PaPh Assessment 8 Professor Hints
Lecture 1: Esophagus: clinical features of gastroesophageal reflux ds, complications of longstanding reflux
including Barrett’s esophagus and management thereof, features of atypical presentations of reflux ds
Clinical Features of GERD: Loss of balance between protective (clearance via peristalsis, esophageal barriers,
tissue resistance) and aggressive factors (acid, volume, duodenal contents) leading to regurgitation into to
hypopharynx heartburn worse after meals or upon reclining, belching/hiccups, dysphagia, water brash: sour/salty
fluid in mouth due to increased salivation in response to acid reflux, globus/hoarseness, cough/bronchospasm
Buzz phrases: basal cell hyperplasia, eosinophils, elongation of lamina propriaall mean reflux ds.
Complications of long standing GERD: Aspiration, laryngitis/hoarseness, esophagitis, strictures, Barrett’s esophagus
(predisposing to adenocarcinoma), adenocarcinoma
Management of Barrett’s esophagus:
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Ablate or resect areas of high grade dysplasia to prevent cancer via endoscopy (thermal ablation,
photodynamic treatment, mucosal resection)
Esophagectomy
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PaPh Assessment 8 Professor Hints
Features of Atypical presentation of reflux disease:
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Hypotensive LES
o Pregnancy, scleroderma, myotomy
Dysphagia without anatomic dysfunctiondysmotility
Non-cardiac chest pain and normal pHnutcracker syndrome
Not really sure what she is going for here, feel free to add in.
Lecture 2: Motility disorders: location of receptors, features of the visceral nervous system, clinical features
of achalasia, gastroparesis, constipation
Location of receptors: Sympa slows down GI, Para speeds up, receptors located in meissner’s plexus in submucosa
and myenteric between circular and longitudinal muscle layers.
Features of Visceral nervous system: Interstitial cells of cajal are pacemakerssympa slows down rate, para speeds
up, Ach/Substance PExcitatory enteric transmitters (receptors on interstitial cells of cajal), VIP/NOInhibitory
enteric transmitters (receptors on smooth muscle)
Achalasia: “Doesn’t relax”, usually due to neuronal loss (chaga’s, autoimmune, etc.); Symptoms: Dysphagia, chest
pain in xiphoid area, Heart burn, weight loss, regurgitation/globus, adrenal insufficiency in children (allgrove
syndrome). See air fluid levels, bird beaking on following XR.
Gastroparesis: impaired transit of food (can be due to neuropathy, hyperglycemia, damage of interstitial cells of
cajal, viral infections, etc.); Symptoms: Nausea, abdominal pain, early satiety, vomiting, more rarely malnutrition
and wasting
Constipation: Infrequent BM (<2 wk/12 mo. Or <3 wk/12 mo. w/ straining/hard stool, etc.); Symptoms: Infrequent
stools, hard stools, straining, and incomplete evacuation
Lecture 3: Irritable bowel syndrome: definition, epidemiology, clinical features, normal colonic motility vs.
irritable bowel, differential dx, treatment
Definition: GI syndrome with chronic abdominal pain, altered bowel habits in absence of any known organic cause.
Epidemiology: Male>Female, most patients <45 y/o, Most prevalent GI disease**, associated with psychosocial
distress
Clinical Features: Abdominal pain and altered bowel habits, KNOW THIS. Diarrhea & Constipation. Minor
symptoms: Mucus in stools, abdominal distention, belching, flatulence, dyspepsia
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PaPh Assessment 8 Professor Hints
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Normal Colonic Motility
Irritable Bowel Syndrome
Increases post prandially
Motility abnormalities
Stress increases motility
Visceral hypersensitivity**
Hormones, physical activity, ANS
Psychosocial
Post-Infectious
Differential diagnosis: Lactose intolerance, infectious, colorectal cancer, diverticulitis inflammatory bowel disease,
antibiotic associated diarrhea, hypo/hyperthyroidism, medications, endometriosis, celiac sprue
Treatment: Dietary (no lactose, or certain foods), reassurance, Alosetron (5HT3 antagonist) and loperamide for
diarrhea, Tegaserod (5HT4 agonist), fiber, lubiprostone (chloride chan. Activator) for constipation, antispasmotics
for pain and bloating, SSRI’s for more severe pain
Lecture 4: Pancreas: Pancreatitis: pathophys; causes of acute; clinical features of gallstone, alcoholic and
chronic pancreatitis; complications
Pathophys: Earliest event is activation of pancreatic zymogens into their active forms. Can be due to blockage of
secretion (so that zymogens are activated by fusion of lysosomes due to the proteases activated by low
pH)Autodigestion of acinar cell proteases activate complementC3a/5a recuit PMN’s and
macrophagesInflammation and release of cytokines (TNF,IL6, PA, NO) and thus inflammatory response in the
pancreas (pancrea-titis)\
Acute Causes of pancreatitis: ALCOHOL AND GALLSTONES. Can you say Test question?
Clinical Features of gallstones: Age>50, Female, Amylase>4000 IU/L, AST>100IU/L, ALK phosphatase >300
IU/L. Note: Increased ALP is very indicative of gallstone etiology since it is blocking the bile ducts.
Q1: 55 year old female presents with 4200 IU/L amylase 300 IU/L AST, ALP is 450 IU/L. Patient has epigastric
pain radiating to the back with jaundice, what is the most likely etiology of the pathophysiologic process? Acute
pancreatitis caused by gallstones blocking common ampulla of vater (CBD and pancreatic duct confluence).
Q2: Mr. Hyde, a medical student in his 20’s drinks a pint of whisky after every pharmacology team based learning
experience, especially ones involving scratch off lottery tickets. Mr. Hyde presents with pain radiating to the back,
AST and ALT both elevated, ALP is WNL. Most likely etiology? Acute pancreatitis caused by alcohol.
Alcohol and chronic pancreatitis: Chronic alcoholism causes recurrent bouts of pancreatitis, activation of stellate
cells, fibrosis, malabsorption and pain (diabetes as well, more late in the process). Pathophys: Alcohol sensitizes
acinar cells to CCK. CCK is secreted causing hypersecretion of pancreatic enzymes leading to pancreatitis.
Remember: Alcohol, fibrosis, and pain in chronic pancreatitis.
Complications: Chronic: Diabetes, malabsorption, pain, loss of both insulin and glucagon (hard to control diabetes)
Acute: fluid collections pseudocysts, fistulas, splenic vein thrombosis
PaPh Assessment 8 Professor Hints
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Lecture 5: Diarrhea: distinguish in general terms between osmotic, secretory and inflammatory diarrhea.
Diarrhea Type
Osmotic
Secretory
Etiology
Non-absorbable material causes
osmosis of fluid from the gut into the
lumen.
Examples
Lactase deficiency
Moderate volume, resolves in fasting
Lactulose
Much flatlulence, pH<5.3 of stool,
osmolar gap>125
Basically there is increased secretin
of chloride followed by sodium and
water.
Mannitol
Volumnous, watery, persists in
fasting
Medications
Sorbitol
Bacterial Toxins (V. Cholera)
Laxatives
Caffeine, ETOH
Inflammatory
No flatulence, pH 6-7, Osmolar gap
<50
Enterocyte damage and death,
inflammatory mediators increasing
secretion all lead to villous atrophy
and malabsorption resulting in
diarrhea.
Parasites, food allergies, celiac
sprue, salmonella, whipple’s,
Ulcerative colitis, Crohn’s
Note: Diarrhea is defined physiologically as >200gm stool output per day.
Note: Major cause of acute diarrhea is infection (viral predominates: Norwalk virus, campy is leading cause of
bacteria, giardia is leading parasitic cause)
PaPh Assessment 8 Professor Hints
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Lecture 6: GI malign: risk factors, epidemiology, clinical presentation, how to dx, treatment, familial causes
of colon ca; Pancreatic cancer: cell of origin, risk factors, clinical features, treatment in general
Risk Factors
Epidemiology
Clinical
Presentation
Diagnosis and
Treatment
Colon Cancer
Most common GI malignancy, increases after age 50, FH
increases risk, lack of physical activity, obesity,
cigarettes and alcohol, red meat consumption, chronic
colitis and adenomatous polyps predispose
Most cases are sporadic * (70%), although FAP and
HNPCC can predispose they only account for 5% of
cases
Occult bleeding if in R. colon, obstructive symptoms and
overt bleeding if in L. colon, tenesmus, pain and bleeding
if in rectal area
Surgery
Pancreatic Cancer
Black, Urban, Male, Smoker**,
Diabetic, chronic pancreatitis,
hereditary pancreatitis, genetically
susceptible individuals
Weight loss**, Abdominal pain
radiating to back, jaundice, gastric
obstruction, sometimes pancreatic
insufficiency signs
Curative surgery is treatment, but is
rarely positive, chemotherapy or
palliative surgery are options—poor
prognosis
dx. ERCP double duct sign
Colon cancer via endoscopy.
Familial Causes
FH increases risk (more relatives and closer they are the
higher the risk)
Cell of Origin
Histopathology
N/A to objective
Hereditary pancreatitis and some
individuals more susceptible to
pancreatic cancer
Ductal Cells**Know this
PaPh Assessment 8 Professor Hints
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Lecture 7: Mucosal peptic disorders: risk factors for ulcer ds and gastritis, protective mechanisms of gastric
mucosa,
Risk factors for ulcer ds and gastritis: Alcohol (decreased GSH), H. Pyori, Increased acid secretion (Zollinger
Ellison), NSAIDS
Protective mechanisms of gastric mucosa: PGE turns off acid secretion, also increases surfactant (dipalmityl
phophatidyl choline which makes the surface more “wettable” protects against protons via a diffusion barrier).
PGE also increases blood flow.
Lecture 8: Ischemic and vascular disorders:
Ischemia: etiology, features of different causes
Bleeding: differential diagnosis of upper and lower gi bleeding, clinical features, epidemiology
Type of Ischemia
Presentation
Acute Mesenteric
Ischemia
Early SEVERE
abdominal pain, not
always blood in
stool, ileus is a late
manifestation, no
tenderness early
Chronic Ischemia
Mild pain, blood in
stools, tenderness is
present, Ileus is a
late manifestation
Pain after eating,
due to
atherosclerosis of 2
/3 main splanchinc
vessels (celiac trunk,
SMA, IMA)
Age>60
Association
Dx.
Ischemic Colitis
Colonoscopy
Angiography
Venous Mesenteric
Ischemia
Presentation in
several days
Hypercoaguable
state**
Angiography
Bleeding:
Diff dx.:
Upper GI: peptic ulcer, gastritis, tumors, vascular malformation, esophagitis, varices
Lower GI: Diverticulosis and Angiodysplasia (acute), hemorrhoids and neoplasia (chronic)
Clinical Features:
Melena: black, tarry, loose, malodorous stool is caused by degraded blood in intestines usually indicates upper GI
bleed,
Hematochezia is bright blood usually from rectum, indicates a lower GI bleed unless there is a massive hemorrhage
in the upper GI
Epidemiology:
Upper GI: Most frequent, more common in men and elderly, 80% of upper GI bleeding is self limited, poor
prognosis with recurrent bleeding
PaPh Assessment 8 Professor Hints
Lower GI: Angiodysplasia usually on R . side of colon (>70 yr of age for most patients), Colonic diverticula have an
increased risk of bleeding after each occurrence
Note: remember gastrin, CCK, and secretin are vasodilators, area most susceptible to infarction is top of villus, must
rule out cancer with occult bleeding (especially with anemia)**
Lecture 9: Malabsorption: Know pathophys of various malabsorption syndromes – whom to suspect of
having steatorrhea, diagnostic studies to consider, causes of intestinal cell dysfunction
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Whom to expect of having steatorrhea: Unexplained wt. loss, stools suggesting steatorrhea (fat),
development of osteomalacia (vit. D def.), easy bruising (vit. K), Iron deficiency anemia not due to blood
loss, adult lactose insufficiency, Gastric surgery
o Recall that with fat malabsorption you lose fat soluble vitamins (ADEK) explains a lot of the
symptoms
o Steatorrhea is defined as >5% of dietary fat in feces
Diagnostic Studies to consider:
o Chemical Fat balance
o D-xylose absorption
o Secretin test:
 Causes pancreas to elaborate fluid and bicarbonate
 Tube is placed in duodenum to measure pancreatic volume expelled after a standard
secretin dose
 Basically tells you if the problem is in the pancreas or not
o X-Ray evaluation (barium, CT, flat plate of abdomen)
 Helpful in determining pancreatic calcifications (XR)
 Barium can help with diagnosing diverticular disease
o Hydrogen breath test (H.Pylori)
o Aspiration of duodenal contents for Giardia and quantitative culture
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PaPh Assessment 8 Professor Hints
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Know: Pancreatic insufficiency causes most cases of steatorrhea
Malabsorption
Syndromes
Presentations & Pathophysiology
Basically can be caused by lipase insufficiency or a solubilzation problem
o
Intra-luminal
stage
o
Lipase Insufficiency
 This can be due to chronic pancreatitis, Zollinger Ellison syndrome,
Post gastrectomy (billroth tube bypasses duodenumless pancreatic
stimulation), Cystic Fibrosisclogs pancreatic ducts
Solubilization problem
 Bile acid insufficiency
 Terminal ileectomy, bacterial overgrowth, reduced CCK
release
 All of these can cause bile acid insufficiency
Basically anything that can cause intestinal cell dysfunction
o
o
Celiac disease, Lactose (disaccharidase) deficiency, stasis syndrome, Whipple’s
disease, intestinal ischemia, radiation, tropical sprue, genetic disorders,
anderson’s disease (chylomicron retention disease), Abetalipoproteinemia
Celiac Sprue( Talked a lot about in class)
 Gluten Sensitive enteropathy
 Intestinal cells are immature and in a secretory state,
concentration of bile acids are reduced (dilutional effects of
secretion), absorption of many things is inhibited, cells that
produce CCK are also reducedmalabsorption
Intestinal Stage
Normal
Celiac Sprue
Basically anything that causes lymph obstruction Fat can’t be transported via lacteals
Lymphatic Stage
o
Lymphoma,Whipple’s, lymphangectasia, TB, Carcinoid tumors