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HMS Homeostasis II > Diarrheas > Flashcards

Diarrheas Flashcards

1
Q

Handling of water by GI tract (summary image)

A
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2
Q

Despite the presence of aquaporins in the intestines and colon, most water is reabsorbed ___.

A

Despite the presence of aquaporins in the intestines and colon, most water is reabsorbed paracellularly

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3
Q

Generally speaking, absorption of water has much to do with ___, while secretion of water into the intestinal lumen has much to do with ___.

A

Generally speaking, absorption of water has much to do with the transport of sodium from lumen into cells, while secretion of water into the intestinal lumen has much to do with the transport of chloride into the lumen.

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4
Q

Enteric stretch receptors

A

Stretch receptors in the small intestine elicit local enteric neural reflexes (utilizing Ach and VIP) which then induce chloride secretion from crypt cells.

They also induce entero-chromaffin cell secretion of serotonin.

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5
Q

Nurient-dependent vs nutrient-independent sodium reabsorption

A

In general, nutrient-independent sodium absorption is inhibited when crypt cell chloride secretion is up-regulated.

However, nutrient-dependent sodium absorption is unaffected by this relationship.

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6
Q

Aldosterone in the GI tract

A

Similar to the kidney, aldosterone, in states of volume depletion, also acts on colonocytes to increase expression of electrogenic sodium channels, increasing efficiency of sodium/water recovery in this organ.

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7
Q

NaCl villus/crypt diagram

A
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8
Q

NaCl and water handling in different parts of the GI tract

A
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9
Q

Na+ / Glucose transit

A

Sodium-coupled glucose absorption occurs at the brush border, utilizing the Na+ gradient set up by the Na+/K+ ATPase. Cytosolic glucose will be used or transported into blood stream via basolateral GLUT-2. The electrochemical gradient favors chloride absorption paracellularly as the counter ion to Na+, and water follows by osmosis.

Sodium-coupled glucose absorption is not inhibited by cytosolic increases in cAMP as is the case for electroneutral NaCl transport

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10
Q

Modes of GI water reabsorption

A
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11
Q

In the small intestine, ____ are the dominant mechanism in the absence of nutrients

A

In the small intestine, coupled sodium-hydrogen (NHE)/chloride-bicarb (DRA) exchangers are the dominant mechanism in the absence of nutrients.

In effect, NaCl comes in while H+ and HCO3 go out to lumen. NaCl is transported across the basolateral membrane, drawing in water paracellularly via osmosis.

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12
Q

In the colon, ___ transport sodium.

A

In the colon, coupled NaCl absorption via the NHE/DRA exchangers is still present, while ENaC channels additionally transport sodium.

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13
Q

Colonic ENaC regulation

A

ENaC channel expression and/or function is up-regulated in the presence of the hormone aldosterone, promoting sodium and water removal from the feces.

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14
Q

Colonic NHE/DRA regulation

A

The NHE/DRA system in the colon is negatively regulated by cAMP.

Importantly, cAMP is the major second messenger which gives rise to chloride secretion, so it makes sense that it should suppress the antagonizing pathway.

Normally this wouldn’t be a problem, since the sodium-reabsorption machinery and chloride-secreting machinery are in different cells, however in physiological and pathophysiological contexts when cAMP is elevated, this is generally the case throughout the crypt/villus axis.

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15
Q

Mechanism of chloride secretion

A

Chloride accumulates in the cytosol of crypt cells by the action of basolateral NKCC1, which conducts secondary active transport of potassium and chloride linked to sodium transport.

When appropriately signaled via cAMP second messenger systems, CFTR chloride channels open in the apical membrane, pouring chloride ions into the lumen. Sodium moves into lumen paracellularly, down its electrochemical gradient as the counter ion, and water follows by osmosis. Ca++ or cAMP-activated K+ channels on basolateral plasma membrane open to maintain favorable electrical gradient for chloride to be secreted across apical surface.

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16
Q

Cholera toxin

A

CTa irreversibly binds to stimulatory G-proteins, resulting in excessive amounts of cAMP production.

The capacity to conduct chloride into lumen is enhanced by increasing placement of NKCC1 into the basolateral membrane. The elevated cAMP also inhibits the NHE/DRA sodium reabsorption system, worsening fluid and salt loss.

This may lead to severe hypovolemia within hours to days.

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17
Q

Polyethylene glycol

A

Brand name Miralax

An osmotic stool softener, which acts by increasing the osmotic pressure within the gut lumen, forcing water in.

If used in small doses, it can soften stool. If too much is used, it will cause diarrhea. It may also be used to clear the intestinal tract prior to colonoscopy.

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18
Q

Scientific definition of diarrhea

A

Producing a stool weight greater than 200grams/day in an adult, and greater than 10g/kg/day in a child

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19
Q

Summary statement of diarrhea

A

Water goes where the osmoles are.

If there are too many osmoles in the lumen (eaten, secreted, not absorbed, or all three) then there will be diarrhea

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20
Q

Electrolyte transport-related diarrhea equation

A

290 - 2 x [stool Na + K]

aka the “osmotic gap”

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21
Q

Substrate induced diarrhea

A

When an exogenous osmole (not Na, K, Cl, HCO3) is responsible for keeping water in the lumen by the laws of osmosis.

In this case, the measured osmoles will be relatively low, and the osmotic gap will be high

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22
Q

Watery-diarrhea mechanisms

A
  1. Electrolyte transport-related diarrhea
  2. Substrate Induced Diarrhea
  3. Mixed mechanism
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23
Q

Oral Rehydration Solutions for diarrhea

A

Relies on the fact that nutrient-dependent transport is unaffected in ETReDs such as that caused by bacterial enterotoxins.

An orally ingested solution that stimulates intestinal Na+ absorption by SGLT1 and Na+ -coupled amino acid transporters.

Development of ORS has reduced mortality from diarrheas by 70%

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24
Q

Zinc

A

Zinc has been shown to shorten the duration of acute diarrhea and is part of the WHO-recommended ORS.

. The mechanism of this effect of zinc is unclear.

In epithelial cells, zinc blocks Cl- secretion by inhibiting K+ channels in the basolateral membrane and stimulates the sodium-hydrogen exchanger (NHE3).

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25
Q

Anti-motility agents

A

Drugs that inhibit intestinal motility have been used extensively to treat diarrhea. The putative mechanism of action for antimotility drugs is increased Na+ and fluid absorption as a result of slow intestinal transit.

Loperamide and diphenoxylate are μ-opioid agonists that are widely used for mild, nonspecific diarrhea. They are not recommended in bacterial diarrheas primarily owing to the risk of paralytic ileus, and diphenoxylate also has substantial central opioid effects.

26
Q

Antisecretory agents

A

Inhibiting intestinal fluid secretion to prevent diarrhea.

Crofelemer, has been approved for use in HIV-related diarrheas based on a clinical trial showing efficacy in improving chronic diarrhea in patients with HIV. Crofelemer is a heterogeneous proanthocyanidin oligomer extracted from the bark of the South American tree Croton lechleri. The putative mechanism of action for crofelemer is inhibition of Cl- channels in the apical membrane.

27
Q

Are juice and water effective to administer to patients with watery diarrhea?

A

NO!

Their sugar content is too high while the sodium content is too low.

28
Q

Functional definition of constipation

A
  • Fewer than 3 spontaneous BMs per week
  • In >25% of defecations:
    • Straining
    • Lumpy or hard stools
    • Sensation of incomplete evacuation
    • Sensation of anorectal blockage
    • Manual maneuvers to facilitate defecation
29
Q

Why is colonic motility important?

A

The role of colonic motility is mixing and retention of liquid waste to allow for optimal fluid reabsorption (achieved through segmental propulsions) and the propulsion of solidified waste to the rectum for evacuation when socially convenient (achieved through high-amplitude propagating contractions)

30
Q

Segmental propulsion

A

Segmental propulsion is when contents move back and forth between haustra via short and long-duration contractions.

Short-duration contractions occur in circular muscle and aid in local mixing. Long-duration contractions occur in longitudinal muscle of the taeniae coli and help to propel colonic contents in both oral and aboral direction

31
Q

High-amplitude propagating contractions

A

Distinct colonic patterns that propagate only aborally (away from the mouth) from the cecum to the distal sigmoid. These contractions in health occur about six times daily.

They are provoked by eating (the gastrocolic reflex), defecation, laxatives, or colonic inflammation.

32
Q

Gastrocolic reflex

A

HAPCs provoked by eating is an enteric nervous system ‘reflex’ called the gastrocolic reflex.

This effect is mediated by distention of the stomach and by nutrient presence in the small intestine. Neurocrine and endocrine pathways mediate this response, which may occur so that the cecum can be readied for receipt of additional wastes through the ileocecal valve.

33
Q

Rectoanal inhibitory reflex

A

With filing of the rectum, the internal anal sphincter relaxes via stimulation of intrinsic nerves, which release VIP and NO. This is a reflex called the rectoanal inhibitory reflex.

34
Q

Rectum at rest vs strianing

A
35
Q

Categories of primary constipation

A
  • IBS-C: Characterized by abdominal pain relieved with defecation and often with normal colon transit time
  • Slow-transit: Characterized by delayed transit through the colon and outlet delay
  • Pelvic floor dyssynergia: where the pelvic floor muscles paradoxically contract or do not relax during defecation.
36
Q

Secondary constipation

A

Constipation that is accounted for by a systemic illness, serious medical, surgical, or psychosocial disorder, or a medication or toxin. Broadly speaking, secondary causes relate to either physical or functional (nerve or muscle) impairment of defecation.

Obstructing lesions, spinal cord disorders, hypothyroidism, and various neurological diseases can present with treatment-refractory constipation. Anti-cholinergic and opioid medications cause constipation, while constipation may be a prominent symptom for lead toxicity in children.

37
Q

Hirschsprung’s disease

A

Abnormality characterized by maldevelopment of the enteric nervous system.

Neurons which are supposed to travel from the neural crest along the length of the intestine and populate the enteric nervous system from the mouth to the anus fail to do so. Secondary to mutations in growth and trophic factors.

Most often affects rectosigmoid area, but can also affect colon or small intestine. Diagnosed in infancy.

38
Q

Diagnosing Hirschsprung’s disease

A

A rectal biopsy is considered the gold standard for diagnosis and surgical excision of the segment lacking ganglia is the treatment of choice.

Anorectal manometry can also diagnose HD because the internal anal sphincter will fail to relax in response to rectal balloon inflation.

39
Q

Workup of Constipation

A
  • Digital rectal exam
  • Colonoscopy
  • Radiopaque Marker study
  • Defecography
  • Anorectal manometry
  • Colonic manometry
  • Rectal suction biopsy
  • Barium Enema
40
Q

Radiopaque Marker study

A
  • Measure movement of radiopaque markers through gut
  • X-ray is obtained on day of ingestion and then 5 days later.
  • By day 6, the expectation is that all of the markers would have passed out into the stool.
  • Suggestive of constipation if greater than 5 markers are visualized on a plain abdominal x-ray by day 5.
  • Scattered throughout colon suggests slow-transit etiology
  • Contained within rectum suggests defecatory disorder like dyssynergia
41
Q

Defecography

A
  • Imaging study of rectum
  • Provides anatomical and functional information related to the anorectum
  • Contrast is placed into the rectum and the patient is asked to squeeze and bear down and evacuation of the barium is monitored by fluoroscopy while the patient is positioned on a special commode
42
Q

Rectocele

A

A defect in the rectovaginal septum. A patient with this defect may note obstructive type symptoms when attempting defecation.

Attached is the finding as seen on defecography.

43
Q

ARM/balloon explusion test

A

Anorectal manometry is usually paired with a balloon expulsion test. A 50 ml water filled balloon is filled in the rectum and the patient is asked to expel the balloon within 2 minutes.

An inability to expel the balloon in this amount of time is considered abnormal and suggestive of a defecatory disorder.

44
Q

Normal rectoanal inhibitory reflex on anorectal manometry

A
45
Q

Calretinin

A

A protein highly expressed in intrinsic enteric nerves. This staining is done to assess the potential diagnosis of Hirschsprung’s disease. Abesence of any calretinin staining is consistent with the diagnosis.

46
Q

Constipation treatment and prevention

A
  • Fiber supplementation
  • Surfactants
  • Osmotic laxatives
  • Stimulant laxatives
  • Secretagogues
  • Behavioral approaches
  • Surgery
47
Q

Colace

A

Docusate sodium

A commonly used surfactant for treating constipation.

There is little high-quality evidence supporting the use of these agents in chronic constipation

48
Q

Linaclotide

A

Peptide agonist of guanylate cyclase-C receptor that stimulates intestinal secretion and transit by increasing cGMP and activating the CFTR receptor thereby increasing secretion of chloride and bicarbonate.

Additionally, increased extracellular cGMP decreases firing of visceral afferent nerves, decreasing pain.

49
Q

Biofeedback

A

A behavior approach used to correct inappropriate contraction of pelvic floor muscles and external anal sphincter muscle during defecation in patients with pelvic floor dysfunction.

50
Q

Subtotal colectomy with ileorectal anastomosis

A

Surgical solution reserved for patients with severe refractory slow-transit constipation.

Patients with pelvic floor dysfunction would not benefit from this surgery.

51
Q

If a diarrhea persists even during a fast, then it must be . . .

A

. . . a nutrient-independent diarrhea, or in other words an electrolyte transport diarrhea.

Nutrient malabsorption diarrheas only go on if there are consumed nutrients to act as osmoles. On the other hand, nutrient-independent secretion and reabsorption is happening 24/7.

52
Q

Water moves into and out of the GI lumen until . . .

A

. . . the luminal osmolality matches the serum osmolality, whether in health or disease.

In health this should always be 290 mOsm/kg

53
Q

Mechanical stimulation of chloride secretion

A
54
Q

If you see constipation in a young infant with trisomy 21, then you should suspect. . .

A

. . . Hirschsprung’s

55
Q

Hirschsprung’s disease and the internal anal sphincter

A

In Hirschsprung’s, patients may entirely lack inhibitory neurons supplying the internal sphincter!

So, the sphincter may be unable to relax! This can be treated by administering botulinum toxin to block or reduce acetylcholine signaling at the internal sphinter.

56
Q

Is botox permanent?

A

No!

It needs to be re-injected every couple of months

57
Q

Absence of rectoanal inhibitory reflex on rectoanal manometry is suggestive of. . .

A

. . . Hirschsprung’s disease

58
Q

___ is an unexpected risk factor for dyssynergia, explaining the effectiveness of behavioral therapy.

A

History of trauma is an unexpected risk factor for dyssynergia, explaining the effectiveness of behavioral therapy.

59
Q

A normal liquid stool osmotic gap is between ___.

A

A normal liquid stool osmotic gap is between 50 and 100.

60
Q

Many common laxatives contain ___.

A

Many common laxatives contain magnesium

HMS Homeostasis II (35 decks)

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