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Large & small bowel function Flashcards

1
Q

Fluid absorption

A

9L of fluid emptied into s intestine (2L oral + 7L secretions)
D&J: 5.5L (but very little net fluid absorption due to secretion in duodenum)
I: ~2L
1.5L to colon (1.3 absorbed)
can increase capacity to compensate

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2
Q

Villi

A

projections into the lumen covered with mature, absorptive enterocytes
occasional mucus-secreting goblet cells
lifespan ~days

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3
Q

Crypts

A

tubular invaginations of the epithelium around the villi, lined largely with younger epithelial cells, primarily involved in secretion

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4
Q

Na+ absorption

A

along the entire intestine
proximal SI: Na/H exchanger, Na/solute co-transporter (glucose, galactose, aa)
Ileum/colon: coupled NaCl pathway
Distal colon/rectum: Na channels

Driving force - Na/K ATPase

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5
Q

Na/solute co-transport

A

most important means of Na absorption
Transporter on luminal surface binds both Na and organic molecule
Electrogenic

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6
Q

Na/H exchange

A

Located on apical membrane of proximal SI
Major mode of non-nutrient mediated Na absorption in proximal SI
stimulated by high HCO3-
Protons generated by cell metabolism

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7
Q

Coupled NaCl absorption

A

ileum and colon
Na/H exchange coupled to anion transport via Cl/HCO3 exchanger
electroneutral
most important during interdigestive period

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8
Q

Na channels

A

minor in SI but important in distal colon and rectum
coupled to Na/K ATPase
stimulated by aldosterone

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9
Q

Cl absorption

A

SI: nutrient-coupled Na transport, Cl- follows
distal SI, proximal colon: coupled NaCl
Ileum, colon: Cl/HCO3 exchange alone as well
During interdigestive period - Coupled NaCl absorption

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10
Q

Water absorption

A

Major: paracellular diffusion
Simple diffusion across the lipid bilayer - water drag
Aquaporins - aquaporin 10 highly expressed in enterocytes in ileum
Na-dependent transporters (very high molar ratio of water absorbed)

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11
Q

Function of fluid secretion

A

propel substance out of crypts
maintain fluidity of the intraluminal contents
maintain osmotic equilibrium
dilution of potentially injurious substances

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12
Q

Crypt cell secretion pathway

A

K driven into cell via Na/K ATPase, then moves out through basal K channels
Cl enters cell via NKCC
Cl secreted via CFTR - regultaed by secretagogues
Na moves down gradient paracellularly

Stimulation occurs due to secretagogues: VIP, ACh, 5-HT (serotonin)

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13
Q

Diarrhea definition

A

> 200 g/day, 70-90% water

notable changes in bowel movements including consistency and frequency, usually >3 times/day

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14
Q

Heat-stable enterotoxin mediated infectious enteritis

A

Toxin activates guanyl cyclase
Phosphorylation of intracellular proteins that influence ion transport
Primarily inhibits NaCl absorption

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15
Q

Congenital chloridorrhea

A

absence/defective apical surface Cl/HCO3 antiporter

inability to absorb Cl- –> watery diarrhea

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16
Q

Lactose malabsorption

A

Lactose, osmotically active
Osmotic diarrhea
Colonic bacteria - can metabolize some lactose to produce H2, CO2, other gasses, short-chain FAs

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17
Q

Osmotic laxatives (magnesium hydroxides)

A

similar to lactose malabsorption

attract and retain water in intestinal lumen

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18
Q

IBS

A

functional disorder
abd pain, bloating, marked flatulence, excessive rectal mucus production, alteration of bowel habits, absence of organic cause
patients have motor dysfuncitons
stress-induced uncoordinated contractions of bowels

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19
Q

Bacterial enterocolitis pathophys

A
  1. Cholera enterotoxin binds GM1 ganglioside receptors –> endocytosis
  2. Subunit dissociates –> enters cytoplasm, ribocylates G protein, inhibiting GTPase
  3. continuous actiation of AC –> cAMP –> hyperstimulation of NaCl transport from serosa to mucosa, cause diarrhea

NaCl absorption inhibited
nutrient-coupled Na absorption remains normal: give rice/glucose solution with Na for oral rehydration

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20
Q

Carcinoid syndrome

A

EC cell products cause diarrhea
serotonin, bradykinin, substance P, neurotensin - increase intracellular Ca
PG - stimulate cAMP production

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21
Q

VIPoma

A

islet cell pancreatic tumor, produces VIP

Increases fluid secretion by stimulating cAMP –> increase Cl- secretion and decrease NaCl absorption

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22
Q

Gastrinoma

A

Tumor in pancreas/duodenal mucosa that secretes gastrin
Stimulates acid secretion –> ulcer formation
DIarrhea due to increased volume of fluid entering SI, + increased duodenal secretions
Steatorrhea due to inactivation of lipase, ppt of bile salts, damage to absorptive mucosa

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23
Q

Ulcerative colitis pathophys

A

starts in rectum, spreads proximally
advanced disease - may extend 2-3 cm into terminal ielum
Continuous disease
mucosallybased, no transmural spread (except in fulminant colitis)
Can form muscular strictures, but more uncommon; due to hypertrophy and spasm of muscularis mucosa (not fibrosis)
Granulation leads to bleeding

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24
Q

Ulcerative colitis histo

A

Crypt abscesses involving the crypts of Lieberkuhn

PMNs accumulate in abscesses - frank necrossi of surrounding crypt epithelium

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25
Crohn's disease pathophys
anywhere in GI tract, but most commonly terminal ileum Patchy, discontinuous Transmural inflammation Fibrous strictures (permanent), adhesions and fistulas
26
Crohn's disease pathophys
hyperplasia of perilymphatic histiocytes diffuse granulomatous infiltration discrete noncaseating granulomas in submucosa & lamina propria edema and lymphatic dilation of all layers of the gut monocytic infiltration within lymph nodules and Peyer's patches
27
Adenomatous polyps
gland formation Premalignant cnodition >2cm - 50% incidence of cancer can be anywhere, but more seen in L colon
28
Colon cancer genetics
APC 9low-grade adenoma) --> K-ras (high-grade adenoma) --> p53 (carcinoma)
29
IBD epidemiology
more common in females teens/20s, then 50-60 more common in Caucasians, Ashkenazi Jews
30
Crohn's S/S
``` recurrent mild diarrhea, abd pain, fever 20% RLQ pain, fever, bloody diarrhea fistulas, fissures, abscesses common slowly progressing constant pain, not relieved by bowel movement stool often not bloody ```
31
UC S/S
bloody diarrhea with stringy, mucoid material Lower abd pain/cramps Temporarily relieved by bowel movement Systemic symptoms: fever, anorexia, weight loss, fatigue
32
Dx of IBD
Rule out other causes Leukocytes, CRP may be elevated Imaging Colonoscopy/sigmoidoscopy and biopsy, unless active flare of UC
33
Tx of mild/moderate IBD
1) 5-ASA: mesalamine, balsalazide, sulfasalazine 2) Corticosteroids if cond'n does not improve with 5-ASA 3) Immunomodulating agents 4) biologics
34
Tx of severe UC
If no improvement with corticosteroids (started immediately): anti-TNF therapy cyclosporine surgery
35
UC: surgical indications
severe hemorrhage perforation carcinoma fulminent colitis/toxic megacolon that does not improve within 48-72 hours refractory disease requiring long-term corticosteroids
36
UC surgical procedure
Colectomy + IPAA (ileal pouch anal anastomosis) 5-7 loose bowel movements per day without incontinence pouchitis in >40%
37
Crohn's surgery
75% require surgery within 20 years Indications: intractibility to medical therapy, abscess, massive bleed, obstruction, fistulas Ileotomy, stricturectomy
38
Celiac disease Dx
serology: IgA endomysial Ab & IGA tTG Ab then mucosal biopsy of distal duodenum/proximal jejunum
39
Celiac disease S/S
infants: malabsorption older: chronic diarrhea, dyspepsia, flatulence, extraintestinal manifestations
40
Diverticulosis
herniation of colonic mucosa
41
Diverticulitis
infection/inflammation of diverticulum
42
Diverticulitis pathophys
increased luminal pressure --> hypertrophic muscle with weakness at site of BV penetration --> herniation often at sigmoid colon debris compresses/erodes BV many microperforations --> inflammation
43
Diverticulitis S/S
>80% asymptomatic | fever, LLQ pain, tenderness, nausea/vomiting, altered bowel habits
44
Diverticulitis Tx
simple - high fiber diet bowel rest (liquid diet) broad-spectrum antibiotics: cipro/metronidazole drain abscess if necessary
45
Types of adenomas
Pedunculate (attached by a stalk) sessile (little/no stalk) Tubular: complex network of branching glands Villous: extends straight down, long/finger-like Tubulovillous - combination
46
Mesalazine MOA/PD
bowel-specific, metabolized in the gut blocks COX/PG formation? topical effect
47
Azathioprine MOA
antagonize purine metabolism - inhibit DNA/RNA/protein synthesis inhibit proliferation of leukocytes and lymphocytes incorporated into DNA structure
48
Azathioprine SE
bone marrow suppression | hepatoxicity with regards to 6-MMP
49
Infliximab MOA
TNA-alpha mab | lysis of TNF-producing macrophages and T-cells
50
Infliximab SE's
serious infections | hepatosplenic T-cell lymphoma
51
Loperamide MOA
binds to opiate receptor in the gut wall inhibits ACh/PG release - inhibit propulsive peristalsis, increase intestinal transit time, enhance resorption increases anal sphincter tone
52
Loperamide indication
adjunct to rehydration therapy for symptomatic control of acute, nonspecific diarrhea
53
Most common cause of lower GI bleeding
1. Diverticular disease 2. Colitis 3. Adenomatous polyps 4. Malignancies
54
Tight junctions in s. intestine
Formed by extracellular domains of transmembrane "claudins" Connected to actin cytoskeleton via intracellular scaffold proteins --> gives jxn physical integrity + ability to be contracted (by myosin)
55
Paracellular vs transcellular absorption
paracellular mostly proximal SI | transcellular entirety of small and large intestines
56
Celiac disease pathophys
1) decreased brush border hydrolase resulting in unabsorbed osmols 2) villous atrophy - malabsorption 3) Crypt hyperplasia 4) inflammation-induced hyper-secretion by crypt enterocytes
57
Extracolonic manifestations of IBD
``` Conjunctivitis/iritis Growth retardation Aphthous ulcers/moniliasis Skin eruptions Ankylosing spondylitis Sacroilitis Clubbing Venous thrombosis Erythema nodosum Pyoderma gangrenosum Obstructive hydronephrosis Nephrolithiasis Hepatobiliary disorders ```
58
R-sided colorectal tumour symptoms
fatigue, Fe-deficiency anemia | change in bowel habit - diarrhea
59
L-sided colorectal tumour symptoms
rectal bleeding crampy pain, anemia change in bowel habit often constipation
60
Colorectal cancer stages
1: doesn't penetrate muscle 2: penetrates muscle into fat 3: penetrates fat into lymph nodes
61
Hereditary hemorrhagic telangectasia
Autosomal dominant telangectasia of the skin, mucous membranes, GI, arteriovenous malformations of the lungs, liver most commonly present as recurrent epistaxis or iron deficiency anemia due to GI blood loss >50% patients manifest by age 10
62
Double duct sign
simultaneous dilation of common bile duct and pancreatic duct, most commonly due to a tumour in the head of the pancreas
63
Radiation proctitis
Radiation injury for treatment of cancers of the rectum/cervix/uterus/prostate/bladder/testes Acute - first few weeks Chronic - several months, years Symptoms - diarrhea, rectal bleeding, painful defecation, bowel obstruction Tx: sucralfate, hyperbaric oxygen, corticosteroids, metronidazole and argon plasma coagulation
64
Non-neoplastic polyps
hyperplastic hamartomas inflammatory
65
Colonoscopy guidelines
50 for high-risk (1st degree relative with colon cancer), or 10 years before the first relative if their diagnosis was <50 Otherwise FIT at age 50, followup with colonoscopy if positive

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