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189 Cards in this Set

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  • Back
What are Paneth cells? Where do you find them?
They are secretory cells that occur in all parts of the small intestine, but are especially numerous in the ileum, at base of crypts.
They secrete bacterial lysozyme.
What are serous glands of von Ebner?
They are serous glands in underlying lamina propria of posterior tongue, that flush cellular debris from furrows.
In a taste bud, there are 3 types of cells. Name the three cells.
1. Basal cells.
2. Support cells.
3. Sensory cells (aka taste cells).

The support and sensory cells are hard to tell apart.
What are properties of the villi in the duodenum, jejunum and ileum that help you determine which one you're looking at histologically?
• In duodenum - broader, leaf-shaped
• In Jejunum - taller, finger-shaped
• In Ileum - stubbier, club-shaped
Where do you find Brunner's glands? What do they secrete?
Submucosa of duodenum.
Secrete mucus.
What are plicae? Where are they found?
Plicae are massive macroscopic circular folds in the mucus membrane, especially prevalent in the small intestine.
What is unique about the colon's muscularis externa, as compared to the rest of the GI tract's muscularis mucosa?
The outer longitudinal layer of smooth muscle is organized into three equidistant bands known as teniae coli.
What is another name for the line that separates the ano-rectal junction?
Pectinate line.
What are circumanal glands?
In the rectum, there are short tubular glands which are invaginations of the surface.
What is the specific embryological origin of the liver parenchyma (ie. hepatocytes)?
Foregut endoderm, from the hepatic diverticulum.
What is the embryological derivation of the liver's stroma?
Mesenchyme of septum transversum.
What percentage of blood to the liver comes from the portal vein, and what percentage comes from the hepatic artery?
Portal vein brings 75% of the blood supply. Hepatic artery brings 25%.
What is the space of Disse?
It is the space between a hepatocyte, and the adjacent sinusoidal vein.
What are Kupffer cells?
Macrophages that line hepatic sinusoids.
What are the layers of the gall bladder called?
What enzymes is the middle layer responsive to?
Mucosa
Muscularis - responsive to CCK/pancreozymin.
Serosa/adventitia
What is this?
Bile ductule.
Name the circled structure.
Bile canaliculus.
What kind of papillae is found in the posterior tongue?
Circumvallate papillae.
Is the parotid gland a serous gland, seromucous gland, or a mucous gland?
How about the submandibular gland?
How about the sublingual gland?
Parotid gland - totally serous.
Submandibular - mostly serous, partially mucous.
Sublingual - mostly mucous, partially serous.
What is the lifespan of a hepatocyte?
20 weeks.
In alcoholic hepatitis, what do you expect the ALT and AST ratios to be?
AST:ALT 2:1
Which forms of the hepatitis virus can cause acute attacks, and which ones can cause chronic attacks?
Acute: A, B
Chronic: B, C
What are the markers of cholestasis?
What other conditions can cause elevation of these enzymes?
ALP - also get elevated in bone disease such as Paget, bone metastases, osteomalacia.

GGT (gamma glutamyl transpeptidase) - gets elevated in excessive alcohol consumption, or therapy with phenytoin.
What is the pathogenesis of hepatic encephalopathy? What is the treatment?
* Increased GABA activity
* Hyperammonemia from gut
* False neurotransmitters.

The treatment is lactulose. This acidifies stools, which traps ammonia as ammonium, and gets excreted.
What tests are used to screen for hepatocellular carcinoma in patients with chronic HBV?
* AFP
* Abdominal ultrasound.

Done yearly.
What is the treatment for acetaminophen overdose?
N-acetylcysteine infusion, started within 10 hours of acetaminophen ingestion.
It restores hepatic glutathione.
What is the differences between primary biliary cirrhosis and primary sclerosing cholangitis?
What are the different diagnostic tests done to diagnose them?
PBC:
* lymphocytic destruction of interlobular bile ducts.
* Dx with anti-mitochondrial antibody.

PSC:
* Inflammation, fibrosis and stricturing of larger intra and extrahepatic bile ducts.
* 75% are associated with IBD.
* Dx with ANCA.
What is Wilson's disease?
Autosomal recessive mutation in copper excretion ATPase that normally transports Cu into bile.
Diagnose: low ceruloplasmin levels, increased urinary copper excretion, or high liver copper.
Treatment: chelation with penicillamine p.o.
What are the three subtypes of colon adenomas?
Name them from best prognosis to worst prognosis in terms of progressing into carcinoma.
* Tubular adenoma
* Tubulovillous adenoma
* Villous adenoma
What is the treatment for hepatocellular carcinoma?
Surgical resection. If there is already underlying liver disease, you may want to preserve liver by using local ablation (radiofrequency or alcohol injection), or chemoembolization.
Otherwise, liver transplant.

Note that systemic chemotherapy has poor results.
What is the treatment for cholangiocarcinoma?
Surgical resection.
Palliative: stenting or biliary bypass.

Note that systemic chemotherapy has poor results.
Can you use radiotherapy on liver cancers?
No. The liver does not tolerate radiotherapy.
What is the treatment for metastatic cancers in the liver?
Surgical resection.
Systemic chemotherapy.
What are the main branches of the celiac trunk?
Left gastric artery
Splenic artery
-> L. gastro-omental a.
Common hepatic artery
-> gastroduodenal a.
--> R. gastro-omental a.
-> R. gastric
-> Hepatic proper
--> L. hepatic a.
--> R. hepatic a.
---> Cystic a.
What are the risk factors for developing NASH (non-alcoholic steatohepatitis)?
Obesity, diabetes, hyperlipidemia.
The mechanism is insulin resistance.
Where does a direct inguinal hernia herniate to?
Medial to the inferior epigastric vessels, which are medial to the deep inguinal canal.
What are the parts of the duodenum?
What are the related parts to each section?
Superior part (1st part) - related to gall bladder.
Descending part (2nd part) - has the minor duodenal papilla, and the major duodenal papilla.
Inferior part (3rd part) - related to the superior mesenteric vessels.
Ascending part (4th part) - has no related structures.
What are the contents of the hepatoduodenal ligament?
* Portal vein
* Hepatic artery proper
* Common bile duct
Name the components that make up the H on the posterior surface of the liver.
What does the splenic vein drain into?
What vein drains into the splenic vein?
Splenic vein drains into the portal vein.
The inferior mesenteric vein drains into the splenic vein.
What is the boundary between the midgut and hindgut?
Right 2/3 of the transverse colon is midgut. Left 1/3 is hindgut.
What is the boundary between the foregut and midgut?
The major duodenal papilla, which is the opening of the hepatopancreatic ampulla.
What are 7 differences between the jejunum and ileum?
Walls - jejunum is thicker and more vascular.
Lumen - jejunum is wider.
Fat - jejunum has less fat in the mesentery.
Arterial arcades - jejunum has only 1 level. Ileum has multiple levels of arcades.
Vasa recta - they are longer and fewer in jejunum.
Circum mucosal folds - large, tall and closely packed in jejunum.
Peyer's patches - in the lamina propria of the ileum and lower jejunum.
What are the levels of the celiac trunk, SMA, IMA?
T12, L1, L3 respectively.
What is the sympathetic innervation of the foregut, midgut and hindgut?
How about parasympathetic?
Sympathetic:
* foregut - greater splanchnic (T5-9)
* midgut - lesser splanchnic (T10-11)
* hindgut - least splanchnic + lumbar splanchic (T12 + L1)

Parasympathetic:
* foregut - vagus
* midgut - vagus
* hindgut - S2-4
What general age group (young or old people) does duodenal ulcers happen in?
How about gastric ulcers?
Duodenal ulcers - young people. Caused by hyperacidity and H. pylori.
Gastric ulcers - old people. Not caused by hyperacidity.
Name the 3 types of gastric carcinoma, in order of prevalence (highest prevalence to lowest).
ICD
* Intestinal carcinoma - 50%
* Cardia cancer - 38%
* Diffuse carcinoma - 12%
If you see a signet ring cell histologically in a gastric biopsy, which type of gastric carcinoma is implicated?
Diffuse gastric carcinoma
What are the two main causes of peptic ulcers?
H. pylori (found in 75% of gastric ulcers, 90% of duodenal ulcers)

NSAID use.
What organisms can cause bloody diarrhea?
SSCCEYE
Salmonella
Shigella
Clostridium difficile
Campylobacter
E. coli (enterohemorrhagic strain)
Yersinia
Entamoeba histolytica
Congenital omphalocele
Failure of intestinal midgut loop to return to abdominal cavity. Loop is surrounded by membranous sac formed from amnion.
Umbilical hernia
After returning to the abdomen, the intestines herniate again through umbilicus. The intestines are covered by all layers of the abdominal wall.
Gastroschisis
Due to incomplete closure of the lateral folds during 4th week, the abdominal viscera protrude into amniotic cavity.
Non-rotation of midgut
Results in left sided colon.
Complications of reversed rotation of the midgut
Duodenum is anterior to SMA, transverse colon is posterior to SMA. Transverse colon may be obstructed from pressure of SMA.
Ileal or Meckel Diverticulum
Proximal portion of yolk stalk remains. Can become inflamed. May also contain stomach or pancreatic tissue.
Umbilicoileal (Omphaloenteric) fistula
Persistence of entire intra-abdominal yolk stalk
Duplication of intestine
Improper recanalization causes cystic or tubular duplication.
Name 3 antacids
Magnesium hydroxide
Aluminum hydroxide
Calcium carbonate
MOA of antacids
Act locally in stomach by reacting with H+ to increase pH
Pharmacokinetics of antacids
Ca, Mg and Al may chelate other drugs, so ideally do not give with other drugs that are absorbed systemically, or separate by at least 2 hours.
Indications for antacids
Heartburn, dyspepsia
Contraindications for antacids
None
Side effects of antacids
Mg - diarrhea
Ca - hypercalcemia, bloating, belching, flatulence, nausea, constipation.
Al - hypophosphatemia, constipation.
Name 1 H2 antagonist
Ranitidine (Zantac)
MOA of H2 antagonist
Binds to H2-receptors on parietal cells to inhibit both basal and meal-stimulated release of acid.
Nocturnal acid secretion is heavily dependent on histamine, so H2 antagonists have a greater impact on nocturnal acid secretion than on meal-stimulated acid secretion, which is stimulated by H2, gastrin and ACh.
Pharmacokinetics of H2 antagonist
po, iv, and im forms are available.
Excreted by kidneys, both by filtration and renal tubular secretion.
Cimetidine inhibits CYP450 1A2, 2C9, 2D6, and 3A4, so drug interactions are very common with cimetidine.
Indications for H2 antagonist
GERD, PUD, dyspepsia, prevention of bleeding from stress-related gastritis.
Contraindications of H2 antagonist
None
Side effects of H2 antagonist
Common: diarrhea, headache, drowsiness, fatigue, muscle pain, constipation.
Rare CNS: confusion, delirium, hallucinations, slurred speech.
Rare blood dyscrasias: thrombocytopenia

Cimetidine only: gynecomastia and galactorrhea.
What are some drawbacks to using H2 antagonist as opposed to PPI?
Tolerance can develop as early as 3 days after initiation of therapy.
Not as effective as PPI.
Name 1 proton pump inhibitor (PPI)
Omeprazole (Losec)
MOA of PPI
PPI's enter parietal cell and bind to the H+/K+ pump, irreversibly. Since the binding is irreversible, the effects persist until new pumps are synthesized. The reduction in acid secretion can persist for up to 48 hours after a single dose.
Pharmacokinetics of PPI
(area of absorption, how it is activated, how it should be administered, clearance, drug interactions, and pharmacogenomics)
Must be absorbed in the small intestine, because it is unstable in acidic environment.
The acidic environment of the parietal cell canaliculi activates the drug. Food intake stimulates acid, so PPIs should be taken 30-60 mins before a meal.
Cleared by hepatic metabolism.
Metabolized by CYP450. Only omeprazole is both an inhibitor and inducer.
By reducing pH, PPIs may interfere with absorption of drugs that require an acidic environment, such as vit B12, ampicillin esters, and ketoconazole.
Pharmacogenomics: asians are more likely to have slow CYP2C19, so this may lead to increased toxicity.
Indications for PPI
PUD, GERD, hypersecretory conditions (Zollinger-Ellison syndrome), NSAID-induced gastric ulcers.
Contraindications of PPI
None of significance
Side effects of PPI
GI (common): nausea, abdominal pain, constipation, diarrhea, flatulence.
Less common: hypergastrinemia, due to chronic gastric acid suppression.
What is a concern that some pharmacologists have regarding the long term use of PPIs?
Hypergastrinemia may cause stomach cancer.
GI cytoprotectants - name 1 prostaglandin analogue, and 2 coating agents.
Misoprostol
Sucralfate and Bismuth
MOA of misoprostol
Endogenous PGE-2 binds to EP3 receptors in parietal cells, and inhibits the proton pump, reducing acid secretion. It also stimulates mucus and bicarb secretion, and enhances mucosal blood flow.
PGE-1 analogues are given as adjuncts to NSAID therapy to replace PGE lost from COX-1 being blocked by NSAIDs.
MOA of coating agents
Sucralfate
* negatively charged paste binds to positively charged proteins in ulcer, forming barrier for 6 hours.
* also stimulates mucus and bicarb secretion.

Bismuth
* forms protective barrier on ulcer
* enhances secretion of mucus and bicarb through prostaglandins
* inhibits the growth of H. pylori and prevents H. pylori from adhering to mucosa.
Pharmacokinetics of misoprostol
* short half-life, must be admin'd 3-4 x daily.
Pharmacokinetics of sucralfate (excretion, frequency of administration, drug interactions, how to take)
* minimal GI absorption, excreted in feces.
* contains Al, which is eliminated renally. So patients with chronic renal failure must be cautioned.
* reduces absorption of digoxin, fluoroquinolones, warfarin, and phenytoin. Binds these agents in the GI tract. Need to separate doses by at least 2 hours.
* should not be taken within 30 minutes of antacid, since it requires acidic environment to be activated.
* take 1 hour before meals because it requires acid to activate.
Indications for prostaglandin analogues
* prevention of NSAID induced gastric ulcer.
* obs/gyne - induction of labor, termination of intrauterine pregnancy, evacuation of uterus in cases of fetal/embryonic death.
Indications for coating agents
Sucralfate
* treatment of PUD
* prevention of DU recurrence

Bismuth
* adjunctive therapy in H. pylori eradication.
* acute diarrhea.
Contraindications for misoprostol
Pregnancy. It stimulates uterine contractions.
Contraindications for bismuth subsalicylate
Higher risk of Reye's syndrome in children. Therefore, must be avoided in children or teens with viral infections such as influenza or chicken pox.
People with allergy to ASA.
Side effects of misoprostol
Diarrhea, abdominal cramping.
Uterine contractions.
Side effects of sucralfate
Constipation occurs rarely, due to Al content.
Side effects of bismuth
Black tarry stools (due to reaction with hydrogen sulfide).
Constipation
Tinnitis (at high doses, due to salicylate content)
Name 2 prokinetics
metoclopramide, domperidone
MOA of prokinetics
What is the difference between metoclopramide and domperidone?
They are D2 (dopamine) receptor antagonists.
Increase LES tone.
Causes contraction in the antrum and small intestine. No effect in lower GI.
Act as anti-nauseants by central inhibition of vomiting centre (chemoreceptor trigger zone).

Metaclopramide is more complex than domperidone. It also is a 5HT-4 agonist, and 5HT-3 antagonist, and may sensitize muscarinic receptors on smooth muscle. Domperidone is exclusively a D2-antagonist.
Pharmacokinetics of metoclopramide
(admin forms, metabolism, effects on other drug absorption, toxicity)
Available in po, iv, and im.
Rapidly absorbed, half-life of 4-6h, with duration of action of 1-2h.
Hepatic metabolism, excreted in urine.
Decreases absorption of drugs in stomach, but increases absorption in small intestine, due to prokinetic effect in UGI.
Toxic in overdose, due to oxidation of hemoglibin to methemoglobin. Sign/symptomes include cyanosis, nausea, vomiting, vertigo, tachycardia, tachypnea, convulsions, coma and death.
Pharmacokinetics of domperidone
(bioavailability, when to take, metabolism, CNS penetration)
Rapidly absorbed, but low oral bioavailability unless taken with food.
Must be taken 15-30 mins before eating.
Metabolized by CYP3A4 enzyme.
PGP pump pay be responsible for low CNS penetration, so PGP inhibitors such as cyclosporine and verapamil may facilitate CNS penetration.
Indications for prokinetics
Nausea, vomiting.
GERD
Gastroparesis
Diagnostic procedures
Intestinal intubation, contrast radiography of the GIT
Contraindications for prokinetics
Situations where stimulation of GI motility may be harmful - GI hemorrhage, obstruction, perforation.
Side effects of metoclopramide
Hyperprolactinemia (leading to galactorrhea, gynecomastia, dysmenorrhea).
Extrapyramidal - dystonias (acute), Parkinson-like symptoms (reversible), Tardive dyskinesia (not reversible)

CNS: drowsiness, restlessness, insomnia, anxiety, agitation.
Rare: methemoglobinemia in premature and full term neonates.
Side effects of domperidone
Hyperprolactinemia (leading to galactorrhea, gynecomastia, dysmenorrhea).
Why does domperidone not have the CNS side effects that metoclopramide has?
Domperidone does not cross the BBB as readily as metoclopramide.
How do slow waves occur in the GI smooth muscle?
How long does each last?
Are they more frequent in stomach or duodenum?
Inward voltage dependent Ca2+ channels.
Outward Ca2+ dependent K+ channels.

1-4 seconds each.

More frequent in duodenum.
* 3 cycles per min in stomach.
* 12 cycles per min in duodenum.
What are interstitial cells of Cajal?
They are the pacemakers of the slow waves in the GI system.
Located between the longitudinal and circular muscle layers.
Morphologically similar to fibroblast and smooth muscle cells.
Is the frequency of rhythmic segmentation greater in the upper or lower intestine?
The frequency is higher in upper intestine.
What are two neural pathways involved in peristalsis?
1. Peristaltic nerve reflex
- bolus causes distension.
- contraction of proximal muscles, coupled with relaxation in distal GI.

2. Migrating motor complex
- occurs during fasting.
- moves residual material in stomach and intestines aborally.
- motilin and ghrelin.
What is the difference between primary and secondary peristalsis of the esophagus?
Primary Peristalsis
1. Striated muscles are controlled by vagal somatic nerves
2. Smooth muscles are controlled by vagal parasympathetic nerves synapsing with myenteric plexus.
3. Does not require afferent impulses from esophagus.

Secondary peristalsis
1. If primary peristalsis is insufficient, distension initiates secondary wave.
2. Involves extrinsic innervation initiated in upper esophagus.
3. Only involves the smooth muscle, so only the dorsal motor nucleus of the vagus is involved.
Is the pressure in the body of the esophagus normally higher or lower than in the stomach?
Lower.
That is why you need the lower esophageal sphincter there to prevent reflux.
How many ml are there per day in:
- oral intake?
- salivary secretions?
- bile secretions?
- gastric secretions?
- pancreatic secretions?
- intestine secretions?

How much of this is absorbed?
Oral intake: 2000 ml
Salivary: 1500 ml
Bile: 500 ml
Stomach: 2500 ml
Pancreatic: 1500 ml
Intestine: 1000 ml
Total of 7000 ml endogenous secretions + 2000 ml oral intake = 9000 L.

The total amount absorbed by the intestined is 8800 ml.
- duodenum/jejunum absorbs 5500 ml
- ileum: 2000 ml
- colon/rectum: 1300 ml
What are stimulants for acid secretion on the parietal cell?
Gastrin, via CCK-B receptor.
Histamine, via H2 receptor.
Acetylcholine, via the muscarinic receptor.
Trace the path of a vago-vagal response in the stomach.
- Stretch receptor in the stomach
- vagus afferent
- nodose ganglion
- interneuron in the brain
- DMV vagus efferent
- enteric nervous system intrinsic neuron.
What happens in the intestinal phase of gastric secretion?
Amino acids in the duodenum stimulates acid secretion in the stomach.
What kicks off the inhibitory gastric phase of gastric secretions?
How is it mediated?
When food leaves stomach, and pH drops below 3.0

Somatostatin is released by D cells, which inhibits gastrin secretion.
What kicks off the inhibitory intestinal phase of gastric secretions?
When the duodenum and jejunum receive:
- low pH of 2.5 or less
- hypertonic sugar and salt solutions
- products of fat digestion
What is the enterogastric reflex? How is it mediated?
It is part of the inhibitor intestinal phase of gastric secretion.

Entry of chyme into the duodenum activates neural reflex, mediated via the celiac ganglion. It inhibits acid, pepsin, and gastrin secretion in the stomach, as well as gastric emptying.
What is the mechanism by which H. pylori causes ulcers?
1. CagA and VacA induced epithelial cell damage.

2. Induction of local Immune responses and cytokine secretion

3. Gastrin and gastric acid secretion is increased due to cytokines, decreased somatostatin secretion, and local alkaline environment due to urea breakdown.
What are the gastrointestinal "alarm symptoms" that make you think of malignancy?
Bleeding (GI), weight loss, anemia, dysphagia.
What is diagnostic method for H.pylori?
Urea breath test
Stool antigen
* Patient must be off PPI for 2 weeks, and off antibiotics for 4 weeks, or else they will get false negatives.
* If you receive a negative result, do test again. False negatives are common.
* Do not recommend serological IgG detection, because it will be positive in people who have resolved infections.
What is the treatment for H. pylori?
PPI (lansoprazole 30 mg bid)
Amoxicillin 1g bid
Clarithromycin 500 mg bid
for 2 weeks
What are signs of high risk for re-bleeding in an UGI bleed (in order of highest risk to lowest risk)?
Active arterial bleeding 90%
Non-bleeding vessel 50%
Adherent clot 25-30%
Oozing without vessel 10-20%
What are some differences in the symptoms of NSAID caused ulcers vs. H. pylori caused ulcers?
NSAID ulcers occur more frequently in elderly people.
They are also larger, and more likely to bleed.
What is another name for:
* main pancreatic duct?
* hepatopancreatic ampulla?
* the sphincter surrounding the hepatopancreatic ampulla?
* accessory pancreatic duct?
Main pancreatic duct = Duct of Wirsung.
Hepatopancreatic ampulla = Ampulla of Vater.
Sphincter surrounding hepatopancreatic ampulla = Sphincter of Oddi.
Accessory pancreatic duct = Duct of Santorini.
What is the parasympathetic and sympathetic innervation of the pancreas?
Parasympathetic: vagus nerve.
Sympathetic: celiac and superior mesenteric ganglia.
When the pancreas is stimulated for exocrine secretion, which ion is increased in secretion, and which one is decreased?
HCO3- is increased
Cl- is decreased
Na+ and K+ are stay the same, since they are independent of flow rate.
What are the two models of exocrine secretion in the pancreas?
In both models, secretin and CCK bind to cell receptor, and through cAMP + protein kinase A intracellular messaging, phosphorylates CFTR.

Model A
○ Carbonic anhydrase catalyzed reaction produces most of the HCO3-.
○ Process starts with H+ being exchanged with Na+.
○ Gene replacement therapy is the treatment for pancreatic insufficiency for patients with CF when using this model.

Model B
○ Na+/nHCO3- co-transporter on the blood side transports HCO3- into the cell.
○ CFTR creates +ve charge on the apical membrane, which attracts HCO3- into the cell.
○ Therapy suggested by this model is to activate the NBC (Na+/nHCO3- cotransporter) directly or via membrane depolarization.
What enzymes are activated by trypsin?
In addition to being autocatalytic, trypsin also activates:

Chymotrypsinogen
Proelastase
Procarboxypeptidase A
Procarboxypeptidase B
Procolipase
How does the pancreas prevent autodigestion?
It stores digestive enzymes as zyomogens (inactive enzymes). These enzymes are activates as they are secreted. Eg. trypsinogen is activated by brush border enzyme enterokinase.

Acinar cells produce trypsin inhibitor.

Trypsin-degrading enzymes: enzyme Y and mesotrypsin can also split cationic trypsinogen at Arg 122 if the trypsin inhibitor gets overwhelmed.
What is hereditary pancreatitis?
In hereditary pancreatitis, the cleavage point on trypsinogen is mutated (from arginine 122 into histamine 122) such that it cannot be inactivated by mesotrypsin and enzyme Y.
What phase does CCK and secretin play a role in pancreatic exocrine secretion?
What do they do?
Intestinal phase of pancreatic exocrine secretion.

CCK is stimulated by a.a. and f.a. in duodenum.
* stimulates acinar cells to secrete digestive enzymes.
* stimulates gallbladder contraction and relaxation of sphincter of Oddi.
* stimulates vago-vagal reflex to further increase acinar cell secretion.
* stimulates enterogastrone response, inhibiting gastric acid secretion.

Secretin is stimulated by pH < 4.5.
* stimulates duct cells to secrete HCO3- and water.
What things are absorbed almost exclusively in the terminal ileum?
Vitamin B12 and bile salts.
Why can't pancreatic lipase work on its own?
The fat droplets in the small intestine are coated with bile salts. These bile salts inhibit binding of the lipase. lipase needs to bind to colipase, and then the lipase-colipase complex can bind to bile salt-coated fat droplets.

Note that procolipase is activated to colipase by trypsin.
Name the monosaccharides that are important in the human diet.
Glucose
Fructose
Sorbitol
What are the brush border digestive enzymes?
Enterokinase
Maltase-glucoamylase
Sucrase-isomaltase
Lactase
Trehalase
Aminopeptidase
Dipeptidase
How do monosaccharides get absorbed from the gut across the enterocyte?
On apical membrane:
* Glucose and galatose are absorbed with SGLT1 Na+ symporter. This is coupled to a basolateral Na+/K+ pump.
* Fructose is taken up by GLUT5.

On basolateral side, glucose, galactose and fructose are all transported by GLUT2.
What sugars can be absorbed across the enterocyte?
Gut can only absorb monosaccharides. In specific: glucose, galactose, fructose.

All other sugars either have to be converted to these first, or else they can't be absorbed.
How are proteins absorbed across the enterocyte?
Apical membrane:
○ H+ dependent Pept-1 transporter: Di and tri-peptides, driven by the Na+/H+ exchanger.
○ Na+ dependent and Na+ independent a.a. transporters.
○ Some are specific for one a.a., some are non-specific.
○ Some larger peptides are absorbed into enterocyte and then broken down intracellularly.

Basolateral membrane
○ At least 5 a.a. transporters
○ Peptide transporters.
During which week of development does the midgut loop return to the abdomen?
Week 10.
What is the cloacal membrane composed of (embryological derivatives)?
Endoderm of cloaca.
Ectoderm of proctodeum.
What is the nervous supply, arterial supply, venous drainage, and lymphatic drainage of the upper 2/3 vs. lower 1/3 of the anal canal?
Upper 2/3:
* autonomic nervous system.
* superior rectal artery.
* superior rectal vein, drains into portal system.
* inferior mesenteric lymph nodes.

Lower 1/3:
* pudendal nerve (somatic S2-4).
* inferior rectal artery.
* inferior rectal vein, drains into IVC.
* inguinal lymph nodes.
What does vitamin B3 (niacin) deficiency cause?
Pellagra.
- diarrhea, dementia, dermatitis, death.
- dark patchy skin and rash on legs.
What other mineral is thiamine dependent on?
MgSO4.
What are causes of cobalamin deficiency?
1. Pernicious anemia - autoimmune antibodies to IF, or to parietal cells.
2. Pancreatic insufficiency. Pancreas secretes an enzyme that releases cobalamin from R-protein, and allows it to bind to IF.
3. Bacterial overgrowth.
4. Loss of terminal ileum site (from disease, or surgery).
What is a sensitive test for chronic pancreatitis?
CT scan.
- shows scattered calcification throughout the pancreas.
- may also show dilated pancreatic duct.

Alternatively, can do ERCP, but this is more invasive.
Where does squamous cell carcinoma of esophagus most commonly metastasize to?
Trachea, bronchi, lungs.
What is the prevalence of celiac disease in North America?
What kind of food can they not eat?
About 1 in 200 people.

Anything that contains gliadin:
* Barley
* Rye
* Oat
* Wheat
What test do you order to find out if there is fat malabsorption?
Sudan III stain.
- quantitative examination of the stool for undigested muscle fibers, neutral and split fats.
- a simple screen for steatorrhea.
What is the treatment for chronic pancreatitis?
- Stop alcohol consumption.
- Pancreatic enzyme replacement.
- Analgesics for pain.
What is the most common cause of acute pancreatitis and chronic pancreatitis?
Acute pancreatitis:
- alcohol and gallstones

Chronic pancreatitis:
- alcohol accounts for 75% of cases
- gallstones almost never cause chronic pancreatitis.
Complications of H. pylori gastritis.
Specific to H. pylori gastritis:
Lymphoma and carcinoma of the stomach.

For all gastritis:
Hemorrhage
Gastric outlet obstruction
Perforation
Gastroduodenal fistula
What are possible complications of untreated Celiac disease?
GI lymphoma and adenocarcinoma.
Why is colectomy, with pouch reconstruction done for UC, but less often for Crohn's?
Because in Crohn's disease, there is a high rate of recurrence in the pouch.
What is the maximum absorptive capacity of the small intestines?

What is the maximum absorptive capacity of the large intestines?
12 L

4-6 L
What is the mechanism of Na+ transport in the...
duodenum?
jejunum/ileum?
ileum/colon?
distal colon/rectum?

Which one is most important post-prandially?
Which one is most important during interdigestive period?
Duodenum: no absorption.

Jejunum/ileum:
- Nutrient coupled Na+ symporter. Glucose, galactose and a.a. are the nutrients.
- Na+, H+ exchanger.

Ileum/colon:
- Na+/Cl- neutral absorption. This is achieved via Na+/H+ exchanger coupled to Cl-/HCO3- exchanger.

Distal colon/rectum: Na+ channels.

Postpradial - nutrient coupled Na+ symporter in jejunum/ileum.

Interdigestive - neutral NaCl absorption in ileum/colon
What is the ultimate driving force for Na+ entry into the enterocyte from the lumen of the gut, in all mechanisms of Na+ absorption?
Low intracellular Na+, driven by the basolateral Na+, K+ ATPase.
What inhibits the neutral NaCl absorption in the ileum/colon?
Aldosterone, cAMP, cGMP, Ca2+.
What stimulates Na+ channels in the distal colon/rectum?
What inhibits them?
Aldosterone stimulated the Na+ channels in the distal colon/rectum.
Amiloride inhibits them.
List the methods that water gets across the enterocyte's apical membrane.
List the way that water gets across the basolateral membrane.
Apical membrane:
1. Diffusion.
2. Aquaporins.
3. Co-transported with solutes, such as Na+ and glucose. SGLT1 transporter can transport 260 H2O with every 2 Na+ and 1 glucose.

Basolateral membrane:
GLUT2
How is chloride absorbed across the enterocyte?
Jejunum:
Passively through Cl- channels, in association with Na+/H+ exchangers.

Ileum/colon:
Neutral NaCl absorption.
What is the mechanism of fluid secretion in the..
- duodenum?
- ileum/jejunum?
Duodenum:
- Cl-/HCO3- exchanger.

Jejunum/ileum
- Cl- channels in the apical membrane
- Na+/K+/Cl- channels in the basolateral membrane, coupled to Na+, K+ ATPase.
Definition of diarrhea in terms of stool amount and water content.
> 200 g / day
and 70-90% water.
What are the broad categories of diarrhea causes, and give examples of each.
1. Decreased absorption of fluids or electrolytes.
- inhibited ion transport system (Heat stable E. coli toxin)
- defective ion transporter (congenital Na+/glucose symporter)
- osmotically active agents in lumen (lactase deficiency)
- increased propulsive activity (hyperthyroid, IBS)

2. Increased secretion of fluids or electrolytes.
- bacterial toxin (cholera enterotoxin)
- neuroendocrine tumor (carcinoids, VIPoma, gastrinoma)
- inflammation induced (IBD, salmonella, shigella)
- secretion from hyperplastic crypts (celiac disease)
What hormones/molecules are stimulatory on anion secretion, causing secretory diarrhea?
Ca2+, cAMP, VIP.
What hormones/molecules are inhibitory on neutral NaCl absorption, causing osmotic diarrhea?
cGMP
How does heat stable E. coli cause diarrhea?
It causes malabsorptive diarrhea.
The toxin binds to guanylyl cyclase, which results in increased intracellular cGMP. cGMP is an inhibitor of neutral NaCl absorption.
How does Vibrio cholera cause diarrhea?
Cholera toxin causes secretory diarrhea.
It has 1 A-subunit, and 5 B-subunits.
The A-subunit is the active component. It enters the cell, and ribosylates Gs protein which is associated with adenylyl cyclase. This increases cAMP.
cAMP stimulates Cl- secretion.
It also inhibits neutral NaCl absorption to some extent.

Note that nutrient-coupled Na+ absorption is still functional, and is a target for therapy by giving Na+ and glucose.
Which carcinoid tumor hormones cause secretory diarrhea by increasing iCa2+?
Which ones cause secretory diarrhea by increasing cAMP?
Hormones that increase iCa2+:
- serotonin
- substance P
- bradykinin
- neurotensin

Hormones that increase cAMP:
- prostaglandin
What is a VIPoma?
How does VIPoma cause diarrhea?
AKA Verner-Morrison syndrome.

Islet cell pancreatic tumor that produces VIP.

It causes secretory diarrhea. VIP stimulates cAMP, which increases anion secretion.
It also causes hypokalemia, and hypochlorhydria.
How does inflammatory bowel disease cause diarrhea?
It causes both secretive and malabsorptive diarrhea.

- Neutrophils release signal molecules that stimulate secretion and inhibit NaCl absorption.
- Mucosal destruction and increased vascular permeability allows transudation of plasma, and back-diffusion of water an electrolytes.
- Loss of mucosa causes malabsorption.
What is another name for a gastrinoma?
What is a gastrinoma?
Zollinger-Ellison syndrome.

Pancreatic and duodenal tumors that secrete gastrin.

Causes secretory diarrhea by:

- Increasing fluid volume entering intestine.
- Increasing duodenal secretions.
- Causing steatorrhea by inactivating lipase with low pH, precepitation of bile salts, and damage to mucosa.
What are the possible reasons that a bowel segment is dilated on imaging?
- Infarction
- Ileus
- Obstruction
- Malabsorption
What is the most common cause of small bowel infarction?
Non-occlusive mesenteric ischemia.
- this means vascular collapse due to cardiac arrest or prolonged hypotension.
What is a benign cause of intraperitoneal free air?
Pneumatosis intestinalis - air in bowel wall that breaks into the peritoneal cavity.
What is a contraindication for water-soluble contrast agents?
They are unsafe in lungs. They are hypertonic, and therefore cause pulmonary edema.
So do not use if there is a risk of aspiration into lungs.
What is enteroclysis?
A form of radiological imaging.
It is a small bowel enema.
- Transnasal catheter inserted down to proximal jejunum.
- Ballon inflated.
- Barium pumped in.
- Radiographs taken.
- Invasive procedure, and has largely been replaced by CT/MRI.
What is the most common sign on imaging that a bowel is infarcted?
Dilation is the most common sign.
A less common sign is air within the bowel wall, mesenteric and portal veins.
What serological markers can be helpful in diagnosing Crohn disease and UC?
Crohn disease: ASCA
UC: pANCA
Diagnosis of celiac sprue.
Serology: TTG Iga, EMA Iga.
- can tell you which patients to do biopsy on.

Biopsy is the definitive test.
Which part of the bowel is most commonly involved in diverticular disease?
Sigmoid colon is involved in 90% of the cases.
Which portion of the colon does colon cancer most often affect?
75% of colon cancers occur in the rectum or sigmoid colon.
Following colon cancer surgery, what are the tests for follow-up?
Serum CEA q3m for 2 years
Abdominal US q6m for 2 years
Yearly colonoscopy for 3 years, and then every 5 years if no polyps.
What is the treatment for diverticular disease?
High fiber diet.
If diverticulitis, then antibiotics, abscess drainage, surgical resection.
In ulcerative colitis, what do you expect values of serum albumin, electrolytes and pH to be?
- Hypoalbuminemia, due to loss in stool, and low intake of protein.
- Low K+, Mg2+, Ca2+
- Metabolic acidosis
How much of the bilirubin excreted into the small intestine is actually excreted in feces, and how much is reabsorbed?
When it reaches distal ileum / colon, it gets metabolized by flora into urobilinogens.

80% is excreted in feces.

20% gets reabsorbed into portal system.
- 90% of this is excreted again into bile.
- 10% of this is excreted in urine.
Embryologically, the main pancreatic duct is composed of which parts of the ventral and dorsal buds?
The ventral bud, and the distal portion of the dorsal bud compose the main pancreatic duct.
What are bile salts composed of?
Cholesterol conjugated to glycine or taurine.
What are causes of ALT/AST > 5000 IU/L?
Usually due to drug toxicity, or ischemia.

Very uncommon to have such high ALT/AST in viral hepatitis.
What is hepatorenal syndrome?
Patients with chronic liver disease can develop renal failure.

Pathogenesis:
- increased NO causes splanchnic vasodilation.
- this causes underfilling of arterial circulation, which causes RAS and SNS to be activated.
- vasoconstriction of peripheral vasculature, and renal circulation.
- decreased GFR.
What are the chances of a healthy adult who gets infected with HBV becoming a chronic carrier?
1-5% risk.
Neonates, on the other hand, have nearly a 100% risk of becoming chronic HBV carriers.
What is the serology of someone who has been exposed to HBV, but has no active disease?
HBsAg negative.
HBeAg, HBV-DNA negative.
Anti-HBcAg positive.
Anti-HBsAg positive.
What is the chance of becoming a chronic HCV carrier once infected?
About 80%.
Diagnosis of autoimmune hepatitis.
Elevated ALT, AST.
Increased IgG.
Biopsy shows interface hepatitis.
Serology:
- type 1 autoimmune hepatitis: ANA and ASMA.
- type 2 autoimmune hepatitis: anti-LKM-1
After a needle prick from an anti-HCV positive patient, what is the chance for seroconversion?
2% chance.