GI Flashcards
(74 cards)
1
Q
Midgut development
A
6th week: midgut herniates through umbilical ring
10th week: returns to abdominal cavity, rotates around SMA
2
Q
Apple peel atresia
A
Vascular accident in utero:
- Intestinal atresia distal to duodenum–> bilous vomit
- SMA obstruction–> blind end to proximal jejunem, absence of part of small bowel and mesentary
- Terminal ileum distal to atresia spirals around ileocolic vessel
3
Q
Hepatoduodenal ligament
A
Connects liver to duodenum
Contains:
- Portal triad= hepatic artery, portal vein, common bile duct
- *Pringle maneuver= compress ligament between thumb and forefinger to control bleeding
- Connects greater and lesser sacs
4
Q
Gastrohepatic ligament
A
Connects: Liver to lesser curvature of stomach
Contains: Gastric arteries
5
Q
Gastrocolic ligament
A
Connects: greater curvature and transverse colon
Contains: gastroepiploic arteries (some L also contained in gastrosplenic ligament)
6
Q
Plexi in digestive tract
A
Submucosa (internal)= Meissner’s plexus
- Controls secretory activity
Muscularis externa: Auerbach’s plexus= myenteric nerve plexus
- Controls inner circular and outer longitudinal muscle layers of muscularis externa
7
Q
Hindgut supply/innervation
A
Artery= IMA
Parasympathetic innervation= Pelvic (vs Vagus for mid and foregut)
Vertebral level= L3
Structures:
- Distal 1/3 of transverse colon to upper portion of rectum
8
Q
Pectinate (dentate) line in rectum
A
Formed by endoderm (hindgut) meeting ectoderm
Above:
- Internal hemorrhoids (supplied by superior rectal (portal) and middle/inferior rectal (IVC))
- Visceral innervation: non-painful hemorrhoids
- Arterial supply= IMA (superior rectal artery)
- Adenocarcinoma
- Drains to deep lymph nodes
Below:
- External hemorrhoids (painful)
- Venous: Inferior rectal–> internal pudendal–> internal iliac–> IVC
- Arterial= internal pudendal (inferior rectal artery)
- Squamous cell carcinoma
- Drains to superficial inguinal nodes
9
Q
Hepatic zones
A
Zone 1= first affected by viral hepatitis
Zone 3= portal vein/hepatic artery—> venous drainage to hepatic vain
- Affected first by ischemia
- Contains P450 system
- Sensitive to toxic injury
- EtOH hepatitis
10
Q
Direct hernia
A
Thru Hesselbach’s triangle:
- Between inferior epigastric vessels (lateral) and medial umbilical ligament (medial)
11
Q
Hiatal hernia
A
Sliding= most common
- GE junction displaced (above diaphragm)
Paraesophageal=
- Normal GE junction
- Fundus of stomach protrudes into thorax
12
Q
Gastrin
A
Source:
- G-cells in antrum of stomach
- Stimulates ECL (enterochromaffin-like cells) to secrete histamine–> stimulates parietal-cell acid secretion
- Stimulates Parietal cell acid release
Stimulated by vagus nerve via GRP (vs Ach to parietal cells)
- Increased in Zollinger-Ellison syndrome
- Increased by chronic PPI use
- Stimulated by Phe, Tryptophan
- Gastrinoma: can lead to jejunal ulcers, diarrhea, abdominal pain
13
Q
CCK
A
Source: I cells in duodenum, jejunem
- increase pancreatic secretion (all types), gallbladder contractions (emptying), relax sphincter of Oddi
- Decrease gastric emptying
14
Q
Secretin
A
Source: S cells in duodenum
- Increases pancreatic bicarb secretion, bile secretion
- Decreases gastric acid secretions
- both allow pancreatic enzymes to function
Stimulated by fatty acids in duodenum
15
Q
Somatostatin
A
Source: D cells in pancreatic islets, gastric mucosa
BLOCKS all the things! (stimulated by acid, blocked by vagal stimulation)
- Anti-growth hormone effects
16
Q
Glucose-dependent insulinotropic peptide (GIP)
A
Source: K cells in duodenum
- decrease H+ secretion
- Increase insulin release (endocrine!)
- Oral glucose used more rapidly than equivalent by IV due to GIP secretion
17
Q
Vasoactive intestinal polypeptide (VIP)
A
Source: parasympathetic ganglia in sphincters, gallbladder, small intestine
- Moves things along in GI system
- Increases intestinal water, electrolyte secretion
- Relaxes smooth m., sphincters
Stimulated by distention, vagal stimulation
- Inhibited by adrenergic input
- VIPoma= non-alpha, non-beta islet cell pancreatic tumor
- -> watery diarrhea, hypokalemia, metabolic acidosis (and achlorhydria)
- Treatment= somatostatin
18
Q
Motilin
A
Source: small intestine
Produces MMCs (increased in fasting state)
** Erythromycin= motilin receptor agonist–> stimulates intestinal peristalsis
19
Q
Saliva
A
Parotid gland (IX)
Submandibular and sublingual gland (VII)
- Stimulated by sympathetic and parasympathetic activity
- Amylase–> hydrolyzes alpha1,4 linkages–> disaccharides (maltose, alpha-limit dextrins)
- HCO3- –> bacterial acid
- Lipase (also pancreatic)–> digest medium chain triglycerides—> monoglycerides
Hypotonic d/t reabsorption of ions (CFTR protein) but at high flow is isotonic due to decreased time for reabsorption
20
Q
Chief cells
A
Located in stomach
- Secrete pepsinogen
- Converted from pepsinogen–> pepsin by stomach acid
- -> cleaves polypeptides at aromatic aa sites
21
Q
Brunner’s glands
A
Duodenal submucosa
Secrete alkaline mucous
Hypertrophied in peptic ulcer disease
22
Q
Trypsinogen
A
Converted to trypsin (from zymogen)
- Enterokinase/enteropeptidase (duodenal mucosa enzyme) cleaves trypsin
- Activated trypsin cleaves more trypsinogen (positive feedback)
- Inhibited by serum alpha-1-antitrypsin and BPTI (basic-pancreatic trypsin inhibitor)
- Alcoholic pancreatitis= damage to acinar cell–> abnormal trypsin activation
- Hereditary pancreatitis= mutation in trypsinogen–> not inhibited by BPTI
23
Q
Amylase
A
Salivary amylase: starts digestion
- Hydrolyzes alpha-1,4 linkages to yield disaccharides (maltose, alpha-limit dextrans)
Pancreatic amylase:
- Hydrolyzes starch in duodenum: oligosaccharides and disaccharides
24
Q
Oligosaccharide hydrolases
A
Brush border of intestine: rate-limiting step in carb digestion–> monosaccharides from oligo/di-saccharides
- Only monosaccharides can be absorbed
- SGLT1 (Na+-dependent): glucose, galactose
- GLUT-5: facilitated diffusion of fructose
- Transport sugar to blood via GLUT-2
**D-xylose absorption test= distinguish GI mucosal damage from other malabsorption problems
25
Bile
- Bile salts: bile acid conjugated to glycine, taurine
- Phospholipids
- Cholesterol
- Bilirubin (conjugated heme and glucuronic acid via UDP glucuronosyl transferase)
- Water and ions
** Cholesterol 7-alpha hydroxylase catalyzes rate-limiting step
Functions:
1. Digest/absorb lipids/fat-soluble vitamins
2. Cholesterol excretion
3. Antimicrobial: membrane destruction via emulsification of gram-negative outer membranes
* * Enterococci + Strep bovis can grow in bile
26
Cimetidine
Ranitidine
Famotidine
Nizatidine
H2-blockers (reversible)--> decreased parietal cell H+ secretion due to decreased histamine stimulation
Tox:
- Cimetidine= potent inhibitor of P450; antiandrogenic (prolactin--> gynecomastia, impotence, decreased libido); can cross BBB (confusion, dizziness, h/a) and placenta
- Rantidine + Cimetidine--> decreased renal creatinine excretion
27
Omeprazole, -prazole
Proton pump inhibitors
MOA: irreversible inhibtion of H+/K+ ATPase in stomach parietal cells
Use: ulcers, reflux, Zollinger-Ellison
Tox: increased risk of C. diff (decreased aciditiy), pneumonia
- Hip fractures, decreased Mg+2 with long-term use
28
Bismuth, sucraflate
Bind ulcer base: physical protection
- Allow HCO3- secretion to reestablish pH gradient in mucosa
Use: Ulcer healing, traveler's diarrhea
29
Misoprostol
PGE1 analog: increases production and secretion of gastric mucous, decreased acid production
Use: prevent NSAID-induced peptic ulcers
- Maintain PDA
- Induces labor (but don't use in pregnant women before this!--> abortifactant)
Tox: diarrhea
30
Octreotide
Somatostatin analog
Use: variceal bleeds, VIPoma, carcinoid tumors
Tox: nausea, cramps, steatorrhea
31
Antacids
Can affect absorption, bioavailability, urinary excretion of other drugs: alters gastric, urinary pH, delays gastric emptying
ALL cause hypokalemia
Overuse:
- Aluminum hydroxide--> constipation, hypophosphatemia, muscle weakness, osteodystrophy, seizures
- Magnesium hydroxide: diarrhea, hyporeflexia, hypotension, cardiac arrest
- Calcium carbonate: hypercalcemia, rebound acid increase (can also chelate and decrease effectiveness of other drugs, like tetracycline)
32
Brunner's glands
Submucosal glands in Duodenum
33
Peyer's patches
Lymphoid nodules in lamina propria/submucosa of Ileum
34
Vitamin/mineral absorption
Iron= Fe+2 in duodenum
Folate+ Fats= jejunem
B12 + bile acids= ileum
35
ECL cells
Enterochromaffin-Like Cells
1. Vagal stimulation (+Phe, Tryptophan) to G cells--> gastrin released into circulation
2. Parietal cell direct stimulation (CCKb receptor) and ECL stimulation
3. ECL cells--> histamine--> H2 receptor on parietal cell--> acid
36
Gastric parietal cell
Directly stimulated by:
1. Gastrin (via vagus stimulation of G cell)--> CCKb receptor
- Activates Gq--> IP3
2. Vagal stimulation--> M3 receptor
- Activates Gq--> IP3
3. Histamine (via ECL cell)--> H2 receptor
- Activates cAMP production
Inhibited by:
1. Prostaglandins/misoprostol
- Gi--> inhibition of cAMP
2. Somatostatin
- Gi--> inhibition of cAMP
Lumen side: Cl- channel and H+/K+ ATPase (proton pump)
37
Pancreatic secretions
Isotonic fluid (same K+/Na+ as serum)
- Low flow--> increased Cl- (pumped out)
- High flow--> increased HCO3- (stomach emptying acidic contents into duodenum offset by bicarb)
38
Unconjugated bilirubin
Indirect bilirubin= 0.8 of bilirubin (vs 0.2 direct)
- Breakdown product of heme
- Elevated--> black pigment gallstones due to hemolysis
Bacteria contain beta-glucuronidase--> breaks down conjugated--> unconjugated bilirubin
- Brown pigment stones
39
Conjugated bilirubin
Direct bilirubin (water soluble)
- Unconjugated bilirubin taken up from bloodstream (bound to albumin)- passive
- Converted to conjugated by UDP glucuronosyl-transferase
40
Urobilinogen
Liver-excreted direct bilirubin converted by gut bacteria to urobilinogen
- 80% excreted in feces
- 20% moves to either: enterohepatic circulation (90%), or kidney (10%- yellow color to urine)
41
Osmotic laxatives
Magnesium hydroxide, magnesium citrate, polyethylene glycol, lactulose
- Osmotic: draw water into colon
Treatment for constipation
42
Infliximab
Monoclonal ab to TNF-alpha
Use: crohn's, UC, RA
Tox: infection (reactivate latent TB), fever, hypotension
43
Sulfasalazine
Sulfapyridine (antibacterial) and 5-ASA (antiinflammatory)
- Activated by colonic bacteria
Use: UC, Crohn's, mild RA
Tox: malaise, nausea, sulfonamide toxicity, reversible oligospermia
44
Ondansetron
5-HT3 antagonist; acts on CTZ trigger zone in dorsal medulla (antiemetic)
Use: post-op N/V, chemotherapy
Tox: H/A, constipation
45
Metoclopramide
D2 receptor antagonist (increases resting tone, contractility, LES tone, motility)
- No influence on colon transport time
Use:
- Diabetic, post-op gastroparesis
- Antiemetic
Tox:
- Increased parkinson effects (contraindicated in Parkinson's disease)
- Restlessness, drowsiness, fatigue, depression, Nausea, diarrhea
- Drug interaction with digoxin and diabetic patients
- Contraindicated in small bowel obstruction
46
Whipple's disease
Tropheryma Whipplei infection
- Foamy PAS-positive macrophages in intestinal lamina propria, mesenteric nodes
Presentation:
- Cardiac, arthralgias, neurologic symptoms
- Older men
- Malabsorption
47
Abetalipoproteinemia
Decreased synthesis of ApoB
- -> inability to generate chylomicrons in intestine
- -> decreased cholesterol, VLDL in bloodstream
- -> fat accumulation in enterocytes
Early childhood presentation: malabsorption, neurologic disease
48
Intestinal stomach cancer
Associated with:
- H. pylori infection
- Dietary nitrosamines (smoked food)
- Chlorhydria
- Chronic gastritis
- Type A blood
Seen on lesser curvature: ulcer with raised margins
Signs:
- Virchow's node (L supraclavicular)
- Sister Mary Joseph nodule (subcutaneous periumbilical mets)
49
Diffuse stomach cancer
NOT associated with H. pylori
Histo:
- Signet ring cells (mucin pushes nucleus to periphery)
- Stomach wall= thickened, leathery (linitis plastica)
Signs:
- Virchow's node (L supraclavicular)
- Sister Mary Joseph nodule (subcutaneous periumbilical mets)
- Krukenberg's tumor= bilateral mets to ovaries (abundant mucus, signet ring cells)
50
H. pylori therapy
Triple: PPI, Clarithromycin, Metronidazole/amoxicillin
Quad: PPI, bismuth subsalicylate, metronidazole, tetracycline
51
Ulcer vs erosion
Ulcer= penetrates into (not thru) submucosa
Erosion= does not extend thru muscularis mucosa
- Acute erosions= NSAID, surgical stress, Cushing/Curling, smoking EtOH
52
Ulcer complications
Hemorrhage:
- Gastric, duodenal (posterior > anterior)
- Ruptured gastric ulcer= lesser curvature (bleed from L gastric artery)
- Posterior duodenal ulcer--> gastroduodenal artery
Ulcer: Duodenal (anterior > posterior)
53
Infectious diarrhea: microbe inoculum
```
Lowest:
- Giardia (few)
- Entamoeba, Campylobacter jejuni, Shigella (~200)
- Clostridium perfringens (~500)
- Vibrio parahaemolyticus (~10^6)
- Salmonella (10^7)
- ETEC (10^9)
Highest
```
54
Meckel's diverticulum
Five 2's: 2 inches long, 2 feet from ileocecal valve, 2% population, 2 years, 2 types of epithelia
True diverticulum
- Persistance of vitelline duct
- May contain ectopic gastric/pancreatic mucosa (secrete acid)
Symptoms:
- melena (young children)
- RLQ pain
- Intususception
- Volvulus
- Terminal ileum obstruction
Diagnosis:
Pertechnetate study for ectopic uptake
55
Angiodysplasia
tortuous dilation of vessels--> hematochezia
- Cecum, terminal ileum, ascending colon
Seen in elderly
- Confirm with angiography
56
Adenomatous polyp
Precancerous (precursor to CRC)
- Malignancy associated with size, histology, dysplasia of epithelium
Symptoms:
- Asymptomatic
- Lower GI bleed
- Partial obstruction
- Mucous secretory diarrhea
57
Hyperplastic polyp
Non-neoplastic
| - 50% in rectosigmoid colon
58
Juvenile polyposis
Sporadic lesions in children < 5 years (80% in rectum)
- NOT malignant if SINGLE
Juvenile polyposis syndrome= multiple juvenile polyps in GI tract--> increased risk of adenocarcinoma
59
Peutz-Jeghers
Single polyp= not malignant
Peutz-Jeghers= AD syndrome, multiple nonmalignant hamartomas (can bleed, cause intussiception)
- Hyperpigmented mouth, LIPS, hands, genitalia
Mutation in serine/threonine kinase 11 (STK11) on Chromosome 19
- Increased risk of CRC, other malignancies
60
Familial adenomatous polyposis (FAP)
AD mutation of APC on chromosome 5q
- 2 hit hypothesis
- 100% progress to CRC
- 1000s of polyps, pancolonic, always in rectum
Gardner's= FAP + osseous, soft tissue tumors, congenital hypertrophy of retinal pigment epithelium
Turcot's syndrome= FAP + malignant CNS tumor
61
Hereditary nonpolyposis coloretal cancer (HNPCC/ Lynch syndrome)
AD mutation in MSH2 (DNA mismatch repair gene)
- 80% progress to CRC
- ALWAYS in proximal colon
62
Site of colorectal cencer
Rectosigmoid > Ascending > Descending
- Ascending= exophytic mass, iron deficiency anemia, weight loss (right colon has larger diameter- less likely to see obstruction)
- Descending= infiltrating mass, partial obstruction, colicky pain, hematochezia
** Rare presentation with strep bovis
CEA good for monitoring recurrence (not good screening test)
63
APC/beta-catenin (chormosomal instability pathway of CRC
Normal colon-->
Loss of APC--> At-risk colon
- APC maintains low beta-catenin (oncogenic), and intracellular adhesion
- Decreased intracellular adhesion, increased proliferation (seen in all sporadic, most familial CRC)
- See tubulovillous adenomatous polyps
Loss of k-RAS--> Adenoma
- Unregulated intracellular signal transduction
- See increased size in polyps
Loss of p53--> Carcinoma
- loss required for tumorigensis
64
Carcinoid tumor
MUST metastasize outside GI system to observe effects of 5-HT production (serotonin)
- Wheezing, R-sided heart murmurs, diarrhea, flushing
Originates as neuroendocrine cell "dense core bodies" (EM) in appendix, ileum, rectum
Tx:
- Resection
- Octreotide
- Somatostatin
65
Hepatic encephalopathy
Glutamate released by neurons--> astrocytes--> convert to glutamine
Neurons take glutamine:
- Recycle to glutamate--> neurotransmitters
- Convert to alpha-ketoglutarate--> TCA
Encephalopathy= Ammonia toxicity--> depletion of glutamate and alpha-ketoglutarate--> excess glutamine
- Glutamine= hyperosmolarity in neuron cell, mitochondrial dysfunction (no Alpha-ketoglutarate)--> astrocyte swelling
66
Liver markers of pathology
AST, ALT:
- Viral hep ALT > AST
- Alcoholic hep AST > ALT
Alk Phos: obstructive liver disease (HCC), bone disease, bile duct disease
Gamma-glutamyl transpeptidase (GGT): measure if LFTs increased to rule out bone disease
67
Reye's syndrome
Aspirin + viral infection
Symptoms:
- Mitochondrial abnormalities (decreased beta-oxidation d/t reversible inhibition of enxyme)
- Hypoglycemia
- fatty liver (microvesicular fatty change)
- Vomiting, hepatomegaly, coma
ONLY use aspirin in children with Kawasaki's disease
68
Hepatocellular carcinoma
Due to:
- Hep B, Hep C
- Wilson's
- Hemochromatosis (HLA-A3)
- Alpha-1-antitrypsin
- Alcoholic cirrhosis
- Carcinogens (alflatoxin B1 from aspergillus--> p53 mutations (G:C--> T:A))
69
Angiosarcoma
Malignant tumor of endothelial origin
| - Associated with arsenic, polyvinyl chloride exposure
70
Crigler-Najjar syndrome
Absent UDP-glucouronyl transferase
- Early in life: patients die early
Findings:
- jaundice, kernicterus (bilirubin in brain)
- Increased unconjugated bilirubin
Tx: plasmapheresis, phototherapy
- Type 2 respods to phenobarbital (increases liver enzyme synthesis)
71
Dubin Johnson/Rotor syndrome
Conjugated hyperbilirubinemia (defective liver secretion
- Benign
- Black liver in Dubin-Johnson
72
Gallstone ileus
Fistula between gallbladder and small intestine (large gallstone)
- Air in biliary tree
- Gallstone obstructing ileocecal valve
Women, 70+ years
- Symptoms= crampy abdominal pain, vomiting, abdominal distention, hard mass at ileocecal valve
73
Pancreatic adenocarcinoma
CA-19-9 tumor marker (CEA less specific)
Presents:
- Abdominal pain to back
- Weight loss
* *Trousseau's syndrome**= migratory thrombophlebitis; redness, tenderness on palpation of extremities (CANCER)
- -> hypercoagulability due to adenocarcinoma (pancreas, colon, lung)--> thromboplastin-like substance production
74
Glucagonoma
Gluconeogenesis, lipolysis (weight loss)
| Necrolytic migratory erythema, erythematous rash of groin
