T/F. All veins of the esophagus drain into the portal system.
F. above diaphragm - drain into the SVC; distal esophagus - portal-caval anastomoses
Above the diaphragm, lymph to the esophagus drains mainly into which of the following: (cervical/celiac/gastric/posterior mediastinal/tracheo-bronchial) nodes.
tracheo-bronchial & posterior mediastinal nodes (but lymph drains into all of them)
What does the lesser omentum connect?
stomach and liver
Put the following in order: (antrim/body/cardia/fundus).
cardia, fundus, body, antrim
The greater omentum connects what 2 organs?
stomach and transverse colon
The omental bursa is located where?
posterior to the stomach
The stomach receives a rich arterial supply from the (celiac/superior mesenteric/inferior mesenteric) artery.
T/F. The duodenum is intraperitoneal.
The duodenum is supplied by which of the following: (celiac/superior mesenteric/inferior mesenteric) artery.
celiac and superior mesenteric
Blood from the duodenum is drained into the portal system. Which vein does it go through?
The ampulla empties into the (1st/2nd/3rd/4th) part of the duodenum.
2nd (note ampulla aka papilla)
What is the falciform ligament?
embryological connection between liver and anterior abdominal wall
What is the ligamentum teres? What is it a part of?
remnant of the umbilical vein; part of the falciform ligament
Which of the following is NOT found in the hepatoduodenal ligament: (bile duct/hepatic artery/hepatic vein/lymph nodes/portal vein)
The hepatic artery branches off the (celiac/superior mesenteric/inferior mesenteric) artery.
T/F. All lymphatic drainage of the liver goes to the celiac nodes.
F. most go to the celiac nodes, but some drains into the mediastinal lymph nodes, which are above the diaphragm
Put the following in order: gallbladder (body/cystic duct/fundus/neck)
Where does bile enter the gallbladder?
through cystic duct (same as where bile leaves)
The pancreas is (intra/retro)peritoneal.
retroperitoneal (but starts intraperitoneal in development)
The (head/tail) of the pancreas is closer to the spleen.
The pancreas is supplied by the (celiac/superior mesenteric/inferior mesenteric) artery.
celiac & superior mesenteric
T/F. The pancreas drains directly into the IVC.
F. drains into the portal vein via splenic & superior mesenteric veins
The (ileum/jejunum) is longer.
ileum (distal 3/5)
The jejunum has a (narrower/wider) lumen and (thicker/thinner) walls than the ileum.
wider lumen; thicker walls (think: it needs to work harder)
The ileum has (fewer/more) arterial arcades and a (denser/sparser) blood supply than the jejunum.
The small intestine (excluding duodenum) is supplied by the (superior/inferior) mesenteric artery.
The small intestine (excluding duodenum) is drained by the (superior/inferior) mesenteric vein.
Which parts of the large intestine are retroperitoneal?
cecum, ascending and descending colon (transverse colon is intraperitoneal, anchored to posterior wall by mesentery; sigmoid colon is also anchored by mesentery)
The superior mesenteric artery covers which parts of the large intestine?
ascending and transverse colon (up to the splenic flexure, which is a watershed area)
The inferior mesenteric artery covers which parts of the large intestine?
descending, sigmoid & proximal rectum
The (superior/middle/inferior) rectal veins drain into the IVC.
middle and inferior (superior drains into inferior mesenteric vein, which is part of the portal vein)
Which parts of the large intestine have mesentery?
transverse & sigmoid
All the lymph in the abdominal lymph vessels drain into what?
Which of the following is NOT supplied by the vagus nerve: (bladder, lungs, stomach, pancreas, liver, gall-bladder, genitals)
bladder and genitals (supplied by pelvic splanchnic nerves)
T/F. The distal 1/4 of the GI tract is supplied by the vagus nerve.
F. supplied by the pelvic splanchnic nerves
What is the difference between a direct and indirect inguinal hernia?
indirect starts lateral to inferior epigastric vessels (arise from deep inguinal ring); direct starts medial to inferior epigastric vessels
With a (direct/indirect) inguinal hernia you're not going to get bowel getting blocked.
What are the 4 layers of the tubular GI tract?
mucosa, submucosa, muscularis propria, adventitia/serosa
T/F. Metaplasia is irreversible.
F. is reversible
T/F. Chronic inflammation should be present in the small bowel and colon.
What are the 3 layers of the mucosa?
epithelium, lamina propria, muscularis mucosa
Meissner's plexus can be found in the (mucosa/submocosa/muscularis propria/adventitia).
submucosa (ganglion cell is a neuron outside of the CNS)
Loose connective tissue (fibroblasts, lymphatics, blood vessels) can be found in the (mucosa/submocosa/muscularis propria/adventitia).
Benign glands can be found in the submocosa in the _____ and _____ (parts of the GI tract) only.
esophagus and duodenum
Fibroblasts, lymphatics, & blood vessels can be found in the (mucosa/submocosa/muscularis propria/adventitia).
submucosa, and mucosa (in the lamina propria)
The inner muscular layer of the muscularis propria is (circular/longitudinal) smooth muscle. The outer layer is (circular/longitudinal).
inner - circular; outer - longitudinal
T/F. All parts of the digestive tract have smooth muscle, instead of skeletal.
F. upper esophagus has skeletal muscle in muscularis propria
Between the inner and outer layers of smooth muscle in the muscularis propria are nerves. What are they called?
What is the difference between adventitia and serosa?
adventitia - connective tissue that attaches to other organs (no mesothelial lining) (esophagus and rectum); serosa - connective tissue lined by mesothelium (most of tubular GI tract)
What type of epithelium covers the esophagus?
non-keratinizing squamous mucosa
What is Barrett's esophagus?
replacement of squamous epithelium with glandular epithelium, specifically intestinal goblet cells
T/F. The duodenum makes intrinsic factor for vitamin B12 absorption.
F. stomach makes it
Which of the following parts of the stomach makes acid and intrinsic factor: (antrum/body/cardia/fundus).
fundus and body
Which of the following parts of the stomach tells the body to make acid: (antrum/body/cardia/fundus).
Which of the following parts of the stomach has G cells: (antrum/body/cardia/fundus).
antrum (G cells are endocrine cells that make gastrin)
In the gastric pit (foveolae) epithelium, the mucus is (neutral/basic/acidic). Where is this epithelium found?
neutral; foveolae are found in the antrum and body and fundus
The glands of the fundus consist of parietal cells, which make _____; chief cells, which make _____; and endocrine cells, which make _____.
parietal - acid & intrinsic factor; chief - pepsin; endocrine - histamine
Endocrine cells are located in the _____ (part of stomach) and make _____ & _____.
antrum; gastrin & somatostatin
G cells are located in the _____ (part of stomach) and make _____; D-cells are located in the _____ (part of stomach) and make _____; ECL cells are located in the _____ (part of stomach) and make _____.
G - antrum - gastrin; D - antrum - somatostatin; ECL - body/fundus - histamine
What does gastrin do?
act on histamine-secreting ECL cells to make parietal cells secrete acid; (also directly tells pareital cells to make acid)
What does somatostatin do?
suppress gastrin release by G cells (tell parietal cells NOT to make acid)
What non-endocrine/non-paracrine mechanism tells the parietal cells to make acid?
vagus nerve (uses acetylcholine)
T/F. Goblet cells are a normal finding in the stomach.
F. abnormal; signals intestinal metaplasia (metaplastic atrophic gastritis)
Autoimmune metaplastic atrophic gastritis occurs in the (body/antrum), results in (increased/decreased) gastrin, (results/does not result) in pernicious anemia; (results/does not result) in ulcers).
autoimmune - body; increased gastrin; yes, pernicious anemia, no ulcers
Environmental (H. pylori) metaplastic atrophic gastritis occurs in the (body/antrum), results in (increased/decreased) gastrin, (results/does not result) in pernicious anemia; (results/does not result) in ulcers).
environmental - antrum; decreased gastrin; no pernicious anemia; yes, ulcers
Where are Brunner's glands located and what do they do?
submucosal glands in duodenum; neutralize gastric acid secretion
Circumfrential bowel lymphoid tissue can be found where? Why is this important?
ileum. can lead to intusseption during childhood infection
In Crohn's disease, what are intestinal goblet cells replaced by?
gastric mucin cells
Water is absorbed in the (proximal/distal) colon.
proximal (right-side; ascending and first half of transverse)
When are Paneth cells seen in the colon?
only in right colon (when seen in left colon, suggests chronic inflammation, Ulcerative Colitis)
Exocrine; make trypsin, lipase (acinar/islets of langerhans/ductal cells).
The (acinar/ductal/islet) cells of the pancreas are involved in pancreatic adenocarcinoma.
What is the best indicator of nutritional status?
progress in physical growth
What's the difference between the WHO and CDC growth charts?
WHO - includes more breastfed babies
The weight of the infant at 4 months is __ times that at birth. What about at 12 months?
4 months - twice; 12 months - triple
Energy requirements are highest (per unit body weight) during (infancy/childhood/adolescence).
infancy & childhood
T/F. Cow's milk is recommended for infants, instead of formula, when breast milk is not available.
F. increased risk of sensitization; increased risk of GI blood loss; poor source of iron; renal solute load is excessive
Which one of the following is NOT a disadvantage of early introduction of solid foods: (poor oral motor coordination; insufficient energy and nutrient replacement; increased risk of food allergies; increased renal solute load and hyperosmolarity; risk of underfeeding).
risk of underfeeding (there is a risk of overfeeding, due to disturbance of appetite regulation)
All table foods can be introduced to infants at what age?
Why is fruit juice not recommended for infants?
failure to thrive; obesity (when juice is added to lots of food); short stature
The peak growth velocity occurs earlier for (boys/girls). (Boys/girls) gain more fat during puberty.
Girls peak growth occurs earlier; females gain more fat during puberty
The demand for calcium is greatest during (infancy/adolescence/old-age).
A vegetarian may be deficiency in which of the following: (vitamin B6/vitamin B12/vitamin D/iron/zinc).
A lacto/lacto-ovo may be deficiency in which of the following: (vitamin B6/vitamin B12/vitamin D/iron/zinc).
iron, zinc, B6 (note: a vegan needs all of the answer options)
In an isocaloric diet for men, (saturated/unsaturated) fat is preferred, and there (are/are not) protein and carbohydrate guidelines.
unsaturated fat preferred; no specific protein/carbohydrate guidelines
What is the metabolic syndrome?
3 of 5 of the following: I Require HELP (Insulin Resistance, Hypertension, Elevated triglycerides, Low HDL, Pudgy)
What proportion of US adults are obese?
During pregnancy, women should pay attention to which key nutrients?
iron, calcium, folic acid
When menopause starts, there is a decreased need for (calcium/iron/vitamin D) and an increased need for (calcium/iron/vitamin D).
decreased iron; increased calcium & vitamin D
Calcium (carbonate/citrate) needs to be taken with food.
Older people may experience dysgeusia and xerostoma. What are they?
dysgeusia - loss of taste; xerostoma - dry mouth
Why are people over age 50 at increased risk of vitamin D deficiency?
inability of skin to synthesize and kidney to convert vitamin D
The myenteric plexus (Auerbach) lies between what?
longitudinal and circular musculature
The submucosal plexus (Meissner) lies between what?
circular musculature and submucosal musculature
T/F. Protein is broken down in to individual amino acids to be absorbed.
F. can be absorbed as di and tripeptides
Starch is (glucose/fructose/galactose). Sucrose is what? Lactose is what?
starch - glucose; sucrose - glucose + fructose; lactose - glucose + galactose
95% of the fat in our diet is in the form of what? What is it broken down into to be absorbed?
triglycerides; 2 monoglyceride & 2 free fatty acids
What digestive enzymes are present in the oropharynx?
salivary amylase & lingual lipase
How does the stomach get food into the small intestine?
amtrum squirts food against pyloric valve
What digestive enzymes are present in the stomach?
pepsin & gastric lipase (also HCl)
Where is intrinsic factor synthesized? Why is it important?
stomach; binds vitamin B12
Cells in the antrum secrete _____, which tells the corpus of the stomach to secrete more HCl.
How is the acidic contents of the stomach neutralized in the duodenum?
sphincter of oddi contains lots of NaHCO3
At what point is the content of the digestive tract isotonic?
Most of the digestion and absorbtion of nutrient is accomplished where?
How is the pH of the stuff in the duodenum regulated?
S cells in jejunum secrete secretin that regulates the amount of NaHCO3 going into duodenum
Cholecystokinin is secreted by ___ cells in the _____ and tell the pancreas to _____ and the gall bladder to _____.
secreted by I cells in the jejunum; pancreas to secrete enzymes; gall bladder to secrete bile salts
Where does the chylomicron that the enterocyte makes go?
lymph->thoracic duct->muscle & fat
What 3 enzymes digest things in the jejunum?
pancreatic enzymes; bile salts; tethered hydrolases
What 3 things are absorbed notably in the terminal ileum?
bile salts; ascorbate; B12
Which ions does the colon secrete?
K, H, NH4
Where does aldosterone affect the digestive tract? What does it do?
colon - reabsorb Na; secrete K
How is NaCl reabsorbed in the small intestine?
2 ways: 1. Na/solute cotransport; 2. Na/H and Cl/HCO3 exchange; use of carbonic anhydrase->water absorption follows
T/F. The vast majority of K ingested is absorbed.
T. 50 mmol absorbed; 8 mmol in stool (changed from previous answer: his words didn't match his slides)
Where are 4 constrictions of the esophagus?
cricoid; arch of aorta; where atrium pushes against it; diaphragm
The (mucosa/submocosa/muscularis propria/adventitia) is the source of tensile strength.
T/F. A biopsy of the esophagus sees all layers.
F. only sees mucosa
What are 3 characteristics of Plummer-Vinson syndrome? What is it?
iron deficiency anemia, glossitis, cheilosis (fissuring and dry scaling of lips and mouth); webs and rings in PROXIMAL esophagus
Iron deficiency anemia, glossitis, cheliosis. Diagnosis? What would you find in the esophagus?
Plummer-Vinson syndrome; (cheliosis is fissuring and dry scaling of lips and mouth); webs and rings in PROXIMAL esophagus
What is Schatzki's ring?
webs and rings in DISTAL esophagus
What is achalasia?
degenerative disorder of nerve in distal esophagus (last part of esophagus doesn't have peristalsis); increased tone of lower esophageal sphincter
What are secondary causes of achalasia?
trypanosomes (Chagas disease); diabetes; amyloid
In achalasia, there is (increased/decreased) tone of the lower esophageal sphincter.
increased; incomplete relaxation of LES
What is a stricture?
scar in wall of gut organ (doesn't peristalse, narrows down)
Which of the following is NOT known to cause esophagitis: (aspirin/calcium pills/fosamax/kayexalate/KCl/iron pills/NSAIDs).
calcium pills (fyi kayexalate is something to reduce K in blood; fosamax is for osteoporosis)
A suicidal man drinks lye, but is discovered early enough not to die. He will likely develop _____ and have a lifelong risk of _____.
stricturing; squamous cell carcinoma (as opposed to adenocarcinoma)
When is candida albicans seen in esophagitis in non-compromised hosts?
What are the 2 big viruses that causes esophagitis?
CMV and HSV
T/F. Cytomegalovirus esophagitis affects the epithelium.
F. only the ENDOTHELIUM - need to biopsy deeper
Punched out ulcers in esophagus. Diagnosis?
Herpes Simplex I esophagitis
T/F. HSV affects the epithelium.
T (as opposed to CMV, which affects the endothelium; think C looks like a cup->need to look at the base of the ulcer)
Multinucleated cell with smudged nucleus coming from esophageal epithelium. Diagnosis?
Reflux occurs most commonly in what demographic of people?
adult caucasian males
In gastroesophageal reflux, only the contents of the stomach are refluxed.
F. stuff in duodenum is also refluxed, in addition to pancreatic secretions
Balloon cells in esophagus. Diagnosis?
Bigger basal zone and vascular papillae that go to the top in esophagus. Diagnosis?
In Barrett's metaplasia, the squamous epithelium can be replaced by what 3 types of mucosa?
cardiac (top of stomach), oxyntic (middle of stomach), intestinal
Goblet cells in esophagus. Diagnosis?
Barrett's esophagus (goblet cells are diagnostic)
Barrett's esophagus is a precursor to what?
Esophageal (adenocarcinoma/squamous carcinoma) is more common.
adenocarcinoma (increasing in incidence) (squamous is decreasing in incidence)
Where (geographically) is squamous cell carcinoma of the esophagus common?
developing countries: China, Iran, Africa
What are predisposing factors for esophageal squamous cancer?
black males who smoke and drink (also asians who have alcohol dehydrogenase mutations and get "Asian flush")
Esophageal squamous cancer that is (higher/lower) is worse. Where is it most often?
higher b/c invade things that are dangerous to invade; msot often in middle (50%)
What is the precursor for esophageal squamous cancer?
squamous epithelial dysplasia
Pink "pearls" in cells near epithelium of esophagus. What's going on?
Keratin; esophageal squamous cancer
Lamina propria or submucosa invasion in GI locations other than in the the colon is considered (T1/T2/T3/T4). What stage is it called in the colon?
esophagus (e.g. not-colon) T1; Colon - still called in situ
What is the difference in function between peristaltic and segmental contractions?
peristaltic - push food along; segmental - mix and grind food
How are actin and myosin attached the the cell surface of a smooth muscle cell?
What is the path from Ca entry to myosin head cocking in smooth muscle?
Ca->calmodulin->myosin light chain kinase->cock head
What causes smooth muscles to contract?
slow waves, which periodically cause action potentials
T/F. Slow waves by themselves cause smooth muscle contraction.
F. needs to generate an action potential for contraction; a slow wave does not necessarily cause a contraction
What cells generate slow waves? The upstroke of slow waves consist of an influx of what?
Interstitial cells of Cajal; Calcium
Which of the following stimulates the slow rates to increase the incidence of action potentials: (acetylcholine/norepinephrine/parasympathetics/stretch/sympathetics).
acetylcholine, parasympathetics, stretch
T/F. A person who is brain-dead would have impaired GI function.
F. GI innervated by enteric nervous system; doesn't need sympathetics or parasympathetics to function
Which parts of the digestive tract have striated muscle?
pharynx and upper esophagus and external anal sphincter
The rate of contraction of the (stomach/duodenum) is faster.
duodenum (9x/min); stomach (3x/min)
Migrating motor complexes occur during (eating/fasting) and is associated with which hormone?
fasting (eating time is characterized by disorganized contractions) associated with motolin
Which antibiotic promotes migrating motor complex activity?
erythromycin - similar to motolin
How does the brain control pooping?
contract external spincter when internal sphincter relaxes to prevent pooping
Problem with solids, not liquids: (luminal stenosis/diverticular formation/paresis/sphincteric dysfunction/spastic disorders)
What is Schatzki's ring? Is it necessarily symptomatic?
esophageal stricture - looks like a thin radiotransparent ring around esophagus; not necessarily symptomatic
How do you differentiate a benign from a malignant stricture in the esophagus?
benign - smooth walls; malignant - abrupt wall - tumor protruding in
What is Zenker's diverticulum?
pouch in pharynx (caused by dysfunction of upper esophageal sphincter)
Sclerodermous esophagus: (luminal stenosis/diverticular formation/paresis/sphincteric dysfunction/spastic disorders).
In the context of achalasia, do muscle cells lose responsiveness to all stimuli?
No; still responsive to stimulatory function of acetylcholine & substance P (not responsive to VIP & NO)
How can you treat diffuse esophageal spasm?
(Trivia). About how much chyme does the pyloric valve release into the duodenum each time it opens?
The chief cells in the stomach secrete what?
pepsinogen (note: chief cells are located at the bottom of the gastric pit)
Endocrine cells in the stomach secrete what?
gastrin & somatostatin
The pareital (aka oxyntic) cell in the stomach secretes what?
HCl & Intrinsic Factor
Most of the gastric juice ions in the fasting state consists of what? What about in the eating state?
fasting - Na & Cl; eating - H & Cl
The parietal cell secretes mainly _____ at a rate of _____. The mucus cell primarily secretes _____ at a pH of _____ at a rate of _____.
parietal - HCl, rate of 0.1-7 ml/min; mucus cell - NaCl at pH of 7.7 at a rate of 1ml/min
T/F. Parietal cells secrete HCl into the lumen of the stomach by using a Na/H countertransporter.
F. by using a H/K ATPase
How does the parietal cell turn on and off HCl secretion?
H/K ATPase stored in tubulovesicles that don't have K; when tubulovesicles are fused with cell membrane, then have access to K
How does Cl get from the blood into the stomach lumen via the parietal cell?
Cl/HCO3 antiporter in basolateral membrane; Cl channel in apical membrane (note: by making stomach more acidic, the cell also makes the blood more basic)
What tells the parietal cell to secrete HCl?
Ach from vagus n.; gastrin from G cell; histamine from entero corpus cell
How does the vagus n. tell the parietal cell to secrete HCl via the D cell? (Note: vagus also directly tells parietal cell to secrete HCl)
negatively influences the D cell, which then positively influences the G cell (via somatostatin) (double negative); G cell positively influences parietal cell via gastrin
What is Rovsing's sign? What does it suggest?
palpation of left lower quadrant causes right lower quadrant pain->appendicitis
Visceral abdominal pain is (dull/sharp). Parietal abdominal pain is (dull/sharp).
visceral - dull; parietal - sharp
Rigid abdomen, rebound tenderness, and absent bowel sounds suggest what?
How do gastrin, acetylcholine, and histamine tell the parietal cell to secrete H+?
gastrin and acetylcholine use Ca; histamine uses cAMP
What are the 2 classes of medications that affect gastric secretion?
H2 receptor antagonists & proton pump inhibitors
How do H2 receptor antagonists work?
inhibit release of histame
Drugs that end in "tidine" are what?
H2 receptor antagonists (remember tiDINE histaMINE)
How do proton pump inhibitors work?
block H/K ATPase, decreasing gastric acid output
Drugs that end in "prazole" are what?
proton pump inhibitors (think p for proton pump inhibitors)
Are proton pump inhibitors or H2 receptor antagonists more powerful?
proton pump inhibitors
T/F. Duodenal ulcer pain is worse (after eating/when fasting).
when fasting (2-3 hours after meals) (gastric ulcers hurt more after eating)
What causes duodenal ulcers?
H. pylori (90%)
Gastric ulcers occur most often in which part of the stomach?
T/F. Gastric ulcer pain is worse (after eating/when fasting).
after eating b/c acid release (duodenal - when fasting)
What are 3 causes of gastric ulcers?
H. pylori (70%); NSAIDs, cancer
Which of the following is NOT a risk factor for peptic ulcer disease: (aspirin/acid hypersecretion (zollinger-ellison syndrome)/H. pylori/NSAIDs/smoking/stress/spicy food/type A personality).
stress/spicy food/type A personality
Which of the following is NOT a protective factor against peptic ulcers: (bicarbonate/gastric acid/mucosal blood flow/mucous production/pepsin/prostaglandins)
gastric acid and pepsin are causative factors
T/F. Less than 10% of people have H. pylori in their stomachs.
F. 50-80% do
How does H. pylori protect itself from HCl?
H. pylori does NOT cause which of the following: (peptic ulcer disease/gastritis/atrophic gastritis/MALT lymphoma/gastric adenocarcinoma/iron deficiency anemia/autoimmune metaplastic atrophic gastritis).
autoimmune metaplastic atrophic gastritis (AMAG)
How do NSAIDs cause peptic ulcer disease?
local cell toxicity & inhibit prostaglandin synthesis (lose cytoprotection & mucous secretion)
Cox-1 is (constitutive/inducible). Cox-2 is (constitutive/inducible). What is each responsible for?
1 - constitutive, cytoprotection; 2 - inducible, inflammatory responses
Cytokines, growth factors and endotoxin activate Cox-(1 or 2)?
How do you treat a peptic ulcer that is bleeding but not perforated?
upper endoscopy & give IV PPI
Which drugs would you use to treat H. pylori infection?
PPI + either (clarithromycin+amoxiciillin) or (metronidazole+tetracycline+bismuth)
What causes stress ulcers?
decreased mucosal blood flow due to sepsis, burns, hypotension->decreased PG synthesis->decreased mucous and bicarb secretion
When do you see a Cushing's ulcer?
increased intracranial pressure (stimulate vagus nerve->secrete more H+) (think Harvey Cushing, the neurosurgeon)
When do you see a Curling's ulcer?
burns (think curling iron)
What are signs of Zollinger-Ellison syndrome?
acid hypersecretion; hypertrophy of gastric folds
What is the classic triad of zollinger-ellison syndrome?
acid hypersecretion; post bulbar ulcer (in duodenum); pancreatic islet cell tumor (gastrinoma)
pH in stomach very low; gastrin level very high. Suspicion?
Tumor of pancreas, parathyroid, and pituitary. What gene is mutated? What syndrome can it lead to?
MEN1 (multiple endocrine neoplasia type 1); zollinger-ellison syndrome
Which of the following does NOT cause elevated serum gastrin: (zollinger-ellison/proton pump inhibitors/gastric mucosal atrophy/NSAIDs/renal insufficiency/small intestinal resection/retained antrum after gastrectomy).
NSAIDs (I made it up) (note: renal insufficiency and small intestinal resection DO, which is unexpected)
What is the difference between gastritis and gastropathy?
gastropathy - damage w/o inflammation; gastritis - inflammation
Flat, smooth, white stomach without folds. Diagnosis?
autoimmune metaplastic atrophic gastritis (AMAG)
What are consequences of autoimmune metaplastic atrophic gastritis?
hypochlorhydria, loss of IF production->pernicious anemia;
What is Menetrier's disease? What are its consequences?
gastric mucosal folds enlarged (look like brain gyri); results in hypoalbuminemia (aka protein-losing hypertrophic gastropathy)
What is Dieulafoy's lesion? What are its consequences?
dilated, aberrant submucosal artery; erodes the overlying mucosa w/o producing an ulcer; causes massive upper GI bleeding
Watermelon stomach in patient with scleroderma and cirrhosis. Diagnosis? What are its consequences?
gastric antral vascular ectasia; bleeding and iron deficiency anemia
Upper GI bleeding with diffuse mucosal 'oozing' from white, lacy vessels in esophagus. Diagnosis?
portal hypertensive gastropathy
Pyloric stenosis. What are its symptoms?
projectile vomiting; inability to gain weight (seen in infants due to hypertrophy of the pylorus)
What is a bezoar?
concentrations of material in stomach (e.g. fiber, hair)
What is gastric vovulus?
abnormal rotation of the stomach (e.g. spins 180 degrees along perpendicular or long axis)
Gastric fovealar cells secrete what?
What is the difference between an erosion and an ulcer?
erosion does not pentrate muscularis mucosa; ulcer does
How do G-cells make parietal cells secrete acid?
G cells->gastrin->ECL cells->histamine->parietal cells->acid
What typically causes acute gastritis? Chronic gastritis?
acute - alcohol; chronic - NSAIDs
When is hyperacidity a factor in gastric ulceration?
duodenal ulcer-associated gastric lesion - "pre-pyloric ulcer" & zollinger-ellison syndrome (otherwise gastric ulcers are not caused by excess acid)
What is the difference between an erosion and an ulcer?
erosion - does not break muscularis mucosa; ulcer - does
What is the main cause of environmental metaplastic atrophic gastritis?
T/F. Pernicious anemia is seen in environmental metaplastic atrophic gastritis.
F. NOT seen
T/F. Eliminating H. pylori after stomach cancer reduces the risk of future stomach cancers.
T. (Japanese study)
In addition to adenocarcinoma, what other cancer is associated with H. pylori infection?
Where does the metaplasia take place in the context of H. pylori infection? What about in autoimmune gastritis?
H. pylori - antrum (starts at junction between antrum and body); autoimmune - in body
Autoimmune metaplastic atrophic gastritis is associated with antibodies to what?
parietal cell or intrinsic factor
In autoimmune metaplastic atrophic gastritis, which cells display hyperplasia?
G-cell and ECL cells (ECL makes histamine) (they get antsy when the parietal cells doesn't respond to them)
T/F. B-12 malabsorption, high gastrin, and gastric ulcers are seen in autoimmune metaplastic atrophic gastritis.
F. no gastric ulcer b/c no acid (B-12 malabsorption & high gastrin seen)
ECL hyperplasia can occur in the context of (H. pylori/autoimmune/smoking/drinking) and can progress to what kind of cancer?
autoimmune; carcinoid (well-differentiated neuroendocrine tumor) (relatively indolent)
What are the two forms of gastric cancer? What is the difference between them?
intestinal - well-differentiated protruding masses, associated with H. pylori; diffuse - poorly differentiated, flat, leathery ("signet ring")
With E-cadherin mutations (for autosomal dominant inherited gastric cancer), are men or women more likely to develop cancer?
women by around 25%; women also get mammary lobular carcinoma
The puborectal muscle (contracts/relaxes) during pooping.
What is the major stimulatory neurotransmitter in the gut?
What is the migratory motor complex? What triggers it? What blocks it?
occurs once every 90 minutes to clear stomach and intestine of food and debris; triggered by motilin (also erythromycin); blocked by gastrin
What is gastroparesis?
delayed emptying of stomach in ABSENCE of mechanical obstruction
What is the most common known cause of gastroparesis?
diabetes (note: more common in women (7:1))
What is the gold standard do diagnose gastroparesis?
Which of the following would you NOT suggest to a person with gastroparesis: (small frequent meals/reduced fat intake/increased fiber/liquid supplements).
increased fiber (b/c can lead to beazors)
How does erythromycin work in the context of gastroparesis? Does erythromycin prevent vomiting?
motilin agonist; does NOT prevent vomiting
How does metoclopramide work? What is a side effect?
dopamine ANTAGONIST; antiemetic; induces antral contractions; associated with tardive dyskinesia
How does domperidone work?
peripheral dopamine ANTAGONIST; antiemetic; increases antral contractions; NOT FDA APPROVED
T/F. A person who has fewer than 3 bowel movements per week necessarily has constipation.
F. need that and one other trait (e.g. straining/lumpy or hard stools/manual maneuvers...)
What is Hirschsprung's disease?
arrest in caudal migration of neural crest cells through gut during development
If you stick your finger in someone's anus and a massive amount of stool shoots out, what disease do they most commonly have?
Hirschsprung's disease (these were the words of the lecturer)
What causes slow transit constipation?
alterations in number of neurons and interstitial cells of cajal
What is the only medication that is currently approved to treat chronic constipation in the US?
chloride channel activator
T/F. Fiber is recommended in both slow transit and normal transit constipation.
F. only normal transit; tends to increase symptoms in slow transit constipation
Which one of the following uses cAMP as the second messenger: (acetylcholine/gastrin/histamine).
histamine (gastrin and acetylcholine use Ca)
Food (improves/makes worse) gastric ulcers. What does it do to duodenal ulcers?
makes worse gastric ulcers b/c more H+ secreted; makes better duodenal ulcers b/c more bicarb secreted
What are shortcomings of sodium bicarb as an antacid? What about calcium carbonate?
sodium bicarb - rapidly cleared; alkali and sodium load; calcium carbonate - rapidly neutralized; abdominal distension and belching
Which of the following is the longest neutralizing activity: (sodium bicarb/calcium carbonate/Mg2+ & Al3+)
Mg2+ & Al3+
Which of the following can lead to osteoporosis, encephalopathy, & proximal muscle weakness: (sodium bicarb/calcium carbonate/Mg2+ & Al3+)?
Which of the following can lead to diarrhea: (sodium bicarb/calcium carbonate/Mg2+ & Al3+)?
What is ranitidine?
H2 receptor antagonist (think tiDINE for histaMINE); histimine congeners
H2 receptor antagonists inhibit (basal/feeding) acid secretion.
basal (histamine receptor)
What are side effects of H2 receptor antagonists (e.g. ranitidine)?
inhibition of CYP450; CNS confusion, somnolence; gynecomastia (cimitidine)
What is omeprazole?
proton pump inhibitor (covalent, irreversible) (think PRazOle for PROton pump)
Which of the following is a pro-drug: (calcium carbonate/ranitidine/omeprazole).
Basal acid secretion is controlled better by (ranitidine/omeprazole).
ranitidine (H2 receptor antagonist)
Which of the following is NOT associated with PPIs: (increased risk of community-acquired pneumonia/increased risk of osteoporosis/increased risk of carcinoid tumors due to G-cell oversecretion and ECL hyperproliferation/bacterial overgrowth/inhibitor of P-450.
no increased risk of carcinoid tumors; no bacterial overgrowth (questionable)
What is sucralfate?
sulfated polysaccharide; forms gel that binds to ulcer craters; inhibits pepsin and adsorbs bile salts
What is a problem with taking sucralfate for a long period of time?
accumulation of aluminum with renal failure
What are complications of taking sucralfate?
constipation (from aluminum); reduces bioavailability of other drugs b/c it binds to them
What do prostaglandins do to stomach cells?
reduces production of acid; increase production of mucus
What is misoprostol?
synthetic prostaglandin analogue
What are side effects of prostaglandin analogues?
uterine contractions; diarrhea
How does metoclopramide work?
5-HT4 receptor activation; enhances SM propulsive contractions of upper gut; increases LES tone; antiemetic
Tardive dyskinesia in a GI drug. Which one is it?
Most of digestion and absorption occurs in the (duodenum/jejunum/ileum).
The (villus/crypt) is the site of digestion & absorption. The (villus/crypt) is the site of secretion.
villus - digestion & absorption; crypt - secretion
Which of the following does the GI tract not secrete into the lumen of the GI tract: (water/protein/carbohydrate/salt/fat).
The primary form of carbohydrate in our diet is in the form of what?
What enzyme breaks down starch? Where is it secreted?
alpha-amylase; secreted by pancreas (and to small extent in the saliva)
T/F. Alpha-amylase is secreted as an inactive zymogen.
F. secreted as active enzyme
What is the cleavage product of alpha-amylase?
maltose (disaccharide) or maltotriose (trisaccharide) or alpha-limit dextrins (result of cleavage of amylopectin)
What is the difference between amylose and amylopectin?
amylose - animal, linear; amylopectin - plants, branched
What is the result of cleavage by maltase? Sucrase? Lactase? Isomaltase?
maltase - glucose; sucrase - glucose + fructose; lactase - glucose + galactose; isomaltase - maltose, maltotriose, oligosaccharide
What do SGLT1, GLUT5, and GLUT2 do?
SGLT1 - transport glucose and galactose into cell from lumen (coupled with Na); GLUT5 - let fructose diffuse into cell from lumen; GLUT2 - transport glucose and fructose into blood
What is the difference between GLUT2 and GLUT5?
GLUT2 - transport glucose and fructose into blood; GLUT5 - let fructose diffuse into cell from lumen
Zymogens that the pancreas secretes are made active by what enzyme? What makes that enzyme active?
made active by trypsin; enterokinase makes trypsin active
Which 2 pancreatic enzymes are secreted as active hydrolases?
amylase and lipase (thse enzymes are also present in saliva; do not need to be activated)
What are 2 mechanisms in which salt is absorbed in the GI tract?
1. Na/solute cotransport & Cl secondary movement; 2. Na/H and Cl/HCO3 antiport
The major form of fat in the diet is in the form of what?
T/F. Short, medium, and long chain fatty acids require handling by bile salts to be absorbed.
F. only long chain needs it; short and medium are directly absorbed
Which 2 long chain fatty acids are essential in the human diet?
linoleic (18:2) omega-6 & linoleic (18:3) omega-3
Exocitosis of _____ by the enterocyte delivers triglycerides to the _____ (blood/lymph).
If the secretory rate of pancreatic juice is low, the pancreas is secreting mainly (NaCl/NaHCO3) through the (exocrine pancreas/pancreatic ducts).
NaCl; exocrine pancreas
If the secretory rate of pancreatic juice is high, the pancreas is secreting mainly (NaCl/NaHCO3) through the (expcrine pancreas/pancreatic ducts).
NaHCO3; pancreatic ducts
What molecule tells the pancreatic acinar cells to secrete enzymes? What are 2 sources of this molecule?
CCK; I cells in jejunum (intestinal phase) & vagus nerve (cephalic phase)
How is NaHCO3 secreted into the pancreatic duct?
HCO3/Cl antiporter facing lumen & Na/H antiporter facing blood; CFTR facing lumen (for Cl) and Na escaping between cells toward lumen
What causes plasma secretin to rise?
duodenal pH drops
What are 2 mechanisms in which fluid absorbed in the GI tract?
1. Na/solute cotransport; 2. Na/H and Cl/HCO3 antiport
How does cholera cause diarrhea?
increase cAMP in intestinal cells->dump Cl into lumen by CFTR; reduced absorption b/c 1. no food & 2. Na/H and Cl/HCO3 antiport inhibited
Oral rehydration therapy to treat cholera involves what?
Glucose in the liquid->Na/glucose symporter to work; also has electrolytes in liquid
Where are Brunner's glands and where are they located?
secrete alkaline mucus; located in the duodenum, only
Where are Paneth cells located, and what do they do?
crypt epithelium of small intestine; secrete defensins & antibacterials
Peptic disease has the highest incidence in (western/developing) countries, occur most often in patients (>40/>60/<20) and (male/female).
western; >40; male
What is peptic disease? Peptic disease is caused by (excess gastric acid/altered mucosal defenses). What causes it?
caused by toxic effects on DUODENAL mucosa by excess gastric acid (NOT altered mucosal defenses, which causes gastric ulcers); H. pylori, most often
What can be seen in PEPTIC disease?
gastric mucin-cell metaplasia (stomach cell, should not be in intestine); Brunner gland hyperplasia (hallmark); vilous blunting
Where are Brunner's glands supposed to be located? Where are they located in peptic disease?
duodenum, submucosa; disease - hyperplasia, go above muscularis mucosae
Gastric metaplasia of the duodenum in the context of peptic disease is correlated with (acid exposure/H. pylori infection/altered mucosal defenses).
acid exposure ONLY
How does H. pylori infection result in excess HCl secretion?
tell somatostatin cell (D cell) not to secrete somatostatin, which results in G cells secreting more gastrin
(Crohn's disease/ulcerative colitis/both/neither) affect the upper GI tract.
Crohn's disease, only (look at second word: crohn's Disease - Discontinuous; ulcerative Colitis - Continuous)
What causes Zollinger-Ellison syndrome?
neuroendocrine tumor of pancreas or duodenum
T/F. Lactase deficiency can be acquired.
T. intestinal epithelial damage (i.e. celiac disease, sprue)
Flat mucosa is NOT seen in which of the following: (peptic disease/lactase deficiency/celiac disease).
Celiac disease can be diagnosed based on (demonstration of mucosal damage restoration after gluten-free diet/serologic studies/either one).
demonstration of mucosal damage restoration ONLY (serologic studies alone are UNACCEPTABLE, according to this lecturer)
What is tropical sprue? What are its symptoms?
post-infectious tropical malabsorption; chronic diarrhea and malabsorption after infectious diarrhea
How can you differentiate tropical sprue and celiac disease based on area of involvement?
tropical sprue involves the ileum; celiac disease does NOT
What are the typical demographics of a person with Whipple's disease?
40-60 yo male
What causes Whipple's disease?
What stimulates CCK release? What does CCK do?
food in small intestine; (1. relax sphincter of oddi; 2. bile acids from GB; 3. lipase from pancreas)
What is emulsification? Emulsification takes place in the (stomach/small intestine/colon).
shearing of big fat droplets into smaller fat drops; stomach
Which pancreatic enzyme is secreted as a working enzyme, not a proenzyme?
What does lipase do?
cleave triglyceride into 1 fatty acids and one 2-monoglyceride
Which of the following is not solubilized by bile acids: (fatty acids/2-monoglyceride/triglyceride).
What is the pathway of bile? (i.e. starts in the liver->?)
liver->gall bladder->duodenum->reabsorbed in ileum->portal circulation->liver
What happens to the fatty acids and monoglycerides that the enterocyte takes up?
repackaged as triglyceride; put in chylomicron; secreted into lymphatics
Which of the following problems does NOT cause steatorrhea in humans: (emulsification by stomach; CCK stimulation; lipase production by pancreas; micelle formation; mucosal uptake; reesterification; making of chylomicrons; lymphatics).
reesterification has not been known to cause problems
Malabsorption of _____ leads to anemia.
Fe (microcytic); B12, folate (macrocytic)
Malabsorption of _____ leads to edema.
Malabsorption of _____ leads to tetany.
Malabsorption of _____ leads to bleeding-bruising.
What is the D-xylose test for malabsorption?
have person eat d-xylose; if in urine->small intestine works b/c it was absorbed
What does the bentyramide test look for?
pancreatic function (specifically, chymotrypsin); look for cleavage product in urine
The glucose hydrogen breath test looks for what?
bacteria in intestine (bacteria cleaves H from glucose; gets into breath in 15 minutes
To test for malabsorption, you would use the (D-xylose/bentyramide/glucose hydrogen breath test).
D-xylose (if in urine->small intestine works)
To test for pancreatic function, you would use the (D-xylose/bentyramide/glucose hydrogen breath test).
bentyramide; (look for cleavage product in urine)
To test for bacteria in the intestine, you would use the (D-xylose/bentyramide/glucose hydrogen breath test).
glucose hydrogen breath test (bacteria cleaves H from glucose->gets into breath in 15 min) ( H is radioactive)
T/F. B12 is bound to IF in the stomach.
F. B12 bound to R factor in stomach. Pancreatic enzymes cleave off R factor in duodenum; B12 then binds to IF in duodenum
T/F. All gut hormones are synthesized as preprohormones that need to be proteolytically processed to generate bioactive small peptides.
T; generate bioactive small peptides that are <50 AA long
What type of receptors do gut hormones bind to?
What are the members of the gastrin hormone family? What type of receptor do they bind to?
gastrin & CCK; CCK1 & CCK2;
Ca & PKC pathway: (gastrin/secretin/motilin).
gastrin & motilin
Gs & cAMP pathway: (gastrin/secretin/motilin).
Ghrelin is a member of the (gastrin/secretin/motilin) family.
What are 2 parts of the brain that gut hormones act on?
hypothalamus & brainstem
In the hypothalamus, NPY neurons tell the body to (eat/stop eating). The POMC neurons tell the body to (eat/stop eating).
NPY - eat; POMC - stop eating
What is the only gut-derived peptide that promotes eating?
Where is CCK produced?
duodenum & jejunum
Which of the following does CCK NOT do: (stimulate pancreatic secretion; stimulate gall bladder secretion; promote gastric emptying; inhibit food intake).
promote gastric emptying (it inhibits it)
What is the incretin concept?
amino acids and glucose cause greater and earlier release of islet cell hormones when eaten than injected
What is GLP-1 and what does it do?
released by L cells in gut when there is glucose present in gut. tell pancreas to secrete insulin
Where is PYY (peptide YY) made and what does it do?
ileum & jeunum; inhibit gastric motility; suppress pancreatic enzyme secretion; reduce appetite
Which of the following are part of acute inflammation of the colorectal mucosa: (basal plasmacytosis/crypt abscess/crypt distortion/crypt loss & atrophy/cryptitis/erosions/metaplasia/ulcers)
cryptitis/crypt abscess; erosions/ulcers
What is the difference between cryptitis and crypt abscess?
cryptitis - infiltrate within the crypt epithelium; abscess - intraluminal neutrophils
Which of the following are chronic inflammation of the colorectal mucosa: (basal plasmacytosis/crypt abscess/crypt distortion/crypt loss & atrophy/cryptitis/erosions/metaplasia/ulcers)
basal plasmacytosis/crypt distortion/crypt loss & atrophy/metaplasia are chronic; the rest are acute
T/F. Paneth cells in the right colon are abnormal.
F. if they were found in the left colon, they would be abnormal; Paneth cells are typically found in the small intestine and right colon
Crypt distortion & basal plasmacytosis occur in (acute colitis/chronic inflammatory bowel disease).
chronic inflammatory bowel disease (NOT acute colitis)
Mucosal ulcerations over hyperplastic Peyers patches suggests what?
What does crypt distortion mean?
crypts not parallel to each other, like test tubes on a rack
Acute inflammatory disease in the context of the colorectum is most commonly associated with what 2 causes?
infection & bowel preps
What is the typical age of presentation for ulcerative colitis and Crohn's disease?
15-25 initial presentation; second peak at 55-65
Ulcerative colitis exhibits symptoms of (acute/chronic/both) inflammatory disease.
What happens after years of ulcerative colitis?
How do you differentiate a pseudopolyp from UC from FAP?
pseudopolyp - no crypts around polyp ("test tubes" only in polyp); FAP - crypts & "test tubes" everywhere"
Ulcerative colitis is (continuous/discontinuous). Crohn's disease is (continuous/discontinuous).
ulcerative COlitis - COntinuous; crohn's DIsease - DIscontinuous (look for second word)
Transmural inflammation: (Crohn's disease/ulcerative colitis).
Crohn's disease - transmural; ulcerative colitis - superficial
Granulomas: (Crohn's disease/ulcerative colitis).
Crohn's disease only
Aphthous ulcer: (Crohn's disease/ulcerative colitis).
Crohn's disease (althous ulcer - punched out region surrounded by normal regions)
Creeping fat: (Crohn's disease/ulcerative colitis). Why?
Crohn's disease; b/c fat covers over transmurally inflamed areas for protection
Affects rectum: (Crohn's disease/ulcerative colitis).
Ulcerative colitis (Unusual for CD)
Perianal strictures and fistula: (Crohn's disease/ulcerative colitis).
In the context of Crohn's disease, which of the following will NOT resolve with colectomy: (ankylosing spondylitis/arthritis/dermititis/sclerosing cholangitis/uveitis).
amkylosing spondylitis & sclerosing cholangitis
Which has a greater risk of developing colorectal cancer: (Crohn's disease/ulcerative colitis).
T/F. Collagenous-lymphocytic colitis is associated with crypt distortion and basal plasmacytosis.
Chronic watery diarrhea w/no abnormalities on endoscopy: (Collagenous-lymphocytic colitis/Crohn's disease/ulcerative colitis).
collagenous-lymphocytic colitis (originally called microscopic colitis b/c no changes seen grossly)
Which of the following is NOT associated with a greater chance of developing cancer: (Collagenous-lymphocytic colitis/Crohn's disease/ulcerative colitis).
What's the problem in collagenous colitis?
thickened basement membrane; no type 4 collagen in subepithelial layer; replaced by type 1 & 2 collagen; no crypt distortion
Collagenous-lymphocytic colitis is NOT associated with (autoimmune disease/cancer/celiac disease/luminal antigen/men/NSAID use).
NOT cancer, NOT associated with men (females affected 8:1)
What is the most common cause of ischemic colitis in the US?
occlusive vascular disease: atherosclerosis
Mucosal necrosis; hemorrhage; heme-laden macrophages in lamina propria; fibrin thrombi: (collagenous-lymphocytic colitis/Crohn's disease/ischemic colitis/ulcerative colitis).
Crypt distortion & plasmacytosis: (collagenous-lymphocytic colitis/Crohn's disease/ischemic colitis/ulcerative colitis).
IBD: Crohn's & ulcerative colitis
How does CMV cause ischemic colitis?
infect cells lining capillaries
T/F. Pseudomembranous colitis is ONLY caused by C. difficile.
F. can also be caused by CMV
What is diverticular disease? Where in the colon does it usually occur? What causes it?
herniation of mucosa through muscularis propria; left colon; lack of fiber
What is the most common cause of acute abdomen in the US?
The neuron innervating the gut smooth muscle is controlled by 3 neurons. What are they, and are they inhibitory or stimulatory?
dopaminergic - inhibitory (think dopamine - dopey - slow); cholinergic - stimulatory; nonadrenergic, noncholinergic - inhibitory
How does metoclopramide work?
serotonergic receptor activation (also dopamine antagonist); enhances smooth muscle propulsive contractions of upper gut
What is lubiprostone?
prostaglandin derivative that binds to Cl- channel on epithelial cells; activates Cl- and fluid secretion; softens stool and stimulates motility (works like cholera) (no need to get into circulation)
What is a drug with the same activity as metoclopramide, but without its side effects and not approved in the US?
domperidone (no tardive dyskinesia b/c doesn't cross blood-brain barrier) (works by dopamine receptor antagonism)
Where is the emetic center?
What is ondansetron (zofran), and how does it work? What class of vomiting would it NOT work for?
anti-emetic; block serotonin receptors in CNS; NOT work for motion sickness b/c that pathway doesn't use serotonin
Ondansetron is NOT used for which of the following: (chemotherapy-induced nausea/hyperemesis of pregnancy/motion sickness/nausea from upper gut irradiation/postoperative nausea).
motion sickness (use histamine and muscarinic pathways only)
How does prochlorperazine work?
block dopamine at chemo-receptor trigger zone; also antihistamine and anticholinergic activity
How does promethazine work? What is it used for?
antihistamine; motion sickness & post-op emesis
How does diphenhydramine work? What is it used for?
antihistamine; motion sickness & post-op emesis
How does scopolamine work? What is it used for?
anticholinergic; motion sickness
What is dronabinol? What is it used for?
cannabinoid (unknown methanism) (anti-emetic)
What is psyllium? What is it used for?
hydroscopic agent (absorb water); antidiarrheal
How does cholestyramine work? What is it used for?
binds excess bile salts to avoid secretion; diarrhea
What is bismuth subsalicylate (pepto bismol) used for?
antidiarrheal (antisecretory, antiinflammatory, antimicrobial effects)
Opioids are used to treat (diarrhea/constipation).
diarrhea; increase fluid absorption, decrease fluid secretion, and decrease motility
How does loperamide (imodium A-D)work? What is it used for?
opioid; antidiarrheal (doesn't cross BBB)
How does docusate sodium work? What is it used for?
anionic detergent lowers surface tension of stool, permitting penetration of stool by more water and fats; constipation
T/F. Fiber is used to treat both diarrhea and constipation.
What chemical element is used to treat constipation?
magnesium; poorly absorbed->increase intraluminal osmolarity->water retention by stool
How does bisacodyl work?
stimulant cathartic; induce low grade inflammation in small bowel and colon->fluid and electrolyte accumulation->intestinal motility
How does anthraquinone (aka aloe, cascara, senna) work?
stimulant cathartic; induce low grade inflammation in small bowel and colon->fluid and electrolyte accumulation->intestinal motility
What are side effects of anthraquinone (cascara, senna)
melanosis coli (reversible); cathartic colon (colon doesn't work great)
What is the main cause of pernicious anemia in the developed world?
autoimmune destruction of parietal cells
At what point in the digestive tract does a meal become isotonic?
In HCl secretion by the stomach, the Cl/HCO3 antiporter is on the apical membrane of the parietal cell.
F. on the basolateral side (H+ dumped into stomach; HCO3- dumped into blood)
T/F. Na-coupled absorption of glucose is accompanied by equimolar absorption of Cl.
T/F. An apical K channel allows recycling of potassium at the apical membrane of the parietal cell.
T/F. SGLT1 is critical for both galactose and glucose transport.
T/F. Galllbladder contraction is mediated by secretin released by the jejunal I cell.
F. by CCK secreted by the jejunal I cell
T/F. The incidence and mortality of gastric cancer worldwide has gone down.
F. Incidence has gone down but mortality has not
T/F. H. pylori is the most common cause of gastric cancer.
The most common deficiency in celiac disease is what?
The cephalic phase of HCl secretion depends solely on what?
vagal enervation to the fundus and corpus
T/F. A single intestinal cell can be responsible for both ion absorption and secretion.
F. separate cells
__ (Na/K/Cl) is the major ion actively absorbed in the intestine, while __ (Na/K/Cl) is the major ion actively secreted.
Na - absorbed; Cl - secreted
During the fasting state, how is Na absorbed?
neutral NaCl brush border uptake
How is neutral NaCl uptake accomplished?
2 linked neutral transport processes: Na/H exchanger and Cl/HCO3 exchanger
How does the intestinal secretory cell work?
Na/K/2Cl (NKCC1) on basolateral side; Cl goes out apical side through CFTR
The two most common causes of diarrhea are: (inhibition of active electrolyte absorption/stimulation of active electrolyte secretion/increased luminal osmolarity/increased tissue hydrostatic pressure).
inhibition of active electrolyte absorption & stimulation of active electrolyte secretion (note: all 4 are mechanisms)
Cholera is necessarily bacterial.
F. also pancreatic cholera
How does the cholera toxin cause diarrheal disease?
activating intestinal adenylate cyclase; act on 2 cells: 1. Na absorber cell: (only result is inhibiting Na/H exchanger (NHE3) (reduce uptake of NaCl) (note: does NOT affect Na-glucose transporter)); 2. Cl secretion cell: (increases activity of Cl secretion through CFTR)
How does pancreatic cholera cause diarrheal disease?
high blood level of VIP binds to hormone receptor site of adenylate cyclase
How does increased cAMP affect the Na absorptive cell and the Cl secretory cell?
Na absorptive - stop absorbing NaCl; Cl secretory cell - increase brush border permeability to Cl
What are the 2 main electrolyte abnormalities in severe diarrheal diseases?
low K and low HCO3
What are 3 substances that tell the intestinal cell to secrete Cl?
cAMP, Ca, cGMP
Diarrhea caused by a carcinoid tumor can be treated by what? Why?
serotonin antagonist; tumor production of serotonin, which increases GI motility and inhibits active NaCl absorption
Carcinoid tumors secrete what hormone, primarily? How does it cause diarrhea?
serotonin; decreased Na absorption (NOT increased Cl secretion)
What are 3 characteristic findings in pancreatic cholera syndrome?
diarrhea; hypokalemia; hypochlorhydria
What are the top 2 causes of death of children <5 yo in developing countries?
respiratory diseases; diarrheal diseases
T/F. The majority of diarrheal diseases in the US are foodborne.
F. only about 1/3 are foodborne; acute gastroenteritis (non-foodborne) causes 2/3
T/F. Younger people are admitted more often to the hospital and die more often from diarrhea than older people.
F. admitted more often, but older people die more often.
In terms of quantity of water lost in stool, what is the threshold for diarrhea?
>200 ml/24 hrs.
In the absence of sodium transport, is there secretion of water?
yes; due to hydrostatic pressure
What channel transports Na from the lumen into the epithelial cell of the LEFT SIDE of the colon?
ENAC channel (Epithelial NA Channel)
What channel transports sodium linked with glucose or galactose into the epithelial cell?
SGLT1 (Sodium-Glucose-Linked Transporter 1) (note: 2 Na transporter per 1 glucose)
T/F. Neutral NaCl absorption in mammalian small intestine is linked to SGLT1.
T!, according to a paper the lecturer wrote
Why does meconium ileus occur in CF?
increased neutral NaCl absorption in the small intestine
In cholera, you would have problems with the ionic concentrations of which of the following ions: (Na/Cl/K/HCO3).
K and HCO3; (NOT Na/Cl); Cl-dumping cell also dumps K & HCO3 (dumps 1 HCO3 for every 10 Cl dumped); NaCl reabsorption cell takes in Cl that Cl-dumping cell dumped and then dumps HCO3
T/F. Cholera causes diarrhea by only acting on Cl secretory epithelial cells.
F. also has effect on Na absorptive cells; affecting enteric nerves; release intestinal prostaglandins and enteric serotonin containing cells
How do E. coli enterotoxin and yersinia entercolitica enterotoxin cause diarrhea?
How does hyperthyroid cause diarrhea?
increased motility->decreased absorption
Which of the following does NOT respond to oral rehydration solution: (celiac sprue/cholera/rotavirus).
celiac sprue b/c problem with absorption all over
Which of the following is NOT a source of osmotic diarrhea: (lactose/fatty acids/sucrase/trehalase/lactulose)
fatty acids - not osmotic b/c in micelles
T/F. The osmotic effects of lactose in the colon directly cause diarrhea.
F. bacteria in colon convert lactose to glucose and galactose; colon does not have SGLT1; increased osmotic load of glucose and galactose in colon causes diarrhea
Mucosal inflammation: (ulcerative colitis/crohn's disease). Transmural inflammation: (ulcerative colitis/crohn's disease)
mucosal - UC; transmural - CD
Limited to rectum and colon: (ulcerative colitis/crohn's disease)
IBD is more common in (developed/developing) countries.
developed (europe & north america), even accounting for immigration (Note: Crohn's 20% less than UC in US)
T/F. Smoking increases the risk of both ulcerative colitis and crohn's disease.
F. decreases risk for UC; increases for crohn's
A NOD2 mutation is associated with increased risk of (Crohn's disease/ulcerative colitis)
T/F. According to experiments, bacteria is necessary for colitis to develop in Crohn's disease.
(Ulcerative colitis/Crohn's disease) is increased in Turner syndrome.
Antibody therapy against what molecule is used to treat Crohn's disease.
Natalizumab (Tysabri) is an antibody against what? What is it used for? What are its risks?
alpha4-integrins (needed for T cells to transmigrate across gut epithelium); Crohn's disease; progressive multifocal leucoencephalopathy caused by JC virus
What drug is a 1st line therapy for mild to moderate ulcerative colitis?
5-ASA (inhibits NK cell activity and synthesis of pro-inflammatory mediators and cytokines)
(Women/men) are at a greater risk for Crohn's disease. What about UC?
women - greater for Crohn; UC - 50-50
T/F. The incidence of IBD is increasing. What is the typical age of diagnosis?
Ulcerative colitis and Crohn's disease are the only inflammatory bowel diseases.
F. microscopic colitis, diversion colitis, diverticular colitis, and pouchitis are others
Strictures and fistulas: (Crohn's disease/ulcerative colitis/microscopic colitis).
Which of the following extra-intestinal manifestations of IBD are related to the activity of the colitis: (ankylosing spondylitis/episcleritis/erythema nodosum/periperhal arthritis/primary sclerosing cholangitis/sacrolitis)
erythema nodosum (inflammation of fat cells); episcleritis; peripheral arthritis (superficial + arthritis) (note: ankylosing spondylitis (back problems); sacroilitis, and primary sclerosing cholangitis (bile duct scarring) are NOT)
A person presents with primary sclerosing cholangitis. What else do you suspect they have?
PSC - inflammation, scarring, and destruction of bile ducts; suspect ulcerative colitis (80% have IBD; UC)
Which of the following is an accepted (as opposed to questionable) trigger for IBD flares: (infections/non-adherence to medications/NSAIDs/seasonal changes/stress).
non-adherence to medication regimen
CRP is a better predictor of disease activity in (Crohn's disease/ulcerative colitis). Why is this important?
Crohn's disease; elevated CRP - more likely to respond to biologic therapy
pANCA is associated with (UC/CD). ASCA is associated with (UC/CD).
pANCA - UC; ASCA - CD
More positive antibody biomarkers present with increased risk of what?
internal penetrating and stricturing
T/F. Short-term symptom improvement in IBD has been demonstrated to alter the natural history of the disease.
T/F. Symptom scores correlate well with endoscopic disease activity in IBD.
For patients with mild ulcerative colitis, what 2 drugs would you treat them with?
5-ASA agents (aspirin specifically for the gut) & topical steroids
For patients with moderate ulcerative colitis, what 3 drugs would you treat them with?
oral steroids; infliximab; thiopurines
For patients with severe ulcerative colitis, what 4 treatments would you recommend?
surgery; cyclosporine; infliximab; IV steroids
5-ASA agents are used in (Crohn's disease/ulcerative colitis).
ulcerative colitis - no real role in Crohn's disease
You would use oral corticosteroids in (mild/moderate/severe) ulcerative colitis and _____ Crohn's disease
moderate to severe; inflammatory
You would use parenteral corticosteroids in (mild/moderate/severe) ulcerative colitis and _____ Crohn's disease.
T/F. Steroids can be used long-term for Crohn's disease.
F. only short-term efficacy; toxicity profile unacceptable for long-term use
T/F. Steroids improves quality of life and prevents cancer for ulcerative colitis.
F. no evidence
T/F. Immunomodulators can be used for induction therapy in the context of IBD.
F. only for steroid-induced remission
T/F. Steroids are used to treat perianal Crohn's disease.
F. antibiotics, anti-TNF, 5-MP/Azathioprine
T/F. Celiac disease destroys the small bowel mucosa and reduces both absorption and secretion.
F. only reduces absorption. secretion in crypts unaffected.
Why does iron deficiency anemia occur in celiac disease?
iron is absorbed in duodenum; celiac disease decreases absorption there
Why does osteopenic bone disease occur in celiac disease?
vitamin D and calcium absorption (note: vitamins ADEK are fat-soluble)
Why does coagulopathy occur in celiac disease?
vitamin K deficiency
A screening test with what is best for celiac disease? What do you do for diagnosis?
tTG IgA (tissue transglutaminase) (note: antibody does not play a role in pathogenesis, only useful as screening test); diagnosis - duodenal biopsy & response to gluten free diet
T/F. A person does not necessarily have to have HLA-DQ2 or HLA-DQ8 to have celiac disease. If a person is HLA-DQ2 or HLA-DQ8 positive, what is their risk of having celiac disease?
F. necessary presence of HLA-DQ2 or HLA-DQ8; have either - 2-3%
What are the 3 main things that a person with celiac disease should avoid?
wheat, rye, barley (they tolerate corn and rice)
T/F. B12 and folate deficiency can occur with celiac disease.
T. (B12 - absorbed in ileum, but overgrowth of bacteria due to impaired motility and dilation can lead to loss)
Night time diarrhea. Irritable bowel syndrome or celiac disease?
celiac disease (irritable bowel syndrome does not present with night time diarrhea
Dermatitis herpetiformis. What is it? What is it associated with?
erythematous macule on elbows, shins, butt; celiac disease
Morbid obesity is characterized by a BMI greater than ___.
Leptin is an appetitie (suppressant/stimulant) hormone secreted by (fat/muscle/stomach).
Ghrelin is an appetitie (suppressant/stimulant) hormone secreted by (fat/muscle/stomach).
Surgery plays a role for people with BMI > ___.
>35 with co-morbidities; >40 regardless of co-morbidities
Pharmacotherapy plays a role for people with BMI > ___.
How does xenical (orlistat) work? What is a side effect?
inhibit pancreatic lipase, decreases fat absorption; anal leakage
Why did jejunoileal bypass not work?
bacterial growth in small bowel->endotoxin->liver->cirrhosis->die
Why do patients who get the duodenal switch not get liver failure, as opposed to those with jejunoileal bypass?
bile and pancreatic juice still going down; flush out bacteria
What's the difference between the roux-en-y and the duodenal switch?
duodenal switch - take distal bowel and stick it onto stomach (malabsorptive); roux-en-y - take distal bowel and stick it onto esophagus (restrictive)
After gastric bypass, most of the weight loss occurs within what time frame?
What is the number 1 killer of people who die during surgery for gastric bypass?
Why do people who get gastric bypass need vitamin B12 after gastric bypass, when the stomach is still present?
stomach is not stimulated to produce intrinsic factor
Diagnostic criteria for irritable bowel syndrome: Recurrent abdominal pain or discomfort at least __ days per month in the last __ months associated with __ or more of the following: (what are the 3 things)?
3 days/month; 3 months; 2 or more of the following: improvement with defecation; onset associated with a change in frequency of stool; onset associated with a change in form (appearance) of stool
Irritable bowel syndrome is NOT associated with: (abdominal pain/anemia/bleeding/bloating/constipation/diarrhea/weight loss)
No evidence of: anemia/weight loss/bleeding
Irritable bowel syndrome is associated with (constipation/diarrhea).
People who have irritable bowel syndrome - diarrhea have (more/less) serotonin than people who have irritable bowel syndrome - constipation.
diarrhea - more
Post-infectious IBS has been reported following outbreaks of what?
salmonella, shigella, giardia, campylobacter
What are risk factors of developing post-infectious IBS?
long duration of diarrhea (>3 week); female; psychological factors
What causes post-infectious IBS?
release of tryptase and histamine excite visceral sensory afferent nerves leading to gut sensory and motor dysfunction
T/F. IBS is a type of colitis or inflammation.
F (although 25% is post-infectious, suggesting its pathophysiology in some cases is related to intestinal inflammation)
T/F. IBS may develop into cancer.
IBS is associated with disturbances in (acetylcholine/histamine/norepinephrine/serotonin) metabolism.
T/F. Colorectal cancer is preventable.
T. if optimal screening is employed
Colorectal cancer is the number ___ killer of cancers in men and in women.
(Stage/grade) of colorectal cancer predicts survival.
About __ % of large bowel adenocarcinomas are located in the colon and ___ % in the rectum.
70% colon; 30% rectum
The death rates of colorectal cancer is going (up/down).
T/F. A polyp necessarily leads to an increased risk of cancer.
F. not necessarily but could (a polyp is any mass projecting into the lumen)
T/F. An adenoma is malignant.
F. benign precancerous growth with dysplastic features
What is the difference between sessile and a pedunculated?
sessile - attached by broad base; pedunculated - attached by stalk
What is the difference between a villous and tubular adenoma?
villous - finger-like projections (greater chance of evolving into cancer); tubular - tube like glands
Balloon with fingers inserted in the context of colorectal cancer. What is it?
In the context of dysplasia, what happens to the nuclei of colorectal cells?
no longer confined to basal 1/6 of cell
The probability of carcinoma occuring in an adenoma goes up NOT as a function of (size/proportion of villous component/proportion of tubular component/presence of high grade dysplaisa).
proportion of tubular component (note: villous - sounds like villain)
Oncogenes: mutations (restricted/widespread); mutations (activating/deleterious); loss of heterozogosity is (common/uncommon); (methylated/not methylated).
mutations restricted; mutations activating; LOH uncommon; not methylated
Tumor suppressors: mutations (restricted/widespread); mutations (activating/deleterious); loss of heterozogosity is (common/uncommon); (methylated/not methylated).
mutations widespread; mutations deleterious; LOH common; methylated (suppressed)
(FAP/HNPCC) results in CRC occuring earlier in age than the other.
CRC is associated with a mutation initially in which gene? What does it do?
APC (adenomatous polyposis coli) gene; (degradation of beta catenin)
APC (adenomatous polyposis coli) gene is a (protooncogene/tumor suppressor gene)
tumor suppressor gene
Sporadic colorectal cancers occur more often in the (left/right) colon. HNPCC occurs more often in the (left/right) colon.
sporadic - left (70:30) (can screen easily doing colonscopy); HNPCC - right (70:30)
HNPCC is NOT associated with which other cancer: (endometrium/liver/ovary/pancreatic/renal pelvis/small bowel/stomach/ureter)
NOT liver & pancreatic
Spots (mucocutaneous lesions) and polyps. Which syndrome is it?
What is the most commonly mutated gene in all human cancer?
p53 (tumor suppressor gene) (responsible for checkpoint control) (causes chemotherapy and radiation resistance)
What is the difference between Dukes A, B, & C stages?
A - does not invade through muscularis propria; B - through, but lymph node neg.; C - lymph node pos
What is the difference between stage 1, 2, 3, and 4 colon cancer?
1 - not through muscularis propria; 2 - through muscularis propria; 3 - mets into lymph nodes; 4 - distant mets
What is the mainstay chemotherapeutic agent in colon cancer?
5-FU (after surgery) (incorporated into RNA and prevents processing) (inhibits thymidylate synthase)
Using an EGFR inhibitor in a person with colorectal cancer and a ___ mutation would not be effective.
RAS/RAF b/c those are downstream
What is the definition of a peptic ulcer?
mucosal break 3 mm or greater that can involve the stomach or duodenum
What are the 4 most important contributing factors to peptic ulcers?
H. pylori, NSAIDs, acid, pepsin
There is a higher prevalence of peptic ulcer disease in (developing/developed) countries.
developing (H. pylori)
(Duodenal/gastric) ulcers are more common. They occur more often in (men/women) with blood group __.
duodenal (4:1 ratio); men (4:1 ratio); blood group O
Duodenal ulcers in the anterior side that perforate cause what? What about posterior?
anterior - gas under diaphragm; posterior - bleeding
Gastric ulcers occur more often in (men/women) with blood group __.
men (2:1 ratio); blood group A
Duodenal ulcer pain occurs during (fasting/eating). Gastric ulcer pain occurs during (fasting/eating).
duodenal - fasting (less bicarb); gastric - eating (more acid)
What is ileus?
paralysis of the bowel
What are the 3 most common causes of small bowel obstruction in adults?
postoperative adhesions (most common); incarcerated hernia; cancer
What are the 2 most common causes of small bowel obstruction in children?
hernia and intussuception
An obstructed bowel presents with what lab tests?
elevated white count, acidosis, elevated lactate
Elevated pancreatic enzymes in serum: acute or chronic pancreatitis?
acute (chronic has progressive loss of pancreatic endocrine and exocrine function)
In the context of acute pancreatitis, what serum enzymes would you look for to confirm the diagnosis?
serum amylase and lipase
What are the 2 major causes of acute pancreatitis?
alcohol and biliary problems (e.g. gallstone obstruction)
In familial type I dyslipidemia, _____ is increased, and there are elevated blood levels of (triglycerides/cholesterol/both).
I - hyperchylomicronemia; chylomicrons; TG + cholesterol
In familial type IIa dyslipidemia, _____ is increased, and there are elevated blood levels of (triglycerides/cholesterol/both).
IIa - familial hypercholesterolemia; LDL; cholesterol
In familial type IV dyslipidemia, _____ is increased, and there are elevated blood levels of (triglycerides/cholesterol/both).
IV - hypertriglyceridemia; VLDL; TG
Which of the following types of familial dyslipidemia is NOT associated with hypertriglyceridemic pancreatitis: (I/IIa/IV/diabetes mellitus).
IIa - only cholesterol increased, not TG
How does Protease, Serine 1 (PRSS1) lead to acute recurrent pancreatitis?
trypsinogen gain-of-function; premature/excessive activation; blocks autolysis; (note: increased risk of pancreatic adenocarcinoma)
How does Serine Protease Inhibitor, Kasal Type I (SPInK1) cause acute recurrent pancreatitis?
normally protects pancrease from early trypsinogen activation by secreting an inhibitor
T/F.In the context of acute pancreatitis, systemic inflammatory response syndrome (SIRS) necessarily involves infection.
F. NO infection (2 or more of: high temp, high RR, high HR; WBC excess or deficiency)
What is the Grey Turner sign? What does it signify?
bruising of flanks; predict severe attack of acute pancreatitis (sign of retroperitoneal hemorrhage)
What is Cullen's sign? What does it signify?
superficial edema and bruising in subcutaneous fatty tissue around umbilicus; predict acute pancreatitis (forms from digested blood tracks)
In complicated acute pancreatitis, is feeding by jejunal tube or total parenteral nutrition preferred?
What is the main cause of chronic pancreatitis?
Serum IgG4 high and hypergammaglobulinemia. What is a possible disease association?
autoimmune pancreatitis (lymphoplasmacytic infiltration of the pancreas)
What's taken out in the Whipple operation?
head of pancreas; duodenum; gall bladder
The bulk of the pancreas is composed of what cells?
acinar cells (make digestive enzymes)
The vast majority of cancers of the pancreas involve what cells?
What is the demographic of patient that gets pancreatic adenocarcinoma?
tall, obese, diabetic >60 yo (black or Jewish) male smoker who eats lots of meat and has chronic pancreatitis (non-O blood group)
Which of the following genes (all of which are risk factors for pancreatic cancer) leads to the GREATEST risk: (BRCA2/familial atypical multiple mole melanoma/familial pancreatic cancer/familial pancreatitis/HNPCC/Peutz-Jeghers).
Which gene mutation is responsible for familial atypical multiple mole melanoma syndrome: (bcl-2/brca2/p16/p53)
Melanocytic macules of the lips, buccal mucosa, and digits. Multiple gastrointestinal hamartomatous polyps. Diagnosis?
What is Trousseau's sign? When combined with painless obstructive jaundice, back pain, and new onset diabetes mellitus, what does it imply?
migratory thrombophlebitis; pancreatic cancer
Arthalgias, eosinophilia, subcutaneous fat necrosis. Diagnosis?
acinar cell carcinoma of pancreas, caused by lipase excreted into bloodstream (15% of acinar cell carcinomas)
Expression of synaptophysin: (ductal/acnar/neuroendocrine) pancreatic neoplasm.
neuroendocrine (synaptophysin is a marker of neuroendocrine differentiation) (neuroendocrine - islet cell in pancreas)
MEN1: (ductal/acnar/neuroendocrine) pancreatic neoplasm.
Where do tumors appear in MEN-1?
pituitary/parathyroid (can lead to kidney stones)/pancreas-duodenum (gastrinomas arise in duodenum) (MEN-1 is a tumor suppressor gene on chromosome 11)
What are the top 5 hormones neuroendocrine pancreatic neoplasms make?
Necrolytic migratory erythema. What is it? In addition to anemia, diarrhea, and weight loss, what is the diagnosis?
rash in lumbar region, above butt. Glucagonoma, in the context of neuroendocrine pancreatic cancer. (also hyperglycemia and hypoaminoacidemia are symptoms)
Pancreatic cholera syndrome. What's the cause?
VIPoma (neuroendocrine tumor) (also called WDHA-syndrome (Watery Diarrhea with Hypokalemia & Achlorhydria)
Mucin oozing from the ampulla of Vater. Possible cause?
Intraductal papillary mucinous neoplasm
Intraductal papillary mucinous neoplasms are precursors to what?
ductal cancer only (NOT acinar or neuroendocrine)
What needs to be reconnected in a pancreaticoduodenectomy?
tail of pancreas->intestine; stomach->intestine; bile duct->intestine
Obstructive jaundice and weight loss suggests what?
What complication is seen most often in pancreaticoduodenectomy?
delayed gastric emptying
In addition to intraductal papillary mucinous neoplasms, what is another precursor to ductal pancreatic cancer?
pancreatic intraepithelial neoplasm (PanIN)
What are the two main categories that intraductal papillary mucinous neoplasms can be put into?
main duct and branch duct IPMN
The risk of having a cancer is greater with (main/side) duct intraductal papillary mucinous neoplasm.
What is the CEA (carcino embryonic antigen)?
breakdown product of mucin; colon, pancreatic, and bile duct cancers can have a high CEA
What is CA-99?
tumor maker; high for pancreatic and bile duct cancers
Weight is a better measure for (short/long) term nutrition. Height is a better measure for (short/long) term nutrition.
weight - short; height - long
Head circumference is a useful measure of nutrition until what age?
3 years old
How does total body potassium measure lean body mass and body fat?
fat does not contain potassium; use naturally occurring radioactive isotope 40K to determine total body K
What does the DEXA (dual energy x-ray absorptiometry) measure?
soft tissue composition (bone mass)
Alternating light and dark bands of color along individual hair fibers ("flag sign"). What's wrong?
Inflammation of the lip (cheilitis). Cause? What about angular chelitis?
B12 deficiency. (also could be iron deficiency or oral candidiasis); angular chelitis - riboflavin (B2)
Skin breakdown and thinning of hair. Deficiency of what?
Dermatitis, alopecia, edema, glossitis, red skin lesions. (Diarrhea, dermatitis, dementia, death). Diagnosis?
pellagra; niacin deficiency
Discoloration bands in teeth. Cause?
too much fluoride in childhood
Very thin child. Diagnosis? What about a very thin child with a distended belly?
thin - marasmus (energy malnutrition); distended belly - kwashikor (protein malnutrition)
What is the difference between primary and secondary malnutrition?
primary - reduced caloric intake; secondary - inadequate digestion/absorption
Malnutrition in the US occurs more frequently in the (elderly/young).
elderly (around 10%); young (around 1%)
Ghrelin stimulates (hunger/satiety). Leptin stimulates (hunger/satiety).
ghrelin - hunger; leptin - satiety
During starvation, is more nitrogen excreted in the urine at first or after weeks?
more nitrogen excreted at first (1st 5-7 days)
Which of the cells doesn't necessarily have to use glucose as an energy source (as opposed to ketones): (cardiomyocytes/CNS/RBC/WBC)
cardiomyocytes and CNS (CNS initially needs glucose but then can convert to using ketones, but RBCs and WBCs don't have mitochondria) (WBCs DO have mitochondria) (The point made is that after a long period of starvation, only RBCs and WBCs necessarily need glucose to work)
During starvation, plasma insulin levels are (increased/decreased).
decreased (therefore, can free up fatty acids) (glucagon increases)
T/F. Exclusive breast feeding for too long will result in energy malnutrition but not protein malnutrition.
F. results in both
Aflatoxins can cause what cancer?
What is the difference between marasmus and kwoshkor?
marasmus - starvation, no edema, no fatty liver, no skin changes; kwashiorkor - lowering of albumin and visceral proteins; edema, fatty liver, dermatosis
Acrodermatitis enteropathica. What is it? A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
periorificial (mouth, groin) and limb dermatitis (crusty); zinc
Glossitis. A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
iron and folate
Pretibial petechiae. A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
Hyperpigmentation and hepatosplenomegaly. A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
Cretinism. What is it? A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
severely stunted physical and mental growth. iodine
Impaired taste and immunity. A deficiency of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
Pseudotumor cerebri. What is it? A (deficiency/excess) of (calcium/folate/iodine/iron/vitamin A/vitamin C/vitamin D/zinc) causes it.
pressure inside skull increases (can see swelling of optic disk); excess vitamin A
Diarrhea, dermatitis, dementia. Diagnosis? What causes it?
pellagra; vitamin B6 (niacin) deficiency;
Casal's necklace (what is it?); sideroblastic anemia and peripheral neuropathy. What causes it?
hyperpigmentation around neck; vitamin B6 (niacin) deficiency
What causes beriberi? What is the difference between wet and dry beriberi?
vitamin B1 (thiamine) deficiency; wet - cardiomyopathy; low output heart failure (wet - think liquid - think heart); dry - painful polyneuropathy
Wernicke-korsakoff syndrome is caused by a deficiency of what?
vitamin B1 (thiamine)
Which 3 micronutrients are important in wound healing?
zinc, vitamin A & C
What is refeeding syndrome? What's the first sign?
when you refeed a starved person quickly, they may die b/c body starts to make ATP too quickly and depletes phosphate (hypophosphatemic->respiratory failure, arrhythmias); first sign - edema
Which of the following is NOT present in the mucosa of the gall bladder: (columnar absorptive cells/goblet cells/lamina propria/mucous glands/neuroendocrine cells)
goblet and neuroendocrine cells are NOT present (note: mucous glands are in the neck only)
Which of the following layers is NOT present in the gall bladder: (mucosa/submucosa/muscular wall/serosa)
submucosa (also no muscularis mucosa)
What is the most common disease of the gall bladder?
gall stones (cholelithiasis) (90% cholesterol)
What are Rokitansky-Ashoff sinuses?
diverticula in the wall of the gallbladder caused by the presence of stones and increased pressure
The liver has __ (number) zones. The zone closest to the hepatic vein is zone ___.
3 zones; closest to hepatic vein - zone 3
Swollen hepatocyte (ballooning injury). Diagnosis? Cause?
fatty liver disease; loss of osmotic control
Hepatocyte with foamy cytoplasm. Diagnosis? Cause?
feathery degeneration in chronic cholestasis; biliary obstruction->toxic effect of bile salt
Groups of ghost cells in liver. Diagnosis? Cause?
coagulative necrosis (nuclei difficult to see). hepatic artery thrombosis->ischemic injury
Individual mummified haptocyte (apoptosis). Cause?
Inflammation and hepatocytes (necroinflammatory injury). Cause?
chronic viral hepatitis
Histologically, what defines cirrhosis?
NODULES of liver cells in context of bridging FIBROSIS
What is the difference between acute and chronic hepatitis?
chronic - >6 months; acute - days to weeks
T/F. Acute hepatitis can be caused by hepatitis A, B, C, D, and E.
NOT E. (A, B, D > C)
What is the difference between parenchymal collapse and lobular disarray in the context of acute hepatitis?
parenchymal collapse - portal tracts smashed together; lobular disarray - portal tracts AND central vein smashed together
T/F. Chronic hepatitis can be caused by hepatitis A, B, C, D, and E.
B, C (A, D, E NOT included on list in slide)
Which of the following can you definitely use to distinguish chronic from acute hepatitis: (apoptosis/fibrosis/lymphocytes/necroinflammatory necrosis).
fibrosis present in chronic, not in acute; others present in both
Trichrome stains what? What would you use it for in the context of the liver?
collagen; fibrosis in cirrhosis
T/F. The vast majority of people with hepatitis B will die from it.
F. only about 4%
T/F. IgM anti-HBc + HBs Ag is a sign of chronic hepatitis B infection.
F. acute; if chronic - HBs Ag but no IgM anti-HBc
Ground glass hepatocytes. Diagnosis?
T/F. The vast majority of people infected with hepatitis C develop chronic hepatitis.
T (85% do) (Think hepatitis C - Chronic)
T/F. A vaccine exists for HCV.
F. no vaccine b/c it uses a poor fidelity RNA polymerase that gives rise to mutants
HBV is a (DNA/RNA) virus. HCV is a (DNA/RNA) virus.
HBV - DNA; HCV - RNA
Inflammation in portal tracts. HBV or HCV?
HCV (HBV cells looks like ground-glass cells)
Why is autoimmune hepatitis dangerous?
can progress to cirrhosis
What is the most common form of hepatitis?
Acetaminiohen toxicity hepatitis is characterized by zone (1/2/3) coagulative necrosis with (substantial/minimal) inflammation.
zone 3 (around hepatic vein)(with minimal inflammation)(can be confused with ischemic injury or hepatitis)
Isoniazid toxicity hepatitis is characterized by what? What can it mimic?
diffuse necrosis. periportal lymphocytic inflammation; mimic viral hepatitis
Procainamide toxicity hepatitis is characterized by what? What can it mimic?
enhanced smooth ER; ground glass appearance; HBV
Methotrexate toxicity hepatitis is characterized by what? What can it mimic?
portal fibrosis; chronic viral hepatitis (HCV)
Ischemic injury or hepatitis mimics (acetaminophen/isoniazid/methotrexate/procainamide) toxicity.
HBV injury mimics (acetaminophen/isoniazid/methotrexate/procainamide) toxicity.
HCV injury mimics (acetaminophen/isoniazid/methotrexate/procainamide) toxicity.
T/F. Both arteries and veins have the ability to autoregulate resistance.
F. veins can't. that's one reason the liver needs an arterial supply in addition to the portal vein
T/F. If you wipe out the hepatic artery, both the liver and bile duct will survive.
F. the bile duct will die b/c doesn't have portal venous supply
What cell type lines the liver sinusoids? Is the apical or basolateral side facing the lumen?
hepatocyte (called cords); basolateral side faces lumen; apical side faces bile canaliculus
What are kpuffer cells?
macrophages that reside in the liver
What do stellate cells do? Where are they located?
fibroblasts in the liver (responsible for fibrosis)
T/F. The spleen drains directly into the inferior vena cava.
F. drains into portal system->portal hypertension->splenomegaly
After biotransformation, what are 2 methods that substances can be excreted?
bile or urine
What does phase I in modification in the liver involve? What does it?
attaching small water soluble groups (e.g. OH or sulfate groups) to make water soluble; C-P450
Cytochrome p-450 is located in which parts of the cell?
endoplasmic reticulum and microsome
What does phase II in modification in the liver involve?
conjugation to glucuronate, sulfate, or glutathione
T/F. It is necessary to first go through phase I modification, then phase II.
F. some go through II only
Why is taking acetaminophen with alcohol bad?
alcohol upregulates CYP450 2E1; CYP450 2E1 preferentially changes acetaminophen into NAPQI, a toxic reactive intermediate (as opposed to other routes acetaminophen could take); also alcohol depletes glutathione, which is required to conjugate NAPQI
How does acetylcysteine (mucomyst) help with a bad situation involving alcohol and acetaminophen?
repletes glutathione, which is needed to conjugate NAPQI, a reactive intermediate
How is bilirubin taken to the liver?
attached to albumin
How is bilirubin handled by the liver? What does it do with it?
conjugated to glucuronide (single or double); put it in bile
What happens to bilirubin glucuronide in the bile?
bacteria in small intestine convert it to urobilinogen; reabsorbed; goes to kidneys and excreted as urobilin
What causes jaundice?
accumulation of bilirubin in blood and tissues
What are Crigler-Najjar and Gilbert syndromes?
problems with bilirubin conjugation->jaundice
In the context of bile, what do hepatocytes do? Cholangiocytes? Gallbladder?
hepatocytes - secrete bile; cholangiocytes - add electrolytes; gallbladder - concentrates
Bile acids are made of what?
cholesterol (note: can add taurine or glycine to make more water soluble)
Gluconeogenesis and urea synthesis occur in zone (1/2/3).
zone 1 (nearest triad); requires lots of energy
Glycolysis and lipogenesis occur in zone (1/2/3).
Receptor-mediated and active transport occurs in zone (1/2/3).
all; they are zone-independent
Gluconeogenesis is accomplished using mainly what 3 substrates?
lactate (60%); amino acids (30%); glycerol (10%) from lipolysis
Short-term gluconeogenesis is stimulated by what? What about long-term?
short - glucagon; long - glucocorticoids
T/F. LDL is directly formed in the liver.
F. VLDL is formed in the liver; after TG's are taken from VLDL in the plasma, it becomes LDL
Where is HDL made?
liver and small intestine
What do ALT and AST normally do?
transfer amino groups to form pyruvate (ALT) and oxaloacetate (AST) (for gluconeogenesis)
T/F. Elevated ALT and AST levels indicate that increased gluconeogenesis is occuring in the liver.
F. indicates liver injury
Where is AST located in the cell?
mitochondria (m-AST) and cytoplasm
Where is ALT located in the cell?
T/F. The levels of AST and ALT are uniform in zones 1-3.
F. ALT higher in zone 1 than 3 (think ALT - A LoT in zone 1 (lower case L looks like 1)). AST equal in all (think ASt - All Same)
In ischemia, zone (1/2/3) is damaged first.
zone 3 (farthest from triad)
(AST/ALT) has a shorter half life.
AST (think S - shorter)
In early ischemia, is AST or ALT higher? What about later?
early - AST higher (zone 3 damaged; there is little ALT in zone 3); later - ALT (ALT has longer half life than AST)
In tylenol toxicity, is AST or ALT higher initially?
AST (tylenol needs oxygen to be metabolized; central area (zone 3) has little oxygen)->it is damaged more)
AST:ALT ~ 2:1. AST < 350. Diagnosis?
Where is alkaline phosphatase located in the hepatocyte? What does it do?
apical side membrane; digest phosphate esters from lipids
What happens to alkaline phosphatase in cholestasis?
increased alkaline phosphatase in serum; cholestasis - flow of bile blocked->more alkaline phosphatase made in hepatocyte and expressed on cells lining bile duct->more alkaline phosphatase in blood
In bile duct injury, what happens to bilirubin?
bilirubin gets into hepatocyte->gets conjugated with glucuronidate->no energy to make it go into bile->go into blood (this is conjugated bilirubin)
T/F. Elevated alkaline phosphatase in the blood is an indication of hepatocellular, as opposed to cholestatic, injury.
F. alkaline phosphatase is an indicator of cholestatic injury.
T/F. Checking alkaline phosphatase in a pregnant woman can determine cholestatic injury.
F. alkaline phosphatase comes from placenta->irrelevant in pregnant woman; use bile acids in blood instead
T/F. Elevated conjugated bilirubin in the blood is an indication of hepatocellular, as opposed to cholestatic, injury.
F. indicates either hepatocellular or cholestatic->sign of liver insufficiency
T/F. Jaundice is a disease, symptom, and disorder of bilirubin metabolism.
F. not disease
Total bilirubin high; indirect bilirubin high; direct (conjugated) bilirubin - no change; alkaline phosphatase no change. (Hemolysis/liver dysfunction/biliary disease).
hemolysis (indirect is high b/c liver overwhelmed; direct is normal b/c liver working normally)
Total bilirubin high; indirect bilirubin high; direct (conjugated) bilirubin high; alkaline phosphatase no change. (Hemolysis/liver dysfunction/biliary disease).
liver dysfunction (indirect is high b/c liver not processing bilirubin; direct is high b/c hepatocytes don't have ATP to pump it into bile)
Total bilirubin high; indirect bilirubin no change; direct (conjugated) bilirubin high; alkaline phosphatase high. (Hemolysis/liver dysfunction/biliary disease).
biliary disease (indirect is normal b/c liver conjugating bilirubin fine; direct is high b/c can't get rid of it in bile)
What is the difference between acute and chronic hepatitis?
acute < 6 months; chronic > 6 months
AST: 200 (nl 35); ALT: 90 (nl: 35); Alk phos. 130 (nl: 110). Hepatitis or cholestasis?
What is cholestasis? What is a lab measurement indicating cholestasis?
liver disorder characterized by impaired bile flow; elevated serum alkaline phosphatase (w or w/o bilirubin; AST/ALT only mildly abnormal)
(Don't bother knowing) What's going on in Dubin-Johnson Syndrome?
multi-drug resistant protein (MRP2) mutation; can't transport organic ions into bile canuliculus
(Don't bother knowing) What's going on in progressive familial intrahepatic cholestasis type I (Bylers)?
problem in FIC1 (Familial Intrahepatic Cholestasis); can't transport organic ions into bile canuliculus->cholestasis
(Don't bother knowing) What's going on in progressive familial intrahepatic cholestasis type II and benign recurrent intrahepatic cholestasis?
BSEP (Bile Salt Export Pump) mutation; problem getting bile salts into bile canuliculus
Pruritis, RUQ pain, fevers and chills. Diagnosis?
cholestatic liver disease
Which vitamin deficiencies are found in cholestatic liver disease?
fat soluble vitamins (ADEK)
Where is alkaline phosphatase made?
biliary epithelium & hepatocytes; placenta (3rd trimester); intestines (ischemia; brush border); bone (osteomalacia; Piaget; cancers)
What is 5' nucleotidase?
liver specific phosphatase
What is gamma glutamyltranspeptidase (GGT)? When is it elevated?
liver specific enzyme elevated in cholestasis or with drugs that induce microsomal enzymes (etoh, dilantin)
Which of the following is best for looking at dilated bile ducts: (ultrasound/CT/MRI).
ultrasound (MRCP (magnetic retrograde cholangiopancreatography) and ERCP (endoscopic) also good)
What causes both intrahepatic and extrahepatic cholestatic liver disease?
primary sclerosing cholangitis
What causes primary biliary cirrhosis? Does it occur more in men or women? What antibody is found?
autoimmune destruction of small INTRAHEPATIC bile ducts leading to inflammation and fibrosis; 9:1 women:men; anti-mitochondrial antibody (inner mitochondrial membrane enzymes that catalyze oxidative decarboxylation of keto acids)
Fatigue, pruritis. Elevated immunoglobulins, especially IgM; elevated cholesterol; HDL high. What do you suspect? What would be the next test?
primary biliary cirrhosis (lab tests indicate cholestatic pattern of elevated liver enzymes); anti-mitochondrial antibody
What is sicca syndrome? In what GI disease would you find it?
dryness of eyes and mouth caused by autoimmune destruction; primary biliary cirrhosis (autoimmune, against mitochondria)
Which of the following is NOT associated with primary biliary cirrhosis: (fatigue, prutitis, sicca syndrome, cutaneous calcinosis, Raynauds, portal hypertension, bone disease, atherosclerosis, vitamin ADEK deficiency)
atherosclerosis (HDL elevated compared to LDL; NOT at increased risk for atherosclerosis)
Anti-mitochondrial antibody test positive. Diagnosis?
primary biliary cirrhosis
What drug would you use to treat primary biliary cirrhosis?
ursodeoxycholic acid (itching and liver enzymes); vitamins ADEK; cholestyramine (bind bile salts; itching)
More often in men: PBC or PSC?
PSC (primary sclerosing cholangitis) (men around 40); (note: PBC - primary biliary cirrhosis - autoimmune - women more common (women around 60))
Occurs with UC: PBC or PSC?
PSC (primary sclerosing cholangitis) (think: UC and SC are California schools) (note: UC does not imply PSC, but PSC implies UC)
Young man with diarrhea, bloody stools, jaundice, fatigue, itching. Alk phos high; bilirubin high; ALT/AST normal. Diagnosis?
P-ANCA and ANA would suggest (PSC/PBC). Anti-mitochondria would suggest (PSC/PBC).
P-ANCA and ANA - PSC; Mitochondria - PBC
What is autoimmune cholangitis?
AMA-negative PBC; (ANA or Anti-SMA+)
Intrahepatic cholestasis, heart, eye, vertebral defects; characteristic facies. Diagnosis? Cause?
Abagille syndrome; AD JAG1 mutation
Cirrhosis by age 10-15. Diagnosis? Cause?
progressive familial intrahepatic cholestasis (PFIC, Byler's disease); AR FIC-1 mutation
Intermittent attacks of jaundice and itching, but no permanent liver damage. Diagnosis?
benign recurrent intrahepatic cholestasis
Which of the following can have a severe form of cholestatic liver disease in immunocompromised hosts known as fibrosing cholestatic hepatitis: Hep (A/B/C/E)/CMV/EBV?
HBV and HCV (note: all can cause cholestatic presentations)
T/F. Bacterial lipopolysaccharide (LPS) impairs bile acid transport.
T (in the context of sepsis)
Hepatojugular reflex (press on liver->jugular vein bulges out) and elevated indirect bilirubin. Diagnosis?
hepatic congestion (due to right-sided heart failure)
What is Stauffer's syndrome?
paraneoplastic syndrome in absence of hepatic metastases or obstruction
How can sarcoidosis affect the liver?
noncaseating granulomas in liver can obstruct or obliterate small bile ducts
What's Charcot's triad? How is it different from Reynold's pentad? What do they suggest?
fever/rigors, jaundice, RUQ pain. pentad - add hypotension and mental status changes. suggest extrahepatic cholestasis
Which infections (that we've heard about from ID) can cause extrahepatic cholestasis?
strongyloides & ascaris
What demographic of people get gallstones?
4 F's: fat, forty, female, fertile
Patient with possible cholestasis. 1st test? Next? After that?
high ALP; confirm with GGT, 5'NT; ultrasound
Young child with painless rectal bleeding. Diagnosis?
What test would you choose to confirm meckel's diverticlum?
If you suspect Crohn's what 2 tests would you order?
CBC (blood loss) and ESR (test for inflammation)
If you suspect Crohn's, what test would you use to confirm the diagnosis?
Esophagogastroduodenoscopy and colonoscopy
If you suspect celiac disease, and the tTG comes back positive, what would you do to confirm the diagnosis?
What is the most common cause of liver disorder in the US?
nonalcoholic fatty liver disorder (steatohepatitis) (NOT alcoholic liver disease)
Insulin (inhibits/stimulates) the release of FFAs from the adipose tissue. Insulin (inhibits/stimulates) the synthesis of FFAs.
inhibits release; stimulates synthesis
NADPH (inhibits/stimulates) the synthesis of FFAs
(Trivia). How many grams of alcohol are in a can of beer?
12g in 12 oz beer
(Trivia) What is the threshold in g etoh/day for developing alcoholic liver disease?
about 2.5 beers/day for a long time
The metabolism of 1 mol alcohol into acetate results in the production of ___ mol (NAD/NADH).
2 mol of NADH (1 for alcohol->acetaldehyde by alcohol dehydrogenase)(1 for acetaldehyde by aldehyde dehydrogenase)
Why does alcohol favor the synthesis of FFAs?
increase in NADH/NAD ratio; NADH->NADPH
T/F. Histologically, there would be differences between the livers of a person with non-alcoholic fatty liver disease and alcoholic fatty liver disease.
F. no difference!
What 5 characteristics does the metabolic syndrome consist of?
I Require HELP (Insulin Resistance/Hypertension/Elevated triglycerides/Low HDL/Plumpness) (note: metabolic syndrome is associated with non-alcoholic fatty liver disease)
How does insulin resistance contribute to fatty liver? What are the ramifications?
adipose tissue keeps on releasing FFAs -> liver makes more VLDL->LDL; liver makes less HDL
Why do individuals with the PNPLA3 mutation develop fatty liver?
abolish ability of liver cells to break down triglyceride; homozygotes are more likely to develop fatty liver
How does the metabolism of alcohol in the liver create oxidant stress?
Jaundice; nausea and anorexia; abdominal pain; hepatomegaly; fever. Suspicion?
Leukocytosis. AST & ALT < 400; AST double ALT; prolonged prothrombin time; elevated bilirubin, primarily conjugated. Suspicion?
What is a medical treatment of alcoholic hepatitis?
corticosteroids (reduce TNF and IL-6) (reduce short term mortility; not help 2 year mortality)
Mild elevation of AST & ALT; ALT>AST usually less than 3x; high triglycerides, low HDL; high insulin. Elevated uric acid and ferritin; autoimmune markers. Diagnosis?
T/F. Obese people with non-alcoholic fatty liver disease die of liver failure most often.
F. die of cardiovascular problems
T/F. You would use corticosteroids to treat non-alcoholic fatty liver.
F. b/c these people already have insulin problems
What is the most common cause of abnormal liver enzymes?
non alcoholic fatty liver disease
CYP450 is involved in phase (1/2/both) metabolism. It involves (oxidation/reduction).
phase 1; oxidation
What does phase II conjugation involve?
glutathione, sulfonates; glucuronic acid; amino acids
What does CYP450 do? What does it require?
oxidation; transfer electrons from substrate to ferric iron to oxygen; requires NADPH (converted to NADP+)
Phase (1/2/both) conjugation can result in toxic compounds.
What is the extraction ratio?
fraction of drug that is metabolized by "first pass" through stomach and liver after oral administration
What is the oral bioavailability?
1-extraction ratio (amount of drug that goes systemically immediately after eating it)
For drugs with (low/high) extraction ratio, IV and oral doses result in equivalent drug levels.
When is intrinsic clearance the determinant of clearance in drugs with high extraction ratio?
cirrhosis; high extraction ratio->flow limited in normal liver; in cirrhosis, liver enzymes don't work great, so intrinsic clearance (depends on enzymatic metabolism) is determinent
Which of the following are NOT predictors of drug metabolism in cirrhosis: (albumin/ALP/ALT/ascites/AST/bilirubin/encephalopathy/nutritional status/PT)?
NO correlation w/ALP/ALT/AST
T/F. Patients with end stage cirrhosis have (high/low) conjugated bilirubin.
high conjugated; liver disease doesn't affect glucuronidation much; however no ATP to get conjugated bilirubin into bile
You NEED to modify doses of drugs using phase (1/2/both/neither) conjugation in a person with liver disease.
phase 1 (CYP450); phase 2 is preserved in liver disease
(Trivia). What is the most common reason drugs are withdrawn from the market?
drug-induced liver injury
What is the difference between intrinsic and idiosyncratic hepatotoxins?
intrinsic - dose-related; short time to effect; reproducible in animals; idiosyncratic - not dose-related; dependent on host; not reproducible in animals
T/F. Innate immune response is a component of immunologic idiosyncrasy in the context of hepatotoxins.
F! component of metabolic idiosyncrasy (adaptive is a component of immunologic)
The most frequent cause of acute liver failure due to drug ingestion is due to what drug?
Why does ingesting too much acetaminophen cause liver problems?
metabolized by P450 2E1 to NAPQI; deplete glutathione addition to NAPQI; results in bad consequences b/c NAPQI is toxic
How do you treat aceminophen poisoning?
give n-acetylcysteine (component of glutathione, which conjugates to NAPQI)
T/F. Using cortisteroids in the context of drug-induced liver damage is standard.
You would want to monitor liver function in patients taking taking which 3 drugs: (amoxicillin-clavulinate/chlorpromazine/dantrolene/diclofenac/estrogens/INH/ketoconazole/minocycline/phenytoin/sulindac).
isoniazid, chlorpromazine, dantrolene (note: all of them cause liver reactions in people; these 3 are associated with the greatest frequency)
(Trivia). How much bile does the liver secrete per day?
Bile is composed mostly of (bile acids/cholesterol/lipids/protein).
Endogenous cholesterol synthesis in the hepatocyte uses (Acyl CoA-chol ester transferase/cholesteryl ester hydrolase/HMG CoA reductase).
HMG CoA reductase
Formation of bile salts from free cholesterol uses: (7a-hydroxylase/Acyl CoA-chol ester transferase/cholesteryl ester hydrolase/HMG CoA reductase).
Bile salts are made of _____. They are conjugated with ____ and ____ (amino acids).
made of cholesterol; conjugated with taurine and glycine (to make more water soluble)
Primary bile salts are made in the ____. Secondary are made in the ____. Tertiary are made in the ____.
primary - liver; secondary - colon; tertiary - liver
What does lecithin do?
increases ability of bile acids to solubilize cholesterol & protect biliary tract epithelium from damaging detergent effects of bile salts
Through which membrane do hepatocytes secrete bile salts?
Enterohepatic circulation through the small intestine is (active/passive). What about through the colon?
small intestine - active; colon - passive
What hormone is the strongest stimulus for gall bladder contraction?
Why does obstructive jaundice occur with biliary tract obstruction?
bilirubin cannot get excreted->gets backed up into blood
Most gallstones in the US are (cholesterol/pigment) stones. What are pigment stones made of?
cholesterol; pigment stones made of bilirubin
What are the demographic of people with cholesterol gallstones? Why?
female (hormones increase hepatic uptake of cholesterol) >65yo (decrease 7a-hydroxylase activity->decreased bile acids and increased cholesterol)
Which of the following is NOT a contributor to the formation of black pigmnet stones: (chronic hemolysis/cirrhosis/infection/total parental nutrition).
infection (it is a contributor to the formation of brown pigment stones, not black)
What are brown pigment stones made of? What causes them to be made?
calcium bilirubinate and calcium soaps; bacterial infections - associated with infections
What proportion of the US population has gallstones?
10% (only 30% of that 10% have symptoms)
What is the difference between acalculous and calculous acute cholecystitis? The vast majority of cholecystitis is which kind?
presence and absence of stone in; 90% calculous obstruction of cystic duct
What is choledocholithiasis?
stone lodged in common bile duct
What is gallstone ileus? Where does it most commonly occur?
bowel obstruction caused by a gallstone; ileocecal valve
What is Bouvaret's syndrome?
large gallstone that erodes into duodenum from inflamed gallbladder
What drugs can be used to prevent gallstones for people on rapid weight loss programs?
ursodiol & aspirin/NSAIDs (block mucus hypersecretion and cholesterol nucleation)
What's the demographic of people who get gallbladder carcinoma?
elderly female with gallstone (note: it is the most common GI malignancy in Native Americans)
What are symptoms of early gallbladder cancer? What does treatment involve?
nothing; nothing; (median survival 5 months after diagnosis)
Regenerative nodules surrounded by fibrous tissue. Liver tissue. Diagnosis?
What defines portal hypertension? When would complications occur?
When porto-venous gradient is greater than 5 mm Hg; complications - >10 mm Hg
Schistosomiasis causes (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic) portal hypertension.
pre-sinusoidal (eggs shower to veinules; get stuck)
Budd-Chiari syndrome causes (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic) portal hypertension.
The hepatic venous pressure gradient (measured by using wedged and free pressures) is NORMAL in (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic) portal hypertension.
pre-hepatic and pre-sinusoidal (b/c no direct connection from wedge to other side of blockage) AND post-hepatic (both increased) (heart failure)
The hepatic venous pressure gradient (measured by using wedged and free pressures) is INCREASED in (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic) portal hypertension.
sinusoidal and post-sinusoidal
Most complications of cirrhosis result from what?
What happens to the microvasculature in the context of cirrhosis?
activation of stellate cells (lose vitamin A); starts fibrosing in space of Disse
In cirrhotics, the heart beats (faster/slower).
faster, due to dilation of blood vessels, which drops bp
Which of the following is NOT a marker of transition from compensated to decompensated cirrhosis: (ascites/elevated liver enzymes/encephalopathy/jaundice/variceal hemmorhage).
elevated liver enzymes
Why does encephalopathy occur with cirhosis?
portal hypertension->liver doesn't see everything dangerous; liver insufficiency - liver doesn't process everything dangerous
What is the median survival for people with cirrhosis? What about decompensated? Compensated?
9 years; decompensated - 1.6 years; compensated - 12 years
T/F. A hepatic-to-portal pressure gradient greater than 12 mm Hg necessarily leads to varices and/or ascites.
F. not necessarily, but varices and ascites necessarily need a gradient greater than 12 mm Hg to occur
Which of the following is NOT a predictor of esophageal variceal rupture: (Child B-C/pressure/red signs/variceal size).
pressure (not included on list)
(Vasoconstrictors/venodilators) work better for the treatment of esophageal varices.
vasoconstrictors (venodilators don't do much b/c pressure is already low on the venous side)
For a person with esophageal varices, would you use a (beta-1/beta-2/both) blocker?
both; both slow heart rate and constrict arteries->decrease portal hypertension
How does octreotide work in the context of acute esophageal bleed?
constrict arterioles; decrease portal blood flow (synthetic analog of vasopressin)
T/F. Obstructing the portal vein will cause ascites.
F. does NOT; however obstructing the hepatic vein does (need sinusoidal congestion)
Sodium excretion is (increased/decreased) in people with ascites.
decreased; body thinks bp is low, retain sodium
In Budd-Chiari, the protein content of the ascites is (low/high). In cirrhosis, the protein content in the ascites is (low/high).
budd-chiari - high; cirrhosis - low (in cirrhosis, the hepatic sinusoid is LESS leaky b/c fibrous tissue deposition)
Cirrhosis & late budd chiari. Serum-ascites albumin gradient (high/low). Ascites protein (high/low).
SAAG high (little albumin in ascites); Ascites protein low (sinusoids not permeable b/c fibrosis)
Cardiac ascites, early budd chiari, veno-occlusive disease. Serum ascites albumin gradient (high/low). Ascites protein (high/low).
SAAG high (little albumin in ascites); Ascites protein high (sinusoids normal - let protein through but not albumin)
Malignancy, TB. Serum ascites albumin gradient (high/low). Ascites protein (high/low).
SAAG low (lots of algumin in ascites); Ascites protein high (everything goes through b/c lots of inflamed tissue).
In management of ascites you would NOT recommend (diuretics/reduced Na intake/reduced water intake).
reduced water intake b/c not a problem with ADH
What is the difference between diuretic-intractable and diuretic-resistant ascites?
intractable - dose cannot be achieved due to complications; resistant - no response
What is hepatorenal syndrome?
renal failure in the context of cirrhosis (renal vasoconstriction b/c activation of neurohumoral systems->failure)
Cirrhosis->(increased/decreased) arteriolar resistance->(increased/decreased) effective arterial blood volume->activation of neurohumoral systems.
decreased arteriolar resistance; decreased effective arterial blood volume
What is asterixis? What does it suggest?
hand flaps when told to stop traffic; hepatic encephalopathy
Which of the following would you NOT suggest for a person with hepatic encephalopathy: (reduce protein/TIPS/lactulose).
TIPS - make worse b/c liver already doesn't take out NH3 well (note: lactulose makes colon more acidic->traps ammonia)
Hepatitis (A/B/C/D/E) can be transmitted fecal oral.
A&E (think 1st and last letters of the possibilities - like mouth and anus)
A patient who has sex with someone who is hepatitis (A/B/C/D/E) positive would be MOST likely to contract that virus.
B & D most likely (C possible)
A mother who is hepatitis (A/B/C/D/E) positive would be MOST likely to transmit it to her fetus.
B & D
Vaccines can protect against hepatitis (A/B/C/D/E).
A,B, and D by association with B
Can a person who has both HBsAg and anti-HBs negative weeks after possible infection be positive for HBV?
yes; window period around 32 weeks (usually don't see HBsAg with anti-HBs b/c cleared)
Which develops first: anti-HBc or anti-HBs?
anti-HBc (think C comes before S in alphabet)
A person with anti-HBs, negative for anti-HBe, negative for anti-HBc. What happened?
vaccinated for HBV
Elevated HBV DNA and ALT. What's going on?
chronic hep B
In addition to anti-retrovirals, what else is used to treat HBV?
pegylated interferon alpha (about 1/3 are cured)
The standard of care for treatment of hepatitis C is what 2 drugs?
pegylated interferon alpha (not for insane people) and ribavirin (not for pregnant women)
(alpha1-antitrypsin deficiency/cystic fibrosis/hemochromatosis/familial intrahepatic cholestasis/Wilson's) is the most common inherited liver disease in infants. What about in adults?
infants - alpha1; adults - hemochromatosis
What's the problem in Wilson's disease?
AR disease for transport of copper; mutation in metal-transporting P-type ATPase (ATP7B)->cannot get rid of in bile->toxic accumulation in hepatocyte, free copper goes all over body
Kayser-fleischer rings. Suspicion? Does it necessarily lead to a diagnosis?
Wilson's disease (copper in cornea); cholestatic diseases can also present
Serum ceruloplasmin is normally (increased/decreased) in Wilson's disease?
normally decreased (formation of ceruloplasmin requires P-type ATPase to get copper into same location as aceruloplasmin)
What is D-penicillamine?
chelating agent used in the treatment of Wilson's disease
What is trientine?
chelating agent used in the treatment of Wilson's disease
Why should people with Wilson's take zinc?
use same transporter in intestine; decrease uptake of copper
What's the problem in hereditary hemochromatosis?
AR disorder, excessive iron deposition in tissues, especially liver; HFE gene causes increased intestinal iron absorption and utilization
Cirrhosis, bronze skin, diabetes. Diagnosis? Why the diabetes?
hemochromatosis; diabetes - iron deposition in kidneys->diabetes
How do you treat hemochromatosis?
bleed the person; avoid vitamin C, which mobilizes iron
Where is alpha-1 antitrypsin made? If patient has a deficiency, what's the result?
only in hepatocyte; lung problems b/c alpha-1 antitrypsin prevents elastase from working (w/o alpha-1, elastase does too much)
Why does alpha-1 antitrypsin deficiency result in liver injury?
can't export misfolded proteins->overload liver cell->die; (however if it's a double-null mutation, there will not be liver injury)
Supplementing alpha-1 antitrypsin in a person with this deficiency will improve liver status.
F. alpha-1 antitrypsin is not needed in the liver; it's overload causes the problems
What is the most common primary tumor of the liver?
hemangiomas (benign neoplasms composed of dilated blood vessels)
What is the most common tumor in the first year of life?
infantile hemangioendotheliomas; (can lead to high-output cardiac failure due to AV shunting or thrombocytopenia due to platelet sequestration)
Exposure to thorotrast (contrast), vinyl chloride (dry cleaning), arsenic (groundwater) cause what liver tumor?
angiosarcoma (malignant vascular neoplasm) AND hepatocellular carcinoma
Focal nodular hyperplasia in the liver. What is the demographic? What cell is the tumor made of?
30-50 year old female; hepatocyte (it is benign)
Well circumscribed tumor of liver, less than 5 cm. CENTRAL SCAR. What is it? Is it dangerous? Is it clonal?
focal nodular hyperplasia; no risk for malignancy; not clonal (thought to arise from vascular malformations)
Hepatic adenoma. what is the demographic?
women of reproductive age with oral contraceptive use in past
Patient with history of androgen use and/or glycogen storage diseases (types I and III). Which hepatic neoplasm are they most likely to have: (focal nodular hyperplasia/hepatic adenoma/von myenberg complex/bild duct adenoma/cystadenoma).
Person comes in with hepatic adenoma. What 2 risks do you tell them about?
10% progress to cancer; rupture can lead to intraperitoneal hemmorhage
Male infant with mutation in Wnt-signaling pathway and elevated AFP. Suspicion: (hepatocellular carcinoma/cysadenocarcinoma/cholangiocarcinoma/angiosarcoma/hepatoblastoma).
hepatoblastoma (needs to be less than 3 yo for this to be viable diagnosis) (male:female 2:1)
Elevated AFP necessarily implies hepatoblastoma, as opposed to other liver cancers.
F. can also imply hepatocellular carcinoma
Histologically, predominately primitive epithelial cells with admixture of immature mesenchymal cells: (hepatocellular carcinoma/cysadenocarcinoma/cholangiocarcinoma/angiosarcoma/hepatoblastoma).
hepatoblastoma (biphenotypic presentation)
What is the most common primary liver carcinoma?
hepatocellular carcinoma (80%) (note: most common carcinoma (hemangioma is most common primary tumor))
The main reason why hepatocellular carcinoma is common and increasing in the US is due to (HBV/HCV/fatty liver)
HCV due to exposures in '70's
Person who's 25 years old with non-cirrhotic liver. More like to be fibrolamellar carcinoma or typical hepatocellular carcinoma?
FLC (note: FLC is a subtype of HCC (average age of presentation of HCC is 60))
If a fibrolamellar carcinoma of the liver metastasizes, where does it go?
What is a Klatskin tumor?
cholangiocarcinoma arising in the hilum of the liver
Which of the following is NOT a risk factor for INTRA hepatic cholangiocarcinoma: (alcohol/Caroli's disease/cirrhosis/HCV/parasitic infections/PSC).
Caroli's, parasites, PSC (these cause EXTRA hepatic cholangiocarcinoma) (note: Caroli's disease is an inherited disorder causing dilation of the bile ducts) (things associated with cirrhosis cause INTRAhepatic cholangiocarcinoma
Other than pancreas, stomach, colon, what other cancers commonly metastasize to the liver?
lung & breast
Why does thrombocytopenia occur with cirrhosis?
How can effective arterial blood volume be decreased without volume loss?
What is hepatorenal syndrome?
cirrhosis->active of neurohumoral systems->renal vasoconstriction
Which of the following is the MOST common indication for liver transplantation: (acute hepatic necrosis/biliary atresia/cancer/cholestatic liver disease/non-cholestatic cirrhosis).
Which of the following patients would NOT be a candidate for liver transplantation, according to the Milan criteria: (1 lesion 5 cm/1 lesion 4 cm + 1 lesion 3 cm/3 lesions of 3 cm each/AFP 500).
1 lesion 4 cm + 1 lesion 3 cm (Milan criteria: single lesion < 5cm/3 lesions <= 3 cm/AFP>500)
All of the following may recur after transplantation except: (PBC/PSC/HBV/HCV/Wilson)
Wilson - inherited problem of liver cells
How is acute liver failure defined?
hepatic encephalopathy AND coagulopathy within 8 weeks of jaundice
The King's college criteria for acute liver failure does NOT consider which of the following: (age/bilirubin/creatinine/encephalopathy/enzymes/jaundice/prothrombin time)
enzymes - NO AST or ALT
Which of the following criteria is used for evaluation for acute liver failure: (Child-Pugh classification/King's college criteria/MELD).
King's college. (note: Child-Pugh and MELD are used for chronic liver disease)
A person with a Child-Pugh score of C is in (good/bad) shape.
bad (A - mild; B - moderate; C - severe)
The MELD score takes what 3 factors into account? What does it assess?
SHORT TERM survival for patients with cirrhosis; bilirubin/INR/creatinine
Bilirubin elevation is a sign of (hepatocellular injury/cholestasis/both).
What is the definition of portal hypertension?
portal to hepatic venous gradient > 5 mmHg; complications arise when gradient > 10 mm Hg
The measured hepatic venous pressure gradient using the wedge would be elevated in which of the following situations: (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic).
sinusoidal & post-sinusoidal
The ascites is due to portal hypertension when the serum-ascites albumin gradient is (> or <) than 1.1 g/dl.
> (ascites fluid is a transudate, which doesn't contain cells or protein)
In which of the following would you NOT find ascites: (pre-hepatic/pre-sinusoidal/sinusoidal/post-sinusoidal/post-hepatic).
pre-hepatic and pre-sinusoidal b/c ascites fluid comes from the liver
Which of the following does NOT lead to hepatic encephalopathy: (excess protein/GI bleeding/sedatives/hypnotics/ascites/diuretics/infections/TIPS).
ascites does not directly lead to hepatic encephlopathy, which is caused by increased NH3 (neutral crosses BBB) in the blood
Why does lactulose prevent hepatic encephalopathy?
increase lactic acid in colon->decrease pH->make NH3->NH4+, which doesn't get out of the colon b/c it's charged
(Trivia) Why is the ALT relatively lower in alcoholic hepatitis?
vitamin B6 (pyridoxal phosphate) deficiency
What's wrong in Wilson's disease?
defective ATP7B gene->problem pumping copper into bile & incorporating it into ceruloplasmin
Which vitamin would you avoid in hemochromatosis?
C b/c it releases iron from cells
T/F. An AST:ALT>4 indicates cirrhosis.
F. AST, ALT have no bearing on determining HOW badly the liver is doing; it just says that the liver is doing badly