Wk 2: IBD/Digestion & Absorption Flashcards
1
Q
Acarbose
A
Alpha Glucosidase Inhibitor: slows down CHO digestion, requiring less insulin activity
2
Q
Beano
A
Alpha Galactosidase (enzyme that humans lack) required to break down “Raffinose” and “Stachyose”
3
Q
SGLT2 Inhibitors
A
Inhibit glucose uptake, specifically in kidneys “gliflozin” suffix Ex’s: Canagliflozin, Dapagliflozin, Empagliflozin
4
Q
What are 2 tests to assess CHO metabolism?
A
Breath Test & Reducing sugars in feces
5
Q
How does the breath test work to assess CHO metabolism?
A
Measure unabsorbed CHO by measuring H2, methane (CH4) & other gases and acids
6
Q
What are some examples and exceptions to reducing sugars in feces that can assess CHO metabolism?
A
Reducing sugars: fructose, glucose/galactose, lactose NOT sucrose nor starch
7
Q
What are 3 stimulants of parietal cells?
A
Ach, Gastrin, Histamine
8
Q
How are zymogens from the pancreas activated by the small intestine for protein digestion?
A
Enteropeptidase in duodenum’s microvilli activate Trypsinogen into Trypsin
Trypsin cleaves more Trypsinogen & protease precursors: chymotrypsinogen, procarboxypeptidase, & proelastase into their active forms
9
Q
What substances (& their sources!) pass through the Ampulla of Vater to reach the small intestine?
A
Bile salts (from the common bile duct) & protease precursors (from the pancreatic duct)
10
Q
How do peptides & amino acids enter epithelial cells?
A
PEPT1 at the microvilli surface bring in peptides, which are then broken down into AA’s
Peptidases [AA Transporter] bring in AA’s directly from Na/aa gradient
11
Q
What is Hartnup Disorder & how might it present?
A
Deficiency of neutral AA transporter: SLC6A19=B(0)AT1
Mostly asymptomatic bc neutral aa’s can be taken up as di/tri peptides, although condition can progress…
12
Q
What is Hartnup Disorder?
A
Insufficient neutral aa transport, especially w/ Tryptophan which can then lead to Niacin deficiency
13
Q
How does Hartnup Disorder present?
A
3D’s: Dementia, Diarrhea, Dermatitis (C3/C4 dermatome) w/ a circumferential “broad collar rash”-Casal Necklace
3D’s also described as “Pellagra” disease
14
Q
What is the Tx of Hartnup Disorder?
A
High protein diet & nicotinic acid
15
Q
How does the pancreas digest phospholipids?
A
Pancreas-> Prophospholipase A2 which is then cleaved by Trypsin into Phospholipase A2
16
Q
What can patients lacking a pancreas take to help digest macronutrients?
A
Pancrelipase
Each capsule w/ 5000 USP units of lipase, 17,000 USP units of protease & 27,000 USP units of amylase
17
Q
What are the 3 transport pathways in the GI system?
A
Pumps (active)
Channels (passive)
Carriers (passive); “exchangers:” move in opp directions vs. “cotransporters:” move in same direction
18
Q
What are 2 ex’s of neurocrine effectors that stimulate Cl secretion?
A
Ach & VIP
19
Q
What are the 2 main classes of endogenous regulators in ion transport? (Give ex’s)
A
Cyclic Nucleotide Dependent (i) & Ca Dependent (ii)
i) VIP, Prostaglandins, Guanylin (cGMP) & 5’AMP/Adenosine
ii) Ach, Histamine, 5-Hydroxytryptamine & Bile Acids
20
Q
How is absorption affected by GI motility?
A
Dependent on rate of fluid/nutrients across epithelium
21
Q
How do reflexes control motility & blood flow in the GI?
A
Secondary activation of nerves & myofibroblast sheaths
Long Reflex: vagovagal reflex activates stretch receptors
Short Reflex: activates cholinergic efferents-> Cl as brushing mucosa induces 5-HT from eterochromaffin cells
22
Q
How does food move in the small intestine post-prandially? Which region is the exception?
A
Via low amplitude, irregular contractions; mixing
EXCEPT in distal ileum: forceful bolus contractions
->emptying (giving an added pause to salvage fluids/nutrients)
23
Q
Describe the 2 motor activities of the GI system; which is the main motor reponse to eating?
A
1) Propagation: moving out (HAPC/LAPC)
2) Segmental: mixing (single/bursts) *majority*
24
Q
Contrast High Amplitude Propagated Contractions (HAPC) vs. LAPC
A
HAPC:
amplitude >100 mmHg
frequency: 3-6x/day
function: mass mvt of colonic contents
defecation
LAPC:
amplitude <50 mmHg
>100x/day
transport fluid
assoc w/ abdominal distension & flatuluence
25
What are the 2 intestinal *ion transport mechanisms* that the small intestine and colon share?
**Cl secretion** & **Electroneutral NaCl absorption**
26
What are intestinal ion transport mechanisms unique to the small intestine?
HCO3- secretion
Na (& bile acid) coupled nutrient absorption
Proton coupled nutrient absorption
Ca (throughout) & Fe absorption (proximal)
27
What are intestinal ion transport mechanisms unique to the colon?
Electrogenic Na absorption
Short chain FA absorption
K absorption/secretion
28
Where are indigestible fibers and carbohydrates degraded? Effects?
In colon by bacteria, generating short chain FA's-\>
colonocyte fuel
29
Describe 2 mediators involved in Cl secretion
**Guanylin** & **5' AMP/Adenosine**
30
Describe the source of **Guanylin** & its effects
Source: enteroendocrine cells
Stimulates epithelial Cl secretion & affects kidney salt mgmt
31
Describe the source of **5'AMP/Adenosine** & its effects
Released by *neutrophils* & *micro-organisms* & *cytokines* (largely in setting of infection)
Endogenous cyclic nucleotide dependent regulator of ion transport that activates Cl- secretion
32
Where is most bile reabsorbed & what is its main effect?
Ileum, via nutrient coupled mechanisms
Act as laxative, inducing diarrhea
33
How is the type of diarrhea determined?
Stool Gap: 290 mmol/kg-2[Na+K of stool]
Secretory gap \<50
Osmotic gap\>100
34
Describe osmotic diarrhea
H2O absorbed passively, dependent on luminal substance absorption
*Lactose* can remain behind undigested
Poorly absorbed salts (ie: MgSO4)
*Sorbitol*
35
Describe secretory diarrhea & 1 classic source
Excess Cl- secretion (ie: Vibrio Cholera: non-invasive but potent toxin)
36
Describe the drug class & MOA of the *anti-diarrheal***Loperamide**
Opioid Agonist, acts on colon's *myenteric plexus*
_Long reflex_ ↓ mass movements & SM tone
↑ time of material in colon & fluid absorption
37
Describe the drug class & MOA of the anti-diarrheal *Diphenoxylate-Atropine*
* Diphenoxylate:* opioid-agonist that ↓ propagation & ↑ absorption
* Atropine*: added to ↓ risk of dependence bc high doses causes anticholinergic AE's (ie: tachycardia)
38
Describe the class & MOA of the constipation drug **Bisacodyl**
Stimulant laxative
Stimulates enteric nerves-\>colonic contractions
39
Describe the class & MOA of the constipation drug **Polyethylene Glycol**
Osmotic Laxative
Osmotic gradient used to draw H2O into lumen
40
Describe the class & MOA of the constipation drug **Lubiprostone** [Amitiza]
*Bicyclic Fatty Acid*
Selectively activates *Type II Cl channel* in apical membrane, ↑ intestinal fluid secretion
Activates *Prostaglandin receptors*, mediating intestinal fluid secretion, ↑ tight junction integrity & function
41
Describe the class & MOA of the constipation drug **Linaclotide** [Linzess]
Oligopeptide agonist of guanylate cyclase 2C
↑ HCO3- and Cl- secretion via ↑ CGMP & induction of PKGII and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
42
What are the induction therapies for active mild-moderate, severe & refractory *Ulcerative Colitis*?
mild-mod: **Aminosalicylate** & consider topical application for L sided disease, if local to rectum/sigmoid colon
severe: **Glucocorticoids**
refractory: **Biologic** (*Anti-TNF*); Cyclosporine (rare)
43
What are **maintenance therapies** for *Ulcerative Colitis*?
Aminosalicylates-\>Azathioprine (steroid sparing)
-\>Biologic \*reqs regular IV infusion\*
44
When is *surgery* indicated in **Ulcerative Colitis**? Prognosis?
Refractoriness, Toxic Megalon, Obstruction, Hemorrhage, Dysplasia/Cancer
~30% of patients will have proctocolectomy
UC doesn't recur post-surgery
45
What are the *induction therapies* for active mild-moderate & severe **Crohn's Disease**?
mild-mod: **Aminosalicylate** & **Budesonide**
severe: **Glucocorticoids** & **Biologics**
46
What are the *maintenance therapies* for **Crohn's Disease**?
**Azathioprine** (purine analogue) & **MTX** (folate analogue) & **Biologics**
47
When is *surgery* indicated in **Crohn's Disease**? Prognosis?
Stricture, Perforation, Hemorrhage & Cancer
60-70% of patients w/ \>1 surgeries over lifetime
48
Describe fts of the IBD drug class: **5-Aminosalicylate**
MOA: ↓ Cyclooxygenase & Lipoxygenase
↑ Prostaglandins & Leukotrenes
Ex's: Sulfa**_salazine_** & Mesalam**_ine_**
Sulfasalazine AE's: anemia & oligospermia
49
Describe fts of the IBD drug class: **Antibiotics**
MOA: changes microbiome
Ex's & AE's: **Ciprofloxacin** (-) tendon rupture
**Metronidazole** (-) dysgeusia [taste alteration]
(-) peripheral neuropathy
**Rifaximin**
50
Describe fts of the IBD drug class: **Glucocorticoids**
MOA: ↓ WBC activity & cytokine production
AE: HTN, DM, Osteoporosis, Infection, Cataracts
Ex's: **Prednisone**, **Budesonide**
51
Describe fts of the IBD drug class: **Purine Analogue**
MOA: ↓ nucleic acid synthesis, WBC anti-proliferative effect
AE's: ↓ WBC, pancreatitis, hepatotoxicity, Lymphoma
Ex's: **6-MP**, **Azathioprine**
52
Describe fts of the IBD drug class: **Folate Analogue**
MOA: ↓ DNA synthesis, anti-inflammatory effects
AE's: BM supression, Hepatotoxicity, Pneumonitis
Ex: **MTX**
53
Describe fts of the IBD drug class: **Biologics**
MOA: Inhibits TNF-alpha & adhesion molecules
Ex: **Infliximab**, **Natalizumab**
AE's: Opportunistic Infections, Lymphoma \*shared (-) w/ Purine Analogues\*
54
Describe fts of the acid relief drug class: **Antacids**
MOA: neutralizes gastric acid
Ex's: Magnesium/Aluminum Hydroxide, Calcium Carbonate
AE: Mg(OH)2: diarrhea
AlOH: constipation
55
Describe fts of the acid relief drug class: **Sucralfate**
MOA
AE
Ex
MOA: coats injured mucosa
AE: can bind concomitant medications
Ex: **Sulfated Sucrose w/ AlOH**
56
Describe fts of the acid relief drug class: **H2 Receptor Antagonists**
MOA: competitive antagonist of parietal cell H2R
Ex's: **Ranitidine**, **Famotidine**, **Nizatidine,
Cimetidine** (-) gynecomastia [man boobs]
(-) inhibition of P450
57
Describe fts of the acid relief drug class: **Proton Pump Inhibitors**
MOA: Irreversibly inhibits parietal cell **H+/K+ ATPase**
Well tolerated but associations w/ (-) C Diff, Dementia, Osteoporosis, Pneumonia
Ex's: Ome**_prazole_**, Lanso**_prazole_**, Rabe**_prazole_**, Panto**_prazole_**, Esome_prazole_
58
What does this upper endoscopy reveal?
**Erosive Esophagitis (GERD)**
Erosion: linear white line, which enters *mucosa* but not submucosa
59
What are symptoms of GERD?
Burning chest, dysphagia & regurgitation
60
What are atypical (extra-esophageal) GERD symptoms?
Chest pain, cough, asthma flares, hoarse voice
61
Which receptor binds gastrin on the surface of the parietal cell?
Which receptor binds Ach on the surface of the parietal cell?
CCK receptor binds Gastrin
Muscarinic M3 receptor binds Ach
62
What dx can follow this upper endoscopy biopsy?
**Barrett's Esophagus**: intestinal metaplasia from stratified squamous-\>columnar
Note: no longer stratified squamous epithelium & presence of *goblet cells*
63
What is the only known precursor lesion for **esophageal adenocarcinoma**?
**Barrett's Esophagus**
64
What are RF's for **Barrett's Esophagus**? What is NOT a RF that distinguishes it from squamous cell cancer?
Older age \>50 y/o, M, Caucasian, Central Obesity, Long standing GERD, Tobacco
Alcohol is NOT a RF unlike in squamous cell
65
How is nondysplastic **Barrett's Esophagus** treated & managed?
Tx: **Omeprazole** (PPI) vs. reflux but also to ↓ risk of progression from nondysplastic-\>dysplastic cancer
Repeat endoscopy in 3 yrs for surveillance
66
Why would **Barium swallow** not be recommended in pt w/ Barrett's Esophagus that has progressed?
Ba can end up in lungs if pt cannot even handle food or her own saliva
Structural/motility dysphagia can handle Ba but NOT oropharyngeal type
67
What does this upper endoscopy reveal? & What risk does this carry?
**Food impaction**; if left for \>24 hours, can cause *perforation/ischemia*
68
What does this upper endoscopy reveal?
Erosion
69
What can cause food impaction & is described as "*chronic reflux esophagitis*?"
**Peptic Stricture:** 90% benign esophageal strictures, occurs in 7-23% of patients w/ GERD
Although may be ↓ bc of improved GERD Tx
70
Following dilation for peptic stricture, how soon should pt F/U for repeat endoscopy? What other surveillance measure is required?
1 mo or even sooner if dysphagia continues
Repeat endoscopy in 3 yrs for Barrett's esophagus surveillance
71
What type of metastatic disease has a predilection for the GI tract & is often pigmented?
**Metastatic Melanoma**
72
What type of tumor is in this upper endoscopy?
**Esophageal Adenocarcinoma**
73
Compare the 2 main types of **esophageal cancer** re area of impact, RF's & epidemiology
**Squamous Cell Carcinoma**:
Upper/middle 1/3 of esophagus
RF: *Smoking*, _Alcohol_
EPI: most common in E Eur & Asia
**Adenocarcinoma:**
Lower 1/3 of esophagus
RF: *Smoking*, Caucasian race, M, Obesity
EPI: Most common type in N. America & W hemisphere, incidence still rising
74
When is manometry used as a diagnostic test?
Only after structural disease is ruled out, which is why upper endoscopy is done 1st
75
Describe what you observe in this upper endoscopy:
Trachealization or "felinization" of esophagus
76
What does this Barium Swallow reveal?
Ridges can be seen, consistent w/ esophageal ridges or strictures
77
What would you expect to see in *biopsy* of **Eosinophilic Esophagitis**?
Acute mucosal inflammation w/ \>15 eosinophils/high powered field (HPF) \*doesn't meet criteria if any fewer eosinophils\*
Blue circle: Nucleus
Red circle: Eosinophil
78
What is the EPI, associations & symptoms of EOE?
EPI: Young, Caucasian men
Associated w/ **Atopic Triad**: Asthma, Seasonal allergies & Eczema (often w/ family Hx)
Sx: esophageal dysfunction: dysphagia, odynophagia, chest pain, reflux "burning"
79
What are some secondary causes of EOE & how would these present histologically?
\<15 eosinophils/HPF
Celiac Disease, Crohn's Disease, Infection, Hypereosinophilic Syndrome, Achalasia, Drug Hypersensitivity, Vasculitis, Pemphigus, CT Diseases, Graft vs. Host Disease
80
What is the 1st line Tx of EOE? What if that fails? In severe cases?
1st line: **PPI**, helps gauge responsive eosinophilia \*if you stay on PPI-don't require steroids\*
If PPI's fail: **Topical Steroids** (topical for esophagus): *Budesonide/Fluticasone* inhaler that is swallowed rather than inhaled
Severe: **Systemic Steroids**
81
What can be done for food elimination in EOE? What specific diet can a patient stick to?
Allergy Testing
6 Food Elimination Diet: Milk, Wheat, Soy, Eggs, Nuts, Seafood \*primary pediatric Tx & adult EOE but difficult to follow\*
82
What does this upper endoscopy reveal?
**Candida Esophagitis**
83
When should **CMV Esophagitis** be suspected?
Ulcers in *immunocompromised* setting (ie: Chemo/HIV)
84
Describe a *biopsy* of **Candida Esophagitis**:
Up to only about 3 eosinophils/HPV
Numerous *fungal forms* w/ *pseudohyphae*
85
What is the best Tx option for **Candida Esophagitis**?
**Fluconasole:** antifungal
86
In setting of *Candida Esophagitis*, what complication can arise w/ steroid Tx? What if Fluticasone is tapered?
Candida can still be a risk w/ steroid Tx w/ chance of recurrence w/ tapering of *Fluticasone*
87
What type of dysphagia is diagnosed most accurately for when a patient points to "where it gets stuck?"
Proximal Dysphagia
88
When would a Ba swallow be preferred over upper endoscopy?
If pt has many comorbidities
89
How does a *Barium Swallow* appear in **Achalasia**?
"Bird's Beak" w/ little contrast passing through esophagus into stomach but not complete obstruction
90
What do these endoscopies reveal & what condition is it associated with?
(L) Dilated esophagus
(R): Residual food particles
91
What are the symptoms of Achalasia? What is its pathophysiology?
Difficulty swallowing (S) AND (L) bc motility problem
Chest Pain
Regurgitation
Weight Loss (in severe cases)
PATH/PHYS: Lack of inhibitory neurons in LES
92
What test confirms the dx of Achalasia after a Barium Swallow? What other tests might be helpful?
Esophageal Manometry
To rule out *pseudoachalasia* from obstruction (ie: tumor) at lower esophagus-*CT scan* or *endoscopic US*/*upper endoscopy* may be helfpul
93
What manometric findings are consistent w/ Achalasia?
Failure of LES relaxation, aperistalsis & high resting LES pressure
94
How does manometry present in setting of *Scleroderma*?
Low LES pressure & hypotensive LES
95
What is a good Tx option for Achalasia in a patient w/ many comorbidities? Give an ex of a more invasive option & why it wouldn't be as strongly considered
Botulinum toxin injection into LES
More invasive *Heller Myotomy* cuts LES & wraps stomach around it; may induce acid reflux
96
What is a concern for performing esophageal dilation to treat Achalasia in a patient w/ many comorbidities?
May require stopping medications like bloodthinners **(Clopidogrel [Plavix])**
97
Describe the treatment outcomes for Achalasia short & long term:
Short Term: *Dilation* & *Botox* work well but don't do as well as time goes on & may req repeat procedures
Long term: *Heller Myotomy* best
98
What is the best diagnostic test in a patient presenting w/ melena?
CBC (may reveal ↓ Hb)
99
What does this upper endoscopy reveal?
"Clean-based" duodenal ulcer: no visible blood vessels nor bleeding
100
What are the 2 types of ulcers in Peptic Ulcer Disease & how do their presentations differ?
Gastric Ulcer: pain worsens after eating
Duodenal Ulcer: pain improves after eating
101
What are RF's for PUD?
NSAID's
H Pylori
Systemic Diseases: CD
* Zollinger Ellison's Syndrome* (hypergastrinemia from neurogastrin tumor)
* Behcet's Disease*: blood vessel inflammation-possibly autoimmune
102
W/ suspicion of PUD & the following biopsy, what is the best Tx?
*Omeprazole* & *antibiotics* in setting of PUD w/ H Pylori
103
Describe H Pylori:
Type of bacteria
Location found
Spread
EPI
Risks
Tx:
Microaerophilic gram (-) bacteria
Found adherent to stomach mucosal layer
Fecal-oral spread
EPI: more common in developing countries
Risks: Gastritis, Ulcers (Gastric & Duodenal\*), Gastric Adenocarcinoma, Mucosa Associated Lymphoid Tissue (MALT) Lymphoma
Tx: Triple therapy: **Omeprazole**, **Amoxicillin** [*Metronidazole*\* if PCN allergic] & **Clarithromycin** (antibiotic)
104
What test can be performed to see if H Pylori has been eliminated? Is further Tx required?
H Pylori Breath Test
Even if asymptomatic, Omeprazole may be continued for 1 more month
105
Describe the criteria to dx **Functional Dyspepsia,** characteristics & EPI
20% w/ sx: major economic impact, resembles ulcer sx
not life-threatening but affects QOL
EPI: F\>M, Smokers, NSAID Users
106
What is the 1st step to treat **functional dyspepsia** in a patient \<60 y/o? If \>60 y/o?
When is an endoscopy not called for in a patient \<60 y/o?
If \<60 y/o: Check H Pylori stool antigen
If \>60 y/o: Endoscopy to test for malignancy
No endoscopy for pt \< 60 y/o if "alarm features" absent ex: weight loss, GI bleed, dysphagia
107
W/ suspicion of Functional Dyspepsia & H Pylori stool antigen (-), what is the best Tx option?
Omeprazole & lifestyle modifications (ie: caffeine reduction, smoking cessation)
108
In a diabetic patient, what condition might be a concern in setting of dysphagia? What is the best diagnostic test?
Diabetic Gastroparesis
Gastric Emptying Test
109
What are the Sx of Gastroparesis? How can it be diagnosed? Etiology?
Sx: Early satiety, Nausea, Vomiting, Abdominal pain (although not predominant sx)
Dx: Gastric Emptying Test: gold standard; documented delay in gastric emptying required\*
*Liquid emptying may be normal but emptying of solids may lag*
Etiology: Idiopathic (post-viral) 35.5%, Diabetes (29%)
110
Rank order of gastric emptying time among macronutrients
Fats\>Proteins\>Carbohydrates
111
Following upper endoscopy, what might a video swallow reveal in a Parkinson's patient w/ dysphagia?
Pooling in valleculae (groove), penetration of barium, pyriform sinus residue, no frank aspiration & evidence of cricopharyngeal bar (muscle contour-hypertensive UES; not diverticulum but due to HTN)
112
Describe characteristics of a Cricopharyngeal Bar
Tx?
Upper Esophageal Sphincter
Frequent incidental radiological finding: usually asx, so look for other causes of dysphagia
Tx: Refer to ENT for *endoscopic dilation* & *cricopharyngeal myotomy*
113
Describe **Oropharyngeal Dysphagia**
Clinical Px
Causes
Tx
Px: coughing during swallow, food sticking in throat, nasal regurgitation
Causes: Neurologic (Parkinson's, Stroke, ALS), Tumors, Zenker's Diverticulum (false; herniation)
Tx: Dietary modification, speech therapy, repairing underlying mechanical cause
114
What is an Upper GI Series?
Similar to Ba Swallow but looks further & for longer (ie: stomach-\>small intestine)
115
How might DES spasm present in Ba Swallow, Esophageal Manometry, & pH Impedance Testing?
Among these, what is the gold standard for Dx?
Ba Swallow: Corkscrew appearance
Manometry\*: sev simultaneous high amplitude contractions; very pink colors-high P \*gold standard for Dx\*
pH Impedance testing normal on omeprazole
116
What are the Sx of DES? Tx's?
Sx: Esophageal dysphagia to (S) & (L), *exacerbated by T extremes,* Retrosternal chest pain
Tx: 1st line- CCB (Diltiazem), TCA
2nd line-Botulinum Toxin, Sildenafil (Vasodilator-Viagra)
