GI Tract Flashcards
1
Q
Interstitial cells of Cajal
A
Pacemaker cells
Create the bioelectrical slow wave potential that leads to contraction of the smooth muscle
2
Q
Odynophagia
A
Painful swallowing, in the mouth or esophagus
3
Q
Ileus
A
Inability of the intestine (bowel) to contract normally and move waste out of the body
FAILURE OF PERISTALSIS
AKA GI atony
4
Q
Which bacteria can cause renal failure?
A
Enterohemorrhagic E. coli
5
Q
Mucosal scalloping is associated with?
A
Celiac disease
6
Q
Hamartomatous polyps
A
A distinct subset of polyps, mostly occurring in childhood
“tumor-like” overgrowth / mature tissue / developing where it is NORMALLY present
= tissue that DOES belong there, but is overgrown and disorganized
Most arise in the presence of syndromes —> need regular screening
7
Q
Urease breath test
A
Indicative of H. pylori infection in the setting of GERD, worsening pain
8
Q
Tx for H. pylori infection?
A
Triple therapy:
1) amoxycillin
2) clarithromycin
3) PPI (omeprazole)
ACP!
9
Q
Somatostatin
A
Inhibits the release of gastrointestinal and pancreatic enzymes (gastrin, CCK, insulin, glucagon, etc.)
10
Q
Gastrin
A
Stimulates secretion of gastric acid (HCl) by parietal cells of the stomach
11
Q
CCK
A
Stimulates release of bile, pancreatic enzymes in order to digest fats and proteins.
Mediates digestion in the small intestine by inhibiting gastric emptying and decreasing gastric acid secretion.
Synthesized by I-cells in the SI
Secreted by duodenum
Trypsin normally breaks down proteins. However, when protein level is low, trypsin acts on CCK/monitor peptide & inhibit CCK production, release. = self-regulating system
12
Q
Secretin
A
Helps regulated the pH of the duodenum by stimulating the production of bicarb by the pancreas, inhibiting gastrin release from the stomach
Released by duodenum
Produced in S cells of the duodenum
13
Q
G cells
A
Release gastrin
Present in pyloric antrum of stomach, duodenum, and pancreas
14
Q
D cells
A
Somatostatin-producing cells
Found in the stomach, intestine and pancreas
15
Q
What is the pathogenesis of cholesterol gall stones?
A
- cholesterol supersaturation
- phospholipid deficiency (acts as a detergent)
- over-absorption of water in gall bladder
- mucin plug or foreign body nidus (sand in oyster)
16
Q
What are the risk factors for pigment gall stones?
A
- bile duct obstruction
- excess bilirubin (hemolysis)
- East Asian ancestry
- parasitic infxns
17
Q
What are the risk factors for gall stones?
A
5 F’s!
- forties
- fat
- female
- fertile/fetus
- family hx
Also, Latin American/Native American ancestry, rapid weight loss, or biliary obstruction
18
Q
What is biliary colic?
A
Stone in the duct, obstructing gall bladder –> pain
Sx: intermittent pain in epigastrium, RUQ after meals (esp. fatty foods). Builds over an hour, remits 3-8 hrs later
Occurs with movement of stone into cystic duct or gall bladder neck
Tx: cholecystectomy; poss. bile acid supplement (UDCA)
19
Q
What is ascending cholangitis?
A
A bacterial infxn of the bile duct
Usually a complication of choledocholithiasis
Sx: Charcot’s triad
20
Q
Charcot’s triad
A
RUQ pain
Fever
Jaundice
21
Q
Reynold’s pentad
A
Charcot’s triad (RUQ pain, fever, jaundice) + hypotension + altered mental status
22
Q
Choluria
A
Bile in the urine - looks dark (Coca-Cola colored)
The presence of choluria is a useful symptom to distinguish if somebody presenting with jaundice has liver disease (direct hyperbilirubinemia) or hemolysis (indirect hyperbilirubinemia). In the first case, patients have choluria due to excess conjugated (“direct”) bilirubin in blood, which is eliminated by kidneys. Hemolysis, on the contrary, is characterized by unconjugated (“indirect”) bilirubin which is bound to albumin and thus not eliminated in urine.
23
Q
What are the sx of biliary stricture?
A
Sx of cholestasis:
- jaundice
- dark urine
- acholic stool
- pruritis
RUQ pain
LFTs elevated in cholestatic pattern
24
Q
What disease is associated with PSC?
A
UC
90% of PSC pts have UC
25
PSC
Strictures of the large and small bile ducts (intra- and extra-hepatic)
Males > Females
A/w UC
Risk of liver cirrhosis!
Increased risk of cholangiocarcinoma
26
Sphincter of Oddi dysfunction
Occurs mostly in young females
Mimics choledocholithiasis
27
How do gallstones cause acute pancreatitis?
Obstruction of pancreatic duct --> ↑ ductal pressure --> leakage of enzymatic fluids into pancreatic tissue --> tissue injury, inflammation, edema, ischemia due to auto-digestion of the pancreas
28
How does alcohol cause acute pancreatitis?
1) sphincter of Oddi contraction
2) stimulation of pancreatic secretion; premature release of enzymes
3) defective packaging of enzymes
4) proteinaceous plugs within pancreatic duct
29
Zollinger-Ellison Syndrome
Gastrin-secreting tumor in the pancreas
Pts p/w PUD
30
What is the most common pancreatic neuroendocrine tumor?
Insulinoma (42%)
Pts p/w fainting episodes due to hypoglycemia
31
What are the 6 main constituents of saliva?
1) water
2) bicarb (to buffer pH when vomiting)
3) mucins
4) amylase
5) lysozyme, lactoferrin, IgA (immune protection)
6) epidermal and nerve growth factors (mucosal growth/protection; dog licking a wound)
32
Structure of the salivary gland
1) myoepithelial cells help push secretions out
2) acinar cells secrete a hypertonic solution into the acinus
3) sol'n goes through intercalated duct
4) sol'n continues through striated duct, where ductal cells modify the content: adjust the level of solutes, water, etc.
33
Parasympathetic effect on salivary secretion
Increased acinar cell secretion; vasodilation of blood vessels surrounding the acini
Results in protein/fluid/ion rich solution = watery
34
Sympathetic effect on salivary secretion
Increased acinar cell secretion
High protein/low fluid solution = viscous
35
Fast vs. slow flow rate in salivary secretion
Fast flow = still get secretions, but don’t get time to reabsorb. Thus, much more Na, Cl present in secretions, much less K and HCO3
Slow flow = production in acinus, moves into striated duct, & because it has time, get a lot of reabsorption of Na, Cl; secretion of K and HCO3
SLOW = keep the SALT (NaCl)
36
List 3 stimuli that increase pancreatic secretion
1) Acetylcholine (ACh) - released from vagus and ENS systems; stimulates the release of digestive enzymes from ACINAR cells (mostly cephalic stage)
2) Secretin - released in the proximal SI in response to acid; stimulates the release of a bicarb sol'n from pancreatic DUCT cells
3) CCK - released from proximal SI in response to fats & proteins; stimulates the release of digestive enzymes from pancreatic ACINAR cells
37
What does CCK do, and where?
Gallbladder - stimulates contraction, bile secretion (for fat absorption)
Pancreas - stimulates acinar secretion of enzymes
Stomach - delayed emptying
Sphincter of Oddi - relaxation
38
What is the big compositional difference between salivary and pancreatic juices?
Saliva: KHCO3
Pancreas: NaHCO3
39
What are the 8 salivary gland diseases?
1. Mumps
2. CMV sialadenitis
3. Bacterial sialadenitis
4. Sarcoidosis
5. Sjogren's Syndrome
6. Salivary Lymphoepithelial Lesion
7. Xerostomia
8. Halitosis
40
Pleomorphic adenoma
Diverse microscopic pattern
Cuboidal cells arranged in duct-like structures
41
Warthin's tumor
Benign tumor of the parotid gland
Has both lymphoid and epithelial component
WHALE = Warthin’s Has Abundant Lymphoid and Epithelial components
42
Epigastric pain, radiating to the back is classic for?
Pancreatitis
43
What is the #1 cause of acute pancreatitis?
Gallstones
44
What are the etiologies of acute pancreatitis besides gallstones and alcohol?
```
Iatrogenic (ERCP)
Drug-induced
Hypertriglyceridemia
Hypercalcemia
Pancreatic cancer
Pancreas divisum (cong. ductal abnormality)
Penetrating trauma
```
45
Serum lipase, amylase are elevated >3x normal. Dx?
Acute pancreatitis
46
What disease can occur in severe acute pancreatitis?
ARDS
A/w pancreatic necrosis. Fully reversible - tx: support.
47
What are causes of chronic pancreatitis besides alcohol?
CF, hereditary pancreatitis, and hyperlipidemia
20% are idiopathic
48
What are some sx of pancreatic insufficiency?
Weight loss, steatorrhea (fat malabsorption)
Bleeding problems (Vit K = fat-soluble = malabsorption)
Anemia (Vit B12)
49
Autoimmune pancreatitis
Diffuse or focal enlargement of pancreatic parenchyma
Infiltration by IgG, plasma cells, lymphocytes
Males, typically 40-70
A/w other autoimmune diseases
May masquerade as pancreatic cancer!
Sx: abdominal pain, jaundice, weight loss, (rarely) pancreatitis
Tx: PO steroids x 6 weeks
50
"Ringed" esophagus?
Eosinophilic esophagitis
51
Eosinophilic esophagitis
Esophageal STRUCTURAL disorder
Chronic immune/antigen-mediated dis.
Sx: vomiting, pain, dyspepsia, progressing to odynophagia and stenosis
**Concentric rings in the esophagus**
A/w food allergies, atopic sx
Tx: 3 D's = drugs, diet, and dilation
```
Drugs = topical steroids that are swallowed
Diet = 6 food elimination diet (milk, eggs, wheat, soy, seafood, nuts)
```
52
Zenker's
Diverticulum in the uppermost portion of the esophagus
Sx: regurgitation, halitosis, aspiration
A/w reduced UES compliance
53
Which type of esophageal cancer is more common worldwide?
Squamous cell carcinoma
54
Dysphagia to both solids and liquids?
Sx of esophageal dsfxn - MOTILITY disorder
55
Achalasia
Esophageal propulsive/motility disorder
IMPAIRED RELAXATION of lower esophageal sphincter + absence of normal peristalsis
Etiology: selective loss of inhibitory neurons in myenteric plexus, resulting in unopposed excitatory (cholinergic) neurons --> hypertensive non-relaxed esophageal sphincter
56
Scleroderma in GI
Multi-system disorder characterized by:
- obliterative small vessel vasculitis
- CT proliferation w/ fibrosis of multiple organs
GI manifestations in 80-90%
Principally consist of smooth muscle atrophy & gut wall fibrosis --> weak peristalsis, weak LES --> dysphagia, GERD, esophageal strictures
Predominantly MYOPATHIC process
57
Dysphagia initially with solids, progressing to liquids
Esophageal STRUCTURAL disorder
58
Intrinsic factor
Secreted by parietal cells in the stomach
Necessary for the absorption of Vitamin B12 later in ileum
59
Stomach acid facilitates absorption of which nutrients?
Iron, calcium, and Vitamin B12
60
H. pylori
Microaerophilic GNR that produces abundant urease which produces ammonia and raises the local pH
Burrows through mucus layer of the stomach, colonizes gastric mucosa
Most people will never have any sx. Can cause thickened gastric folds.
Dx'ed via urea test (labeled urea ingested; if urease is present, labeled CO2 will be produced, analyzed by breath test machine)
ANTRAL infxns tend to have high levels of acid secretion, may develop duodenal ulcers
61
Tx for H. pylori infxn?
TRIPLE THERAPY
1) PPI (Abs work better at low pH)
2) Amoxicillin
3) Clarithromycin
"Classic" therapy = quadruple therapy
1) PPI
2) bismuth
3) tetracycline
4) metronidazole
Per the Kyoto guidelines, H. pylori infxn should be treated whenever diagnosed
62
Ethanol gastropathy
Similar to early NSAID-type injury
Increases acid secretions, disrupts mucosa
PUD with high concentration, high use, etc.
63
Effects of prostaglandins in the stomach
- mucus layer thickness
- cell membrane hydrophobicity
- bicarb secretion
- mucosal BF
- epithelial cell proliferation
^^^All of this things are inhibited by NSAIDs!!!!!
64
Cushing's ulcer
Seen in ICU pts w/ increased ICP, CNS injury
65
Curling's ulcer
Burn victims
66
How do you treat PUD?
PPIs tx - ulcer(s) will heal in 4-8 weeks
H. pylori test & treat
Risk factor avoidance: NSAIDs, smoking
67
What is the 2nd most common cancer & cause of death from cancer worldwide?
Gastric adenocarcinoma
68
Menetrier Disease
Rare
Hypertrophic rugal folds
Histologically: massive foveolar hyperplasia with cystic dilation
Sx: abdominal pain, weight loss, & bleeding
69
GIST
Gastrointestinal stromal tumors
Most common mesenchymal tumor of the stomach
Cells of origin: interstitial cells of Cajal (pacemaker cells)
70
What mutation occurs in GISTs?
c-kit (CD117) mutation in transmembrane receptor tyrosine kinase
Treated with surgery, imatinib (small molecule RTK inhibitor)
71
Autoimmune atrophic gastritis
Autoimmune attack against parietal cells, IF
Achlorhydria (lose production of acid)
Pernicious anemia (B12 low, IF absent)
Atrophy seen (loss of rugae)
72
MALT
Mucosa Associated Lymphoid Tumor
A/w H. pylori infection
***Eradication of H. pylori can sometimes induce regression of lymphoma***
73
Pathophysiology of celiac disease?
Gluten digested by brush borders --> exposed to α-gliadin peptide --> auto-Ab formation --> inflammation, tissue damage, villous atrophy, etc.
Host factors: Class II HLA-DQ2 or HLA-DQ8 allele. These Class II MHC are uniquely able to present immunodominant peptides derived from gliadin (one of two kinds of gluten proteins) to Th1/Th17 cells. The dominant immunopathology is a "chronic frustrated immune response" against gliadin peptides, by Th1 and Th17 cells.
Autoimmune component:
TTG2 binds to gluten, tries to take off amino group, cleave gliadin --> gets “stuck” & becomes unable to release its substrate. Then, you have a foreign molecule linked essentially covalently to a self-molecule. As you remember, this is the setup for “illicit help.”
A B cell that’s anti-TTG2 (that never normally gets helped by Tfh) takes up the complex, and presents FOREIGN gliadin peptides to Tfh (specific for gliadin on DQ2 or DQ8), which then help the B cell make antibody to TTG2 (where it bound the complex).
As far as we know, the auto-antibody is not pathogenic. Useful as a diagnostic tool.
►Because this is happening in the gut, the class of antibody is IgA.
Eventual cross-rxn with TTG3 by epitope spreading --> dermatitis herpetiformis
A/w other autoimmune diseases (Type I DM, Sjögren's Syndrome)
74
What is the test for celiac disease?
IgA to TTG
Need to check IgA levels concurrently
75
What are the 3 characteristic findings of celiac disease on tissue biopsy?
1) villous blunting
2) increased intraepithelial lymphocytes
3) lymphoplasmacytosis of the lamina propria
76
Whipple's Disease
Cause by gram positive bacilli T. whippelii
Absorbed by WBCs, sit in lymph nodes --> lymphatic obstruction --> malabsorptive diarrhea
Clinical signs: fever, joint pain, diarrhea, abdominal pain, CNS/neurologic symptoms
Tx: 1 year of abx
77
What causes pseudomembranous colitis?
C. diff
78
What are the watershed areas for ischemic colitis?
Superior and inferior mesenteric arteries (at corner of transverse and descending colon aka splenic flexure)
Inferior mesenteric and hypogastric arteries (at corner of descending and sigmoid colon aka rectosigmoid)
79
Etiology of IBD?
Combination of defects:
- host interactions with intestinal microbiota
- intestinal epithelial dysfunction
- aberrant mucosal immune responses
80
Features of Crohn's
- mouth to anus
- skip lesions
- transmural inflammation
- 35% have granulomas
- inflammatory strictures
- fissuring ulcers, fistulae
Malabsorption --> steatorrhea
Sx: intermittent attacks of non-bloody diarrhea, fever, MID or LOWER abdominal pain
Extraintestinal manifestations: uveitis, ankylosing spondylitis, erythema nodosum
81
Features of ulcerative colitis
- ALWAYS rectal involvement
- retrograde continuous diffuse disease
- ONLY in the colon
- mucosal inflammation only
- no fissures, etc.
Sx: bloody diarrhea w/ LOWER abdominal pain, cramps, tenesmus
Associations: PSC
82
Diverticular disease etiology
Results from decreased fiber in diet --> decreased stool bulk --> elevated intraluminal pressure --> mucosal herniation through focal defects in the bowel wall
83
Diverticulosis
Presence of diverticula
NOT inflammation
84
Diverticulitis
Inflammation of the diverticula, usually secondary to obstruction
Complications include perforation, abscess formation, bleeds, fistulae
Sx: LLQ pain, nausea, fever
Pts are usually very sick
85
Tenesmus
Strong urge to defecate
86
Pseudopolyps are a sign of what?
UC
87
Microscopic colitis
Typically older females (50-80 yo)
Autoimmune; trigger unknown
Sx: chronic secretory diarrhea
Watery, non-bloody, 4-10 stools per day, minimal nocturnal sx
88
What are the subtypes of microscopic colitis?
1) lymphocytic colitis
Chronic inflammation with lymphocytic infiltration
2) collagenous colitis
Thickened subepithelial collagen band, lymphocytic surface injury
89
How do you diagnose microscopic colitis?
Biopsy is definitive:
- lymphocytic infiltration of mucosa and SM (LC)
- thickened collagenous band (CC)
Colonoscopy is usually normal
90
What are some triggers for ischemic colitis?
Vasospasm, dehydration, hypotension, or cardiopulmonary insult (MI, PE, etc.)
90% of pts >60 yo
91
What is the presentation for ischemic colitis?
Abrupt onset, crampy, lower abdominal pain
Urgent need to defecate
MILD diarrhea and/or hematochezia
92
Diverticular hemorrhage
5% of patients with diverticulosis
Usually from R colon
Painless hematochezia, often heavy, typically stops within 2-3 days
Does NOT occur with diverticulitis
93
Pt presents with N/V, abdominal distention, constipation or obstipation (change in bowel habits)
Colonic obstruction
Dx'ed by X-ray or CT
94
Tumors of the appendix
Carcinoid (most common)
Benign (mucinous cystadenoma or villous adenoma), malignant adenocarcinoma or lymphoma, mets
95
Clinical presentation & causes of fat malabsorption
Clinical signs: weight loss, steatorrhea, diarrhea, vitamin deficiencies
Causes:
- surgery (gastric bypass, small bowel resection)
- bacterial overgrowth
- meds
- pancreatic insufficiency
- liver disease
- intestinal inflammation/villus flattening
- ulceration
- ischemia
- infiltration (amyloidosis)
96
Small bowel bacterial overgrowth
Normal bacteria =
97
What are some of the extra-intestinal manifestations of celiac disease?
- iron deficiency anemia
- dermatitis herpetiformis
- AST/ALT elevation
- cerebellar ataxia
- osteoporosis
- oral aphthous ulcers
98
4 different types of diarrhea, based on stool characteristics
1) fatty (malabsorption; maldigestion)
2) water (osmotic, secretory)
3) inflammatory/exudative (blood in the stool)
4) functional
99
Osmotic vs. secretory diarrhea
Measure stool Na + K
Normal serum osmolality is 290 mOsm
Osm gap = 290 - 2(stool Na + K)
If difference is >50 = osmotic
If difference is
100
Inflammatory vs. non-inflammatory diarrhea
Non-inflammatory:
- usually large volume
- watery
- small bowel
Inflammatory:
- fever, fecal WBCs and RBCs
- usually small voume, lots of times/day, feel better afterwards
- colon
101
Organisms that cause inflammatory diarrhea
Campylobacter jejuni, shigella, salmonella
+/- E. coli O157:H7, C. diff
Largely in your left colon
102
Organisms that cause non-inflammatory diarrhea
Norwalk, rotavirus
| Giardia, ETEC, cholera
103
Leading cause of morbidity and death with diarrhea
Dehydration
Thus, rehydration is the mainstay of tx
104
Which organism is the leading cause of death from diarrhea in the US and worldwide?
Rotavirus
Disease largely in children
105
Basal electrical rhythm
Spontaneous contractions in smooth muscle , ~12/minute
Myogenic, or muscle-derived
Without external input = depolarization events fail to reach a membrane threshold sufficient to induce a contractile response.
In the presence of ACh, the membrane threshold is exceeded and contractions occur with the frequency of the BER.
106
Migrating motor complexes
Between meals, MMCs sweep down the stomach and small intestine & clear out any remaining undigested material and bacteria
Every 90 min
107
Haustrations vs. mass movement in colon
Haustrations: muscles of the colon wall contract intermittently to divide the colon into functional segments (haustra)
Mass movements: huge peristaltic waves 1-3x/day
108
What happens with internal & external anal sphincters when rectum is filled --> defection occurs?
Filling of the rectum causes relaxation of the internal anal sphincter via release of VIP and NO from intrinsic nerves. At same time, the external anal sphincter contracts - rectoanal inhibitory reflex
Defecation occurs when the external anal sphincter is voluntarily relaxed and is enhanced by an increase in intra-abdominal pressure
109
Parietal cells secrete what?
Acid (HCl) and IF (simultaneously)
110
Phases of HCl secretion
1) Interdigestive (basal) phase - between meals. Highest HCl production in evening and lowest in morning prior to waking
2) Cephalic phase - neural regulation
Sight/smell/swallowing of food initiates release of ACh/histamine/etc. Accounts for 30% of acid production
3) Gastric phase - entry of food into stomach
Food distends gastric mucosa --> activates a vagovagal reflex as well as local ENS reflexes. Partially digested proteins stimulate antral gastrin (G) cells, which release gastrin. 50-60% of total acid secretion
4) Intestinal phase - mostly endocrine reg
Largely inhibitory - once your gastric contents pass into duodenum, stomach doesn’t need to produce HCl anymore.
111
Effect of ACh on HCl secretion
ACh --> ↑ Ca2+ --> activates protein kinases --> phosphorylates H+/K+-ATPase = ↑ activity
112
Effect of gastrin on HCl secretion
↑ in Ca2+ --> ↑ activity in H+/K+-ATPase
113
Effect of histamine on HCl secretion
Histamine --> H2 receptor --> AC --> cAMP --> ↑ activity in H+/K+-ATPase
114
What type of sugars can be absorbed?
Only simple monomeric sugars
115
What are the 4 mechanisms of protein uptake?
1) Sodium-dependent cotransporters that utilize the N+/K+-ATPase gradient (major route)
2) Na-independent transporter of amino acids
3) Specific carriers for small peptides (di- and tri-) linked to H+ uptake
4) Pinocytosis of small peptides by enterocytes (infants). Intestines are so leaky that peptides can just wash across the cell barrier
116
How is fat absorbed?
Bile salts + lipase + colipase
Lipase binds to colipase --> binds to bile salts --> binds to fat
Inside the enterocytes, triglycerides are re-synthesized from monoglycerides and fatty acids. They are then packaged into lipoprotein particles called chylomicrons. End up in the lacteals (lymphatic capillaries) --> thoracic duct
Bile acids are formed by liver from cholesterol; secondarily by bacteria in gut
Bile acids + glycine/taurine = bile salts
Bile salts are reuptaken in distal ileum = enterohepatic circulation
117
What does Olestra do?
Inhibits normal lipase function --> prevent uptake of fat
Can eat normally fatty foods, take up less... however, you get steatorrhea :)
118
Sitz marker
24 radioopaque markers given on Day 1
Plain abdominal x-ray on Day 5
5 markers in recto-sigmoid = defecatory disorder
>5 markers scattered through colon = slow transit
119
Hirschsprung's Disease
Congenital absence of myenteric neurons of the distal colon
No recto-anal inhibitory reflex - no ability to relax the internal sphincter. Difficult to mount enough pressure to bypass it.
If not treated, can lead to life-threatening megacolon
120
H2 receptor antagonists
Bind H2 receptors in basolateral membrane of parietal cells
Better at blocking nocturnal (H2 mediated) than meal-stimulated acid secretion
Rapidly absorbed - advantage in ACUTE gastritis
121
Examples of H2 receptor antagonists drugs
Ranitidine, Cimetidine, Famotidine, Nizatidine
122
Misoprostol
Prostaglandin analogue
PGs in gastric parietal cells inhibit cAMP formation --> ↓ H+ secretion
Also stimulate acid neutralizing HCO3− formation and cytoprotective mucus formation
Major indication: NSAID-induced ulcers
BUT, rarely used because of 4-time daily dosing and adverse effects - diarrhea and/or uterine stimulation in 30%
Contra-indicated in pregnancy
123
Sucralfate
Mucosal protective agent
Selectively binds to necrotic ulcer tissue to form protective barrier.
Activated by acid pH
124
Antacids
CaCO3, Mg(OH)2, Al(OH)3, NaHCO3
Rapidly raise stomach pH to 4-5 (above the optimum of pepsin)
Constipation (Ca2+ and Al3+ antacids) or diarrhea (Mg2+ antacids) is common
125
Metoclopramide
Antagonist (-) at presynaptic dopamine receptors (D2) that inhibit the release of acetycholine --> indirectly increases agonist activity at smooth muscle M3-receptors
Pro-kinetic agent --> will produce coordinated contractions that enhance transit of luminal contents
High doses used to treat nausea/vomiting of cancer chemotherapy
BLACK BOX WARNING: somnolence, dystonic reactions, tardive dyskinesias -- EXTRA-PYRAMIDAL SE!!
126
Ondansetron
MOA: Block of serotonin (5-HT3) receptors at chemoreceptor trigger zone (CTZ in CNS), solitary tract nucleus, and on visceral afferents (GI tract)
Clinical uses: Prevention and treatment of vomiting caused by chemo tx. Also used for nausea/vomiting a/w post-op use of opioid analgesics & used by pregnant women for morning sickness
AE: **associated with QT prolongation!**
127
Prochloroperazine
MOA: Blockade of dopamine receptors in chemoreceptor trigger zone
Clinical uses: treatment of N/V
128
Meclizine
Antihistamine
Primary use for motion sickness and postoperative emesis
129
Diphenhydramine (dimenhydrinate, Dramamine)
Antihistamine
Primary use for motion sickness and postoperative emesis
130
Scopolamine
Anticholinergic agent
Primary use is prevention and treatment of motion sickness; some efficacy in post-operative nausea and vomiting
Most commonly administered transdermally with duration of action of 72 hours
131
AEs of an H2 receptor antagonist?
Cimetidine - gynecomastia with chronic high doses
Cimetidine also inhibits CYP450 metabolism
Annnnd causes CNS dysfxn in elderly in high doses
132
Psyllium Seed (Metamucil®)
Fiber/bulk-forming
Recommended first - they approximate physiological mechanism (facilitate passage and stimulate peristalsis via absorption of water and subsequent bulk expansion)
Effective in 12-24 hrs to 3 days; always take with 8 oz water/juice
133
Polyethylene glycols (Golytely®, Colyte®, Miralax®)
High volume solutions (4 liters of Golytely® or Colyte®) widely used for bowel cleansing prior to radiologic, surgical, or endoscopic procedures. Contain sodium and potassium salts to prevent net transfer of electrolytes into lumen.
Smaller volume solutions (250-500 ml of Miralax®) now used for difficult to treat constipation; given as daily dose for treatments of less than 2 weeks duration. Prolonged, frequent, or excessive use may lead to electrolyte depletion.
134
Bisacodyl (Dulcolax®)
Thought to act via increase in peristaltic activity by inducing low-grade inflammation (local irritation) in bowel to promote accumulation of water and electrolytes and stimulation of intestinal motility
Effective, but potentially dangerous side effects (electrolyte / fluid deficiencies, severe cramping)
135
Docusate
Stool-wetting agent
Acts as stool-softener (facilitates admixture of aqueous and fatty substances)
Role is primarily prevention. Used in patients with cardiovascular disease / hernia / postpartum patients. Often used in combination with stimulant laxative when initiating opioid analgesic therapy.
136
Loperamide
Anti-diarrheal drug
MOA: several different mechanisms via opioid receptors, including effects on intestinal motility (μ), intestinal secretion (δ), and absorption (μ and δ)
Has anti-secretory activity against cholera toxin. Effective against traveler’s diarrhea +/- antimicrobials
137
Polycarbophil
Anti-diarrheal
Marked capacity to bind to free fecal water
Useful in diarrhea (absorbs 60X weight in H2O) AND constipation (prevents fecal desiccation)
138
Kaolin / Pectin (Kapectolin®)
Adsorbent
Take after each loose bowel movement until diarrhea controlled. Can usually manage mild to moderate diarrhea (promote “formed stools” and perception of decreased fluidity, but small effect on fluid volume excreted)
139
Tegaserod (Zelnorm®)
Treatment of IBS with CONSTIPATION in women GO
Serotonin 5-HT4 agonists - leads to release of NTs involved in peristaltic reflex, promoting gastric emptying and intestinal motility
Approved for treatment of IBS patients with predominant constipation or chronic idiopathic constipation who haven’t responded to other treatments
140
Alosetron (Lotronex®)
Treatment of severe IBS with DIARRHEA in women
--> STOP
Serotonin 5-HT3 antagonist - block of 5-HT3 receptors on sensory and motor neurons reduces pain and inhibits colonic motility
AEs: constipation in 30%, **ischemic colitis in 3/1000 pts with some deaths**
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Peutz-Jeghers syndrome
Presents usually 10-15 yo
Mutation: LKB1/STK11
GI lesions: arborizing polyps, SI > colon > stomach; colonic adenocarcinoma
Extra-GI: mucocutaneous pigmented lesions
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Juvenile polyposis
Presents usually
143
Hyperplastic polyps
Location: L colon including rectum (90%)
Increase with age, small, sessile, SERRATED
Not dysplastic, but need to be distinguished from sessile serrated polyp/adenoma, which iS pre-malignant
144
What are the first & second hits on the adenoma --> cancer pathway?
Loss of both copies of the APC gene (tumor suppressor)
When the APC protein is absent, the destruction of β-catenin (which requires an APC complex) cannot occur. Thus, cell is under constant stimulation by the WNT pathway --> promotes cell cycle progression
145
What are the 3 main molecular pathways for developing colon cancer?
1) Wnt/APC/β-catenin (classical adenoma-carcinoma sequence)
2) K-ras/MAP kinase/PI3 kinase signaling pathways - activating mutations
3) Microsatellite instability - defects in mismatch repair proteins
146
What chromosome is the APC gene located on?
Chr 5
"Polyp" has 5 letters :)
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Lynch Syndrome
AKA Hereditary non-polyposis colorectal cancer
= develop colon cancer at earlier age than sporadically; tend to be R sided
Inherited mutation of mismatch repair gene + lose 2nd allele over time --> microsatellite instability
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Infantile hypertrophic pyloric stenosis
Non-bilious projectile vomiting a/w upper abdominal mass ("olive-shaped mass")
Usually presents around 3 weeks of life
149
Meckel's Diverticulum
Out-pouching of the intestine
Most common malformation of the small intestine. Abnormal remnant of vitelline duct, between yolk sac and intestine.
Rule of 2's: 2 cm from ileocecal junction, 2% of population, presents around age 2
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Omphalocele
1/2000 live births
Failure of intestines to return to abdomen following physiologic herniation at weeks 6-10 of development. Peritoneal and amniotic covering.
30-50% associated with other congenital abnormalities
151
Gastroschisis
Paraumbilical abdominal wall defect (rectus muscle) - no amniotic covering, no associated malformations
152
What type of intestinal atresia is most common? What is the most common co-existing condition?
Duodenal atresia
40% have Down Syndrome
153
Neonatal necrotizing enterocolitis
Typically occurs as a result of prematurity
PDA is a risk factor
154
What is the etiology of ground glass-appearing cells on liver biopsy?
Viral inclusions
= hepatitis
155
Which hepatitis viruses are fecal-oral?
A & E
156
Which hepatitis virus is the only one that is DNA?
B
157
What is the likelihood that Hep C infection will go on to be chronic?
80%
158
What is the major cause of chronic liver disease worldwide?
Hepatitis B
159
What is an important method of transmission of Hepatitis B?
Vertical
Also leads to a higher viral load
160
Hepatitis D
Only occurs with coinfection w/ Hep B
Potentiates effects of HBV: increased risk of fulminant hepatitis, increased activity, and faster progression to end stage liver disease
161
Hepatitis E
Very uncommon
Higher mortality in pregnant women
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Primary Biliary Cirrhosis (PBC)
Immune-mediated attack of intrahepatic SMALL CALIBER bile ducts
Most commonly affects: MIDDLE-AGED WOMEN
Insidious onset: pruritis, jaundice
Test: anti-microbial antibody (AMA) - 90%
25% with liver failure at 10 years
--> this disease is a risk factor for osteoporosis
Tx: UDCA (secondary bile acid made by bacteria; improves bile acid transport, “detoxifies” bile and provides cytoprotection)
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Primary Sclerosing Cholangitis (PSC)
Immune-mediated obliterative fibrosis of intra/extrahepatic LARGE CALIBER bile ducts
Men > women
70% will have UC
Asymptomic w/ persistent alk phos elevation; progressive fatigue/pruritus/jaundice
Dx: chlangiography shows alternating bile duct strictures & dilations ("beads on a string")
Histology shows "onion skin" fibrosis around the bile duct
--> this disease is a major risk factor for cholangiocarcinoma
No effective medical tx; focused on stenting bile ducts to keep them open
164
What are Mallory bodies?
Ropey inclusions in hepatocytes due to abnormal aggregation of cytoskeletal elements
Seen in alcoholic liver disease
165
Hemangioma
Benign neoplasm of dilated vascular spaces
Most common primary hepatic tumor (2% of pop.)
F > M
Usually small and asymptomatic. Sx can include RUQ pain, early satiety, N/V
166
Focal nodular hyperplasia
Benign mass-like proliferation of hepatocytes
Arises due to a local vascular flow anomaly
F > M
Usually asymptomatic
Central stellate scar is characteristic on biopsy/resection
167
What do hepatocytes do with bilirubin?
They conjugate it into a water-soluble form
Conjugated bilirubin gets transported into the biliary drainage systems —> bile ducts —> duodenum
Undergoes enterohepatic circulation - gets recycled in GI tract
Also gets excreted in feces (gives them brownish color)
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Physiologic jaundice
Most infants have it
Onset is in first week, but NOT in first 24 hours
Increased unconjugated (indirect) bilirubin
Generally benign, resolving in 10 days to 1 month, although some cases may require phototherapy to prevent kernicterus (toxic accumulation of unconjugated bilirubin in neonatal brain)
169
Pathological infantile jaundice
Onset in first 24 hours or >14 days after birth
Rapid increase in total bilirubin and DIRECT bilirubin = post-hepatic cause
170
Crigler-Najjar Syndrome
Mutation in bilirubin-UDP-glucuronosyltransferase (UDP-GT), which conjugates bilirubin
Type I (AR): no functional enzyme; require phototherapy/transplantation (markedly elevated bilirubin levels in neonates result in neurotoxicity) = severe jaundice, neurologic impairment
Type II (AD): decreased enzyme activity; less severe = lower serum bili, no neurologic impairment
171
Gilbert's Disease
Mutation in promoter region of gene encoding for UDP-GT resulting in reduced activity --> recurrent, stress-induced hyperbilirubinemia
You get delay in moving unconjugated bili into the liver. Pts will have mildly elevated total bilirubin levels; mostly indirect bili. Indirect bili is an antioxidant; may protect against some cancers & heart disease
Common (5-10% of Western population homozygous for condition)
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Dubin-Johnson Syndrome
Mutation in multi-drug resistance protein 2 (MRP2), the protein responsible for transporting conjugated bilirubin from hepatocyte into bile canaliculus --> defect in excretion of **conjugated bilirubin**
Variable hyperbilirubinemia, esp in setting of stress
Benign, no rx needed
173
What is the treatment for biliary atresia?
Kasai procedure - hepatoportoenterostomy
**Better prognosis if performed before day of life 60**
174
Hepatoblastoma
90% present F
NOT associated with underlying liver disease
Sx: anorexia, weight loss, N/V, pain
90% have elevated serum alpha-fetoprotein levels (useful tumor marker)
175
AST & ALT
Important in amino acid synthesis
When elevated, sign of hepatocellular damage
176
Differences between AST & ALT
AST:
- located in liver, heart, muscle, blood
- in hepatocyte, located in cytosol and mitochondria
- when elevated alone, not necessarily sign of liver damage
ALT:
- located in liver only
- in cytosol
- when elevated, sign of liver damage ONLY
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AST:ALT ratio
Typically 1 seen in cirrhosis
Ratio >2 suggestive of alcoholic liver disease
178
Etiology of severe (>15 nml) AST and ALT elevations
- Acute viral hepatitis (A-E, herpes)
- Meds/toxins (acetaminophen)
- Ischemic hepatitis (found down)
- Autoimmune hepatitis
- Wilson's disease
- Acute Budd-Chiari Syndrome
- Hepatic artery ligation or thrombosis
179
Alkaline phosphatase
Present in liver, bone, placenta, intestines
Elevated during:
- CHOLESTASIS
- bone disease/mets
- pregnancy
- bowel perforation
180
5'-nucleotidase
Significantly elevated only in liver disease
Highest levels in cholestatic disease
181
γ-glutamyltransferase (GGT)
Elevated after alcohol consumption and almost all types of liver disease
182
How do you calculate a MELD score?
6.4 + 9.8 x log(INR) + 11.2 x log(Cr) + 3.8 x log (t bilirubin)
183
Octreotide
First-line immediate tx for someone who is having a massive variceal bleed
= inhibits release of vasodilator hormones such as glucagon causing splanchnic vasoconstriction --> reduces portal HTN --> brings down rate of variceal bleeding, temporarily
184
Serum-ascites albumin gradient (SAAG)
Serum albumin - ascites albumin
Correlates with sinusoidal pressure. The higher above 1, the greater the HVPG
If SAAG > 1.1 and ascitic fluid total protein 1.1 and ascitic fluid total protein >2.5 = heart failure
SAAG
185
Criteria in dx of hepatorenal syndrome?
- advanced hepatic failure and portal HTN
| - Cr > 1.5 or Cr clearance
186
What are the two things that are always present in hepatorenal syndrome?
Ascites and hyponatremia (due to water retention)
187
What is the tx for spontaneous bacterial peritonitis?
Abx + albumin
188
How does lactulose treat hepatic encephalopathy?
Acidifies stool, makes ammonium which can’t be absorbed
Increases flow through colon - less time to reabsorb ammonia
