-
Net absorption of water occurs in __________. The primary absorptive segments are __________.
___________are the primary determinants of water and electrolyte absorption. The ________ of the mature intestinal cells express the transporters responsible for ion absorption.
- both the small intestine and proximal colon
- the jejunum and ileum
- The membrane permeability and specific transporters present
- villus tips
-
Compare the apical transport mechanisms responsible for absorption for secretion of Na+, Cl¯,HCO3¯ and K+ by the cells of the jejunum, ileum and colon.
- Na+
- jejunum: co-transporter, NHE absorb Na from lumen
- ileum: co-transporter, NHE absorb Na from lumen; lower density
- proximal Colon: NHE absorb
- distal colon: ENaC
- Cl-
- jejunum: passive paracellular
- ileum: passive paracellular and Cl/HCO3 exchanger
- colon: passive paracellular and Cl/HCO3 exchanger
- HCO3-
- duodenum: secretion; neutralize gastric contents
- Jejunum: absorb as CO2
- Ileum and colon: secretion with Cl/HCO3 exchanger.
- K+
- jejunum: absorption; solvent drag; paracellular diffusion
- ileum: absorption; solvent drag; paracellular diffusion
- colon: mainly secretory secondary to the absorption of Na, paracellular; can absorb too via K/H ATPase
-
List the sources and the approximate fluid volume that daily enters the small intestine. Compare the relative volumes of solutes absorbed in the duodenum, jejunum, ileum and colon. Discuss membrane properties that contribute to these differences and the role of the standing osmotic gradient mechanism.
- 2000 ingestion
- 1500 salivary galand
- 2000 gastric juice
- 2000 bile and pancreatic juice
- 1500 small intestine
- absorb 8.5L
- duodenum: no net absorption of water; hypertonic luminal content
- jejunum: primary site for absorption; standing osmotic gradient
- ileum: ??
- proximal colon: 400ml; standing osmotic gradient
- distal colon: none
- membrane permeability
- duodenum>jejunum>ileum>colon
-
Compare the causes of osmotic, secretory and psychogenic diarrheas. Explain the relationship between diarrhea and excessive K+ loss. Describe the symptoms.
osmotic: luminal contents contain large amount of particles can't be absorbed; water secreted osmotically
secretory: bacterial enterotoxin -> excess secretion
psychogenic: tension induced parasympathetic stimulation on GI tract, result in secretion
- during prolonged diarrhea, K+ loss too much -> hypokaliemia, may lead to cardiac arrhythmia
- >200ml water/24hrs
-
Describe water imbalance in patients infected with vibro cholera. Discuss the role of glucose and ions in rehydration therapy of these patients.
- cholera toxia binds to alpha-unit of Gs -> permanent binding Gs-GTP -> constant cAMP stim -> constant open of CFTR -> Cl- secretion -> water follows
- crypt cells have excessive secretion of water, exceeding the ability of villus cells to absorb.
- to provide energy and water.
- Na-Glucose cotransporter intact, can provide the body with glucose....
-
Discuss and compare the causes of chloridorrhea and celiac disease (gluten enteropathy). Describe their symptoms.
- chloridorrhea
- absence of Cl/HCO3 transporter at ileum and colon, retains Cl- in lumen, water stays, underabsorption. NHE provides H+, can't be neutralized by HCO3, produces acidic stool. HCO3 stay in the cell together with the loss of H+ result in metabolic alkalosis
- celiac desease
- congenital defect in interstinal surface, develops sensitivity to gluten. ingestion of gluten results in allergic inflammatory response -> villi blunted or lost, reduced capability of absorption. loss I and S cells, loss CCK and secretin, loss bile cycling, fat in stool, weight loss and malnutrition.
-
Water Absorption Drivers
- 1 Nutrient Driven – after eating
- - osmotic gradients - created by absorption digestive products
- 2 Non Nutrient – between meals
- - primary extracellular drivers
- - Na+ and Cl- and electrochemical gradients
- - modulated - neurocrines, endocrines, paracrines
-
Sources and Volumes (ml) of Water
- - 2000 - ingestion
- - 1500 - saliva
- - 2000 - stomach
- - 2000 - pancreas and bile
- - 1500 - small intestine secretions
- ---------------------
- - 9000 24 hr TOTAL
-
Absorption of Water
- how
- small intestine summary
- - osmotically follows absorption nutrients or ions
- - transcellular and paracellular
- Small intestine
- - primary site - 8500 ml absorbed - 40% maximum capacity, can double if necessary
- - surface area large - folds, crypts, villi, microvilli
- - paracellular pathways - primary - leaky tight junctions
- - permeability gradient - differences in tight junctions
- duodenum > jejunum > ileum > colon
- - absorption failure: diarrhea
-
Water absorption
- Duodenum
- Jejunum
- Colon
- Duodenum
- - hypertonic solution -> no net water absorption
- - emptied gastric contents
- - pancreatic enzymes
- Jejunum
- - primary site nutrient and electrolyte absorption
- - standing gradient osmosis - like gallbladder
- Colon - receives 500 mls
- - proximal colon
- - 400 ml absorption
- - paracellular pathways
- - standing gradient osmosis
- - distal colon
- - little paracellular transport
- - tight junctions
- - 100 ml excreted in feces
- - small intestine falters - can absorb 4-6L
-
Sodium Transport and Absorption - Small Intestine
- source
- absorption
- efficiency
- driving force
- sites
- transporters
- loss
- 20% from diet; 80% from intestinal secretions
- - recovered 95%
- - driving force - electrochemical gradient – basolateral Na-K-ATPase
- - jejunum: primary site
- - ileum: secondary site – decreased density transporters; high efficiency of jejunum
- - co-transport with glucose and amino acids
- - countertransport with H
- - aldosterone sensitive
- - 5% feces
-
Specialized Sodium transporters
- - Jejunum and Ileum
- - Co-transport
- - glucose, amino acids, bile salts
- - Countertransport
- - hydrogen (NHE)
- - aldosterone ( adrenocortical steroid) released when blood pressure drops, stimulates Na and water absorption, also increase transporter expression
-
Sodium absorption - Colon
- - tight junctions: resist water flow, resulting in large electrochemical gradient
- - No sugar or amino acid absorption
- - proximal colon - Na-H exchanger
- - distal colon - electrogenic Na channel (ENaC) - primary
- - aldosterone - increases number of channels
-
Chloride Transport
- Jejunum
- ileum and colon
- jejunum
- - absorption
- - paracellular (voltage dependent) pathway - primary
- - secondary to Na+ co-absorption with glucose and amino acids
- - lumen negative relative to blood
- - Cl- lumen -> blood
- Ileum and colon
- - paracellular pathway retained
- - new Cl-HCO3
- - secondary active countertransporter
- - chloridorrhea – congenital absence of exchanger -> luminal Cl retained
-
Bicarbonate Transport
- duodenum
- jejunum
- ileum and colon
- duodenum
- - actively secreted
- - stimulated by cAMP, cGMP
- - neutralizes acid from stomach
- jejunum
- - absorbed from lumen as CO2
- - lipid soluble - enters blood
- Ileum and colon
- - high cytosolic HCO3
- - secretion coupled with Cl- absorption
- - lumen alkaline
-
Potassium Transport
- jejunum and ileum
- colon
- Jejunum and ileum
- - no specific transporters
- - driving force - solvent drag - leaky paracellular pathways
- - water absorption – concentrates lumenal potassium
- - absorption - down concentration gradient
- colon
- - secretion and absorption, both contribute to homeostasis
- - secretion - primary
- - paracellular - secondary to Na+ absorption
- - normally large secretion, not of concern since volume lost is small
- - prolonged diarrhea - K+ loss - life threatening
- - hypokalemia, cardiac arrhythmias, dehydration
- - absorption
- - apical K-H (ATPase) – last effort to conserve
- - 70% homology to parietal pump
- - omeprazole insensitive
-
Other Regulators for Electrolytes Transport/Absorption
- All secondary
- endocrine regulators
- enteric nervous system
- - parasympathetic – increases stimulation (secretion)
- - sympathetic - inhibits
- - immune system -> inflammatory mediators -> increase stimulation
-
Fluid balance maintained by _____ secretion and ________ absorption.
- crypt cell
- villus epithelial cell
-
Diarrhea
- > 200 ml water/24hrs
- - deadly disruption of fluid balance - especially children
- - decrease in blood pressure
- - circulatory collapse
- - cardiac abnormalities
- - subsequent increased motor response / secretion - protective
- - rapidly removes noxious offending substances - bacteria and bacterial toxins
-
-
Secretory Diarrhea
- - excess stimulation of crypt cells -> secretion
- - imbalance between crypt cell secretion and villus cell absorption
- - stimulates apical Cl- channels - CFTR - most important
-
Causes of Secretory Diarrhea
- Bacterial Enterotoxins
- - E- coli - contaminated food
- - Vibro Cholera - contaminated water
-
Cholera toxin - mechanism
- - enters cell
- - causes GTP permanently binds to alpha subunit of G-protein (Gs)
- - permanently activates cAMP
- - cAMP permanently locks open apical Cl– channels (CFTR)
- - Cl-, and Na and water (osmotically, paracellularl) continually secreted
-
Other enterotoxin effects
- - inhibit apical Na+- H+ countertransporter
- - driving force of water reduced; disable absorption?
- - activate K+ secretion from colon
- - more water and K loss - (hypokalemia)
- - increase secretion HCO3 -> hyperchloremic metabolic acidosis
- - water loss life threatening if untreated
- - 85% mortality
-
Treatment of secretory diarrhea
- - medical treatment
- - cholera runs course 3-5 days
- - cells undergo apoptosis and toxins lost
- - pharmaceuticals - available in developed countries
- - somatostatin analogue
- - inhibits cAMP – Cl channel can close
- - oral rehydration therapy – used in underdeveloped countries
- - Na+ – dependent glucose or amino acid absorption – unaffected
- - Na+ - K+ pump - unaffected
- - administer osmotically balanced solution - electrolytes, Na, glucose, amino acids
- - water follows Na-dependent glucose and amino acid absorption
- - net water absorption exceeds loss
-
Osmotic Diarrhea
- definition
- causes
- - accumulation non-absorbable solutes in lumen
- - osmotic gradient draws water from blood into intestinal lumen
- - Laxatives (MgOH)
- - Lipid malabsorption - steatorrhea
- - Carbohydrate malabsorption
-
Chloridorrhea
- - defective anion transporter
- - congenital defect in Cl-HCO3 exchanger in ileum and colon
- - Cl not absorbed, accumulates in lumen
- - HCO3 – retained in cell
- - H+ - secreted by Na-H exchanger produces acid stools
- - loss H and retention of HCO3 - metabolic alkalosis
-
Celiac Disease (___________)
gluten-enteropathy or tropical sprue
- - intestinal surface defect
- - due to inherited gluten sensitivity
- - protein in wheat
- - allergic inflammatory response
- - blunted villi - may disappear in severe cases
- - deficiency brush border enzymes
- - loss of I (CCK) and S (secretin) cells
- - excess fats in stool (steatorrhea)
- - reduction bile recycling
- - weight loss - loss of nutrients, vitamins in stool
- - potential delays in diagnosis
-
Psychogenic Diarrhea
- - hypermotility - neither secretory or osmotic
- - parasympathetic nerves - excess stimulation from nervous tension
- - increased gastric motility and mucous secretion -> decreased water absorption
|
|
