclusions (Cowdry type A) in multinuclear squamous cells at margins of ulcers
CMV esophagitis: endoscopy, microscopy
Endoscopy: linear ulcerations
Microscopy: intranuclear & cytoplasmic inclusions
Which structure is the esophagus on CT scan?
Esophagus courses between the trachea and vertebral bodies. It is typically collapsed with no visible lumen. Trachea is a good landmark because the radiolucency of the air inside it allows you to differentiate it from the esophagus posteriorly and the great vessels anteriorly.
Arsenic poisoning: risk factor, manifestations (6), treatment
Risk factors: ingestion of arsenic-containing insecticides
Manifestations: n/v, abdominal pain, diarrhea, altered mental status, tachycardia, garlic odor on breath
Treatment: dimercaperol (displaces arsenic ions from sulfhydryl groups of enzymes, facilitating their excretion)
Dimercaperol: indications (2), AE (2)
Indications: arsenic poisoning, lead poisoning
AE: nephrotoxicity, hypertension
CaNaEDTA: MOA, indications (2)
MOA: forms complexes with mono-, di- and trivalent ions
Indications: acute lead poisoning, mercury poisoning
Pathogenesis of ascites in cirrhosis (4)
1. Mechanical compromise of portal vein by fibrotic tissue
2. Vasoactive agents cause dilation of splanchnic arterial vasculature, causing further intrahepatic vasoconstriction
3. These processes cause increased portal vein hydrostatic pressure, leading to ascitic fluid formation and decreased systemic perfusion pressure.
4. Kidney senses decreased perfusion pressure and responds with avid retention of Na & H2O, promoting further increase in ascites
Treatment of ascites secondary to cirrhosis
Restriction of Na intake + furosemide + spironolactone
Which structure is the portal vein on CT scan?
Seen at the level of T12/L1 -- same level as celiac trunk. Portal vein lies medial to or just within the right lobe of the liver, and anterior to the IVC.
Hirschsprung disease: barium enema, histology
Barium enema: narrowing in rectosigmoid area, dilation proximal to the obstruction
Histology: SUBMUCOSA of rectum demonstrates absence of submucosal (Meissner) plexus, MUSCULARIS EXTERNA of rectum demonstrates absence of myenteric (Auerbach) plexus
Histology of primary biliary cirrhosis (7)
Precirrhotic stage: granulomatous inflammation ('florid duct lesion'); destruction of interlobular bile ducts; infiltration of portal tract by macrophages, lymphocytes, plasma cells, eosinophils; looks similar to GVHD
Progressive damage secondary to obstruction of bile flow: upstream portal tracts undergo ductular proliferation, inflammation and necrosis of adjacent parenchyma
Liver gradually becomes grossly green and uniformly micronodular due to generalized cholestasis
End-stage: similar to secondary biliary cirrhosis and chronic hepatitis
Alcoholic hepatitis: histology (4)
Histology: hepatocellular swelling & necrosis, Mallory bodies, neutrophilic infiltration, fibrosis
Reye syndrome: pathogenesis, manifestations (5), labs (6), histology (2), electron microscopy (3), prevention
Pathogenesis: viral infection (flu, measles, varicella) --> ingestion of aspirin --> some inborn error of metabolism causes sensitivity to toxic effects of salicylates whcih cause mitochondrial dysfunction
Manifestations: vomiting, hepatomegaly, jaundice is rare, hepatic encephalopathy, cerebral edema
Labs: increased ALT, AST, ammonia, bilirubin, PT, PTT
Histology: microvesicular steatosis (small fat vacuoles in cytoplasm), no necrosis or inflammation
EM: swelling, decreased number of mitochondria, glycogen depletion
Prevention: do not give aspirin in children <16y/o (unless Kawasaki)
Alpha-1 antitrypsin: source, function, disease (2)
Source: produced primarily in the liver
Function: inhibits several proteolytic enzymes (pancreatic trypsin, chymotrypsin, neutrophil elastase)
Disease: panacinar emphysema, cirrhosis
CREST syndrome: definition, pathogenesis, manifestations, labs, complications (2)
Definition: variant of systemic sclerosis that mainly involves skin of face and fingers
Pathogenesis: an unknown antigen stimulates accumulation of CD4 cells in skin and other tissues --> CD4 cells secrete cystokines (esp. TGF-beta) that stimulate fibroblasts to produce collagen and ECM proteins --> excessive tissue fibrosis, esp. in small arterioles and capillaries
Manifestations: Calcinosis, Raynaud syndrome, Esophageal dysmotility, Sclerodactyly (atrophy of skin of hands), Telangiectasia, more benign course than diffuse scleroderma
Labs: anti-centromere antibodies
Complications: pulmonary HTN, pericardial fibrosis
Esophageal dysmotility in CREST sydndrome: pathogenesis, manifestations (4), barium swallow (3), sequelae
Pathogenesis: atrophy and fibrous replacement of esophageal muscularis --> esophageal body and LES become atonic and dilated --> esophageal hypomotility and severe reflux
Manifestations: heartburn, regurgitation, dysphagia, delayed gastric emptying
Barium swallow: dilated esophagus, absent peristalsis, incompetence of LES
Sequelae: Barrett esophagus, esophageal adenocarcinoma
Sliding hiatal hernia: definition, manifestations
Definition: GE junction + part of stomach move up through esophageal hiatus
Manifestations: increased risk of GERD
Porcelain gallbladder: pathogenesis, manifestations (3), diagnosis, histology, sequela, treatment
Pathogenesis: chronic cholecystitis --> chronic irritation/inflammation causes Ca salts to deposit intramurally
Manifestations: often asymptomatic; may have RUQ pain or firm nontender RUQ mass
Diagnosis: x-ray shows rim of Ca deposits that outline the gallbladder
Histology: bluish, brittle, calcium-laden gallbladder wall
Sequela: 11-33% develop gallbladder carcinoma
Treatment: cholecystectomy
Adjustable gastric band wraps around cardiac part of the stomach. What structure must it pass through?
Lesser omentum
Adjustable gastric band: description, function (3)
Description: inflatable silicone device placed around gastric cardia; to encircle the upper stomach, it must pass through the lesser omentum
Function: slows passage of food, increases satiety, limits amount of food consumed
Lesser omentum (4)
Double layer of peritoneum that extends from the liver to the lesser curvature of the stomach and beginning of duodenum.
Divided into hepatogastric ligament connecting to lesser curvature and hepatoduodenal ligament connecting to duodenum.
Between the 2 layers and close to the right-sided free margin are the hepatic artery, common bile duct, portal vein, lymphatics, hepatic plexus.
Between the 2 layers and near attachment to stomach are right & left gastric arteries and gastric veins.
Falciform ligament
Origin: embryonic ventral mesentery
Anatomy: attaches liver to anterior body wall; contains round ligament (remnant of fetal umbilical vein)
Greater omentum: anatomy, gastrocolic ligament (3)
Large fold of visceral peritoneum that extends from greater curvature of stomach, travels inferiorly over small intestine, reflects on itself and ascends to encompass the transverse colon before reaching posterior abdominal wall.
Gastrocolic ligament is the section that stretches from greater curvature to transverse colon. It forms part of the anterior wall of the lesser sac. It is often divided during surgery to provide access to anterior pancreas and posterior wall of stomach.
Splenorenal ligament (3)
Derived from peritoneum
Lies between left kidney & spleen
Contains splenic vessels & tail of pancreas
Histology of liver in right-sided heart failure
Centrilobular congestion
Krukenberg tumor: definition, histology
Definition: metastatic spread of gastric adenocarcinoma to one or both ovaries
Histology: mucin-producing signet ring neoplastic cells in ovarian stroma
Metastasis of gastric adenocarcinoma (4)
1. extends through gastric wall to serosa
2. metastasis to left supraclavicular sentinel node (Virchow) is often the first clinical manifestations of occult gastric cancer
3. metastasis to periumbilical region forms a subcutaneous mass (Sister Mary Joseph nodule)
4. extensive peritoneal seeding and widespread mets to liver, lungs or ovary (Krukenberg)
Origin of metastatic ovarian cancer (4)
Stomach (Krukenberg)
Gallstone ileus: pathogenesis, risk factors (2), manifestations (5), diagnosis (2), treatment
Pathogenesis: large gallstone (>2.5cm) erodes into intestinal lumen via cholecystoenteric fistula --> travels down intestinal passage causing intermittent obstruction --> eventually gets tuck in ileocecal valve and causes mechanical bowel obstruction
Risk factors: female, >70y/o
Manifestations: crampy abdominal pain, vomiting, abdominal distention, tenderness to palpation, tinkling bowel sounds
Diagnosis: upper GI series; AXR shows intestinal gas pattern consistent with obstruction & air in biliary tree (pneumobilia)
Treatment: remove stone via small enterotomy
Zymogen: definition, regulation (2), MOA, activated enzymes (5)
Definition: inactive enzyme precursors secreted from pancreas
Regulation: secretion stimulated by CCK & ACh
MOA: pancreatic acinar cells secrete zymogens via exocytosis --> enter pancreatic ductal system --> drain through ampulla of Vater into descending part of duodenum --> duodenal brush border enzyme enterokinase converts trypsinogen to trypsin --> trypsin activates most of the other proteolytic enzymes AND trypsinogen --> self-supporting cycle of proteolytic enzyme activation in duodenum
Activated enzymes: trypsin, chymotrypsin, elastase, carboxypeptidase, phospholipase A2
Function of lipase
Hydrolyzes TGs into fatty acids & glycerol
Function of amylase
Hydrolyzes starch to produce maltose (glucose-glucose disaccharide), trisaccharide maltotriose, and limit dextrins
Digestion of lipids (3)
1. Bile salts, fatty acids, 2-monoacylglycerols and cholesterol form micelles in duodenum that allow transport through aqueous environment of intestinal lumen and close contact with gut epithelium.
2. Fatty acid, cholesterol and monoacylglycerol diffuse through brush border membrane of intestinal cells in jejunum without help from transporter proteins
3. Inside cells, TGs and cholesterol esters are reconstructed and combined with proteins to form chylomycrons
How does lipid digestion change after cholecystectomy?
No storage place for bile, so it is constantly released into the duodenum. This leads to an increase in the rate of enterohepatic circulation. Patients are less able to tolerate a large fatty meal because they don't have the ability to release a large amount of stored bile into the gut in a coordinated fashion with meals.
Causes of nyctalopia (night blindness) (7)
Hereditary retinitis pigmentosa
Vitamin A deficiency
Congenital rubella
Congenital syphilis
Diabetic retinopathy
Crigler-Najjar syndrome type 1: pathogenesis, inheritance, manifestatiosn (4), labs
Pathogenesis: absent UDP-glucuronyl transferase --> bilirubin cannot be conjugated in liver --> excess unconjugated bilirugin binds tightly to albumin --> cannot be filtered by glomerulus --> deposits instead in various tissues, including the brain
Inheritance: autosomal recessive
Manifestations: kernicterus (bilirubin encephalopathy) with severe jaundice, neurologic impairment and death
Labs: indirect bilirubin 20-25mg/dL
Rotor syndrome: defect, inheritance, manifestations (2), lab
Defect: defects in hepatic uptake and excretion of bilirubin pigments
Inheritance: autosomal recessive
Manifestations: jaundice, otherwise no symptoms
Labs: conjugated hyperbilirubinemia
What effect does intestinal bacterial overgrowth have on bile acids?
Colonic bacterial flora that gain access to small intestine can cause deconjugation of bile acids, making them less soluble and therefore less able to form micelles. This impedes active reabsorption of bile acids into portal circulations at terminal ileum, resulting in lipid malabsorption. This can also happen in bowel stasis, blind loops, extensive diverticulosis, or inadequate bile salt reabsorption in terminal ileum.
Portocaval anastomoses and their manifestations (3)
Left gastric vein to esophageal vein --> esophageal varices
Superior rectal to middle & inferior rectal veins --> hemorrhoids
Paraumbilical to superficial & inferior epigastric veins --> caput medusae
Portal HTN: pathology, cause (4), treatment
Pathology: increased resistance to portal flow at hepatic sinusoids
Cause: cirrhosis, Budd-Chiari, portal vein thrombosis, primary biliary cirrhosis
Treatment: transjugular intrahepatic portosystemic shunt (TIPS) to shunt blood from portal vein to hepatic vein and systemic circulation
Stool osmolality: definition, low gap, high gap
At maximum, it approaches serum osmolality (290). Most stool osmolality is accounted for by Na, K, colonic fermentation products.
When electrolytes comprise mose of luminal osmolality, osmotic gap is low (<50).
When poorly absorbable substance are present, osmotic gap is high (>100).
Intussusception: definition, locaiton, manifestations (4), treatment (2), epidemiology
Definition: invagination of a portion of intestine into lumen of adjacent intestinal segment, leading to impaired venous return, ischemia and necrosis of the invaginated segment of bowel
Location: ileocolic junction
Manifestations: colicky intermittent abdominal pain, n/v, current jelly stools with blood & mucus, palpable tubular mass in RLQ
Treatment: barium enema +/- surgery
Epidemiology: occurs in children <2y/o without structural cause; in pts older than 2y/o, look for a lead point (Meckel, foreign body, tumor)
Kaposi's sarcoma in colon: macroscopic, microscopic
Macroscopic: reddish/violet flat maculopapular lesions, hemorrhagic nodules, polpyoid masses
Microscopic: spindle-shaped tumor cells with cytologic atypia, small vessel proliferation, extravasated RBCs with hemosiderin deposition
CMV colitis: macroscopic, microscopic
Macroscopic: multiple ulcers and mucosal erosions in colon
Microscopic: cytomegalic cells with inclusion bodies
Cryptosporidium: macroscopic, microscopic
Manifestations: profuse watery nonbloody diarrhea
Risk factor: AIDS with CD4 <180
Macroscopic: inflammation of colon, no ulcers
Microscopic: basophilic clusters on surface of intestinal mucosal cells
Where is pancreas on CT scan?
Head, neck and body are retroperitoneal. Tail is peritoneal.
Head lies in the curve of the duodenum and overlies the L2 vertebra.
Body overlies L2 & L2 vertebrae and is anterior to aorta, SMV and left kidney.
Tail courses with splenorenal ligament alongside splenic vessels.
Extraintestinal manifestations of Crohn's (14)
Skin: erythema nodosum, pyoderma gangrenosum (more in UC)
Joints: arthritis, ankylosing spondylitis
Eyes: iritis, uveitis, episcleritis
Malabsorption: oxalate kidney stones, anemia, hypoproteinemia, B12 and folate deficiencies, gallstones
Liver: primary sclerosing cholangitis (more with UC), increased risk of cholangiocarcinoma
Why do pts with Crohn's get kidney stones?
Normally, bile acids are reabsorbed in the terminal ileum. When the wall of the terminal ileum is inflamed, as in Crohn's, most bile acids are lost with feces. This causes impaired fat absorption. Excess lipids in the bowel bind calcium ions, and these soap compleses are excreted in the feces. Normally, dietary calcium binds dietary oxalate to produce insoluble Ca-oxalate salts and enable oxalate excretion. In Crohn's, Ca is unavailable since it is found to lipids. So an increased amount of oxalate is absorbed, promoting the formation of urinary stones.
Features of drugs with high intrinsic hepatic clearance (4)
High lipophilicity: enters hepatocytes more easily
High volume of distribution
Good oral absorption
High rate of redistribution
Features of highly lipophilic drugs (3)
Wide distribution to many tissues
Drug crosses cellular barriers more easily --> easily cleared by liver
Rapidly crosses renal tubular cell membranes after filtration to reenter tissues --> poorly eliminated in kidney
Ischemic colitis: cause, most common locations (2), manifestations (2)
Cause: systemic hypotension, hypoperfusion
Location: watershed areas --> splenic flexure (SMA & IMA), distal sigmoid colon (IMA & hypogastric arteries)
Manifestations: abdominal pain, bloody diarrhea
Anal fissure: definition, most common location, risk factors (2), manifestations (2), histology (2)
Definition: longitudinal tear in mucosa of distal anal canal (distal to dentate line)
Location: >90% are at posterior midline of anal verge, because this area is poorly perfused and more susceptible to trauma
Risk factors: constipation, low-fiber diet
Manifestations: severe tearing pain associated with bowel movements, minimal amounts of bright red blood
Histology: new fissures involve only epithelium of anal mucosa; chronic fissures may have enlarged anal skin tag distal to fissure (due to spasm of internal anal sphincter)
Serotonin: locations (4), function (4)
Locations: GI tract, brain, platelets, retina
Function: regulates secretion, peristalsis, vomiting, emotions (limbic system)
Risk factors for cholesterol gallstones (15)
Female sex hormones
Malabsorption of bile acids (e.g. ileal disease)
Rapid weight loss
Glucose intolerance
Drugs: fibrates, octreotide, ceftriaxone, bile acid-binding resins
Gallbladder hypomotility: pregnancy, advanced age, fasting, hypertriglyceridemia, prolonged TPN
Catalyzes conversion of androgens to estrogens
Condenses two equivalents of acetyl-CoA to form acetoacetyl CoA (substrate for HMG-CoA synthase)
Motilin: source, function
Source: small intestine
Function: promotes intestinal motility
Describe components of pancreatic juice (3)
Na + K in same concentrations as in plasma
HCO3 in higher concentrations than plasma (increases with secretin)
Cl in lower concentration than plasma (decreases with secretin)
7-alpha hydroxylase
Converts cholesterol to bile acids. Inhibited by fibrates.
Indinavir: MOA, AE (5)
MOA: protease inhibitor
AE: lipodystrophy, hyperglycemia, p450 inhibitor, nephrotoxicity, nephrolithiasis
Adverse effects of protease inhibitors (5)
Lipodystrophy: increased deposition of fat on back & abdomen, decreased adipose tissue on extremities, buffalo hump
Insulin resistance and hyperglycemia
Inhibition of p450
Treatment of TB in HIV-infected pt
If patient is on a protease inhibitor, do NOT give rifampin (p450 inducer). Instead, give rifabutin.
AE of zidovudine (2)
Bone marrow toxicity
First-pass metabolism
When a drug is absorbed by the GI tract after oral administration, it first enters portal circulation before reaching systemic circulation. If the drug is metabolized extensively by the liver (high first-pass metabolism), the amount that reaches the systemic circulation, and therefore the bioavailability, will be low. The amount of drug exposed to the liver within portal blood flow is the major determinant of first-pass metabolism.
Examples of drugs with high first-pass metabolism
Nitroglycerin: given sublingually
Lidocaine: given subcutaneously or IV
Tubular adenomas (3) vs. villous adenomas (6)
Tubular: smaller, pedunculated, dysplastic colonic mucosal cells that form tubular-shaped glands
Villous: larger, often sessile, may have velvety or cauliflower-like projections, dysplastic epithelial cells that form villi-like projections from polyp surface down to stroma, more dysplastic than tubular adenomas, may secrete large amounts of mucus
Symptoms caused by large colon polyps (8)
Lower GI bleeding: positive FOBT, microcytic hypochromic anemia
Partial obstruction: bowel habit changes, crampy abdominal pain, abdominal distention
Villous adenomas may secrete large amounts of mucus, leading to secretory diarrhea, hypovolemia and electrolyte imbalances
Peutz-Jeghers syndrome: manifestations (3)
Manifestations: multiple hamartomatous polyps, black spots on skin & mucosa, presents at young age
Causes of acute pancreatitis (GET SMASHED)
Surgery, structural abnormalities of pancreatic duct or ampullary region
Mumps and other infections: measles, EBV, VZV, coxsackie, mycoplasma pneumoniae, M. TB
Scorpion bite, snake bite
Hypertriglyceridemia, hypercalcemia
Drugs: azathioprine, sulfasalazine, furosemide, valproic acid
How does hypertriglyceridemia cause pancreatitis?
Normally fatty acids are bound to albumin in serum. If serum TG >1000, concentration of FFA exceeds binding capacity of albumin. TGs cause direct injury to acinar cells and pancreatic capillaries.
Complications of TPN (4)
Hyper or hypoglycemia
Electrolyte imbalances
Acalculous cholecystitis
Why do pts on TPN get gallstones? How can you prevent this?
1. lack of enteral stimulation decreases CCK release, leading to biliary stasis
2. disturbance of enterohepatic bile acid circulation, leading to supersaturation of hepatic bile with cholesterol (only if ileal resection)
Prevent via exogenous CCK administration
Causes of pill-induced esophagitis (3)
KCl pills
Arteries that supply the stomach (5)
Proximal lesser curvature: left gastric (from celiac)
Distal lesser curvature: right gastric (from celiac --> common hepatic --> proper hepatic)
Proximal greater curvature: left gastroepiploic (from celiac --> splenic)
Distal greater curvature: right gastroepiploic (from celiac --> common hepatic --> gastroduodenal)
Proximal greater curvature above splenic artery: short gastrics (from celiac --> splenic)
Appendicitis: precipitants (5), pathogenesis, manifestations (4), macroscopic findings, complication, epidemiology
Precipitants: fecalith, hyperplastic lymphoid follicle, foreign body, tumor, nematodes
Pathogenesis: obstruction of appendicular lumen (usually fecalith) --> retained mucus causes appendicular wall to distend --> impairs venous outflow --> resulting hypoxia causes ischemia and associated bacterial invasion --> inflammation & edema of wall cause further distention --> necrosis of wall with rupture may occur
Manifestations: periumbilical pain that migrates to RLQ, n/v, diarrhea, fever
Macroscopic: inflamed hyperemic edematous appendix
Complications: rupture may cause peritonitis
Epidemiology: peak incidence at 6-10y/o
Acute mesenteric ischemia: causes (2), histology (4)
Causes: venous thrombosis, arterial spasm
Histology: affected segment of bowel is dusky red & congested; subserosal ecchymoses, edema, well-defined areas of necrosis
Phases of HBV infection
Proliferative phase: Entire virion and all related antigens of HBV DNA are present in hepatocyte. Viral HBsAg & HBcAg are expressed on hepatocyte cell surface, leading to activation of CD8 cells. These cells destroy the infected hepatocytes (HBV is not directly cytotoxic).
Integrative phase: HBV DNA is incorporated into host genome of hepatocytes that survive the immune response. When antiviral antibodies appear, viral replication stops, infectivity ceases and liver damage tapers off. Risk of HCC remains elevated.
How does anti-HBs antibody work?
Anti-HBs Ig bind HBsAg and prevent it from interacting with hepatocyte receptors. This occurs before the virus enters the hepatocyte.
What is the role of antigen-antibody complexes in HBV? (7)
Cause some early symptoms: arthralgias, arthritis, urticaria
Cause some chronic complications: immune complex glomerulonephritis, cryoglobulinemia, vasculitis, polyarteritis nodosa
Autoimmune hepatitis: pathogenesis
Pathogenesis: antigen mimicry --> CD4 cells recognize self-antigen --> damage hepatocytes
Type B chronic gastritis
Chronic gastritis that is antrum-predominant and associated with H. pylori.
Hostology of acute gastritis
Type A chronic gastritis
Autoimmune chronic gastritis, which affects the body of the stomach where parietal cells are located.
Cyclin D: function, mutation (4)
Function: proto-oncogene that regulates cell cycle
Mutation: overexpression in breast, lung, esophageal cancers and lymphoma
Pt has tumor in 3rd part of duodenum. What structure is at greatest risk for direct penetration by tumor?
Anatomy of duodenum: first (3), second (3), third (3), fourth (2) parts
First part: horizontal, overlies L1 vertebra, intraperitoneal
Second part: courses from L1 to L3, close relation to head of pancreas, pancreatic secretions & bile enter via ampulla of vater
Third part: horizontal at L3, courses anterior to abdominal aorta & IVC, courses posterior to SMA, close relation to uncinate process of pancreas and SMA/SMV
Fourth part: courses superiorly and to the left of L2 & L3 vertebrae, becomes jejunum past ligament of Treitz
Anatomy of common bile duct (3)
Formed when common hepatic bile duct & cystic duct join in porta hepatis region of hepatogastric ligament
Courses inferiorly, posterior to pylorus and within head of pancreas
Drains into 2nd part of duodenum
SMA: anatomy, supply
Anatomy: leaves aorta at L1 level, normally forms ~45 degree angle with aorta, courses over left renal vein and 3rd part of duodenum
Supply: duodenum to 2/3 transverse colon, pancreas
SMA syndrome: pathogenesis, cause (6)
Pathogenesis: angle between aorta & SMA is <20 degrees (instead of 45) --> transverse portion of duodenum gets entrapped --> symptoms of partial small bowel obstruction
Cause: any condition causing diminished mesenteric fat between SMA & aorta (low body weight, recent weight loss, severe burn, prolonged bed rest); lordosis; after surgical correction of scoliosis
Pathogenesis of NSAID-induced gastric injury (3)
1. Inhibit prostaglandin synthesis --> reduces mucin and HCO3 secretion, gastric epithelial cell proliferation and gastric perfusion --> decreases stomach's protective abilities
2. Increase gastric acid secretion
3. As weak acids, NSAIDs can penetrate cells of gastric mucosa and cause direct cell damage
Pancreatic secretory trypsin inhibitor (PSTI): source, function (2)
Source: secreted by pancreatic acinar cells
Function; inhibits any trypsin abnormally activated in pancreas; prevents trypsin-mediataed activation of other proteolytic enzymes and autodigestion of pancreatic tissue
Hereditary pancreatitis: defect, pathogenesis, complication
Defect: mutation in gene that encodes trypsinogen
Pathogenesis: synthesis of abnormal trypsinogen that is not susceptible to inhibition by trypsin or pancreatic secretory trypsin inhibitor (PSTI) --> recurrent attacks of acute pancreatitis
Complications: increased risk of pancreatic adenocarcinoma
Acute calculous cholecystitis: diagnosis (2), complications (3)
Diagnosis: U/S shows distended gallbladder, gallbladder wall thickening, pericholecystic fluid, positive sonographic Murphy sign; no gallbladder filling on HIDA scan
Complications: gangrene, perforation, abscess
Increased size of cells. Number of cells is unchanged. Muscular gain is a typical example.
Increase in number of cells, leading to increased size of organ. Typical examples are BPH and endometrial hyperplasia.
Irritable bowel syndrome
Alternating diarrhea and constipation, abdominal pain relieved by defecation.
How do protease inhibitors cause lipodystrophy?
Impair hepatic chylomicron uptake and triglyceride clearance.
5-aminosalicylates: drugs, MOA, indication
Drugs: sulfasalazine
MOA: inhibit prostaglandin and leukotriene synthesis during inflammation
Indications: IBD
Hepatic steatosis: causes (5), histology (3)
Causes: alcohol abuse (most common), hypoxic injury, toxic injury, protein malnutrition, diabetes, obesity
Histology: excessive accumulation of fat vesicles in hepatocytes esp. in centrilobular zone, hepatocyte nucleus displaced eccentrically by one or more large fat droplets, stain with Nile red or Sudan black
Causes of portal inflammation (8)
Alcoholic hepatitis
Acute or chronic viral hepatitis
Secondary biliary cirrhosis due to biliary tract obstruction
Primary biliary cirrhosis
Sclerosing cholangitis
Chronic GVHD
Acute transplant rejection
Idiopathic neonatal hepatitis
Liver sulfate conjugation: definition, examples (2)
Definition: One of the primary phase II metabolic pathways that biotransforms drugs into more polar drugs for excretion. Sulfate reacts with a substituent on drug molecule to form a new chemical compound that is more water soluble and easily excreted.
Examples: phenol, chloramphenicol
Liver hydroxylation: definition, examples (2)
Definition: Oxidation transformation catalyzed by cytochrome p450 system. A hydroxyl group is added to the drug to produce a less lipid soluble compound.
Examples: pentobarbital, phenobarbital
Liver hydrolysis: definition, examples (3)
Definition: Phase 1 type reaction of liver metabolism in which a drug is cleaved by adding water. It usually precedes phase II conjugation metabolism in the liver. Most liver hydrolysis reactions involve esterase or amidase enzymes.
Examples: procaine, lidocaine, aspirin
Plasma hydrolysis: definition, examples (3)
Plasma hydrolysis: Rapid biotransformation or inactivation of drugs by blood or plasma esterases. This allows for short-acting profiles of many drugs.
Examples: succinylcholine, tetracaine, remifentanil (anesthesia drugs)
Histology of duodenum: superficial lamina propria, deeper lamina propria, submucosa
Superficial lamina propria: contains villi that are covered by simple columnar epithelium with a brush border (surface absorptive cells) interspersed with goblet cells and APUD (amine precursor uptake and decarboxylation) cells
Deeper lamina propria: simple tubular glands (crypts of Lieberkuhn) lie immediately atop muscular mucosae and deliver secretions into intervillar spaces
Submucosa: compound tubular Brunner's glands, which secrete alkaline mucous into ducts that track upward through muscularis mucosae and into crypts of Lieberkuhn; unique to duodenum
Histology of jejunum (3)
Contains more goblet cells than villi of duodenum
Crypts of Lieberkuhn open into intervillar spaces
Heavy lymphocytic infiltration of lamina propria is common
Histology of ileum (3)
Contains more goblet cells than villi of duodenum
Crypts of Lieberkuhn open into intervillar spaces
Lymphatic nodules (Peyer's patches) immediately adjacent to villi and crypts; unique to ileum
Histology of colon (2)
Crypts of Liberkuhn are heavily populated by mucus-producing goblet cells
No pits or villi
Microvilli (2)
Small cylindrical extensions of apical plasma membrane that contain actin filaments. Cover apical surfaces of intestinal epithelial cells.