GI Flashcards
appendicitis
visceral pain - due to luminal distention –> stretching of smooth muscle
- for the appendix - afferent pain fibers enter superior mesenteric plexus at level of T10 –> vague, referred pain at umbilicus
somatic pain - well-localized
- irritation of the peritoneum at well-localized spot - due to inflammed peritoneum
- worse with deep inspiration and pushing (McBurney’s point)
- location of appendix can change pain profile - obturator internus (pain with internal rotation of hip), psoas muscle (pain with hip extension)
- pts with retrocecal appendix may not have significant RLQ pain
psoas, obturator and Rovsing signs - if ruptured
colon cancer
right-sided = exophytic mass
left-sided = infiltrate intestinal wall
rectosigmoid cancer - hematochezia
- rectal adenocarcinoma - painful defecation and small caliber stools
CEA - also elevated in pancreatic, gastric, and breast cancers, IBD, COPD, cirrhosis, higher levels in smokers
node-positive colorectal adenocarcinoma - surgery + oxaliplatin adjuvant
UC and Crohns
both are associated with MSK abnormalities - AL, sacroilitis, migratory polyarthritis, erythema nodosum
UC - low-grade fevers
- bloody diarrhea
- begins at rectum, continuous mucosal involvement, inflammation of mucosa and submucosa only
- pseudo-polyps, loss of haustra, crypt abscesses (TH2 and neutrophils)
- associated with 1 sclerosing cholangitis (p-ANCA)
- complication - toxic megacolon –> perforation
- sulfasalazine (side effect is reversible oligospermia)
Crohns
- abdominal pain
- skip lesions, cobblestone appearance, knife-like fissures, enterovesical fistulas
- non-caseating granulomas (Th1)
- transmural inflammation - string sign (narrowed intestinal lumen)
IBS - relief with defecation
CRC is the most common malignancy in these pts - esp in UC pts. Unique features:
- progress from flat and non-polypoid dysplasia
- mucinous/signet ring histology
- early p53 and late APC gene mutations (opposite of sporadic disease) - higher grade
- multifocal in nature
- present in proximal colon
Compare to sporadic CRC - often arise from a polyp
malabsorption
many causes -… bacterial overgrowth (GI surgery, abnormal motility)
fats are the earliest and most severely affected in generalized malabsorption
- test for fat in stool with Sudan 3 satin
cholestasis
erythromycin, OCPs can cause cholestasis
Fe regulation
hepicidin = regulator of Fe homestasis
- produced by hepatic cells
- low hepcidin level favor Fe absorption and accumulation in body
- high hepcidin - decreases intestinal absorption, inhibits release by macrophages
ferroportin - BL surface of enterocytes, transports Fe into blood
- binds hepcidin –> is internalized and degraded
transferrin - circulating, shuttles Fe from macrophages to bone marrow
- transferrin receptors are on all cells
ferritin in macrophages (which degrade RBCs) and enterocytes
- ferroportin on macrophage surface
renal tubular cells - secrete lactoferrin, binds Fe in urine
gallbladder
cystic duct + common hepatic –> common bile duct
bile - cholesterol, bile salts, PC, bilirubin
- also has antimicrobial activity - disrupts membranes
- enteral passage of fat and aas into the duodenum triggers release of CCK –> contraction of gallbladder
- ileal resection - cant reabsorb bile acids
- blood supply - cystic artery
- markers: alk phos, GGT (is NOT present in bone, so can narrow down differential if you have a high alk phos)
choledocal cyst - congenital dilation of common bile duct, presents will recurrent abdominal pain and jaundice during childhood
primary biliary cirrhosis - autoimmune
- bile ducts are destroyed, lymphocytic inflammation –> bile stasis
- necrosis and micronodular regeneration of periportal tissues
- looks like GVHD - donor T cells infiltrate the skin, liver, and GI tract
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cholecystitis - E coli, Enterococcus, Kleb, Enterobacter
- ouflow obstruction –> damage to protective mucosal layer (lecithin hydrolysis) –> chemical irritation (bile salts, which are bile acids plus glycine or taurine) –> inflammation and gall bladder hypomotility –> increased pressure and ischemia
porcelain gallbladder = thickened gallbladder with rim of calcification
- occurs due to chronic cholecystitis
- increased risk of adenocarcinoma of the gallbladder
alternatively - chronic cholecystitis can also lead to a shrunken, fibrotic gallbladder
acute ascending cholangitis - gram-negative infection after biliary duct obstruction
acalculous cholecystitis - occurs in critically ill (sepsis, immunosuppressed)
- secondary to gallbladder stasis and ischemia –> inflammation and injury
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pigment gallstones
- black - UCB (hemolytic anemia, Crohns disease due to increased enterohepatic cycling of bilirubin)
- brown - with biliary tract infections (microbes produce b-glucuronidase)
gallbladder hypomotility - slow emptying of gallbladder following CCK stim
- biliary sludge (gallbladder absorbs water from bile)
gallstone ileus - cholesterol-containing mass at ileocecal valve
- cholecystoenteric fistula (base of gallbladder adheres to SI) - can also get pneumobilia (air from the intestine that enters the gallbladder)
Whipple disease
distended macrophages in LP
malabsorptive diarrhea, weight loss, joint pain
pancreatic beta cells
glucose enters via GLUT2
1) first enzyme is glucokinase…enters TCA –> ATP
2) high ATP closes K channel (which normally causes K to leave the cell) –> depolarization –> Ca2 channel opens
3) Ca and cAMP (from GLP-1 receptor) cause insulin to exocytose
glucokinase has a lower glucose affinity than other hexokinases - glucose sensor in b-cells
- mutations cause a decrease in beta cell glucose metabolism and decreased insulin release
= MODY
- homozygous mutations lead to fatal growth retardation and severe hyperglycemia at birth
side note: glycolytic enzymes will present with hemolytic anemia
- aldolase A, enolase, PFK, PK
Wilsons disease
AR - reduced formation and secretion of ceruloplasmin
- and decreasing hepatic secretion of copper into the biliary system
Kayser-Fleischer ring - deposition of copper in the cornea
Cu deposits in the basal ganglia –> atrophy
treat with d-penicillamine trientine
cholesterol gallstones
cholesterol:
1) thiolase condenses two molecules of acetyl-coA
2) acetoacetyl-coA + acetyl-coA –> HMG-coA
3) RLS = HMG coA reductase turns HMG-coA into mevalonate
4) mevalonate –> cholesterol
cholesterol stones
- fibrates upregulate LPL –> increased fatty acid oxidation
- fibrates inhibit cholesterol 7a-hydroxylase (enzyme that turns cholesterol into bile acids, so increased risk of cholesterol gallstones)
- risk factors: obesity or rapid weight loss, female sex, glucose intolerance, hypomotility of the gallbladder (pregnancy, prolonged fasting)
- estrogens - upregulate HMG-coA
bile acids
b-glucuronidase - deconjugates bilirubin
Campy
curved gram negative rod - moves in a corkscrew fashion
acquired from
- dogs, other domestic animals - think little kids, farmers, lab workers
- contaminated food
inflammatory diarrhea - initially watery, later bloody
VS
S. aureus - ingest a preformed exotoxin, mayonnaise, vomiting
B. cereus - heat stable enterotoxin
Shigella - fomites (not animals)
V. parahemolyticus - shellfish
ulcer v.s. erosion
mucosa - muscularis mucosa - submucosa - muscularis propria - serosa
- gastric glands are located in the LP
erosion- through submucosa
- NSAIDS, surgical stress, burns, smoking, alcohol
- PGs normally –> stimulate mucin and bicarb secretion, gastric epithelial cell prolifeartion, and gastric secretion
- NSAIDs -… also increase gastric acid secretion
ulcer - through submucosa
hemachromatosis
AR
HFE mutation - HFE normally interacts with the transferrin receptor, on BL membrane –> sensor of Fe stores
- HFE mutations cause enterocytes and hepatocytes to detect falsely low Fe levels
- -> enterocytes increase Fe absorption, hepatocytes decrease hepcidin synthesis
bronze diabetes (but exocrine pancreatic function is preserved)
hepatitis
acute viral hepatitis - pt presents with low-grade fever, anorexia/nausea, dark colored urine, RUQ pain
- HAV
- hepatocyte swelling and cytoplasmic emptying = ballooning degeneration aka hepatocyte necrosis
- -> hepatocyte apoptosis, cell shrinkage, Councilman bodies
- -> mononuclear inflammation
B (DNA virus, incorporates into genome) = sexual
- chronic infection - HBsAG accumulates in infected hepatocytes –> eosinophilic, ground glass hepatocytes
- host cells have HBV - HBx protein is produced – >it inactivates p53
C (RNA virus, no RT, will not integrate into host genome)= drug use, infection is most often asymptomatic
- chronic infection - lymphoid aggregates in portal tracts and focal macrovesicular steatosis
v.s. alcoholic hepatic steatosis - can see Mallory bodies (clumped, eosinophilic intracytoplasmic inclusions - made up of tangled IFs)
pancreatitis
acute interstitial pancreatitis
- why? - MVC and kids, steroids, scorpion, sulfa drugs, NRTIs
- digestion of adipose cells by lipase –> liquefactive necrosis and hemorrhage
- edematous pancreas with focal fat necrosis
- complications - shock, DIC, ARDS (digestion of alveolar-capillary interface)
- pancreatic pseudocyst - fibrous tissue forms around liquefactive necrosis, persistently elevated amylase
- pancreatic abscess - E coli, persistently elevated amylase
inflammatory process can continue –> acute necrotic pancreas
- blood flow is compromised because of the edema
- -> ischemia leads to abnormal activation of trypsin
- hemorrhage can occur
- white chalky fat necrosis and hemorrhage on gross exam
chronic alcoholic pancreatitis
- due to alcohol induced protein-rich secretion –> ductal plugs –> that calcify (epigastric calcifications)
- ductal plugs –> atrophy and fibrosis of pancreas –> exocrine insufficiency
chronic pancreatitis with dystrophic calcification
- secondary to DM
- increased risk for pancreatic adenocarcinoma
mu opioids (morphine) - cause contraction of the smooth muscle cells in the sphincter of Oddi –> increase in common bile duct pressures –> pts can develop severe RUQ, cramping, and biliary colic
diverticuli
true - Meckel, appendix
- traction - inflammation and subsequent scarring –> pulling and outpouching of all layers of wall
- can occur in esophagus due to mediastinal lymphadenitis or TB infection
false - mucosa - submucosa - serosa (no muscle layer)
- pulsion - increased intraluminal pressure, layers herniate through weakness in muscle wall (where vasa recta traverse MP)
- with diverticula - you can get colovesicular fistula
- treat diverticulitis with cipro and metro
Meckel diverticulum - due to failure of vitelline duct (connects midgut to yolk sac) to involute completely (now if infant is passing meconium, then duct has not involuted at all)
stomach
vessels
- lesser curvature - left gastric
- ulcers arise on this face, in the transitional zone - greater curvature - gastroepiploic
- splenic runs behind stomach, as does gastroduodenal, common biliary duct, and portal vein
- short gastric artery branches off the splenic - common hepatic artery arises superior to the duodenum
gastrochisis - abdominal folds fail to merge
omphalocele - herniation of bowel into umbilical cord, normally happens but a 90deg rotation (around SMA) pulls bowels back into body
body:
1) parietal cells (Gq, eosinophlic) - secrete HCl and IF
- gastrin, Gq- stimulates HCl secretion and has a trophic effect on parietal cells
- histamine and Ach stimulate gastric acid secretion
- potentiation - Ach and gastrin act on ECL cells to increase histamine release
- HCl secretion phase - cephalic (vagus nerve - Ach, GRP), gastric phase, intestinal phase
- HCL inhibition - decreased pH, somatostatin, PGs, GIP, secretin
2) chief cells - pepsin, cephalic and gastric phases, local acid
in a gastric pit - mucous cells near top - parietal cells - chief cells
antrum:
G cells
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Gastritis:
acute (erosive) - due to increased acid burden (ex Cushing ulcer - increased ICP –> increased vagal stimulation)
chronic
- type A (fundus, body) - pernicious anemia (type 4 HSR) –> increased risk for gastric adenocarcinoma (chronic inflammation –> intestinal metaplasia –> Peyers patches and goblet cells)
- type B - H pylori, increased risk for MALT lymphoma (marginal zone post germinal B cells)
PUD
- cagA toxin destroys gastric mucosa
- increased risk for gastric carcinoma - punched out ulcers v.s. heaped up margins
- H pylori increases acid secretion (inhibits somatostatin secretion) and/or decreases mucosal protection
- duodenal ulcers - pain that improves with meals (duodenum increases its defenses)
- consequences - hypertrophy of Brunner glands (mucinous glands of duodenum), hemorrhage (gastroduodenal), acute pancreatitis
- PPIs –> lead to decreased serum Mg2+
- H2 blockers - cimetidine - CYP inhibitor, antiandrogen, can cross BBB and placenta
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adenocarcinoma - general prognosis depends on depth + nodes (Virchow, periumbilical)
- signet ring carcinoma, diffuse type - leather bottle stomach (linitis plastica)
- loss of E-cadherin
- intestinal- type adenocarcinoma - glandular
- grow as nodular, polypoid, well-demarcated masses that rapidly expand in the gastric lumen
- often ulcerate/bleed (in antrum) - have to be differentiated from gastric ulcers by biopsy
- risk factors - chronic gastritis, nitrosamines, blood type A
ZE syndrome - rugal thickening and acid hypersecretion
Menetrier disease - associated with overproduction of TGFa
- rugal hypertrophy (mucosal cell hyperplasia) with parietal cell atrophy and DECREASED acid secretion
- precancerous
erythromycin
motilin receptor agonist - used for gastroparesis
