Sunteți pe pagina 1din 21

1

Autoimmune hepatitis may present as acute, fulminant, or most commonly, chronic


- More common in F, more aggressive in younger pts, half will have another autoimmune dz
- Sx: profound fatigue, nausea/anorexia, upper abdominal pain
- Dx: ANA, pANCA, ALT/AST, alkPhos normal, hypergammaglobulinemia
- Tx: steroids, azathioprine
Viral hepatitis may present as acute, fulminant, or chronic, depending on virus
- Biopsy only indicated if herpes virus is suspected
- Uncommon viruses
CMV: mild hepatitis in children, lethal in immuno, doesnt become chronic
EBV: common w/ mono, self-limiting
HSV: seen in immuno, high mortality, viral inclusions bodies on LM, tx w/ acyclovir, vidarabine

TRANSMISSION TYPE LABS CLINICAL Tx


Hep A Fecal-oral ssRNA HAV IgM Ab (active) Rarely acute failure Vaccine
HAV IgG Ab (prior) Icterus/mortality greater in adults than kids Supportive
Prolonged cholestasis jaundice
No carrier or chronic state (Relapsing pattern
but always resolves)
Hep B Blood (IVDU) Incomplete See below acute failure / Jaundice in 25% Vaccine
Sex (STD) dsDNA IgM anti-HBc Prog to cancer<>cirrhosis<>failure Acute tx is
Vertical (More PCR of HBV DNA Risk of carrier state: neonate 90%, adult 5% supportive
in Asian area) 2/3 of carriers chronic = risk of HCC Chronic tx=
If exposed, both vaccine and HBIg are given IFN, tenofivir,
Can reactivate and itll look like acute hepatitis entecavir
Hep C Blood (IVDU) RNA PCR of HCV RNA Most common cause chronic viral hepatitis Direct Acting
Transfusion (genotype impt px) Most common cause of liver transplant Antivirals
Sex (STD) Very mild sx but if sx cirrhosis (DAA)
Vertical Good cure rates
Hep D Blood (IVDU) RNA virus Will see HBsAg+ Co-infection (acute B + D) often resolves Tx HepB
Sex (STD) w/HBsAg (Needs B for infxn) Superinfection (acute D + chronic B) 80+%
Vertical coat get cirrhosis in 5-10y, bad px!
Hep E Fecal-oral RNA PCR of HEV RNA No carrier or chronic state Supportive
(pig/poultry) Fatalities only in pregnant women

- Acute liver failure (ALF)


HBV (probably w/ HDV) is most common agent causing acute liver failure, very rare but high mortality
Suspect if PT, liver size, hypoglycemia/encephalopathy ( transplant)
- Hep B antigens
HBeAg /HBV DNA: indicate viral replication/active infxn, order IgM anti-HBcAg
HBsAg: often used to screen for infxn since first Ag to appear
a. (+) ONLY in active infxn if recovered/vaccinated, you will not see this
b. Window as Ag is cleared and Ab are synth in which infected person is (-)
c. Thus, always order IgM anti-HBc!!
HBc Ag: core Ag is only seen w/ current (IgM)/prior (IgG) infxn, NOT vaccination
IgM anti-HBc: present during active infxn, covers the window
IgG anti-HBs: present if recovered or vaccinated
2

1) Cholestasis
Failure of bile secretion bile retention in hepatocytes (toxic necrosis/fibrosis/cirrhosis) and hyperbilirubinemia (conjugated)
a. Intrahepatic causes: toxins, sepsis, PSC (1 sclerosing cholangitis), PBC (1 biliary cirrhosis)
i. Canaliculi are invaginations of hepatocyte apical membranes w/ attached alkPhos
ii. If any dysfxn in membrane cholestasis + markedly high alkPhos
b. Extrahepatic causes: obstruction via calculi, stricture, tumor, PSC
c. Pathology: hepato accum of bile/bile plugs (transport dysfxn), ductal prolif, foamy degen (accum of lipids), bile infarct
d. Sx: cutaneous jaundice (excess conj. bilirubin)/xanthomas (excess chol)/pruritis (bile acids itch), fat/fat-soluble
vitamin malabsorption, osteoporosis (VitD defcy), coagulopathy (Vit K defcy), acholic stools (pale, clay-colored)
e. Dx: very high alkPhos (highest in PBC) due to overproduction (not leakage), confirmatory 5 nucleosidase (specific for
liver), prolonged PT, imaging (r/o obstruction), AMA in PBC
f. Tx: surgery if obstruction, cholestyramine (bile salt binding resin), parenteral VitK, medium chain triglycerides (fat
that doesnt require bile salt for absorption), transplant if PSC/PBC

2) Cirrhosis
Slowly progressive disruption of normal hepatic architecture by combination of cell death, fibrosis, and regenerative nodules
a. Often caused by chronic hepatitis/cholestasis due to EtOH (most common), viral infxn, biliary dz, hemochromatosis
b. Often progresses to chronic failure
c. Stellate cell transforms into myo-fb collagen fibrotic nodules which collapse normal reticulin framework
i. resistance to blood flow portal HTN (see below)
ii. Impaired diffusion of metabolites
iii. Impaired flow of bile
d. Complications: risk HCC, ascites peritonitis, variceal rupture shock, congestive splenomegaly hypersplenism
e. Pathology
i. Gross: firm, rubbery, nodular liver w/ cobblestone appearance
ii. Micro: nodules surrounded by fibrosis, Mallory hyaline/fatty changes if due to EtOH
f. Sx: range from asx hepatocellular dysfxn (bleeding, fatigue, jaundice, muscle wasting, hypogonadism, endocrine
dysfxn common including gynecomastia and spider angiomas due to high E2 levels) portal HTN
g. Dx: firm/nodular liver, ascites/caput medusae, hypoalbumin, hx of liver dz

3) Liver Failure
End stage liver, in which transplant is the only cure
a. Loss of >90% hepatocellular function
b. Acute
i. Best example is fulminant hepatitis
ii. Confluent necrosis encephalopathy/coagulopathy w/in 3mo of sx onset w/o pre-existing liver disease
iii. Sx: jaundice, mental status changes (seizures, asterixis, hyperreflexia), shrunken liver, hypoglycemia
iv. Labs: ALT/AST initially high, then as necrosis progresses, hyper-bilirubinemia (conj.) and -ammonemia
(cant make urea), hypoglycemia (no GNG), long PT (clotting factor synth), EEG abnormal/cerebral edema
v. Tx: transplant, supportive while wait - e.g. control glucose, prevent infxn/bleeding, tx cerebral edema
c. Chronic (Acute Sx + portal HTN + wasting)
i. Best example is severe cirrhosis
ii. Assoc w/ portal HTN and all its manifestations
iii. Seizures uncommon, liver would be firm/nodular rather than shrunken
3

2. Portal HTN
a. Due to resistance (mechanical obstruction, i.e. excess collagen, VC), flow (anastamoses, VD)
b. Causes
i. Pre-hepatic (ex) portal v thrombosis
ii. Intrahepatic (ex) alcoholic cirrhosis
iii. Post-hepatic (ex) hepatic v thrombosis (Budd-Chiari), R heart failure
c. Manifestations
iv. Splenomegaly
1. Congestion slow mvmt of cells thru spleen destruction aka hypersplenism
2. Labs show thrombocytopenia, leukopenia, hemolysis bilirubin
v. Varices
1. Backup into umbilical v remnant caput medusae
2. Backup into coronary v (aka L gastric v) esophageal varices
a. Most clinically significant since rupture has high mortality
3. Tx: portal BP via somatostatin analogue (octreotide), TIPS (surgical portal-systemic shunt)
vi. Ascites
1. Cell death synth of albumin oncotic P + portal HTN weep excess fluid into abdomen
2. Liver releases NO VD effective plasma vol kidney activates RAS/ADH Na/H20 retention
3. production and flow of hepatic lymph weeping through hepatic capsule
4. DDx includes malignancy, heart failure, TB, thus analyze ascitic fluid
a. If (serum albumin) (ascites albumin) > 1.1 = portal HTN (SA-AG gradient)
b. If malignant cells in fluid = cancer
c. If WBCs, culture = infxn
5. Complications include peritonitis, umbilical hernia w/ rupture (Floods syndrome), pleural ascites
6. Tx: Na/H20 restriction, diuretics, paracentesis, sometimes transplant
vii. Portosystemic encephalopathy
1. Acute: seen in acute/fulminant hepatitis, BBB breach/edema/mental status progress to coma
2. Chronic: seen in cirrhosis/chronic failure, reversible if precipitating factors tx
a. Precipitating factors: excess protein intake, GI bleed, hypoTN, alkalosis, hypoK, infxn
b. Sx: mental status , hyperreflexia, asterixis (hand flap)
c. Assoc w/ hyperammonemia and GI flora infiltration
3. Tx: fix precipitating factors, lactulose (draws out ammonia)
viii. Hepato-renal syndrome
1. Renal failure due to advanced liver disease
2. Severe oliguria but normal tubular fxn (i.e. NOT due to ATN)
3. Must rule out pre-renal azotemia (ie. due to hypoTN/hypovolemia) w/ volume expansion trial (sx
wont resolve if its a liver problem)
4. Tx: transplant

3. Drug induced hepatotoxicity (aka DILI or drug-induced liver injury)


a. Leading cause of ALF
b. Diagnosis of exclusion, thus high suspicion w/ any unexplained liver dz
c. RF: elderly, female, obese, underlying liver or systemic dz, polypharmacy, EtOH, genetics
d. Example presentations
i. Acute hepatitis - phenytoin
ii. Chronic hepatitis - -methydopa, Macrodantin (nitrofurantoin), Acetominophen
iii. Cholestasis - estrogens
iv. Mixed hepatitis/cholestasis chlorpromazine, Augmentin
v. Macro fatty liver corticosteroids
vi. Micro fatty liver tetracycline OD
vii. Cirrhosis (fibrosis) - MTX
viii. Granulomatous - allopurinol
ix. Neoplastic - vinyl chloride
x. Vascular pre-bone marrow transplant chemo, some bush teas
e. Drug metabolism
i. Lipophilic drug Phase 1 (p450) products of oxidation/reduction/hydrolysis Phase 2 (conjug) water
sol
f. Predictable, i.e. anyone taking it will get some dose-related toxicity with known histologic changes, repod in animals,
fixed latent period, no allergic rxn (rash, eosinophilia, arthralgia)
i. Acetominophen, CCl4, Amanita Phalloides
ii. Acetaminophen centrilobular (zone 3) confluent necrosis
1. Normal dose phase 2 conjugation(glucouron/sulfat) = safe
2. Over dose or p450 (phase 1) induction by chronic Alc phase 1 rxn overproduction of toxic
metabolites. Glutathione (phase 2 conj) will try to remove these metabolites, but its overwhelmed.
Glutathione stores are decreased w/ Alc and malnutrition
3. Antidote is N-acetylcysteine, which glutathione stores
4

g. Unpredictable, i.e. idiopathic (majority of reactions, not dose related tox) = phenytoin, NSAIDS
i. Phenytoin acute hepatitis, delayed onset, DRESS (hypersensitivity)
ii. Theory #1: drug metabolite + carrier protein = new Ag immune response (hypersensitivity) and hepatotox
(possibly due to cross reactivity or drug causing immune dysreg [autoAb] to hepatocytes)
1. Delayed onset + common allergic presentation (rash, eosinophilia, fever) support this theory as
does the fact that subsequent exposures result in more rapid rxn (sensitization)
iii. Theory #2: drug + genetic abnormality unusual toxic metabolite/high levels hepatotox
h. Tx: most resolve when d/c drug, more serious may req supportive care or transplant
PANCREAS
1. Anatomy
a. Pancreas is a mixed retroperitoneal gland, ~80% exocrine, 2% endocrine, 18% supporting tissues and ducts
b. Fxnl unit is acinus drains into ductules interlobular ducts main pancreatic duct (Wirsung) common bile duct
c. Both acinar (digestive enzymes) and ductal (HCO3) cells contribute to pancreatic juice, ~3L/d
i. Zymogens: trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase, amylase, lipase, nucleases
2. Function
a. Secretion of pancreatic juices necessary for digestion
i. Cephalic phase: vagal stimulation from smelling food acinar secretion
ii. Gastric phase: antral distention secretin release H20/HCO3 secretion by ductal cells
iii. Intestinal phase: duodenal acidification/AAcids CCK release digestive enzyme secretion by acinar cells
3. Disorders
a. Pancreas normally protected: (1) PROenzymes (2) transported in granules (3) trypsin inhibitor accompanies enzymes
b. Islet cells are normally spared in acute, thus no sx of diabetes
c. Necrotizing pancreatitis occurs in ~10% of acute pancreatitis pts
i. G- bacteria (klebsiella, e coli, enterococcus)
ii. Tx w/ aspiration, debridement, abx

ACUTE PANCREATITIS CHRONIC PANCREATITIS


Definition Acute inflammation/necrosis/enzymatic digestion of Gradual, persistent, progressive inflammatory
pancreatic tissue due to acinar cell injury destruction and fibrous replacement of tissue
Interstitial type: microcirculation preserved, no necrosis,
self-limiting w/ low mortality
Necrotizing type: high risk of infxn/failure/mortality
Etiology Obstructive causes: gallstones (#1, never chronic), Alcohol (#1) (Alc can also cause Acute, but stone more
pancreatic cancer, pancreas divisum (anatomical defect, likely for acute)
single pancreatic duct never formed) Cystic fibrosis, due to mucous plugs
Metabolic causes: hyperTG, hyperCa, ischemia/vasculitis Autoimmune (present w/ jaundice) = IgG4
Congential causes: mutation in trypsin makes it lysis-
resistant VERY high risk of pancreatic cancer
Drug causes: azathioprine, 6-MP
Infxn: more common in developing countries
Pathogenesis Duct obstruction blocked secretions zymogens EtOH hypersecretion ductal ppt of proteins
accum & fuse w/ lysosomes (crinophagy) enzyme obstruction gradual fibrosis/acinar atrophy/ducts dilate
activation (trypsin) acinar cell injury/digestion Autoimmune pancreatitis: elevated IgG4/IgM, ANA,
Local effects: inflamm, fat necrosis (liberated lipase), sausage-like enlarged pancreas w/capsule-like rim,
hypoCa (from saponification), pseudocyst (cavity biliary duct abnormalities
lined by granulation tissue, filled with necrotic
material), GI hemorr (due to gastric varices ro splenic
artery aneurysm)
Systemic effects: vessel breakdown (elastase, kallikrein,
chymotrypsin), WBC chemotaxis (complement), DIC
(thrombin), surfactant (phospholipase A2), shock,
ARDS, renal failure
Clinical 2 phases = early (w/in 1 week) systemic inflamm 50% asx
response syndrome (SIRS) and/or organ fail Sx: pain, steatorrhea (when lose 90% lipase), wt
Late (>1 week) local complications loss/wasting (cant absorb fat!), glucose intolerance
Abdominal pain that radiates to back + aggravated Calcification common w/ EtOH, CF
by food intake + relieved by bending forward
N/V, low grade fever, jaundice if obstructive etiology
Volume depletion from proteinacious fluid leaking
Retroperitoneal hemorrhage: Grey Turners sign (flank
discoloration), Cullens sign (periumbilical discoloration)

Paralytic ileus (no bowel sounds)


Cholangitis if gallstone etiology
Px depends on degree necrosis, other organ involvement
Dx/Labs Elevated serum amylase, lipase (3x normal) ERCP/EUS are most sensitive for abnormal ducts (low
Abd xray shows sentinel sign (colon cut-off) HCo3 on secretin test)
CT w/ contrast shows degree of necrosis, very specific Abd xray shows calcifications
Fxn tests (ex) low HCO3 on secretin test, low serum
trypsinogen, low PABA uptake (bentiromide test)
5

Tx Aggressive fluid replacement w/ ringer Pain remove inciting process (stop drinking!),
lactate/monitoring (If BUN or hematocrit is rising analgesics, suppress pancreatic secretion, Whipple
bad Px sign) Steatorrhea lipase supplementation (w/ acid
Bowel rest (NPO) suppression), fat intake
Remove stones ERCP DM loss of both insulin/glucagons, thus need tight
Only Sx pseudocysts treated control
Analgesics for pain

4. Pancreatic Cancer
a. Ductal adenocarcinoma makes up 80% of pancreatic tumors
b. Poor px (5% 5yr survival), common cause of death, tx is usually only palliative
c. Assoc with carcinoma of unknown primary (CUP) tumors, mutation in k-ras gene in 90%, chronic pancreatitis
d. Risk factors: blacks, males, >60y, smoking, developed countries
e. Pathology
i. Usually involves head of pancreas
ii. Schirrous, i.e. highly infiltrative and desmoplastic (firm and gritty)
iii. Originates from ductal epithelium (rarely acinar)
f. Clinical
i. If infiltrates common bile duct obstructive jaundice
ii. If infiltrates duodenum bleeding/ulcers
iii. If infiltrates retroperitoneum perineural spread, pain
iv. Other sx: wt loss/cachexia, new onset DM, migratory thrombophlebitis (hypercoaguable state due to serine
protease), jaundice, depression
v. Courvoisiers sign (palpable non-tender gallbladder, dilated due to tumor obstruction)
vi. Migratory thrombophlebitis = Trousseau Syndrome
vii. Often mets to liver
g. Dx: imaging, usually abdominal CT, endoscopic ultrasound, or biopsy (percutaneous fine-needle aspiration)

GALLBLADDER
1. Cholelithiasis
a. Very common, majority of biliary dz
b. Gallstones due to either excess cholesterol or bilirubin
c. Most asx (until blockage) and surgery is very successful
d. About 15% choledocholithiasis (stones either de novo, or from GB, in common bile duct), similar clinical picture

ETIOLOGY PATHOGENESIS CLINICAL PATHOLOGY


Cholesterol 4Fs - Forty Fat Supersaturation of bile Sx: biliary colic (pain from irritation), Yellow-brown
cholelithiasis Fertile Female w/ cholesterol, forms a jaundice (from obstruction), fever Ovoid, firm, multi faceted
nidus w/ mucin/Ca often radiolucent (use US)
Pigment Hemolytic biliary unconjugatd Complications: acute/chronic cholecystitis, Black type: small, many,
cholelithiasis anemia, SS bilirubin ppt w/Ca, Cholangitis, pancreatitis, perf, gallstone ileus crumbling, radioopaque
forms nidus w/ mucin Brown type: few, soft,
Indication for cholecystectomy (GB removal) fatty, assoc w/ infxn
= stones, hemolytic anemia (sickle cell,
spherocytosis, porcelain GB, GB adenoma,
gastric bypass surgery)

Acute acalculous Cholelithiasis form RUQ pain with referral to right shoulder Edema thick wall
cholecystitis form due to lysolecithin epithelial Jaundice, fever, Murphys May ulcerate empyema
serious illness injury attack by bile Complications: sepsis, perf , gallstone ileus Serositis
(burns/sepsis) detergents necrosis
+ inflamm
Chronic Multiple acute events Hx of RUQ pain Fibrosis thick wall
cholecystitis progressive mucosal Thick, shrunken gallbladder usually w/calculi Aschoff-Rokitansky sinuses
damage by calculi Predisposition to adenocarcinoma Dystrophic calcification
indication for GB ectomy porcelain gallbladder
Cholangitis Majority from G-/anaerobes spread Charcots triad: pain, jaundice, fever
Impacted stone rapidly 2 to pressure Tx - Abx + decompression necessary.

Jaundice, pruritus, asc cholangitis, weight


loss = carcinoma of extraheptiac biliary duct
6

Adeno- Rare Assoc w/ cholelithiasis Very poor Px


carcinoma

ESOPHAGUS
1. Anatomy
a. Upper 1/3 skeletal muscle, smooth muscle throughout
b. Sphincters
i. UES: via cricopharyngeus, inf pharyngeal constrictor (small space btw important in Zenkers diverticulum)
ii. LES: thickening of circular smooth muscle just below crura of diaphragm
c. Veinous drainage
i. Upper 1/3: SVC, mid 1/3: azygos vein, lower 1/3: gastric (coronary) v portal vein
d. Lymphatic drainage
i. Upper 1/3: cervical nodes, mid 1/3: mediastinal nodes, lower 1/3: celiac/gastric nodes
e. Layers
i. Mucosa: stratified squamous epithelium
ii. Submucosa: secretory glands, Meissners plexus, and veins
iii. Muscularis propia: upper 1/3 predominately skeletal m, lower 1/3 predominantely smooth m
1. Inner circular/outer longitudinal, with Auerbachs between
iv. No serosa
f. Innervation
i. PS via vagus
ii. Auberbachs myenteric plexus coordinates peristalsis
iii. Meisseners submucosal plexus is sensory
g. Clinical tests of anatomy
i. Barium esophagogram: X-ray used to visualize anatomy, non-invasive, no complications (pic)
ii. EGD: endoscope visualizes mucosa detail of upper GI with biopsy/therapeutic capabilities
iii. Endoscopic US: visualizes layers of GI including intra/extra-mucosal, best for tumors (biopsy capabilities)
2. Function
a. Transfer: movement of food from oropharynx to esophagus
b. Transport: movement of food down the esophagus to stomach
i. Primary peristalsis (swallow-initiated), secondary (stretch-initiated), tertiary (uncoordinated)
c. Definitions
i. Aspiration breathing in food
ii. Dysphagia difficulty swallowing/food gets stuck
1. Transfer: hard to get food to esophagus (ex) stroke, botulism, MG, PM/DM, achalasia or Zenkers
2. Transport: motor and mechanical d/o
iii. Odynophagia pain when swallowing, tx w/ myotomy (incision of sphincter) or Botox
d. Clinical tests of fxn
i. Manometry: probe can measure changing pressure in the esophagus, best for motor d/o
1. Normal would show a progression of muscular contractions + opening of LES at time of swallow
ii. pH monitoring: measure pH in esoph over time, best for reflux studies and to r/o cardiac etiology
3. Disorders
a. Mechanical Disorders (obstructive)
i. Progressive dysphagia due to narrowing of lumen
ii. Solids worse than liquids
iii. Often acute presentation due to impaction of food bolus
Dx CLINICAL Tx
Strictures/ Barium xray, EGD Acquired fibrous thickening of esophagus (submucosa) Dilation
Stenosis Causes: chronic injury (GERD), scleroderma, caustics (bougies/balloons)
Neoplasms Barium xray, EGD Concentric constricture Chemo, surgery, stent
Webs Barium xray, EGD Shelf-like protrusions of mucosa in upper esophagus Dilation
Women >40y (bougies/balloons)
Plummer-Vinson: web, Fe defcy anemia, cheilosis, glossitis
Rings Barium xray, EGD Schatzki rings = web near GE junction, assoc w/hiatal hernia Dilation
(bougies/balloons)
Diverticula Barium xray, EGD Abnormal pouch/sac from esophageal wall
Zenkers Diverticulum occurs just above UES due to
incomplete relax of UES, food accum neck mass/aspiration
Traction diverticula mid-esophagus, as a result of nearby
scar tissue pulling on normal esophagus
Epiphrenic diverticula results in nocturnal fluid regurgitation
Atresia Barium xray Thin, non-canalized portion proximal/distal pouches
Often occur at level of bifurcation
7

Often co-exists w/ other congenital abnormalities


Polyhydramnios in utero, severe cough/regurg at 1st feeding
Fistula Barium xray Abnormal connection/passageway btw esophagus/trachea
(prox/distal) Common problem is aspiration pneumonia
Sliding Most common type Widened space btw muscular diaphragmatic crura/esophagus
hiatal hernia 20% adults Part of stomach above diaphragm abnormal LES fxn/reflux
Assoc w/ age
Para-esophag Widened space btw muscular diaphragmatic crura/esophagus
hiatial hernia Separate portion of stomach enters thorax
Often due to previous surgery

b. Motor Disorders (functional)


Dx CLINICAL Tx
Achalasia Barium xray (dilation) Aperistalsis in esophagus Pneumatic dilation
Manometry dx Failure of LES relaxation w/ dilation proximal to LES (splits LES muscles)
EGD necessary to rule Dysphasia to both solids/liquids Myotomy
out pseudoachalasia Due to loss of Auerbachs plexus Botox
Pseudoachalasia stomach tumor destruction of Auerbachs
Predisposes to GERD, reflux, Barretts
Diffuse Barium xray Simultaneous, high amplitude, non-propulsive Reassurance
esophageal (corkscrew) contractions interspersed with normal peristalsis Smooth m relaxants
spasm Manometry dx (but Dysphasia
rarely catches it) Sx worsened by emotional stress, very hot/cold liquids
Nutcracker Manometry (see high Extremely high pressure peristalsis Same as above
esophagus amplitude contractions) Chest pain
Scleroderma Manometry Collagen deposition (blue in pic) in smooth m distal
Low pressure waves aperistalsis + incompetent LES
Gastroesophageal reflux is main complication

Esophageal Lacerations due to severe vomiting


Mallory Weiss Syndrome - longitudinal tears at GE jxn upper GI bleeding
Boerhaave syndrome (rare) distal esophageal rupture mediastinitis

4. Esophageal varices
a. Most important clinically: lower 1/3 of esophagus and upper stomach is drained to portal system
b. Portal HTN backup and dilation of submucosal venous plexus in stomach/esophagus
1. Esophageal varices = just above GE junction, can extend up
2. Gastric varices = extend from esophageal varices or arise independently
Complications: bleeding!
3. Accounts for up to 1/3 of all deaths in cirrhotic pts
4. Corossion hypothesis (reflux causes erosion)
5. Explosion hypothesis (excessive HTN from portal HTN)
c. Sx: hematemesis and melena (lower GI blood is hematochezia)
d. Tx: hemodynamic stability, sclerotherapy, ligation
5. Esophagitis (primarily GERD)
a. Any symptomatic condition or histologic alteration assoc w/ gastric acid reflux
1. Very common, highest rates in pregnant women
b. Reflux esophagitis is pathologic definition, i.e. GERD resulting in lesions identified by endoscope
1. Microscopically see elongation of papillae, inflammation w/ eosinophils
c. Stomach acid exposure via: LES incompetency, abd P, sliding hiatal hernia, delayed gastric emptying
d. Sx: heartburn, acid taste in mouth, dysphagia
e. Dx: endoscopy shows red, inflamed mucosa, hyperplasia and elongation of lamina propria papillae
f. Complications: esophageal ulcers/bleeding/strictures/obstruction, chest pain like acute MI, Barretts esophagus
g. Tx: lifestyle changes (quit smoking, wt loss, avoid big meal before bed) + pharm (PPIs, H2 blockers, antacids)
h. Other causes seen in immuno (ex) herpes (punched out lesions w/ multinucleated inclusions/ground glass
nuclei), CMV, candida
1. Rare causes: caustics, radiation, allergy
6. Barretts Esophagus
a. Irritation squamous to columnar glandular metaplasia in distal esophagus (an adaptive response)
b. Seen in same population as GERD (considered a consequence) but far more common males
c. Dx: patchy red areas extend above GEJ on endoscopy, glands w/ goblet cells in esophagus
d. Complications: 40x risk of esophageal adenocarcinoma

7. Cancer
a. Risk factors: synergistic effect of EtOH + tobacco, GERD/Barretts, achalasia
b. Tx: surgery or chemo/radiation (cure rates poor due to infiltrative nature + late presentation), dilation for palliation

SQUAMOUS CELL CARCINOMA ADENOCARCINOMA


Incidence Men > 50 (higher in Blacks) Men >50 (higher in Caucasians)
Higher in smokers Pre-exist Barretts intestinal type glands in distal esoph.
8

Site of Proximal esophagus Distal esophagus, sometimes stomach


involvement Mets common due to rich venous/lymphatic supply Mets common due to rich venous/lymphatic supply
Histology Nests of squamous epithelium Glandular dysplasia w/in mucosa

STOMACH
1. Anatomy
a. Cardia, fundus, antrum, body, pylorus
i. Body: short pits, very glandular (pic at right)
ii. Antrum: long pits, NO glands
iii. Grossly: rugae, look for these to id stomach via endoscope
b. Cell types
i. NO goblet cells
ii. Mucous cells: line entire surface, secrete mucus and pepsinogen
iii. Parietal cells: glands in fundus and body, secrete HCl and intrinsic factor (eosinophilic)
iv. Chief cells: glands in fundus and body, secrete pepsinogens (basophilic)
v. Enteroendocrine cells: secrete somatostatin, serotonin, histamine (bind H2 R on parietal cells H release)
vi. G cells: secrete gastrin
c. Innervation
i. Extrinsic: vagus and splanchnic nerves
ii. Intrinsic: myenteric plexus
iii. MechanoR: proximal stomach sense distension /distal stomach senses contractions (mid senses both)
2. Function
a. Digestion
i. Cephalic phase: sight, taste, smell or act of chewing/swallowing stimulates vagus gastrin H release
ii. Gastric phase: gastric distension or vagus gastrin H release
iii. Intestinal phase: digested protein to duodenum G-cells of duodenum/jejunum secrete gastrin H release
b. Contractile activity
i. Slow, sustained 6 minute contractions (majority) + rapid, phasic contractions of a few seconds
ii. Proximal = vagovagal reflex (responds to volume: relaxation when swallow or stomach distended)
iii. Distal = pacemaker contractions every 20 seconds, can be modulated (ectopic pacemaker w/ vagotomy)
iv. Pylorus = narrowing of stomach resistance to flow which prevents passage of large food pieces

3. Cancer
a. Adenocarcinoma
i. Risk factors: H pylori/chronic gastritis, diet high in nitrates (cured/smoked foods), men >50y, low SES
ii. Px most related to depth of invasion, usually advanced at presentation
iii. Sx: wt loss, early satiety, pain, bleeding, vomiting
iv. Dx: Virchow node = supraclavicular sentinel node, often 1st manifestation
v. Tx: surgery, tx H pylori

vi. Types
1. Intestinal: intestinal metaplasia, i.e. glands w/ goblet cells
2. Diffuse infiltrating/signet ring: single tumor cells with intracytoplasmic drop of mucin pushing
nucleus to side
a. Diffuse infiltrative pattern leather bag appearance (aka linitis plastic; bottom pic to R)
b. Lymphoma (MALToma) [revisited below in SI section]
vii. Strong assoc w/ H pylori, may resolve if infxn eradicated
viii. No normal mucosa, i.e. all of mucosa has lymphocyte infiltrate
c. Gastrointestinal Stromal Tumor (GIST)
ix. c-Kit mutation (pancreatic cancer is k-ras)
x. Malignant cells derived from interstitial cells of Cajal (pacemaker cells)
9

4. Disorders
a. Acute erosive gastritis
i. Acute, direct damage (or interruption of blood supply) to mucosa acute hemorrhage, erosions or ulcers
ii. Etiology
1. EtOH by direct cellular injury
2. NSAIDs block prostaglandin synth mucous production
3. Severe physiologic stress (major burns, surgery, multisystem organ failure) due to blood flow
a. Curlings ulcers occur after severe burns
4. Head trauma w/ ICP vagal tone H secretion Cushings ulcers
5. Post-gastric surgery bile reflux, which can break down mucosal barrier
iii. Clinical: N/V + epigastric pain, dx by EGD, tx is supportive
iv. Path: erosions (limited to mucosa) + ulcers (extend into muscularis propria), edema/hyperemia/petechial

b. Chronic gastritis
i. Chronic inflamm + loss of gastric glands + mucosal atrophy
ii. Etiology
1. Helicobacter pylori infxn (vast majority), usually in antrum
2. Autoimmune, usually in body/fundus
3. IT IS NOT ALCOHOL
iii. H. pylori type B
1. G- lives in mucous layer (non-invasive), has flagella for motility + urease ( NH4 to buffer acid)
2. Very common, around 50% of population is infected with H.pylori but most are asymptomatic
a. However, H.pylori is major risk factor for peptic ulcer disease
b. Releases toxins: LPS, cagA, vacA
3. Dx: breathing test (NH4), culture, CLO (urease test), IgG titers for H pylori, stool test
4. Test for eradication: C13/14 urea breath test (give labeled urea orally, measure labeled CO2 exhaled)
5. Pathology
c. Early: PMNs at pit bases (pit abscess), diffuse lymphos, org can be seen in mucus
d. Late: atrophy of mucosa, intestinal metaplasia (goblet cells) cancer
6. Tx: triple therapy (see pharm lectures) = 2 ABx + PPI, ~90% effective (may also add bismuth to tx)
iv. Autoimmune gastritis = type A
1. Auto-Ab against parietal cells hypochlorhydria, mucosal atrophy
a. Loss of GIF pernicious anemia (cant absorb Vit B12)
2. Dx: elevated gastrin (no HCl negative feedback), anti-GIF Ab, biopsy
3. Pathology: mainly plasma cells
4. Tx: inject B12 (dont have GIF to absorb oral supplement)

c. Peptic ulcer disease


i. Presence of chronic ulcers which induce intense inflammatory/immune response (IL2, IL6)
ii. Location
1. Stomach/gastric ulcer: larger, @ lesser curvature, pain 30min post-meal NOT relieved by eating
2. Duodenum/duodenal ulcer: smaller, in 1st portion, pain btw meals + relieved by eating
iii. Etiology: majority caused by H.pylori, also by NSAIDs (COX 2 (-) less bad), gastrinoma
iv. Demographics: duodenal most common in 30-50y M, gastric most common in 60y F
v. Pathology: ulcers extend into submucosa, can erode all the way through (perforation)
1. 4 layers necrotic debris + inflamm + granulation tissue + scar tissue
vi. Dx: endoscopy + biopsy to r/o cancer, barium swallow imaging can be helpful
vii. ALARM sx: anorexia, N/V, wt loss, GI bleed
viii. Complications: bleeding, perforation w/ free air under diaphragm
ix. Tx
1. Lifestyle changes quit smoking and drinking and being fat and lazy
2. PPIs (most effective), H2 blockers, bismuth/antacids/Sucralfate, eradicate H pylori
3. Young/healthy w/ PUD + H pylori can be tx empirically, i.e. no need for biopsy
4. Old or have alarm sx EGD (esophogastroduodenoscopy)
x. Zollinger-Ellison syndrome
5. Triad of severe PUD, gastric acid hypersecretion, gastrinoma (tumor usually in head of pancreas)
10

6. Dx: secretin stimulation test (paradoxical gastrin after IV infusion), elevated gastrin while fasting
7. Sx: PUD and/or chronic diarrhea (damage of bowel from excessive acid)
8. Tx: high-dose PPI, octreotide (somatostatin analogue)

SMALL INTESTINE
1. Anatomy
a. 6 meters of absorptive surface from pylorus to ileocecal valve
b. Ligament of Treitz (marks duodenal jxn w/ jejunum) links to posterior abd wall
c. Layers
i. Mucosa: folds (plicae circulares) w/villi, simple columnar epithelium w/ microvilli (plasma memb projections)
a. Microvilli make up the so-called brush border
ii. Lamina propria = some inflammatory cells, blood vessels + lacteals
iii. Submucosa: Meissners plexus, Brunners glands (duodenum only), Peyers patches (distal ileum)
iv. Muscularis externa: Auerbachs plexus (between inner circumferential, outer longitudinal)
v. Serosa
d. Cells
i. Villi: goblet cells (secrete mucus) + enterocytes (absorbtive)
ii. Crypts: above + paneth (enzymatic) + endocrine (CCK, serotonin, VIP) + stem cells
2. Function
a. Whats absorbed where?
i. Mouth: some lipase and amylase (start fat/starch breakdown)
ii. Stomach: EtOH, Fe (acid facilitates), B12 binds GIF
iii. Duodenum: Fe, Ca, B-vitamins (except B12) and other H20-soluble vitamins
iv. Jejunum: AAcids, FFAs, monosaccharides
v. Terminal ileum: B12, conjugated bile salts (along w/ fat, fat soluble vitamins)
1. Bacterial overgrowth breaks up conjugated bile salts malabs of fat, fat soluble vitamins
vi. Colon: oxalate, fluids, electrolytes, short-chain FAs (food for colocytes, the colon parenchyma)
b. Axes
i. Vertical axis: crypt to villus tip with apoptosis/replacement, functional absorption, phenotypic switching
ii. Longitudinal axis: 90% of digestive absorption is in initial part of intestine
c. Phases of absorption
i. Luminal phase: chemical alteration of nutrients ability to absorb (proper pH, pancreatic zymogens, bile acid)
ii. Intestinal phase: occurs at level of enterocyte, req sufficient surface area
1. Transcellular route
a. Extracellular (luminal) enzymes in glycocalyx break down nutrients for absorption
i. Disaccharidases (Na-glucose cotransport), lipases (micelles), peptidases (AAcids)
b. Intracellular chylomicron assembly, export of nutrients
1. Paracellular route
a. Apical uptake of Na/glucose via Na/glucose co-transport draws Na/glucose through cell
b. Osmotic gradient pulls in water from lumen paracellularly
c. GLUCOSE must be given with Na for rapid H20 replacement since its a co-transporter
3. Malabsorption
a. Etiology: surgical resection, bacterial overgrowth, pancreatic insufficiency, stomach damage, intestinal damage
b. Sx
i. Weight loss, muscle wasting, edema, diarrhea, cramps, flatulence
ii. Anemia (Fe deficy hypochromic microcytic, B9 macrocytic hypersegmented PMNs, B12 pernicious)
iii. Coagulopathy due to Vit K deficit
iv. Osteopathy due to Vit D, Ca deficits
v. Renal oxalate stones
1. Normally oxalate joins w/ Ca in intestine and removed together, but when bile acids arent reabsorbed
(due to no ileum or bacterial overgrowth), FFAs arent absorbed FFAs compete w/ oxalate for Ca
binding (form soaps) free oxalate then reabsorbed by colon, joins Ca outside colon kidney stones
vi. Gallstones due to bile salt reabsorption cholesterol in bile concretions
c. Manifestations
i. Fat absorption is complex, thus malabs syndromes will usually result in steatorrhea (hallmark of malabs)
1. In lumen, lipases from pancreas FFAs and glycerol
2. FFAs bind bile salts absorbed, re-esterified into TG, packaged as chylomicrons, absorbed by lacteals
a. Exception: short/medium chain TG not ordinarily abundant in diet, but are absorbed directly
into intestinal capillaries ( portal v) w/o any lipolysis/micelle/chylomicrons necessary
11

2. Dx: Sudan stain, or by 72-hr stool collection w/lipid quantification ( 18-21g abnormal)
a. Must be consuming 80-100g/day fat
ii. Vit B12 absorption - Dx w/ Schilling test
1. Acid releases B12 from food, then bound to R factors
2. Pancreatic enzymes release R factors so it can bind GIF, complex is absorbed in terminal ileum
a. Bacterial overgrowth breaks complex, which can minimize absorption
d. Bacterial overgrowth
i. Can B12 and bile salt reabsorption
ii. False results of D-xylose test (bacteria metabolize xylose/remove it, so test will falsely imply absorption)
iii. Dx: early peak in hydrogen breath test, colony count, abx trial, imaging
iv. Causes: achlorhydria, gastric surgery, motility disorders, diverticula, loss of ICV, scleroderma
e. Tests
i. Nutritional tests include CBC (for anemia), albumin levels (low protein absorption), vitamin deficiencies
ii. Check stool for ova/parasites
iii. Check pancreas: secretin stimulation should HCO3 secretion (paradoxical HCl in gastrinoma)
iv. Intestinal vs pancreatic
a. D-xylose test: pancreatic enzymes not reqd for xylose absorption (so SI problem= low URINE xylose)
v. Hydrogen breath test: w/ dissachase defcy, sugar remains in gut so bacteria metabolize H blown off
4. Disorders
a. Congenital abnormalities
SITE AFFECTED CONSEQUENCES
Hypertrophic Most common in White 1st-born M, family hx Non-bilious vomiting after feedings
Pyloric Hypertrophy of muscularis propria/wall thickens Firm, movable olive-size mass in epigastrum
Stenosis Tx: pyloromyotomy (cut through outer muscle) May see peristaltic waves of stomach post-feeding
Stenosis, Duodenum most common (vascular insult) Obstruction
Atresia Complete (atresia) vs partial (stenosis) Perforation meconium peritonitis
Malrotation Improper rotation of gut when returning into High chance of volvulus strangulation of bowel necrosis
embryo, no fixture via ligament of Treitz
Omphalocele Defective formation of abd musculature When assoc w/ other anomalies (common), mortality is
herniate abd contents into membranous sac HIGHER MORTALITY THAN GASTROSCHISIS
Still covered by skin, umbilical cord above defect
Gastroschisis Abdominal wall defect due to absent portion of Px depends on viability of intestine, degree of defect
abdominal wall extrusion of the intestine Not assoc w/ other anomalies
Defect is beside umbilical cord (paraumbilical)
Duplication Ileum most common cystic structures

Meckels Most common malformation of GI Rule of 2s: w/in 2 ft of ICV, 2% population, 2M:1F, 2% have sx
Diverticulum Vestigial remnant of vitelline duct (connects Ulceration (esp w/ ectopic gastric mucosa) bleeding
umbilicus/bowel) blind pouch in ileum anemia, acute abd (intussusception part of intestine slips
Often ectopic tissue (stomach/pancreas) into another like collapsing telescope)

b. Phases: intra-luminal digestion (luminal phase), absorption (mucosal), nutrient processing (post-absorptive)
DEFECT PATHOGENESIS Dx/PATHOLOGY Sx/CLINICAL
Cystic Luminal phase autoR CFTR mutation (F508, Meconium ileus in Most common lethal autoR dz
fibrosis defect chr7) dysfxnl Cl transport neonatal period sweat glands: poor reabs of NaCl
thick secretions Dx by elevated sweat Cl pancreas: viscous secretions
pancreatic insufficy (clogged Pancreas issues in utero obstruction panc insuffiency
ducts) Lung issues begin after birth steatorrhea, acinar necrosis
lungs: Na/H20 reabs thick,
deH20 mucus pneumonia (via
pseudomonas), bronchiectasis
Lactase Microvilli lack Usually acquired (often AA) Normal histology Diarrhea, cramps
defcy enzyme Insufficient lactase lactose Dx: H breath tests lactose
(Mucosal accum osmotic diarrhea (orgs break it down),
phase defect) tolerance test
Celiac dz Intestinal Autoimm rxn to gliadin (gluten Villous flattening, crypt Most common malabs d/o
(Sprue) surface area protein) found in hyperplasia, Tcell inflamm (esp. Caucasians)
(Mucosal wheat/barley/rye Affects mainly proximal SI Dermatitis herpetiformis
phase defect) enterocyte damage villi (spares ileum/LI) Diarrhea/malnutrition
flattening less SA malab abnormal lactase test risk of intestinal cancers
Dx: celiac panel (anti- Tropical Sprue tx w/ ABx
gliadin, anti-TTG IgA),
auto-Abs
Abetalipo- Intestinal, autoR mutation in ApoB Epithelial cells pale (engorged Predictable sx based on fat and
proteinemia metabolic fxn interferes with chylomicron w/fat b/c absorb but cant fat soluble vitamin malabs
defect (Post- (ApoB48) synthesis and thus package into chylomicrons)
absorp phase) fat/vit-ADKE absorption See acanthocytes (burr cell)
Whipples dz Intestinal SA & Systemic infxn T. whippelii Pale foamy macrophages Arthritis, malabsorption,
cellular export See in middle-aged, White M No significant inflammation lymphadenopathy,
12

defect (Post- Dx: PAS staining bugs hyperpigmentation


absorp phase) See dilated lymphatics
Short bowel Bile acid defcy Resected bowel short bowel Depends how much resected
syndrome SA defect syndrome markedly >1m bile acid malabs
reduced SA for absorption syndrome = loss of bile acid/fat
Ileal resection B12 deficiency
Postenteritis Prolonged diarrhea damaged Acute diarrhea lasting >2 wks
syndrome epithelium secondary (usually viral)
lactose malabsorption Tx w/ lactose free diet
Giardia Drinking contaminated water Protozoan can be seen in VERY common
lumen (non-invasive) Tx with metronidazole
Cows milk Villous atrophy, eosinophils Skin/respiratory/GI sx
allergy

5. Inflamm Bowel Dz
a. Usually older adults w/ other problems (like atherosclerosis)
b. Damage due to hypoxia/hypoperfusion and to reperfusion oxidative injury
c. Extent of injury depends on type/location of insult (hypoperfusion usually more superficial damage than occlusion)
i. Transmural infarcts have high mortality
d. Acute Ischemia
i. Purple-red region of bowel (intraluminal hemorrhage)
ii. Mucosal sloughing/ulceration/hemorrhagic necrosis/variable degree of acute inflamm
e. Chronic Ischemia
i. Mucosal ulceration/acute + chronic inflamm/fibrosis
6. Necrotizing Enterocolitis (NEC)
i. Seen in premature infants (bowel not ready to receive bacteria, even normal flora)
ii. Sx: abd distension, bloody stool, hypovolemic shock
iii. HIGH mortality rate
7. Cancer
a. Primary cancer rare, mets common
b. Benign (adenoma, lipoma, leiomyoma) >> malignant
c. Carcinoid is most common SI malignancy (unlike most other organs, carcinomas not very common)
i. Neuroendocrine tumor that secretes serotonin
ii. Nests of small round cells w/ salt + pepper chromatin, dense secretory granules, scant cytoplasm
iii. Slow growing, low grade, rarely met, usually asx but may cause kinks, commonly in rectum/ileum/appendix
1. Location matters ileum worst px b/c chance of met to liver carcinoid sydrome
iv. Carcinoid syndrome
1. Sx: tricuspid insufficiency, pulmonic stenosis, skin flushing, diarrhea (last two due to high serotonin)
2. Patho: infiltrative mass w/desmoplasia obstruct, neurosecretory granules (dense core w/ halo)
3. Tx: surgery, octreotide (inhibits serotonin release)
d. Primary GI Lymphoma
i. Uncommon, but GI is most common primary site outside lymph nodes
ii. Types:
1. B cell lymphomas (most common, generally good px)
a. MALT lymphoma (assoc w/ H pylori infxn; see above in stomach section)
b. Mediterranean lymphoma (Mediterranean kids/teens, preceded by malabsorption)
c. Burkitt lymphoma (aggressive, assoc w/ c-myc translocation (t8;14) and EBV
2. T cell lymphomas (poor px), see in young adults w/ long-standing malabsorption
iii. Superficial plaque-like thickening w/ monotonous atypical lymphocyte infiltrate (1 st in mucosa, then through)

Irritable bowel syndrome


Dx recurrent pain or discomfort for at least 3 days/month in last 3 months w/ symptom onset at least 6 months before Dx
and assoc w/ 2 or more of following
-improvement w/ defecation
- onset assoc w/ a change in freq of stool
- onset assoc w/ a change in appearance of stool
Classification
IBS-C = predom constipation
IBS-D = predom diarrhea
Treatment symptomatic tx + fiber sup + low FODMAP
IBS-C = linaclitide, lubiprostone
IBS-D = eluxadoline, rifaximin, alosetron
13

COLON
1. Anatomy
a. ~1.5m in length: cecum, ascending, transverse, descending, sigmoid, rectum
b. Wall structure: mucosa (no folds), lamina propria (no lymphatics), taenia coli (longitudinal m outside haustra)
c. Mucosa: no villi, crypt (proliferative), surface (many goblet), endocrine, Paneth in R colon only (if L = metastasis)
d. Splenic flexure most susceptible to damage due to hypoTN b/c it is watershed where SMA/IMA zones overlap
2. Function
a. Reabsorption of remaining 10% of water and electrolytes
i. If voluminous diarrhea, think SI cause
b. Formation and storage of feces
c. Microbial fermentation
d. Site of oxalate absorption in malabsorption syndrome ONLY (pathological consequence)
3. Disorders
a. Congenital
i. Hirschsprung disease: defect of migration of ganglion cells aganglionic segment beginning at rectum,
extending prox lack of (-) input tonic contraction + aperistalsis functional obstruction + dilation of
proximal segment (when do surgery, remove small normal-looking part and leave bulging proximal part)
1. Assoc w/ Downs syndrome, M>F
2. Delay in meconium (normally w/in 24h of birth) and chronic constipation
3. Dx via biopsy suction biopsy shows absence of Meissners (favored method), full-thickness
biopsy required to show absence of Auerbachs b/c that is deeper btw layers of muscularis externa
ii. Cloacal Dysgenesis Syndrome: imperforate anus, UGS persists (joined rectum/vagina/bladder)
b. Inflammatory bowel disease (UC/Crohns)
i. Idiopathic chronic relapsing inflamm of intestine
1. Familial association: genetic predisposition if HLA-DR1 (Crohns) or HLA-DR2 (UC)
2. Peak presentation 15-25y, more common in whites/females
ii. Assoc w/ sclerosing cholangitis (esp. UC) = inflamm/fibrosis of bile ducts
1. Sx: jaundice, pruritis
2. Patchy, thus not often seen on biopsy, but onion skin fibrosis is diagnostic
3. Characteristic beading of barium on ERCP

PG.271 UC CROHNS
CHART
Shared Sx: abdominal pain, N/V/D, hematochezia (maroon stool from lower GI bleed), weight loss, toxic megacolon
Extraintestinal sx: polyarthritis, sacroilitis, ankylosing spondylitis, erythema nodosum (subQ fat inflamm), clubbing
Clinical Continuous inflamm in rectum, extending proximally Segmental (skip lesion), granulomatous inflamm
Sclerosing cholangitis onion skin inflamm of Gallstones, Ca-oxalate kidney stones
hepatic bile ducts, risk cholangiocarcinoma Can involve any part of GI (but rectum often spared)
Pathology Limited to the mucosa (not transmural) Transmural destruction
Friable, edematous, hemorrhagic mucosa Granulomas are diagnostic
NO wall thickening/strictures/fistulas/creeping fat Thickened wall (SM hypertrophy) strictures
Large, broad ulcers w/ crypt abscesses (PMNs) Deep/linear fissuring ulcers abscesses/fistulas
Pseudopolyps, cryptitis Creeping fat, serositis, cryptitis, adhesions
Dysplasia ( goblet cells) adenocarcinoma Cobble-stoning due to irregular ulcers (skip areas)
Molecular pANCA (ASCA rarely ) Serum ASCA (pANCA rarely )
Tx Surveillance colonoscopy for mucosal dysplasia (ie Mesalamine, corticosteroids, ABx, anti-TNF monoclonal
lose goblet cells) to catch cancer early colectomy Abs (ifliximab), strong immunosuppressives (azathioprine,
Mesalamine (5-ASA), corticosteroids, TNF (-) 6-MP, MTX), budesonide (glucocorticoid), natalizumab
Total Colectomy is curative in severe cases (anti-4-integrin Ab)
Surgery: fulminant disease, perforation, cancer Surgery/Resection of affected bowel is not curative, high
recurrence rate
Surgery: fulminant disease, perforation, cancer
14

TNFa = high conc esp in crohns mucosa


Stim TH1 cells to produce inflamm cytokines, stim endothelial cells to produce adhesion molecules, stim collagen
production in fibroblasts
Anti-TNFa
Natalizumab = anti a4 integrin but crosses BBB so SE is PML (brain infection)
Vedolizumab = anti-a4 integrin stays in GI, doesnt cross BBB

c. Colonic Diverticular Dz
i. L-sided dz of older people on Western diet, usually asx
ii. Outpouchings of colonic wall around neurovascular bundles (where there is loose CT)
iii. Diverticulosis = markedly hypertrophied colonic wall w/ protrusions of flattened mucosa/submucosa
iv. Diverticulitis = diverticulosis + acute/chronic inflamm and fibrosis
d. Appendicitis: usually seen in kids/teens
i. Lumen obstruction intra-luminal pressure venous obstruction hemorrhagic infarction + bacterial infxn
ii. Fibrinopurulent maerial/shaggy exudate/PMN infiltrate/suppurative necrosis
e. Angiodysplasia: dilated/tortuous mucosal/submucosal veins in older people (due to intermittent mechanical obstruction)

f. Polyps
i. Benign (NON-neoplastic)
1. Hyperplastic (usually 40y)
a. If isolated find, NO need for colonoscopy
b. Very glandular (goblet cells), sessile, serrated mucosa
c. Saw tooth luminal borders epithelial cells not shedding fast
enough
2. Hamartomatous (usually 20y)
a. Seen in Peutz-Jeghers polyposis, juvenile polyposis
b. Juvenile polyp: distal polyps seen in rectum, no risk of malignancy
c. Smooth surface, large dilated glands filled with mucin (pic)
3. Inflammatory: pseudopolyps seen in IBD
ii. Pre-malignant/dysplastic
1. Adenomatous type (aka adenomas): low-grade, but highly assoc w/ adenocarcinoma (see pic to L)
a. DOES warrant colonoscopy
b. Villous subtype (finger-like) are larger, sessile, w/ greater risk to develop into carcinoma
i. Cigar-shaped hyperchromatic nuclei
c. Invasion into lamina propria and muscularis mucosae of colon is still considered in
situ, b/c lack of lymphatics means virtually no metastatic potential
2. Adenomatous polyps
a. Tubular Adenoma = small/pedunc, tubular glands w/ epithelial dysplasia
b. Tubulovillous adenoma = intermed, intermed
c. Villous Adenoma = large/sessile, villous projections w/ epithelial dysplasia
3. Other type
a. Sessile Serrated Adenoma = small/sessile, serrated glands w/o epithelial dysplasia
iii. If complete, endoscopic resection is curative
g. Hereditary polyposes (all are autoD inheritance)
i. Juvenile polyposis
1. Assoc w/ SMAD4 and BMP R1a
2. Dozens-100s of hamartomatous polyps in kids in distal GI
3. Moderately risk of colon cancer
ii. Peutz-Jeghers polyposis
1. STK11 chr19 mutation
2. Hamartomatous polyps throughout entire GI
3. Pigmented spots on lips/buccal mucosa
4. risk of other types of cancer (endocrine organs)
5. Begin surveillance at age 10
iii. HNPCC- sessile serrated adenoma
1. Usually found in R colon
2. Defect in mismatch repair genes microsatellite instability
3. Lynch I (colon-specific) and Lynch II (multi-organ) types
4. Begin colonoscopy surveillance at 20-25y (or 10y prior to youngest case in family)
iv. Familial adenomatous polyposis (FAP)
15

1. APC tumor suppressor gene mutation


2. Requires second hit mutation of good copy of APC gene adenoma carcinoma
3. 100% develop colon cancer by early 30s, thus prophylactic colectomy
4. COX-2 selective inhibitors and sulindac have been shown to # of polyps somewhat (adjunct tx)
5. Hypertrophy of retinal pigment epithelium
6. Begin flex sig surveillance at 10y
7. Gardner Syndrome FAP + skin/teeth problems, desmoid/fibrous tumors, osteomas
8. Turcot Syndrome FAP + brain tumors

4. Cancer
a. Adenocarcinoma (98%)
i. Most common tumor of GI is colon cancer
ii. Risk factors: long-standing untreated IBD, poor diet, # adenomas, family hx
iii. Sx: obstruction, pain, bleeding, anemia, tenesmus
iv. Morphology: irregular, disorganized, desmoplastic rxn
v. Types same as gastric
1. Intestinal type: very mucinous, its like a goblet cell proliferation
2. Diffuse infiltrating: signet ring type (rare, poor Px)
b. Carcinoid tumor
i. Well-differentiated endocrine neoplasm, usually in appendix
ii. Ileal carcinoids most likely to metastasize
iii. Serotonin , but most are asymptomatic
iv. Carcinoid syndrome (presents with liver mets)
1. Vasomotor disturbances (flush)
2. Intestinal hypermotility (diarrhea, cramps, vomiting)
3. Pulmonic stenosis bronchoconstriction (asthma-like)
4. Tricuspid insufficiency LR: ulcerating tumor, crowded nuclei in adenocarcinoma
c. Genetic cancers
SPORADIC HNPCC Right Colon FAP Left Colon
# adenomas Few Few Pt develops 100s/1000s of polyps
Frequency 95% of colon cancers w/mutation, 80% lifetime cancer risk With mutation, 100% risk by age 45
Epidemiology Age 65 Age 30 Age 20
Molecular Unknown, ?APC gene Defect in mismatch repair genes Mutation in APC gene (needs 2 hits)
(needs 2 hits) Abnormal APC protein binds less to B-
genomic microsatellite instability catenin intracell adhesion and catenin
genetic abnormal regulation of cell in nuclus transcriptional activation of
growth and survival genes genes cell prolif and apoptosis
KRAS protooncogene mutation RAS is
GTP bound continuous mitogenic signal
Loss of tumor sup genes like TGF-B and
TP53
Gross path = exophytic, fungating
mass Gross path = heaped up margins napkin
ring constriction/apple core lesion
Immunohistochem CEA+
Immunohistochem CEA+
Cecum and Ascending colon
Sigmoid colon
Clin manifest = Rectal bleeding iron
deficiency anemia Change in Bowel Habits
Inheritance Multifactorial autoD autoD
Assoc none Lynch II has numerous extracolon sites Retinal pigment epith hypertrophy
tumors Villous adenoma of duodenum

a. Staging of GI carcinomas (note: moderately differentiated is most common grade at presentation)


i. TMN classification is most important px indicator
1. T1/2 still confined to mucosa, N1 for 1-3 nodes/N2 for more, M1 if mets present
2. When distant mets are present, 5y survival <5%

b. Screening guidelines: 2nd most lethal cancer in USA (usually develop from polyps)
ii. Screening is for asx/diagnostic work-up is for sx/surveillance is for hx of pre-malignant/malignant
16

iii. Average risk pt screen starting at 50y, colonoscopy q10y, flex sig q5y, FOBT q1y
iv. risk pts:
1. 1 relative (60y) w/ CRC OR two 1 relatives w/ CRC (any age) 40y or 10y prior to youngest CRC
2. 1 relative (60y) w/ CRC OR 2 relatives w/ CRC (any age) 40y (though risk is average)
v. Pts w/ personal hx:
1. Hx of advanced polyp or 3 adenomatous polyps f/u colonoscopy in 3y
2. Hx of 1/2 small adenomas f/u colonoscopy in 5y
3. Hx of large sessile adenoma or incomplete removal use clinical judgement
4. Hx of CRC f/u colonoscopy in 3y (unless couldnt perform complete colonoscopy prior to CRC
surgery, then have f/u colonoscopy in 6mo) if normal @ 3y, f/u every 5y
5. Hx of chronic IBD (UC/Crohns) colonoscopy every 1-2y starting 8-10y post-dx
a. Take 4 circumferential biopsies every 10cm to lock for dysplasia preventative colectomy

INFECTIOUS DIARRHEA
1. 2nd leading cause of infectious death worldwide (esp. kids)
2. Diarrhea = passage of abnormally liquid/unformed stool at frequency (200g or typical Western diet)
3. ABx usually given for: ETEC, Shigella, Campylobacter, V.cholera, C.diff, Giardia, E.histolytica
4. Acute: <2wk, persistent: 2-4wk, chronic: >4wk
a. 90% of acute cases are infectious
b. Others: medications, IBD, tumors, ischemic colitis, diverticulitis
5. Mechanisms
a. Non-inflammatory: usually affects SI, copious watery stools, dehydration common, (-) blood/fecal leukos/tenesmus
i. Toxin-mediated (ex) vibrio cholera, ETEC (travelers)
ii. Altered villous absorption (ex) EPEC, giardia, cryptosporidium, rota/norovirus (viral villous tip blunting)
b. Inflammatory: usually affects LI, mucoid/bloody stools, dehydration uncommon, (+) blood/fecal leukos/tenesmus
i. Mucosal invasion (ex) shigella, salmonella, campylobacter
ii. Cytotoxin (ex) c diff (see pseudomembranes)
c. Systemic
i. Salmonella typhi/paratyphi ( typhoid fever) vs. non-typhoid Salmonella ( gastroenteritis)
6. Enteric fever: intestinal infxn caused by a variety of bacteria sustained, systemic febrile illness
a. 95% of cases are due to salmonella typhi or paratyphi
SALMONELLA TYPHI/PARATYPHI SALMONELLA NON-TYPHI
Route ONLY exists in humans, thus only passed via Zoonotic spread from animal (poultry, reptiles) to human
direct/indirect contact w/contaminated human feces
Patho Ingested adheres to SI mucosa invades via type III secretion (injects protein directly into host cell) membrane
ruffling (actin rearrangement) and internalization via M cells phagoed by M of Peyer patch replication/necrosis
With s typhi, bacteria spread to lymph nodes then bloodstream bacteremia + onset of sx dissemination to liver,
spleen, bone marrow + chronic state if gets into gallbladder (chronic if persists in feces for 1y)
With NON s typhi, locally invades but rarely causes bacteremia local inflammatory response + fluid secretion diarrhea
Micro Blunted villi, peyer patch swelling/ulceration/sharp borders, M w/ bacteria, liver typhoid nodules (small necrotic foci in
which hepatocytes are replaced by leukocyte aggregates)
Sx Asx period of 1-2wk Asx period of 2d
High grade, sustained fever for ~2wk Gastroenteritis/colitis
Abdominal pain/distension, diarrhea OR constipation IF gets in blood infxn of damaged vasculature
CNS changes (ex) confusion, delirium (esp aortic aneurysms)
Rose spots (blanching maculopapular rash)
Complications: intestinal perf/hemorrhage/peritonitis,
endocarditis, liver abscess, meningitis, septic joints
Dx BLOOD cx (stool/urine/skin/BM may also be ) STOOL cx
Tx 3rd gen cephalosporin, quinolone (resistance in India) No abx if uncomplicated, self-limiting in 3-7d
Note: typhoid vaccine does NOT protect from S. paratyphi

7. Other common causes


EPIDEMIOLOGY PATHO Dx Tx
ETEC Most common bacterial Heat labile/stable toxin NOT available most labs Ciprofloxacin, bactrim
cause worldwide Copious watery diarrhea (TMP-SMX)
Cause of travelers
EPEC Epidemic infantile Brush border effacement NOT available most labs
(hospital nursery)
EHEC O157:H7 most common Shiga-like toxin ONLY E coli in routine NO abx (may HUS)
Undercooked beef Copious bloody diarrhea lab (sorbitol-negative
w/o fecal leukos/fever on MacConkey)
Assoc w/HUS ( ped RF)
EnteroInvasive rare Similar to Shigella NOT available most labs
17

EnteroAggregative rare Stacked brick pattern NOT available most labs


Shigella Ssonnei (most common) Shiga toxin dysentery, Available in routine lab Abx if severe (shortens)
Sflexneri (w/AIDS) HUS, toxic megacolon via stool culture
Vibrio cholera Poorly cooked shellfish Cholera toxin cAMP Available in routine lab Aggressive rehydration
active Cl secretion via stool culture Tetracycline/azithromycin
(water follows) (shortens)
diarrhea + dehydration
Campylobacter Most common bacterial Guillian-Barre Available in routine lab Erythromycin
cause in USA (chicken) via stool culture
Infected poultry
C. diff Hospital-acquired from Cytotoxin inflam colitis Available in routine lab Metronidazole, vancomycin
preceding abx use + pseudomembranes via stool EIA
Giardia Most common parasitic 1-3wk incubation Available in routine lab Metronidazole
Fecal-oral, contam H2O No invasion via stool cyst exam
Prolonged diarrhea
Norovirus #1 MOST common Lasts only 1-2d Only state labs/CDC ssRNA
cause of diarrhea Food poisoning
Winter, epidemic
Rotavirus Winter, sporadic Lasts 4-8d Available in routine lab dsRNA
Most common cause via stool ELISA
severe diarrhea in kids
SYSTEMIC D/O
1. Many GI factors which predispose for systemic conditions
a. Large and complex blood supply
b. Largest RES system in body (Peyers patches, IgA, MALT/GALT)
c. Autonomic nervous system
d. Extensive smooth m
e. Nutrition feeds the body
2. Metabolic / Endocrine
a. Diabetes
i. Diabetic neuropathy gastroparesis (poor emptying) BEZOARS/N/V/bloat/diarrhea/fecal incontinence
ii. Dx: gastric emptying study for gastroparesis, ano-rectal manometry studies for sphincter pressures
iii. Overwt woman get steatohepatitis w/ fibrosis, cirrhosis, Mallorys hyaline (just like EtOH)
iv. Intestinal stasis
1. Bile salt deconj; fat malabsorb Vit b12 IF deconj; megaloblastic anemia
2. Dx w/ SB series, H2 breath test
v. Diabetics have resting Internal anal sphincter pressure
b. Hypothyroidism constipation vs hyperthyroidism hyperdefecation/diarrhea
c. Hyperparathyroidism/hypercalcemia constipation and hypergastrinemia (high Ca high gastrin) PUD
i. Multiple endocrine neoplasia (MEN) syndromes = gastrinoma/zollinger ellison
3. Renal Failure
a. Angiodysplasia/-ectasia GI bleeding
4. Drugs/Toxins
a. Antichol/CCB = constipation/GE reflux
b. Anti-deppressants (CAs) = constipation
c. Antacids
i. Mg = diarrhea
ii. Al = constipation
d. Heavy metals
i. Lead = abd pain, constipation
ii. Arsenic = emesis, diarrhea, dysphagia
iii. Gold = enterocolitis
e. Abx pseudomembranous colitis from C. diff
i. C dif Tx = Metro/Vanco
f. Erythromycin (macrolide) is motilin agonist gastroduodenal hyperperistalsis
5. Autoimmune/immunologic
a. Scleroderma motility dysfxn entire length of GI tract due to collagen replacing smooth m
b. SLE/RA/Polyarteritis nodosa
i. Ischemia to gallbladder acalculous cholecystitis
ii. Ischemia to pancreas pancreatitis
c. Polymyositis/dermatomyositis poor bolus transfer in esophagus (skeletal muscle) and may have problems w/ the
external anal sphincter not contracting properly when IAS opens during sampling of rectum contents
6. Infections
a. HIV candida/CMV/HSV in esophagus + MAV/TB in small intestine
7. Cancers
a. Liver mets are very common
8. Pregnancy
a. GERD/hemorrhoids due to abdominal pressure and b/c E2/progesterone relax the LES
9. Aging
a. Peptic ulcer disease (w/ heavy NSAID use), but usually GI ages well
10. GVHD = protein losing enteropathy, vanishing bile duct syndrome
18

VASCULAR & MECHANICAL D/O (stuff he raised his hand on is in bold)


1. Obstruction is either functional or mechanical
a. Mechanical barrier frequency spike potentials as bowel tries to clear complete emptying of anything distal to
obstruction + dilation/backup proximally changes in flora and then you throw up your own poop
2. If IMA ligated during aortic aneurysm surgery sigmoid colon death, pt classically presents with post-op bloody diarrhea

MECHANICAL OBSTRUCTION FUNCTIONAL OBSTRUCTION


Esophagus Cancer, diverticula, stricture
Sx: dysphagia, regurgitation
Stomach Gastric outlet obstruction (PUD, malignancy) Post operative
Sx: fullness, NON-bilious projectile vomiting Diabetic gastroparesis
Duodenum Atresia (double bubble), annular pancreas, tumor
Sx: BILIOUS projective vomiting
Small bowel Most common site of obstruction Ileus: anesthetic, infxn, bowel manipulation, K abnormalities
Adhesions, tumors (luminal causes rare)
Sx: crampy pain, simple or closed loop strangulated
Tx: surgery, fluids (due to 3rd space losses)
Large Bowel Malignancy, volvulus (L>R, laxative abuse in elderly) Ogilvies Syndrome (like ileus), Hirschsprung
Sx: constipation, distension, usually elderly

PATHOPHYSIOLOGY
Diverticulitis Due to perforated diverticula inflamm, bleeding
Can be emergency but normally stays local, healing w/ strictures obstruction
Tx w/ abx and sometimes proximal colostomy w/ resection
Appendicitis Tx usually w/ abx, rarely surgery anymore except in pregnancy
Emboli Bowel supplied by branches of celiac, SMA, and IMA, which anastamose extensively
Thrombi Present w/ pain out of proportion of physical findings (distension causes tenderness/guarding, not ischemia)
Ischemia Usually assoc w/ heart disease (recent MI or a fib)
Embolus: distal SMA most commom, thus MCA not blocked duodenum/transverse colon spared
Bergans triad: acute abd pain/hx cardiac dz/spontaneous GI emptying
Thrombus: early SMA most common, so duodenum/transverse colon will be necrotic
Most common cause of mesenteric ischemia, 80% mortality
Non-occlusive mesenteric ischemia (common in ICU), affects SMA distribution
Chronic intestinal ischemia: triad of wt loss/abd pain/diarrhea, abd bruit in 50% (must resect)
19

PHARM
1. Treatment of H pylori-associated PUD
a. Tx only pts who test positive for H pylori empiric therapy w/o confirmatory testing is not recommended
b. Regiments should include at least 2 ABx + 1 anti-secretory agent
i. First line: triple therapy of omeprazole (PPI) + clarithromycin + amoxicillin
ii. Second line: quadruple therapy of omeprazole + bismuth + metronidazole + tetracycline
1. Can be first line if known penicillin allergy or prior macrolide use
Anti-secretory agents (all enter bloodstream and act on parietal cells from basolateral side)
DRUG MOA INDICATIONS SE / CONTRAINDICATIONS
Omeprazole PPI, inhibits active proton PUD (part of triple therapy) SE: GI related
Lansoprazole pumps on parietal cells GI bleed (ie NSAID-induced) No dose adj for renal/hepatic dz
Best acid suppression Anything due to excess acid DDI w/ pH-dependent drugs (anti-
Take w/ food to stimulate pumps fungals and protease inhibitors)
No tolerance development
Cimetidine H2 blockers, inhibit H2 R on Very similar to PPIs, less effective Must adj in renal pts CNS risks
Ranitidine parietal cell less HCl made Potential for CYP interactions
(gastrin & ACh still work though) (cimetidine inhibits CYP450)
Tolerance development

2. Treatment of GERD
a. Non-pharm always dont eat before bed, reduce fat intake, avoid inciting foods, stop smoking, lose wt, sleep at angle
b. If Sx are intermittent, tx via lifestyle modification + OTC drugs like antacids/H2blockers
c. If Sx are severe, tx via lifestyle modification + high dose PPI, with maintenance therapy
d. Drugs include PPI, H2 blockers (both above), antacids, pro-motility agents
DRUG MOA INDICATIONS SE / CONTRAINDICATIONS
Antacids
CaCO3 Neutralize stomach acid Rarely used (drugs more effective) SE: GI related
MgOH2 Accum of Al/Mg in renal dz
DRUG MOA INDICATIONS SE / CONTRAINDICATIONS
Promitility agents ( delayed gastric emptying GERD)
Metoclopramide Dopamine R antag + 5HT agonist GERD EPS
ACh smooth m contraction Gastroparesis Contra: Parkinsons pts
Cisapride 5HT stimulates myenteric plexus TAKEN OFF MARKET Caused arrhythmias
Erythromycin Stimulate motilin R in smooth m N/V/cramping
LES tone/gastric emptying QT prolongation (torsades risk)

3. Treatment of GI bleeding
a. Non-variceal UGI bleed: remove offending agent (usually NSAID), tx H pylori if present, PPI
b. Variceal UGI bleed: often life-threatening, requires hemodynamic stabilization
i. FIRST is fluid resuscitation (normal saline) and blood replacement
ii. Endoscopy + sclerotherapy is tx of choice for actively bleeding varices significant reduction in mortality
iii. Prevent musocal damage
1. pH >4 is target for prevention of stress-related mucosal damage
2. pH >6 is target for prevention of peptic-ulcer recurrence
c. Pharm: octreotide/vasopressin acutely, PPI for prevention
Acute tx
DRUG MOA INDICATIONS SE / CONTRAINDICATIONS
20

Octreotide Somatostatin analog with long Variceal bleeding SE: GI related, flushing, edema
t contraction of vascular
smooth m reduction LIVER
& SPLANCHNIC blood flow
Vasopressin (ADH) Stimulates V1 R in periph Variceal bleeding SE: arrhythmias, MI
vessel blood flow to varices
Sucralfate In acidic pH, forms viscous gel Debatable, needs low pH to work, SE: Al overload in renal pts
that preferentially coats ulcers so giving w/ PPI may not help

4. Tx for Gastroparesis
a. Delayed gastric emptying due to CNX damage (often DM) or smooth m damage (scleroderma)
b. Tx w/ pro-motility agents (major ones listed above)
i. Cholinergic agonists (bethanechol) SM stimulation; SE profile (bradycardia, flushing, diarrhea)
ii. AChE(-) (neostigmine) accum of ACh; above SE + life-threatening bradycardia/AV block
iii. Dopamine antags (domperidone, metoclopramide) ACh(-); SE profile (dry mouth, rash, drowsy, abd pain)
1. Extrapyramidal sx (dystonia/tremor) occur much more w/ metoclopramide b/c crosses BBB easily)

5. Tx of Ulcerative Colitis
a. Dz classification:
i. Mild: 4 stools/d (w/ or w/o blood), no systemic sx, normal ESR
ii. Severe: 6+ stools/d (w/ blood), systemic sx (anemia/fever/tachycardia), ESR
iii. Fulminant: 10 stools/d (w/ continuous blood), systemic sx and ESR, transfusion requirements

DRUG MOA INDICATIONS SE / CONTRAINDICATIONS


Anti-inflammatory
Mesalamine Local anti-inflammatory via (-) DOC for proctitis/mild colitis N/V
(rectal 5-ASA) prostaglandin/LKT synthesis Used in both acute/maintenance
Sulfasalazine Same DOC extensive/severe colitis Sulfa allergies with sulfasalazine
(oral 5-ASA) Used in both acute/maintenance Cannot be used alone
Corticosteroids Anti-inflamm + Oral: acute tx of extensive colitis SE: hyperglycemia, Na/H20 retain
immunosuppressant Rectal: acute tx ONLY Adrenal insufficiency
IV: acute tx in systemic toxicity
Immune-modulators
Azathioprine Antagonize purine metabolism If steroid-refractory/dependent SE: pancytopenia, must monitor CBC
(-) DNA/RNA synthesis
6-Mercaptopurine Same Same SE: liver necrosis + pancytopenia,
must monitor CBC, LFTs

6. Tx of Crohns Disease
a. More difficult to treat, more reliance on corticosteroids
i. Mild-moderate: 1st line is oral aminosalicylate, then sulfasalazine (mesalamine if lesions in distal colon)
ii. Severe: prednisone, budesonide
iii. Fulminant: IV steroids
7. Tx of Irritable Bowel Syndrome
a. Majority only require lifestyle modifications
b. Pharm tx includes
i. Anticholinergics: usually as adjunct w/ some sedative, CONTRA in glaucoma, myasthenia gravis, GI obstruction
1. Hyoscyamine, atropine, propantheline, methscopolamine, dicylcomine
ii. Typical SE profile of dry mouth, constipation, impaired motility
8. Tx of Nausea/Vomiting
DRUG MOA INDICATIONS SE / CONTRAINDICATIONS
Ondansetron 5-HT antagonist Chemotherapy induced N/V
(-setrons)
Metoclopromide Dopamine R antagonists Chemotherapy induced N/V SE: EPS (esp. metoclopromide)
Droperidol Fatal QT elongation
Aprepitant Substance P/neurokinin R antag Chemotherapy induced N/V Potent P450 34A (-)
CONTRA: cisapride, terfenadine
Women seek other forms of OCP
Diphenhydramine H1 R blocker Motion sickness SE: drowsiness, dry mouth
Trimethobenzamide Central (-) chemoR trigger zone
21

5HT/dopamine
antagonists

ChemoR Trigger Zone

Vestibular Apparatus
VOMIT CENTER

Anti-histamines Anti-ACh

Visceral Afferents
from GI