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GI Week 3 - WLB > Fluid Absorption and Intestinal Motility - Prunuske > Flashcards

Fluid Absorption and Intestinal Motility - Prunuske Flashcards

1
Q

Define Anismus.

A

anal sphincter dyssynergia

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2
Q

Define Haustra.

A

one of the pouches of the colon, produced by adaptation of its length to the taenia coli

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3
Q

Define Haematochezia.

A

blood in the stool

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4
Q

Define Ileus.

A

Failure of forward movement of intestinal contents

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5
Q

Define Purgative.

A
  • substance that promotes bowel loosening and movement
    • cathartic
    • laxative
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6
Q

Define Tenesmus.

A

feeling that you need to pass stool even when bowels are empty

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7
Q

What processes drive the absorption of fluid in the small intestine and colon?

A
  • Osmotic gradients
  • Driven by electrogenic or electroneutral ion transport processes
    • Electroneutral NaCl absorption mediates fluid uptake
    • Electrogenic uptake of Na+ and glucose (amino acids, bile salts) drives fluid absorption in small intestine
    • Chloride Secretion in Crypts of Lieberkuhns promotes fluid entry in the Small Intestine
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8
Q

What is the pathophysiology diarrhea?

A

***

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9
Q

What three transmembrane ion transport processes help move stuff in the GI system?

A
  • Pumps- Active transport, Na+/K+ ATPase and H+/K+ ATPase
    • uphill transport against an electrochemical gradient
    • effective at low concentrations
    • demonstrate saturable kinetics
    • require cellular energy
    • demonstrate high ionic specificity
  • Channels (pores) Na+, CFTR, K+
    • passive movement along the prevailing electrochemical gradient
  • Carriers
    • movement of ion or substance against electrochemical/concentration gradient by coupling it to movement of another ion moving with electrochemical gradient (Secondary active transport)
    • Exchangers- substances move in opposite directions (antiporter)
      • NHE Na+/H+ and Cl-/HCO3-
    • Cotransporters- substances move in same direction (symporter)
      • 2 Na+/ glucose, bile salts, amino acids
      • Pept1 H+/peptide
      • 2 Cl-/Na+/K+ found on basolateral import Cl- into cell
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10
Q

What are the four properties of the epithelium control of fluid movement?

A
  1. Water can move through cells (transcellular route) or between cells (paracellular route)
  2. Tight junction permeability is regulated by cytokines, bacterial toxins, and hormones which modify claudins.
  3. Water movement follows osmotic gradients.
  4. Driven by electrogenic or electroneutral ion transport processes.
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11
Q

What are the 7 net movements of ions in the small intestines?

A
  1. Electroneutral NaCl absorption
  2. Bicarbonate secretion
  3. Sodium-coupled nutrient absorption
  4. Proton-coupled nutrient absorption
  5. Chloride Secretion
  6. Sodium-coupled bile acid absorption
  7. Calcium and iron absorption (not a major determinant of fluid transport)
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12
Q

Both fluid absorption and excretion can occur simultaneously in small intestine. Where do these processes occur?

A
  • Cells at the tips of the villi absorb fluid
  • Cells in the crypts secrete fluid driven by chloride ion secretion.
  • Huge surface area created by folded mucosa allows for high capacity for absorption.
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13
Q

How is NaCl absorption an Electoneutral process?

A
  • Coupled activity of:
    • sodium/hydrogen exchanger (NHE)
    • chloride/bicarbonate exchanger in the apical membrane
  • Water follows to maintain osmotic balance
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14
Q

Why is uptake of Na+ and glucose (amino acids, bile salts) in the small intestine an Electrogenic process?

A

No active transport of a counterion instead, anions (largely chloride) and water follow passively via the tight junctions

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15
Q

How does Chloride Secretion in the Crypts of Lieberkuhns promote fluid entry in the Small Intestine?

A
  • Major electrogenic mechanisms promoting fluid entry into the intestinal lumen:
    • Chloride is actively taken up by the Na+, 1K+, 2Cl- symporter (NKCC1) at the basolateral membrane.
    • Chloride leaves the luminal side of the cell via CFTR.
    • Potassium leaves basilar side via a Ca2+-activated K+ channel.
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16
Q

Where/how is the majority of calcium absorbed?

A
  • Absorbed predominantly in duodenum through paracellular and transcellular routes
    • Ca2+ channel on brush border membrane inwardly driven by the elctrochemical gradient
    • Intracellular calcium is bound to calbindin.
    • Basolateral Ca2+-ATPase pumps, calcium exchanged with sodium, or calcium is exocytosed.
    • Vitamin D enhances expression of Ca2+ channels.
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17
Q

Where does the majority of iron absorption take place?

A
  • Primarily in duodenum
  • only 3-6% of ingested iron (mostly from meat) is absorbed
  • Gastric secretions dissolve the iron and aid its reduction to the Fe2+ form.
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18
Q

What is the net movement of ions in the Small Intestine?

A
  1. Electroneutral NaCl absorption
  2. Bicarbonate secretion
  3. Sodium-coupled nutrient absorption
  4. Proton-coupled nutrient absorption
  5. Chloride Secretion
  6. Sodium-coupled bile acid absorption
  7. Calcium and iron absorption (not a major determinant of fluid transport)
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19
Q

What are the regulators of ion absorption and secretion?

A
  • Active transport of solutes, especially Na+, requires energy therefore blood flow increases during a meal to increase oxygen and glucose.
  • ACh/VIP stimulate chloride secretion (long reflex)
  • Stroking the mucosa releases 5-hydroxytryptamine from local enterochromaffin cells (short reflex)
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20
Q

Agonists that elevate what promote opening of the CFTR channel resulting in copious secretion in both small and large intestine?

A

cAMP (VIP, cholera toxin)

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21
Q

What gastrointestinal polypeptide secreted by goblet and ECL cells binds GC-C receptor on epithelial cells to promote secretion?

A

Guanylin

(Binding raises concentration of intracellular cGMP increasing Cl- secretion through CFTR into the lumen)

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22
Q

In a healthy adult, the volume of fluid presented to the intestine on a daily basis is approximately 8 liters. Assuming a normal diet, reabsorption of the bulk of this fluid is driven primarily by which of the following?

  • A. Nutrient-coupled electrogenic sodium absorption
  • B. Electroneutral NaCl absorption
  • C. Nutrient-coupled proton absorption
  • D. Potassium absorption
  • E. Electrogenic sodium absorption via ENaC channels
A

A. Nutrient-coupled electrogenic sodium absorption

(transporters = SGLT1, AA/Na+, etc.)

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23
Q

What is the net movement of ions in the Colon (lack of nutrients)?

A
  1. Electrogenic sodium absorption
  2. Electroneutral NaCl absorption
  3. Short chain fatty acid absorption
  4. Chloride absorption/secretion
  5. Potassium absorption/secretion (not a major determinant of fluid transport)
24
Q

Desiccation of stool is facilitated by uptake of what?

A

Na+ uptake

  • An electrogenic Na+-selective channel (ENaC) allows sodium to enter the cell
    • channel also found on renal collecting duct epithelial cells
  • Found predominantly in distal colon
25
Q

What molecules are Secretagogues?

A
  • Positive regulators enhanced secretion and decreased Na+, Cl- and water absorption
    • Parasympathetic activity (Ach)
    • VIP/NO
    • Histamine
    • Prostaglandins
    • gastrin, secretin
    • Motillin
    • Serotonin
    • Long-chain fatty acids
    • bile salts
    • Bacterial toxins
26
Q

What molecules are Absorbagogues?

A
  • Negative regulators decreased secretion and enhanced Na+, Cl- and water absorption
    • Sympathetic activity
    • Somatostatin
    • Aldosterone
    • short-chain fatty acids
    • opiods
27
Q

What are the causes of Secretory diarrhea?

A
  • Excess secretion of chloride and inhibition of NaCl transport
  • Infectious, inflammation
28
Q

What are the causes of Osmotic diarrhea?

A
  • Poor absorption of luminal substances (bile acids, organic acids, magnesium sulfate)
  • Pull water from bloodstream by osmosis
29
Q

How does fluid flux depend on surface area available for ion transport and residence time in the lumen?

A
  • Hypermotility leads to diarrhea
  • Hypomotitlity leads to constipation
  • Loperamide slow transit and increase sphincter tone to increase fluid absorption
  • Slow transit through colon aids efficiency of water recovery
30
Q

Which is longer: the small intestine or the large intestine?

A
  • The small intestine is ~ 5 meters long
  • The large intestine is ~ 1 meter long
31
Q

Why does it take chyme ~2-4 hours to reach the ileo-cecal sphincter in the small intestine and it takes another 2.5 days for chyme to reach the anus in the large intestine?

A

Basal Electrical Rhythm (BER) has higher frequency in the small intestine.

BER is much slower in the large intestine.

32
Q

What are the four motile processes (e.g. types of motility) in the small intestines?

A
  1. Mass peristalsis promote rapid forward propulsion, occur 1-3 times/day.
  2. Segmental contractions that promote mixing with little net forward movement
  3. Alterations in surface configuration of the mucosa (muscularis mucosa)
  4. Tonic contractions of sphincters
33
Q

What factors effect mixing in the small intestines?

A
  • Segmentation:
    • Patterns depend upon on frequency of Basal Electrical Rhythm and amplitude.
      • Mixing → retards transit.
    • Contractions are initiated by focal increases in Ca2+ influx
    • Propagation of excitation is usually limited to a few centimeters.
34
Q

What is the average rate of the BER (Basal Electrical Rhythm) in the small intestines?

A

8-12 BER cycles/min

35
Q

What factors increase small intestinal motility?

A
  • acetylcholine from vagus and enteric plexus
  • motilin
  • serotonin
  • substance P
  • prostaglandin
  • gastrin
  • CCK
  • insulin
36
Q

What factors decrease intestinal motility?

A
  • epinephrine
  • secretin
  • glucagon
  • activation of opioid receptors
37
Q

What system is the primary regulator of motility?

A
  • Enteric Nervous System:
    • Mediates reflexes through enteric sensory and motoneurons, which can be modulated by CNS
    • Many of the sensory neurons are stimulated and serotonin (5-HT) is released from mucosal enterochromaffin cells (ECL).
    • Motoneurons: excitatory fibers release acetylcholine, neurokinin A and substance P and inhibitory fibers release vasoactive intestinal peptide (VIP) and nitric oxide (NO) on smooth muscle cells.
38
Q

When does the Migrating Motor Complex occur in the small intestine?

A

In “fasted” state 4 hrs after a meal

39
Q

Why is important for the MMC to function in the small intestine?

A
  • Sweeping out bacteria, desquamated cells, and undigested meal residues
  • Sphincter of Oddi opens during MMC
    • leads to bile storage in small intestine may be important for preventing cholestasis
40
Q

What local conditions influence the ileocecal sphincter tone?

A
  • Distension of ileum due to a peristaltic wave reduces tone and promotes emptying of the ileum.
  • Distension of cecum increases tone and decreases emptying of the ileum due to sympathetic input from the splanchnic nerve.

***The ileocecal sphincter is tonically contracted (brake) to limit reflux of colonic contents into the ileum.

41
Q

What is the “Peristaltic reflex”?

A
  • initiated by distension of gut wall
    • “Law of the Intestine”
    • depends upon an intact enteric nervous system and coordinates proximal contractions with distal relaxation
    • Increased or decreased by autonomic input.
42
Q

What is the Gastro-ileal Reflex?

A
  • increased gastric activity increases ileal contractions
    • relaxes cecum and ileocecal sphincter
    • long reflex plus hormonal component (gastrin and CCK).
43
Q

What is the Intestinointestinal Reflex?

A
  • over-distension or traumatization results in relaxation of the entire gut (“adynamic ileus”)
  • It depends upon intact extrinsic neural connections.
    • (This is the usual condition after abdominal surgery.)
44
Q

What is the Ileal-gastric Reflex?

A
  • distension of the ileum decreases gastric motility
    • long reflex involving the vagus nerve
45
Q

What is the average rate of the BER in the large intestine?

A

2-6 BER cycles/min

Motility is very slow with the frequency of BER 2/min at the ileocecal valve and 6/min at the sigmoid colon.

46
Q

What is unique about the tissue structure of the large intestine?

A
  • No villi or lympathic vessels
  • Epithelium- coloncytes, goblet cells (mucus and trefoil peptides), entero-endocrine, and Paneth cells
  • Taenia coli = three bands of longitudinal muscle that is not well coordinated with circular muscles
47
Q

What is the Colonocolonic reflex?

A
  • distension in one part of the colon relaxes other parts of the colon
    • mediated by the enteric nervous system and modulated by sympathetic input
48
Q

What is the Gastro-colic reflex?

A
  • gastric distension evokes an increase colon motility and an urge to defecate
    • 5-HT and ACh are important mediators
49
Q

What is the nervous system control of the Defecation Reflex?

A
  • Afferent parasympathetic sensory nerve fibers- anal sampling to determine if gaseous, solid or liquid
  • Parasympathetic pelvic nerves provide extrinsic input to colon and trigger relaxation of the internal anal sphincter in response to filling
  • Somatic pudendal nerves stimulate the external anal sphincter
50
Q

What structures in the rectum partially occlude and retard flow making it a reservoir?

A

transverse folds

51
Q

What is the rectosphincteric reflex? What initiates it?

A
  • urge to defecate
    • relaxation of internal anal sphincter (NO/VIP)
    • reflex contraction of external anal sphincter to prevent inadvertent expulsions
  • initiated by: distention of the rectum
52
Q

What involuntary and voluntary actions lead to successful defecation?

A
  1. Descending colon, sigmoid colon, and rectum contract
  2. Relaxation of both sphincters
  3. Contraction of diaphragm and abdominal muscles (Valsalva maneuver)
  4. Relaxation of the pelvic floor
53
Q

What causes inflammatory bowel disease?

A
  • Crohn’s disease or ulcerative colitis
  • Release of inflammatory mediators
    • damage to epithelial barrier
    • increased inducible nitric oxide synthase
    • generation of excessive nitric oxide
54
Q

What causes Irritable Bowel Syndrome?

A
  • Manifestation of different peripheral mechanisms disturbing motor and sensory functions
    • may be triggered by infection
    • structure of bowel is normal
55
Q

What peripheral biological factors contribute to IBS?

A
  • Colonic motility delayed: Constipation predominant
  • Slow colonic transit: prokinetics, intestinal secretagogues
  • Disorder of rectal evacuation: anismus
  • Colonic motility accelerated: Diarrhea predominant
  • Vagal induction of high amplitude propagated contractions
  • Increased sensitivity to food molecules especially bile acids and short chain fatty acids causing release of serotonin.
  • Increase small-bowel and colonic mucosal permeability
    • Changes in tight junction proteins.
56
Q

Following a forceps delivery of her third child, a 36-year-old woman returns to her physician complaining of persistent, mild fecal incontinence when lifting her older children, without any urinary incontinence. Her symptoms are most likely attributable to dysfunction of which of the following?

  • A. Anal sensory nerves
  • B. Internal anal sphincter
  • C. External anal sphincter
  • D. Pudendal nerves
  • E. Puborectalis muscle
A

C. External anal sphincter

57
Q

What is Anismus/Dyssynergic defecation?

A
  • contraction rather than relaxation of the external anal sphincter and puborectalis in response to defecation reflex
    • results in constipation evidence that biofeedback can be helpful

GI Week 3 - WLB (8 decks)

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