Gastric Disorders + Nutrition Flashcards
1
Q
Which of the following will inhibit gastric acid secretion?
a) somatostatin
b) vagal stimulation
c) antral distension
d) histamine
e) calcium
A
a) somatostatin
2
Q
What is the effect on lesions to the lateral hypothalamus on hunger?
A
leads to loss of appetite (hypophagia)
3
Q
What are the major nutritional complications of celiac disease?
A
iron deficiency (anemia)
lactose intolerance
osteopenia
vitamin B deficiencies
altered bowel habits
calorie/protein deficiency
4
Q
What is the clinical workup for carbohydrate malabsorption?
A
breath test with lactose, fructose
lactose intolerance genetic typing
5
Q
What is the impact of liver blood flow on high extraction drugs? Low extraction drugs?
A
high: sensitive
low: insensitive
6
Q
What is this?
A
Peutz-Jeghers syndrome
7
Q
What is adiposity rebound?
A
the inflection point between a declining BMI and an increasing BMI that occurs between age 5 and 7
if rebound occurs earlier, increases risk of being overweight later in live
8
Q
What are the symptoms of iodine deficiency?
A
goiter (thyroid gland hyperplasia in response to elevated TSH), hypothyroidism
can affect fetuses in utero
9
Q
What is the only identified factor that increases hunger?
A
ghrelin
levels increase by fasting, fall after a meal
10
Q
How are smaller sugars (from starches) broken down into monosaccharides?
A
disaccharidases on the brush border
11
Q
What specific genetic variants predispose patients to obesity?
A
leptin deficiency (chromosome 7)
defective leptin receptor (chromosome 1)
defective pro-opiomelanocortin (chromosome 2)
deficient melanocortin 4 receptor (chromosome 18)
obesity-associated FTO gene
12
Q
How are proteins absorbed in brush border endothelium?
A
via carrier protein transport and glutathione transport
13
Q
What are the risk factors for thiamine deficiency?
A
alcoholism, eating disorders, GI surgery
14
Q
Where is amylin released from? When is it released?
A
co-secreted with insulin from pancreatic islet beta-cells
released in response to nutritional stimuli
inhibits gastric emptying and glucagon secretion, reduces short-term food intake
15
Q
What are the major complications of autoimmune gastritis?
A
1) hyperplasia of gastrin producing cells and enterochromaffin-like cells
2) development of carcinoid tumors
3) development of epithelial dysplasia followed by adenocarcinoma
16
Q
What is the pathogenesis of multifocal chronic atrophic gastritis?
A
associated with dietary and environmental risk facters
also associated with H. pylori infection
17
Q
A patient comes in with stomach pain. He is currently taking omeprazole to help with the pain. You give him a urea breath test that comes back negative. What can you conclude?
a) he definitely does not have an H. pylori infection
b) he definitely has an H. pylori infection
c) he might have an H. pylori infection, but he needs serologic testing
d) he might have an H. pylori infection, but he needs fecal antigen testing
A
c) he might have an H. pylori infection, but he needs serologic testing
PPIs interfere with H. pylori growth, leading to false negatives on non-serologic testing
18
Q
What are the main mechanisms that protect the luminal surface of epithelial cells from autodigestion?
A
mucus secretion (impermeable to H+)
bicarbonate secretion (neutralizes acid)
intercellular tight junctions
blood flow removes acid and supplies nutrients
muscularis mucosa limits injury
19
Q
When trying to lose weight, why is exercise less effective as a treatment than dietary restriction?
A
energetically, physical activity and exercise does not burn sufficient calories to cause a significant change in energy balance
20
Q
What is hunger?
A
biological sensation that initiates eating
21
Q
Which of the following mechanisms plays an important role in the development of a gastric ulcer in a 32 year old patient with rheumatoid arthritis taking ibuprofen 800 mg three times daily for one month?
a) reduction in blood flow to the gastric mucosa
b) ion trapping and low pKa of ibuprofen
c) excessive production of acid induced by ibuprofen
d) concomitant infection with H. pylori
e) autoimmune damage to gastric epithelium
A
a) reduction in blood flow to the gastric mucosa
22
Q
How are glucose and galactose transported?
A
active transport via a carrier that also transports Na+ (2 Na/ 1 glucose)
23
Q
What is the pathogenesis of Whipple’s disease?
A
bacteria enter body via small intestine and spread to other organs through lymphatics and blood
primary abnormality is an immunological deficiency in the host that allows this bacteria to cause disease
involvements: mitral and aortic valve, CNS, mesenteric lymph nodes, lungs, kidneys, small intestine
24
Q
What are the macroscopic features of appendicitis? Microscopic?
A
macroscopic: dilation of lumen and congested serosal vessels, dilated distal lumen full of purulent material, organ becomes soft and hemorrhagic
microscopic: acute inflammatory features
25
What is the thermodynamic definition of obesity?
an energy imbalance where energy-in exceeds energy-out (ie. more calories consumed than calories expended)
26
Which of the following statements regarding Helicobacter pylori is not true?
a) transmission of H. pylori mirrors transmission of polio virus
b) H. pylori infection may be a factor in the development of gastric lymphoma
c) postprandial release of gastrin and gastric acid is higher in patients with H. pylori antral gastritis
d) patients infected with H. pylori have an eradication rate of greater than 90% when treated with antibiotics
e) there seems to be "familial clustering" of H. pylori infection
c) postprandial release of gastrin and gastric acid is higher in patients with H. pylori antral gastritis
27
When is CCK released in relation to food intake?
released postprandially from I cells in the small intestine
reduces food intake through CCK-1 receptors on the vagus nerve
28
What is the general process of drug metabolism?
broken into two phases
phase I - usually involves oxidation or reduction by CYP enzymes (activates prodrugs, inactivates standard drugs)
Phase II - modifies drug metabolite with water soluble adducts to enable elimination (ex. glucuronidation)
29
What is the difference between high extraction and low extraction drugs? What are examples of each?
high extraction = very efficiently cleared by the liver, low extraction = less efficient
high: morphine, propranolol, lidocaine
low: digoxin, diazepam, pheytoin
30
What are the complications of appendicitis?
perforation, peritonitis, abscess formation, septic thrombophlebitis
31
What are the dietary risk factors of stomach carcinomas?
dried/salted fish, pickeled vegetables, contaminated foods/rices
32
What are risk factors for iron deficiency?
young age, menstruation, pregnancy, blood loss, malabsorptive disorders (ex. celiac disease), bariatric surgery
33
What are hamartomas?
tumor-like malformations characterized by an abnormal mixture and overgrowth of tissue indigenous to the region of the malformation
34
A patient is given chemotherapy with 5-fluorouracil and irinotecan. After two treatments, the patient had neutropenia. Given that these drugs do not typically cause bone marrow suppression at the doses given to this patient, which of the following factors might have contributed to neutropenia and thrombocytopenia in this case?
a) 5-fluorouracil induced an immune-mediated thrombocytopenia
b) elimination of an active metabolite of irinotecan was impaired in this patient resulting in greater toxicity
c) 5-fluorouracil inhibited the metabolism of irinotecan resulting in greater toxicity
d) the subject has bone marrow infiltration by adenocarcinoma
b) elimination of an active metabolite of irinotecan was impaired in this patient resulting in greater toxicity
35
What is the effect of CCK on hunger?
it enhances satiation
36
Where are the major sites of chronic peptic ulcer?
anterior and posterior walls of duodenum
antral and prepyloric regions of stomach
lower end of esophagus
Meckel's diverticulum with gastric mucosa
37
What are the characteristics of helicobacter pylori (shape, gram stain, etc.)?
curved, motile gram-negative bacterium
requires microaerophilic conditions for growth
38
What is the average weight of a 1 year old?
10 kg
39
What are the secretory components of oxyntic glands? Where are they found?
parietal cell --\> secretes HCl
ECL --\> secretes histamine
Chief cell --\> pepsinogen
some D cells --\> somatostatin
located in gastric body and fundus
40
What is satation?
level of fullness during a meal which regulates the amoutn of food consumed
41
When can BMI be used for children?
\> 2 years of age
42
What is the clinical workup for fat malabsorption?
fecal fat studies (48-72 hour stool collection, fecal elastase, fecal electrolytes)
vitamin B12 specific testing
43
What is the mechanism of hypothalamic obesity?
ventromedial hypothalamus damage --\> hyperphagia --\> no response to leptin --\> weight gain
44
What is the effect of ghrelin on hunger?
increases hunger
45
What are the symptoms of celiac disease?
diarrhea, steatorrhea, weight loss, development of symptoms related to nutritional deficiency
## Footnote
*related to malabsorption*
46
What are the major host defense mechanisms of the mucosal immune system?
physical barrier: mucus, epithelial cells, secretory IgA
antimicrobials: trefoil peptides, paneth cell peptides
specialized immune response: antigen uptake, lymphocyte trafficking, effector cells
*also indigenous microbiota*
47
What enzyme hydrolyzes starch? Where does it come from? What is the mechanism of hydrolysis?
alpha amylase
salivary and pancreatic secretions
attacks interior 1,6 bonds (not at branch points)
48
What are the risk factors for niacin deficiency?
malabsorptive GI disorders, eating disorders, alcoholism, isoniazid use
49
Which function would NOT be directly affected by inhibition of the Na/K ATPase?
a) absorption of 2-monoglycerides
b) absorption of galactose
c) secretion of bile salts by the liver
d) absorption of amino acids
e) salivary secretion
a) absorption of 2-monoglycerides
50
What is the effect of niacin deficiency?
pellagra --\> 4 "Ds": dermatitis, diarrhea, dementia, death
51
If a patient is diagnosed with menetrier disease, what major complication should you be concerned about?
gastric adenocarcinoma
52
What are the unique characteristics of visceral fat cells?
more active lipolysis, extra adrenergic and glucocorticoid receptors, and increased responsiveness to glucocorticoids
53
What are the major risks associated with gastric carcinoma? Cardia carcinoma?
gastric: H. pylori infection, chronic gastritis
cardia: alcohol and tobacco use
54
What are the clinical features of gastric carcinomas?
no specific symptoms, depends on size/location
vomiting if upper GI
anemia from occult blood loss
55
What are the causative factors relating obesity and insulin resistance to metabolic syndrome?
1) FFAs are increased (impairs insulin action)
2) intracellular lipid accumulation
3) circulating cytokines modify insulin action
56
How is Zollinger Ellison Syndrome diagnosed?
measuring fasting serum gastrin (\> 1000)
57
What is the effect of amylin on hunger?
enhances satiation
58
How is helicobacter pylori transmitted?
person-to-person contact
## Footnote
*oral-oral in industrialized countries, fecal-oral in developing countries*
59
What is early gastric carcinoma?
carcinoma confined to the mucosa or mucosa + submucosa of stomach (regardless of lymph metastasis)
60
Which brain regions are involved in hypothalamic obesity?
ventromedial or paraventricular region of the hypothalamus or amygdala
## Footnote
*regions responsible for integrating metabolic info on nutrient stores provided by leptin with afferent sensory info on food availability*
61
What is the role of the ileum in absorption?
fat (and fat-soluble vitamin) absorption
bile salt recycling
ileocecal valve and ileal "break"
62
What are the two key factors in developing metabolic syndrome?
insulin resistance
obesity
63
What is the pathophysiology of zollinger-ellison syndrome?
islet cell tumors that secrete gastrin --\> increases parietal cell mass --\> increased acid secretion
64
What are the gross features of stomach carcinomas?
fungiating, ulcerating, nodular, diffuse, or superficial
65
What controls release of gastrin in the stomach? What is its effect on acid production?
G cells produce gastrin
Gastrin --\> CCK-B receptor --\> GPCR triggers increase of IP3/Ca2+ --\> activates the H/K ATPase to release acid into the stomach lumen
66
What vitamins and minerals do gastric bypass patients need to supplement with either food or oral supplements due to anatomical changes?
B vitamins
iron
fat soluble vitamins
67
What are the functions of IgA?
confines bacteria to the mucus layer of the intestinal lumen
binds to invasive pathogens
neutralizes microbial toxins and other inflammatory products
neutralization of antigens and pathogens, uptake of luminal antigens
68
Where is leptin released from? When is it released?
leptin is produced from adipose cells
secreted in response to an increase in fat mass
69
Why does deposition of fat in lower body segments (buttocks, thigh, hips) reduce the risk for obesity-associated morbidity?
lower body fat is associated less with visceral fat and more with subcutaneous fat
## Footnote
*visceral fat depot releases adipokines that impact multiple organ systems*
70
What is the effect of vitamin D deficiency?
rickets (children), osteomalacia (adults), muscle pain, weakness
71
What is the inductive vs. effector site of mucosal immunity?
inductive site: antigen sampling and presentation
effector site: site of effector immune action
72
What is the pathophysiology of celiac disease?
lack of a specific mucosal peptidase, results in accumulation of gluten or glutamine containing breakdown products and accumulation of toxic peptides
initiates hypersensitivity reactions in the intestinal mucosa
73
What types of drugs are likely to produce weight gain?
psychoactive agents, anti-depressants, anti-diabetic agents, corticosteroids
74
What are crypt abscesses?
collections of neutrophils in the lumen of a gland
75
What are the effects of vitamin A deficiency?
affects function of WBCs, epithelial cells, conjunctiva and cornea of eye
leads to night blindness, bitot spots, and corneal ulceration
76
How is ectopic fat measured?
MRI, magnetic resonance spectroscopy (MRS)
77
What are major pathologic consequences of obesity?
joint immobility and arthralgias (hips, knees, ankles, feet)
GERD and urinary incontinence (increased abdominal pressure)
edema and stasis pigmentation (accumulation of water and hemodynamic changes)
excessive sweating and skin infections
78
Pancreatitis patients often require pancreatic enzyme supplementation to properly emulsify fats and absorb nutrients. Which nutrients are they at most risk of malabsorbing?
a) B-vitamins, fat soluble vitamins, iron and zinc
b) dietary fats, carbohydrates, fat soluble vitamins, zinc
c) iron, B-vitamins, iodine
b) dietary fats, carbohydrates, fat soluble vitamins, zinc
79
What is the pathogenes if H. pylori associated chronic gastritis?
H. pylori can grow in acidic environments due to urease activity that neutralizes the acid
also produces proteins that assist with infection into the gastric mucosa
80
How is H. plyori diagnosed?
serologic testing (IgG antibody)
fecal antigen testing
urea breath test
81
What are the major characteristics of dietary therapy to treat EoE?
typical approach is a hypoallergenic diet that eliminates 6 major allergens
## Footnote
*often can be reintroduced gradually*
82
When individuals with obesity reduce their caloric intake, they typically feel hungry which makes long-term weight loss and maintenace difficult. What are the underlying mechanisms that cause them to feel hungrier?
calorie reduction and weight loss results in biological adaptation
changes in gut hormones that regulate eating behavior and appetite --\> ghrelin rises, GLP-1 and PYY levels fall
83
How is visceral adipose tissue measured clinically?
by measuring waist circumference during the physical exam
84
A patient with previously well documented duodenal ulcer and gastrointestinal bleeding was treated for H. pylori infection with 14 days of omeprazole 20 mg BiD, amoxicillin 1 gm BiD, clarithromycin 500 mg BiD. He presents with recurrent epigastric pain 2 months after completion of therapy. The best approach to this patient would be:
a) treatment with omeprazole 20 mg BiD, metronidazole 500 mg BiD, clarithromycin 500 mg BiD for 14 days
b) upper gastrointestinal endoscopy
c) carbon labeled urea breath test
d) measure serum IgG antibody to H. pylori
e) omeprazole 20 mg QD for 4 weeks and re-evaluate
c) carbon labeled urea breath test
85
What questions would you ask a patient when taking a history to determine what relevant factors may have contributed to his/her weight gain?
when did you start to gain weight?
were there specific life events or factors that played a role (puberty, pregnancy, menopause, smoking cessation, etc)?
86
What are the clinical features of carcinoid syndrome?
paroxysms of flushing, asthma-like attacks, diarrhea, right-sided heart failure (stenosis of tricuspid and pulmonary valves)
can also cause peptic ulcers and malabsorption
87
What is the effect of cirrhosis on drug pharmacokinetics?
reduced hepatocyte mass (impacts low extraction drugs)
reduced portal blood flow (reduced first pass metabolism)
thickened hepatic sinusoidal basement membrane, shunting blood flow (impacts high extraction drugs)
ascites (increased volume of distribution of hydrophilic drugs)
low plasma albumin levels (impacts low extraction drugs)
88
What is the effect of lesions to the ventromedial hypothalamus on hunber?
induces excessive hunger (hyperphagia)
89
What are the gross findings of celiac disease? Microscopic findings?
gross: mucosa with lost ridges and convolutions (becomes flat)
microscopic: shortening and broadening of villi with loss of villi, enterocytes smaller and crowded, increase in intraepithelial lymphocytes, increased inflammation in lamina propria, increased mitotic activity in crypts (elongation of crypts)
90
What is Gilbert syndrome? What is its effect on drug metabolism?
recessive genetic condition that impairs function of UTGA1 gene
leads to impaired conjugation of bilirubin and select drugs (irinotecan, lamotrigine, raloxifene, simvastatin)
requires dose adjustment due to impaired drug elimination
91
What types of ulcers are associated with pernicious anemia?
non-benign ulcers secondary to autoimmune gastritis with achlorhydria
92
What explains the difference in the time course of azithromycin plasma concentration between patients with and without Roux-en-Y gastric bypass?
a) metabolism of azithromycin is enhanced in post-RYGB subjects
b) oral absorption of azithromycin is impaired after RYGB resulting in lower peak plasma concentration
c) plasma half-life of azithromycin is shorter in post-RYGB subjects
d) distribution of azithromycin to adipose tissue is diminished in post-RYGB subjects
b) oral absorption of azithromycin is impaired after RYGB resulting in lower peak plasma concentration
93
In children, a BMI range of 85-95% is considered:
a) normal
b) overweight
c) obese
d) underweight
b) overweight
## Footnote
*\>95% is obese*
94
What are the effects of vitamin C deficiency?
gingivitis, tooth loss, corkscrew hairs, perifollicular hemorrhages, intraarticular hemorrhages, bruising, poor wound healing
95
What are the complications of diffuse antral chronic gastritis?
1) prepyloric and duodenal ulcers
2) gastric lymphoma
3) risk of gastric carcinoma
96
What is the effect of prostaglandins on acid production in the stomach?
prostaglandins activate a GPCR that decreases cAMP levels--\> inhibits the H/K ATPase to reduce acid release into the stomach lumen
97
What is the role of epithelial cells in innate immunity?
physical and immune barrier
expression of pattern recognition receptors for the PAMPs on bacteria and viral species
98
Clearance of drugs by the liver depends on intrinsic metabolic capacity, hepatic blood flow, and the extent to which the drug is bound by plasma proteins. Which statement best describes clearance of a specific drug in advanced cirrhosis?
a) elimination of digoxin in cirrhosis is enhanced by low hepatic blood flow
b) the bioavailability of morphine is enhanced
c) morphine clearance by the liver is impaired because of hypoalbuminemia
d) the bioavailability of oral morphine is lower in cirrhosis
b) the bioavailability of morphine is enhanced
## Footnote
*cirrhosis leads to reduced portal blood flow, which decreases first pass metabolism and increases bioavailability of high extraction drugs*
99
What is the effect of magnesium deficiency?
diarrhea (in Chron's disease or malabsorptive syndromes)
rare to actually have a true deficiency
100
What is the general pattern of weight changes in women throughout life?
weight status predicted by weight in youth
weight gain during pregnancy is variable
central fat deposition increases after menopause
101
What is the effect of zinc deficiency?
impaired growth, skin rashes, hypogonadism/delayed puberty, hair loss, anorexia
102
What is the histology of Peutz-Jegher's syndrome?
branching bundles of smooth musclee derived from muscularis mucosae
branches covered by normal epithelium with a normal lamina propria
paneth cells and endocrine cells at base of crypts
103
Where is GLP-1 released from? When is it released?
enteroendocrine L cells in the distal ileum and colon
released after food ingestion in response to nutrient intake
104
How are proteins hydrolyzed in the gut?
gastric/pancreatic enzymes breaks downto small peptides --\> final hydrolysis by brush border peptidases --\> hydrolysis to AA in enterocytes
105
What mutations are associated with Puetz-Jegher's syndrome?
mutation in STK11/LKB1 gene
106
What is the role of the jejunum in absorption?
protein, carbohydrate breakdown
absorption
107
Where does visceral fat drain? What is the effect of its drainage?
drains into portal venous system
FFAs are secreted onto the liver to stimulate hepatic triglyceride secretion
108
What is the effect of vitamin B12 deficiency?
elevated homocysteine and methylmalonic acid levels
megaloblastic anemia, glossitis, myelopathy, neuropathy, neurologic features (ex. parasthesias, ataxia)
109
All of the following are unique properties of the gut associated lymphoid tissue (GALT) except:
a) microfold cells
b) initiates both innate and adaptive immune responses
c) induction of immunological tolerance
d) preferential production of IgA
b) initiates both innate and adaptive immune responses
## Footnote
*while innate and adaptive immune responses occur in the GALT, these responses also occur in the peripheral immune system so they are not unique to GALT*
110
What are the causes/risk factors for vitamin B12 deficiency?
uptake requires intrinsic factor
risk factors: advanced age, atrophic gastritis, vegan diet, gastrectomy, bariatric surgery, some medications (metformin, PPIs), pernicious anemia
111
What is the effect of iron deficiency?
hypochromic, microcytic anemia (leading to fatigue, SOB, cold intolerance)
pica (consumption of non-food items)
112
What is satiety?
level of hunger after a meal is consumed which regulates the frequency of eating
113
What is enterohepatic recirculation?
recycling process for drugs that are eliminated through the hepatobiliary tract
involves cleavage of drugs by enzymes and recirculation
114
What is oral tolerance?
induction of mucosal and systemic non-responsiveness to luminal antigens
115
Medications used to treat obesity that target receptors in the appetite center typically cause an 8-12% weight loss. Why arent they more effective? What regulatory processes prevent further weight loss?
redundant biological systems are in place to maintain appetite regulation
it is fundamental to survival to seek food
hormonal and neuropeptide signals have feedback loops to diminish their effects
116
How is trypsinogen activated?
activated to trypsin via enterokinase and by trypsin itself
117
Where does drug absorption predominantly occur? Why?
small intestine
due to large surface area, long transit time, pH of gut lumen (weak bases best absorbed here)
118
What are the symptoms of Crohn's disease?
diarrhea, abdominal pain, weight loss, fever, rectal bleeding and perianal fistulae (if colonic involvement)
119
How is pepsinogen activation triggered?
by H+ production or by pepsin itself
120
Would a drug with a high first pass metabolism more likely have a low or high bioavailability?
low
## Footnote
*high first pass metabolism means much of the drug is eliminated before reaching systemic circulation*
121
What is the role of the colon in absorption?
water, salt, short-chain fat absorption
processing of stool
122
What is the mechanism of H. pylori induced gastritis?
H. plyori preferentially damages D cells, leading to decreased somatostatin release and thus increased acid secretion
123
What are the symptoms of appendicitis?
lower right quadrant pain, nausea, vomiting, low-grade fever
124
How is chymotrypsinogen activated?
activated to chymotrypsin via trypsin
125
What is the etiology/pathogenesis of appendicitis?
bacterial infection often precipitated by obstructed appendiceal lumen (leads to increased luminal pressure, vascular compromise, bacterial overgrowth)
126
After how many months should birth weight double? Triple?
4-5 months
12 months
127
Which of the following statements might be correct regarding drug absorption after Roux-en-Y gastric bypass?
a) absorption of ibuprofen (pKa = 4.4) will be impaired because of reduced gastric surface area
b) a drug with high first pass metabolism such as atorvastatin will have lower availability after RYGB
c) a drug absorbed mainly through the small intestine such as omeprazole will achieve maximum plasma concentrations following an oral dose more rapidly after RYGB
d) certain prodrugs that require biotransformation in the liver such as enalapril may have reduced activity
c) a drug absorbed mainly through the small intestine such as omeprazole will achieve maximum plasma concentrations following an oral dose more rapidly after RYGB
## Footnote
*shorter path for the drug to go before it gets absorbed in the small intestine*
128
What is the effect of intestinal bypass on peak plasma concentration of drugs?
decreases peak plasma concentration (due to lost absorptive surface area)
129
What agent is principally responsible for carcinoid syndrome?
serotonin (derived from dietary tryptophan)
130
Which statement best explains how gastric bypass surgery (e.g. Roux-en-Y) might interfere with oral absorption of drugs?
a) a less acidic luminal pH may enhance absorption of drugs that are weak acids
b) bypassing the proximal small intestine may reduce bioavailability for drugs with high first pass metabolism
c) bypassing the proximal small intestine may enhance bioavailability for drugs that are substrates for p-glycoprotein
d) a more acidic luminal pH may enhance absorption of drugs that are weak bases
d) a more acidic luminal pH may enhance absorption of drugs that are weak bases
131
What is the morphology of diffuse antral chronic gastritis?
acute and chronic nucosal inflammation associated with lymphoid follicles
rarely includes intestinal metaplasia
132
What are the effects of leptin on neurons in the ARC?
1) inhibiting neurons that coexpress the orexigenic (increased food intake) hormones NPY and AGRP
2) stimulating neurons that coexpress anorexigenic (reduced food intake) hormones POMC and CART
133
What are the complications of Crohn's disease?
local: subacute intestinal obstruction, perforation and fistula formation, adenocarcinoma
systemic: amyloidosis, ankylosing spondylitis and polyarthritis
134
What is the role of the mouth, esophagus, and stomach in digestion?
mechanical processing and release of food and liquid to the small bowel
production of intrinsic factor for vitamin B12
135
What is dumping syndrome?
occurs when the contents of the stomach empty too quickly into the small intestine, drawing excess fluid in and causing nausea/cramping/diarrhea
## Footnote
*can occur after gastric bypass surgery*
136
Where are proteins absorbed?
stomach (with pepsin)
small bowel (with pancreatic enzymes, endothelial/brush border enzymes)
137
How does gastric cancer spread?
through gastric wall to adjacent organs
lymphatic spread
vascular spread
Krukenberg: metastasis to ovaries
138
What controls release of ACh in the stomach? How does it affect acid production?
controlled by Vagus innervation
ACh --\> M3 receptor in gastral parietal cell --\> GPCR triiggers increase of IP3/Ca2+ --\> activates the H/K ATPase to release acid into the stomach lumen
139
A 30 y.o. female was recently diagnosed with celiac disease and has started on a gluten free diet. She reports that she would like to get pregnant and is askign for nutrition advice on what vitamins she needs to take to prepare her body for pregnancy. What do you suggest?
a) prenatal vitamins and a blood work to check CBC and iron panel along with serum folate, B12, and vitamin D
b) prenatal vitamins only as they are a good source of extra vitamins needed in celiac disease
c) digestive enzymes, B-complex, multivitamin, iron supplement
a) prenatal vitamins and a blood work to check CBC and iron panel along with serum folate, B12, and vitamin D
140
How does mucus secretion protect the stomach?
mucus is relatively impermeable to H+, so acid does not get through the mucus to the surface epithelial cells
141
What are the two major mechanisms of injury in NSAID induced ulcers?
1) topical mechanism causing a back diffusion of H+ into the cells (short lasting injury, rapid healing)
2) decreased prostaglandin synthesis has systemic effects that take out the protection mechanisms of gastric mucosa (decreased mucus secretion, bicarbonate secretion, and blood flow)
142
What supplements are important to take after gastric bypass surgery?
B-vitamins, vitamin D, calcium, iron
143
What are risk factors for iodine deficiency?
living in areas with iodine-poor soil
avoidance of (iodized) salt
144
What is the effect of riboflavin deficiency?
weakness, glossitis, angular stomatitis, cheilosis
145
Among the various determinants of obesity, which ones are remedial? How would you counsel a patient?
psychosocial or behavioral factors --\> counseling
discontinuing any weight-gaining medications
146
What is the effect of peptide YY (PYY) on hunger?
enhances satiation
147
What are risk factors for zinc deficiency?
malabsroptive disorders, eating disorders, malnutrition, genetic disorder (acrodermatitis enteropathica)
148
A 67 y.o. farmer has a breakfast of eggs, bacon, ham, grits and cheese, fried potatoes, biscuits with syrup, buttermilk, and coffee before beginning a long day in the field. Which of the following hormones is released by the presence of fat and protein in the small intestine and helps to decrease gastric emptying?
a) CCK
b) GIP
c) gastrin
d) motilin
e) secretin
a) CCK
149
What is dysbiosis?
alterations of intestinal flora away from baseeline/equilibrium
150
What controls release of histamine in the stomach? How does it control acid production?
ECL cells release histamine
Histamine --\> H2 receptor --\> GPCR triggers increase of cAMP --\> activates the H/K ATPase to release acid into the stomach lumen
151
What are the microscopic features of chronic peptic ulcers?
four recognizable layers:
zone of fibrinopurulent exudates (surface)
zone of necrotic tissue
zone of granulation tissue
zone of fibrous tissue (deep)
152
Where are disaccharidases located?
glycocalyx of brush border
153
Why is lipodystrophy (reduction or absence of subcutaneous fat) associated with higher risk of metabolic syndrome?
subcutaneous fat depots are important for energy storage
when these are absent, excess energy is stored ectopically in organs (ex. liver)
154
Intestinal epithelial cells serve an immunological function by:
a) initiating innate immune responses
b) serving as a physical barrier that excludes antigens
c) transport and secrete IgA
d) all of the above
d) all of the above
## Footnote
*Intestinal epithelial cells perform function beyond the absorption of nutrients. They initiate innate immune responses through expression of TLRs, exclud antigens via tight junctions, and transport IgA antibodies from plasma cells in the lamina propria to the lumen of the gut.*
155
How do amino acids leave mucosal cells?
slowly via facilitated diffusion
156
Where is visceral adipose tissue?
adipose tissue within the abdominal cavity, below abdominal muscles, that is comprised of omental and mesenteric adipose tissue + adipose tissue of the retroperitoneal and perinephric regions
157
What is the etiology of Chron's disease?
unknown
genetic predisposition (jewish populations and scandinavian countries)
also related to infections, immunologic, psycho-somatic factors
158
What are the microscopic features of Crohn's disease?
sarcoid type granulomas
fissuring ulcerations
transmural inflammation
submucosal widening with inflammation, fibrosis, lymphangiectasia, and neural hyperplasia
occasional crypt abcesses
159
What are the two main compartments of the gastric mucosa?
superficial foveolar compartment --\> surface epithelial cell lining
deeper glandular compartment --\> variable glands in different gastric regions
160
What differentiates acute and chronic gastritis?
acute = active = neutrophils present
chronic = chronic inflammation = lymphocytes and plasma cells
161
What is the function of isomaltase?
breaks terminal 1,6 bonds of saccharides (into glucose)
162
What is the pathophysiology of obesity-induced hypertension?
- underlying hemodynamic alterations
- increase in sympathetic nervous activity
- insulin resistance, activation of the renin-angiotensin system
163
What is the role of the duodenum in absorption?
release of pancreatic enzymes
bicarbonate neutralization
mineral absorption including iron
164
What are the two major functions of the mucosal immune system?
1) host defense
2) tolerance to food antigens and commensal bacteria
165
How is H. pylori infection typically acquired?
usually acquired at a young age due to poor sanitory conditions (especially contaminated water supply)
166
A 56 year old male undergoes a surgical procedure for a benign pancreatic mass resulting on removal of \> 90% of his pancreas. Several months later he complains of ongoing foul-smelling diarrhea which occurs after eating. A 72-hour fecal fat and fecal elastase are sent on a high fat diet. What would you expect to find and why?
a) fecal fat 26 g/day (high), fecal elastase 550 ug/g (normal)
b) fecal fat 4 g/day (normal), fecal elastase 45 ug/g (low)
c) fecal fat 26 g/day (high), fecal elastase 45 ug/g (low)
d) fecal fat 4 g/day (normal), fecal elastase 550 ug/g (normal)
c) fecal fat 26 g/day (high), fecal elastase 45 ug/g (low)
## Footnote
*fecal fat should be elevated due to decreased pancreatic enzymes (like fecal elastase)*
167
What are the major complications of chronic peptic ulcers?
perforation, hemorrhage, fibrosis leading to pyloric stenosis, acquired diverticula, rare malignant transformation
168
Describe the mechanism of diarrhea that may be seen in some patients with Zollinger Ellison syndrome.
excessive amounts of acid that reach the duodenum can denature pancreatic enzymes resulting in maldigestion of fat and protein with resultant diarrhea
secondary mechanism = direct acid damage to small intestinal epithelium with secretory diarrhea
169
What are the risk factors for folic acid deficiency?
alcoholism, malabsorptive GI disorders, bariatric surgery, restrictive diets, certain medications
170
Which one of the following is NOT stimulated by CCK?
a) secretion of bile by the liver
b) secretion of pancreatic HCO3-
c) secretion of pancreatic enzymes
d) relaxation of the sphincter of Oddi
e) contraction of gall bladder smooth muscle
a) secretion of bile by the liver
171
What is the classic presentation of a child with celiac disease?
poor weight gain, distended abdomen
172
What are the major complications of celiac disease?
10-15% develop tumors (lymphomas)
ulcerative jejunoileitis
173
What is the pathogenesis of diffuse antral chronic gastritis?
associated with H. pylori infection
174
What are the symptoms of zollinger-ellison syndrome?
peptic ulcer (frequently in proximal duodenum)
diarrhea (denaturation of pancreatic enzymes)
175
What is the effect of GLP-1 on hunger?
enhances satiation
176
Where is fat absorbed?
mouth/stomach: mechanical digestion and mixing
small bowel: enzymes (lipase) and bile facilitate breakdown and absorption
177
What are the clinical manifestations of malabsorption of fat?
characteristic diarrhea (foul smelling, floats in toilet, difficult to clear with flushing)
178
What is the effect of intestinal bypass on drug absorption due to pH alterations?
impairs absorption of weak acids, enhance absorption of weak bases
179
What is the average daily weight gain in the first 3-4 months? First year? Second year?
3-4 months: 20-30 grams
first year: 15-20 grams
second year: 5-10 grams
180
What is the impact of intrinsic hepatic metabolism on high extraction drugs? Low extraction?
high: insensitive
low: sensitive
* high extraction drug clearance is driven primarily by blood flow*
181
What types of secretory cells are in pyloric glands?
G cells --\> gastrin
D cells --\> somatostatin
*in the antrum of the stomach*
182
What is the function of sucrase?
breaks down sucrose (into glucose and fructose)
breaks down maltose (into glucose and glucose)
183
What is the usual distribution of carcionma of the stomach?
prepyloric region, pyloric antrum, along lesser curvature, and (less commonly) cardia/body
184
What are the three systems for amino acid absorption?
1) neutral system I (for neutral amino acids)
2) basic system (for basic amino acids)
3) neutral system II (imino system - for proline, hydroxyproline, sarcosine, and other glycines)
185
Where is the main site of leptin signaling?
hypothalamic arcuate nucleus (ARC)
186
What are the diagnostic tests for celiac disease?
antigliadin antibodies, antiendomysial antibodies, anti-tissue transglutaminase antibodies
187
What is the gross pathology of Crohn's disease?
discontinuous and serpiginous ulcers
strictures
cobble-stone appearance of involved mucosa
188
What is the impact of protein binding on high extraction drugs? Low extraction drugs?
high: insensitive
low: sensitive
189
What is ectopic fat?
deposition of fat in non-adipose tissue
## Footnote
*major sites: pancreas, skeletal muscle, heart, liver*
190
What is the clinical presentation of Whipple's disease?
systemic bacterial disease, predominantly affecting middle-aged males who present with migratory polyarthralgia, steatorrhea, and wasting
symptoms: malaise, weight loss, diarrhea (malabsorption), arthritis
191
What are paneth cells?
cells at the base of intestinal crypts that produce antimicrobial peptides
## Footnote
*not present in large intestines*
192
What is Peutz-Jegher's syndrome?
a dominant hereditary disorder characterized by intestinal polyposis and mucocutaneous melanin pigmentation
polyps most common in small bowel, lobulated or pedunculated
193
What are the risk factors for riboflavin deficiency?
alcoholism, eating disorders, cystic fibrosis, celiac disease, malabsorptive disorders
194
What is the effect of intestinal bypass on bioavailability?
blunts first pass metabolism --\> increases bioavailability
## Footnote
*drugs that require longer times for absorption may have decreased bioavailability*
195
What are the effects of folic acid deficiency?
increase in homocysteine levels
megaloblastic anemia, fatigue, shortness of breath
neural tube defects in fetuses
196
What is the anatomical distribution of Crohn's disease?
ileocecal region most common
colonic disease or both
197
What is the mechanism of injury in gastric H. pylori infection?
attaches to the apical membrane of gastric epithelial cells causing direct injury
damage results in an immune response that furthers inflammation and damage
198
What is the effect of obesity on the respiratory system?
increases in the mechanical work of breathing leads to ventilatory insufficiency
199
What is the presentation of cystic fibrosis in children?
recurrent respiratory infections, poor weight gain, edema, fat malabsorption
200
How are hexoses transported?
down a concentration gradient with GLUT transporters
## Footnote
*can also be transported against a concentration gradient with a sodium co-transporter*
201
What pathology is associated with the histological changes seen on the right?
chronic gastritis
## Footnote
*superficial plasmacytic infiltrate, lymphoid aggregates*
202
What is the waterlow criteria?
a scale to assess malnutrition based on changes in weight related to height
203
What is the effect of thiamine deficiency?
buildup of lactate and TCA cycle intermediates
manifests as beriberi (dry --\> peripheral neuropathy, wet --\> neuropathy + heart failure, or cerebral --\> Wernicke-Korsakoff)
204
Where are carbohydrates absorbed?
upper GI (mostly digested mechanically and with salivary enzymes)
stomach (mechanically)
small bowel (brush border enzymes)
*absorbed by diffusion and transport*
205
Which statement explains why co-administration of nilotinib with irinotecan might be dangerous?
a) both drugs may independently suppres bone marrow hematopoiesis
b) nilotinib induces UDP-glucuronosyltransferase-1 (UGT1A1) which is required for irinotecan activation
c) nilotinib inhibits UDP-glucouronosyltransferase-1 (UGT1A1) which is required for Phase II metabolism and clearance of irinotecan active metabolites
d) irinotecan inhibits UDP-glucouronosyltransferase-1 (UGT1A1) which is required for Phase II metabolism and clearance of nilotinib
c) nilotinib inhibits UDP-glucouronosyltransferase-1 (UGT1A1) which is required for Phase II metabolism and clearance of irinotecan active metabolites
206
What is somatostatinoma syndrome?
somatostatin-producing tumors that are rare
symptoms: diabetes, diarrhea, steatorrhea, hypochlorhydria
207
Explain the mechanism of iron deficiency in patients with undiagnosed or uncontrolled celiac disease.
patients with celiac disease have villous atrophy in the proximal small bowel, mainly in the duodenum
atrophy impairs absorption
since iron is best absorbed in proximal small bowel (including duodenum), it is affected
208
Where are the neurons of the reward pathways of the brain? What areas receive this information?
dopaminergic neurons in the ventral tegmental area and substantia nigra
nucleus accumbens, striatum, orbitofrontal cortex receive and integrate the info
209
When is the peak of diagnosis for inflammatory bowel disease?
peaks in late adolescence and early twenties
210
How are endocrine neoplasms of the gut classified?
based on embryologic derivation from the site of origin
211
What are M (microfold) cells?
cells above germinal centers in the gut lumen that create pockets for antigens
212
What are the clinical manifestations of protein absorption?
muscle breakdown, anasarca, irregular bowel habits
213
What is the pathogenesis of autoimmune chronic gastritis?
destruction of parietal cells by antibodies directed against parietal cells and intrinsic factor
214
What is the relationship between a sedentary lifestyle and weight gain?
restricted physical activity causes weight gain and often leads to overfeeding
215
What is the relationship between the height of children and their parents?
girls = [(fathers height - 5 in) + mothers height]/2
boys = [(mothers height + 5 in) + fathers height]/2
216
The gastric zymogen, pepsinogen, is converted to the active enzyme pepsin by:
a) gastric HCl
b) gastrin
c) enterokinase
d) acetylcholine
e) intrinsic factor
a) gastric HCl
217
How can risk of NSAID induced ulcers be mitigated?
use of oral prostaglandins (misoprostol) with NSAIDs
acid suppression with PPIs
use of selective COX2 NSAIDs
218
What is the effect of somatostatin on acid production in the stomach?
Somatostatin binds to GPCR --\> blocks increase in cAMP --\> inhibits the H/K ATPase to decrease acid release into the stomach lumen
219
What is the function of maltase?
breaks terminal 1,4 bonds of saccharides (into glucose)
220
What are the three major components of daily total energy exposure?
resting metabolic rate, thermic effect of feeding, energy expenditure of physical activity
221
What is the pathology of autoimmune gastritis?
mucosa of the body and fundus of the stomach is selectively affected (antrum spared)
decreased parietal cells, increased lymphocytes and plasma cells in deep mucosa
pseudopyloric and intestinal metaplasia
222
What are the three factors that determine hepatic clearance?
intrinsic liver metabolism, liver blood flow, plasma protein binding of the drug
223
What is celiac disease?
a malabsorptive disorder, usually starting in childhood, that is due to sensitivity to gluten and/or breakdown products of gluten
leads to mucosal damage
*similar pathology can be seen in soybean or cow-milk protein sensitivities*
224
Where is PPY released from? When is it released?
synthesized and released from endocrine L cells in the distal gut
released in response to food consumption (especially fat), suppressed in the fasted state
225
What characteristics of carcinoids increase likelihood of malignancy?
size of origin, size of intramural penetration
226
What is the presentation of inflammatory bowel disease in adolescents?
poor growth, growth hormone resistance, pubertal delay
227
A 40 year old male has eosinophilic esophagitis and has started on a six food elimination diet protocol to treat his food allergies where he removes wheat, dairy, eggs, soy, nuts, fish. He likes to exercise regularly and is concerned about having a healthy diet. What macronutrients and micronutrients are you concerned could be lacking from this restricted diet?
a) fiber, calcium, iron, sodium, carbohydrates
b) fiber, protein, vitamin D, B-vitamins
c) fiber, calories, protein, monosaturated fats
d) fiber, calories, proteins, trace minerals
b) fiber, protein, vitamin D, B-vitamins
228
What is the pathology of Whipple's disease?
dilated intestine, thick and rigid
thickened mesentery
villous atrophy (variable degree)
numerous macrophages in the lamina propria
229
What is the mechanism of autoimmune gastritis?
autoimmune destruction of parietal cells
results in hypochlorhydia, loss of intrinsic factor (and inadequate vitamin B12 absorption leading to pernicious anemia)
230
What is the clinical workup for protein loss or malabsorption?
small bowel biopsy
231
What is bioavailability?
fraction of an administered dose of unchanged drug that reaches systemic circulation
232
What is first pass metabolism?
the phenomenon in which a drug is eliminated before it reaches systemic circulation
233
What dose adjustments should be considered in patients with hepatic cirrhosis?
reduced dose for high extraction drugs
monitor free drug concentration for low extraction drugs with high protein bindings
higher loading dose for hydrophilic drugs if ascites
caution for drugs with narrow therapeutic windows
use caution for renally eliminated drugs
234
What is the general relationship between obesity and genetics?
multifactorial (genetics + environment)
some genetic syndromes lead to obesity (ex. Prader-Willi)
235
During a patient's hospitalization following a Roux-en-Y gastric bypass, the patient reported to have increased sensitivity to ethanol following surgery. Which of the following provides the best explanation for this observation?
a) weight loss reduced the volume of distribution for ethanol
b) first pass metabolism of ethanol is lower after surgery
c) time to maximum plasma ethanol concentration is shorter after surgery
d) hepatic metabolism of ethanol is enhanced after surgery
c) time to maximum plasma ethanol concentration is shorter after surgery
236
What is the cause of Whipple's diease?
tropheryma whippelii (rod shaped bacterium) infection systemically
237
What factors during pregnancy play a role in newborn body weight and future development of obesity?
poor glycemic control, obesity, and excessive weight gain during pregnancy
238
What factors are secreted by adipocytes?
leptin
cytokines (IL-6, TNF-alpha)
prothrombotic agents (PAI-1)
angiotensinogen
adiponectin
239
What is menetrier disease?
a rare disease associated with excessive secretion of TGF-alpha
causes diffuse hyperplasia of the foveolar epithelium of body and fundus
causes hypoproteinemia
symptoms: weight loss, diarrhea, peripheral edema, icnreased risk of gastric adenocarcinoma
240
What are the major components of management of celiac disease?
CELIAC
## Footnote
**C**onsultation with dietitians
**E**ducation about the disease
**L**ifelong adherence to gluten-free diet
**I**dentification and treatment of nutritional deficiencies
**A**ccess to an advocacy group
**C**ontinuous long-term follow-up by a multidisciplinary team
241
What is the function of lactase?
breaks down lactose (into glucose and galactose)
242
What is a normal amount of weight loss in the first few days of life?
5-10% of birth weight
243
A 35 y.o. man presents with 3 months of abodminal pain, diarrhea with blood, and weight loss. He is mildly anemic with an elevated C-reactive protein. Endoscopy confirms the clinical suspicion of Crohn's disease. Each of the following mechanisms have been suggested to play a role in the pathogenesis of this inflammatory bowel disease except:
a) increased intestinal permeability
b) expression of susceptibility genes
c) impaired IgA production
d) impaired innate immunity
c) impaired IgA production
## Footnote
* the precise pathogenesis of IBD is unknown, however contributing factors have been identified*
* family histories suggests genetic factors that confer susceptibility --\> specifically genes related to innate immune responses*
244
What are the clinical manifestations of carbohydrate malabsorption?
bloating, darrhea, fatigue
245
What are the risk factors for vitamin C deficiency?
alcoholism, restrictive diets, cancer cachexia
246
How is fructose absorbed?
through facilitated diffusion down its gradient
## Footnote
*specific and saturable*
247
What are the causes of hypothalamic obesity? What are the presenting symptoms?
causes: trauma, tumor, inflammatory disease, surgery in posterior fossa, increased intracranial pressure
symptoms: 1) headache, vomiting, diminished vision; 2) impaired endocrine function with reproductive effects, diabetes insipidus, and thyroid or adrenal insufficiency; 3) neurologic and physiologic derangements (convulsions, coma, somnolence, hypothermia/hyperthermia)
248
What are the risk factors for vitamin D deficiency?
exclusive breast feeding (infants), avoidance of sun exposure, dark skin pigmentation, aging, malabsorptive disorders, obesity
