Large & small bowel function Flashcards
Fluid absorption
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
Villi
projections into the lumen covered with mature, absorptive enterocytes
occasional mucus-secreting goblet cells
lifespan ~days
Crypts
tubular invaginations of the epithelium around the villi, lined largely with younger epithelial cells, primarily involved in secretion
Na+ absorption
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
Na/solute co-transport
most important means of Na absorption
Transporter on luminal surface binds both Na and organic molecule
Electrogenic
Na/H exchange
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
Coupled NaCl absorption
ileum and colon
Na/H exchange coupled to anion transport via Cl/HCO3 exchanger
electroneutral
most important during interdigestive period
Na channels
minor in SI but important in distal colon and rectum
coupled to Na/K ATPase
stimulated by aldosterone
Cl absorption
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
Water absorption
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)
Function of fluid secretion
propel substance out of crypts
maintain fluidity of the intraluminal contents
maintain osmotic equilibrium
dilution of potentially injurious substances
Crypt cell secretion pathway
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)
Diarrhea definition
> 200 g/day, 70-90% water
notable changes in bowel movements including consistency and frequency, usually >3 times/day
Heat-stable enterotoxin mediated infectious enteritis
Toxin activates guanyl cyclase
Phosphorylation of intracellular proteins that influence ion transport
Primarily inhibits NaCl absorption
Congenital chloridorrhea
absence/defective apical surface Cl/HCO3 antiporter
inability to absorb Cl- –> watery diarrhea
Lactose malabsorption
Lactose, osmotically active
Osmotic diarrhea
Colonic bacteria - can metabolize some lactose to produce H2, CO2, other gasses, short-chain FAs
Osmotic laxatives (magnesium hydroxides)
similar to lactose malabsorption
attract and retain water in intestinal lumen
IBS
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
Bacterial enterocolitis pathophys
- Cholera enterotoxin binds GM1 ganglioside receptors –> endocytosis
- Subunit dissociates –> enters cytoplasm, ribocylates G protein, inhibiting GTPase
- 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
Carcinoid syndrome
EC cell products cause diarrhea
serotonin, bradykinin, substance P, neurotensin - increase intracellular Ca
PG - stimulate cAMP production
VIPoma
islet cell pancreatic tumor, produces VIP
Increases fluid secretion by stimulating cAMP –> increase Cl- secretion and decrease NaCl absorption
Gastrinoma
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
Ulcerative colitis pathophys
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
Ulcerative colitis histo
Crypt abscesses involving the crypts of Lieberkuhn
PMNs accumulate in abscesses - frank necrossi of surrounding crypt epithelium
Crohn’s disease pathophys
anywhere in GI tract, but most commonly terminal ileum
Patchy, discontinuous
Transmural inflammation
Fibrous strictures (permanent), adhesions and fistulas
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
Adenomatous polyps
gland formation
Premalignant cnodition
>2cm - 50% incidence of cancer
can be anywhere, but more seen in L colon
Colon cancer genetics
APC 9low-grade adenoma) –> K-ras (high-grade adenoma) –> p53 (carcinoma)
IBD epidemiology
more common in females
teens/20s, then 50-60
more common in Caucasians, Ashkenazi Jews
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
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
Dx of IBD
Rule out other causes
Leukocytes, CRP may be elevated
Imaging
Colonoscopy/sigmoidoscopy and biopsy, unless active flare of UC
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
Tx of severe UC
If no improvement with corticosteroids (started immediately):
anti-TNF therapy
cyclosporine
surgery
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
UC surgical procedure
Colectomy + IPAA (ileal pouch anal anastomosis)
5-7 loose bowel movements per day without incontinence
pouchitis in >40%
Crohn’s surgery
75% require surgery within 20 years
Indications: intractibility to medical therapy, abscess, massive bleed, obstruction, fistulas
Ileotomy, stricturectomy
Celiac disease Dx
serology:
IgA endomysial Ab & IGA tTG Ab
then mucosal biopsy of distal duodenum/proximal jejunum
Celiac disease S/S
infants: malabsorption
older: chronic diarrhea, dyspepsia, flatulence, extraintestinal manifestations
Diverticulosis
herniation of colonic mucosa
Diverticulitis
infection/inflammation of diverticulum
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
Diverticulitis S/S
> 80% asymptomatic
fever, LLQ pain, tenderness, nausea/vomiting, altered bowel habits
Diverticulitis Tx
simple - high fiber diet
bowel rest (liquid diet)
broad-spectrum antibiotics: cipro/metronidazole
drain abscess if necessary
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
Mesalazine MOA/PD
bowel-specific, metabolized in the gut
blocks COX/PG formation?
topical effect
Azathioprine MOA
antagonize purine metabolism - inhibit DNA/RNA/protein synthesis
inhibit proliferation of leukocytes and lymphocytes
incorporated into DNA structure
Azathioprine SE
bone marrow suppression
hepatoxicity with regards to 6-MMP
Infliximab MOA
TNA-alpha mab
lysis of TNF-producing macrophages and T-cells
Infliximab SE’s
serious infections
hepatosplenic T-cell lymphoma
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
Loperamide indication
adjunct to rehydration therapy for symptomatic control of acute, nonspecific diarrhea
Most common cause of lower GI bleeding
- Diverticular disease
- Colitis
- Adenomatous polyps
- Malignancies
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)
Paracellular vs transcellular absorption
paracellular mostly proximal SI
transcellular entirety of small and large intestines
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
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
R-sided colorectal tumour symptoms
fatigue, Fe-deficiency anemia
change in bowel habit - diarrhea
L-sided colorectal tumour symptoms
rectal bleeding
crampy pain, anemia
change in bowel habit often constipation
Colorectal cancer stages
1: doesn’t penetrate muscle
2: penetrates muscle into fat
3: penetrates fat into lymph nodes
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
Double duct sign
simultaneous dilation of common bile duct and pancreatic duct, most commonly due to a tumour in the head of the pancreas
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
Non-neoplastic polyps
hyperplastic
hamartomas
inflammatory
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
