Digestion and Absorption of Fluids and Electrolytes

Question 1

What is the fluid movement in the Intestines?

Small?

Large?

Answer 1

–about 8-9 L/day
•1.5-2.5 L/day from diet
•salivary, gastric, biliary and pancreatic secretions too
–Small Intestines
•Produces 1 L/day
•Receives 7.5 L/day
•Absorbs about 6.5 L/day
–Large Intestines
•Receives 2.0-2.5 L/day (ileocecal flow leaving small intestine)
•Absorbs 1.9 L/day
•Results in 0.1 L/day in stool
–Large intestine can make up for decrease in small intestine absorptive function because it has an absorptive capacity of up to 5 L/day

Question 2

What is Net Ion Movement?

Segmental heterogeneity

Surface heterogeneity

Cellular heterogeneity

Answer 2

–Net ion movement
•Difference between movement:
–From lumen into blood
–From blood into lumen
–Segmental heterogeneity
•Differences in transport along the length of the intestines
–Surface heterogeneity
•Differences in transport from the top of a villus to bottom of a crypt
–Cellular heterogeneity
•Differences in transport mechanisms in different cells within the same villus/crypt

Question 3

What ions have a net absorption in the small intestine?

Secretion?

Answer 3

Na+, Cl- and K+ are absorbed and HCO3- is secreted.

Question 4

What ions have net absorptions and excretions in the large intestine.

Answer 4

Na+ and Cl- absorbed and K+ and HCO3- secreted.

Question 5

How are solute and fluid movement coupled in epithelial cells?

Answer 5

Tightly, like white on rice

Question 6

Describe transcellular and paracellular movement.

Answer 6

Holy shit you better have this down by now, go look it up if you dont.

Question 7

What is dependent on paracelluar resistance?

Answer 7

–mucosal resistance is dependent on paracellular resistance which is a function of tight junction permeability and depends on tight junction structure
•Overall, resistance increases as you move away from the mouth
•Overall, resistance increases as you move down the crypt

Question 8

What do secretagogues do? Correct this card if Dr Heck explain this better in lecture.

Answer 8

•Induce secretion
•Agonists
•Increase second messengers
•Bacterial toxins
•Hormones and Neurotransmitters
•Immune regulatory products
•Laxatives
–Bile acids

Question 9

What do absorptagogues, and what do they do?

Answer 9

•Induce absorption
–neural, endocrine or paracrine factors
–few agonists
•Mineralocorticoids
•Glucocorticoids
•Somatostatin
•Norepinephrine

Question 10

Talk about the difference between Osmotic diarrhea and Secretory Diarrhea?

Answer 10

•Osmotic Diarrhea
–Dietary component that is not absorbed
•Ex. lactose intolerance
•Secretory Diarrhea
–Secretion of fluid and electrolytes from the intestine
–Induced by secretagogues
•Enterotoxins from bacteria
–Increase second messengers
–Does not affect Na+ absorption, therefore, administration of Oral Rehydration Solution, enriched with Na+ and Glucose reverses secretory diarrhea

Question 11

How is Na+ transported transcellularly?

Answer 11

–Na,K-ATPase (pump)
•All transcellular Na+ transport is mediated by this pump which moves Na+ across the basolateral membrane
•Results in low intracellular Na+ concentrations
•Gradient used as a driving force for Na+ entry and other molecules through the gradient, Na+ channels or coupled channels

Question 12

What kind of transport is the Nutrient coupled Na+ transport?

Is it inhibited by cAMP?

Answer 12

•Nutrient-coupled Na+ Transport
–Secondary active transport
•Couples uphill movement of nutrients with downhill (energetically favorable) movement of Na+
•Increases intracellular [Na+] which thereby increases Na+ being pumped across the basolateral membrane into blood
–Electrogenic process
•Makes lumen more negative which can be driving force for Cl-
–Only type of Na+ transport not inhibited by cAMP or cAMP agonists
•I.e. No Inhibition by E. coli or cholera enterotoxin
–Glucose coupled Na+ transport
•Na/glucose cotransporter SGLT1
–Apical membrane transport
–Amino acid coupled Na+ transport
•Na/amino acid cotransporters
–Apical membrane transport
–Each specific for different classes of amino acids

Question 13

How does the Na-H exchanger work?

What stimulates the exchanger?

What drives the exchanger?

Where is it found

Answer 13

•Na-H Exchanger (NHE3)
–Couples Na+ uptake to proton (H+) extrusion into intestinal lumen
•Increases intracellular pH
•Decreases luminal pH
–Stimulated by secretion of HCO-3 in the duodenum, pancreas and bile
–Driven by intracellular [Na+]
–Present throughout intestine
–Present in proximal small intestine without Cl-HCO3 exchanger
•Stimulated by [HCO-3] here alone

Question 14

Describe electroneutral NaCl absorption?

When is this type of absorption normally used?

Where is it located?

What is its clinical relevance?

Answer 14

•Electroneutral NaCl Absorption (NHE3)
–Parallel apical membrane exchangers coupled through pH
•Na-H
•Cl-HCO3
–Primary method of Na absorption between meals
•Does not contribute to post meal absorption (nutrient coupled)
–Ileum and throughout large intestine
–Clinical relevance of NHE3:
•Decreasing NaCl absorption important in pathogenesis of diarrhea
•E. coli induced traveler’s diarrhea activates cAMP
•Inhibited by
–cAMP and cGMP
–increasing intracellular calcium

Question 15

What is electrogenic Na+ absorption?

Is it specific?

Where is it found?

What is it enhanced by?

What is it dependent upon?

Answer 15

•Electrogenic Na+ Absorption (ENaC)
–Epithelial Na+ channels on apical surface
•Highly specific
–Very distal colon where Na+ can be absorbed against large gradients
•Important in Na+ conservation
–Enhanced by aldosterone
•Just like kidneys, an aldosterone responsive epithelial tissue
–Dependent upon gradient created by Na-K pump on basolateral surface

Question 16

WHat is Cl- absorption coupled with?

WHat kind of transport is it?

Answer 16

•Chloride (Cl-)
–Often coupled to Na+ absorption through intracellular gradient.
–Passive Transport
•Voltage dependent Cl- absorption
–Cl- absorption is driven by either
»Nutrient coupled Na+ absorption in the small intestine
•Creates a lumen negative potential difference
•Paracellular
»Electrogenic Na+ absorption in the distal colon
•Creates lumen negative potential difference
–Remember: Both are dependent on Na-K pumps in the basolateral membrane.

Question 17

So Cl- also has active transport, what is it?

Answer 17

–Cl-HCO3 Exchanger (DRA)
•Apical surface
•One Cl- brought in from lumen and one HCO3- extruded from cell
•Villous cells of ileum
•Surface epithelium of large intestine
•DRA Exchanger
–Down-regulated in adenoma
•Congenital Cl- Diarrhea
–absence of Cl-HCO3
–extremely high [Cl-] in stool
–high plasma [HCO3-]
»Alkalotic
–Cl- exchangers in blood cells and renal tubules unaffected ( different gene)
–Electroneutral NaCl Absorption
•See previous section

Question 18

What does Cl- secretion promote?

Why is that important?

Answer 18

•Cl- Secretion (CFTR)
–Promotes Na+ secretion resulting in NaCl secretion
–Important in the pathogenesis of diarrhea
–Basal state of secretion is low or 0
–Requires activation by secretagogues (Ca2+ or cAMP)
–Requires 3 basolateral membrane transporters
•Na-K pump
–lowers intracellular [Na+]
–driving force for Cl- entering through Na/K/Cl cotransporter
•Na/K/Cl cotransporter
–Increases intracellular [Cl-]
•K+ channels
–Apical membrane
•Cystic fibrosis transmembrane regulator (CFTR)
–Cl- channel

Question 19

Decribe active and passive transport of K+ absorption.

Answer 19

–Small intestine
–Passive Transport
•Solvent Drag
–Paracellular
–Pulled through tight junctions via the movement of water
–Active Transport
•only in distal colon
•Transcellular
•K+ homeostasis
•Apical
–H-K pump
–Pumps H+ into lumen
•Basolateral
–Na-K pump

Question 20

K+ absorption by active and passive transport happens at what locations and how?

Answer 20

–Small intestine
–Passive Transport
•Solvent Drag
–Paracellular
–Pulled through tight junctions via the movement of water
–Active Transport
•only in distal colon
•Transcellular
•K+ homeostasis
•Apical
–H-K pump
–Pumps H+ into lumen
•Basolateral
–Na-K pump

Question 21

K+ secretion happens where?

Passive secretion is driven by what and takes a paracellular or transcellular path?

Answer 21

–Large intestine
–Passive K+ Secretion
•Predominant route
•Driven by negative lumen (-15 to -25 mV)
•Paracellular
•Most in distal colon
•Dehydration
–Results in aldosterone secretion
»makes lumen negative (Na+ absorption) inducing passive K+ secretion

Question 22

WHat is active K+ secretion activated by?

Where does it occur?

Answer 22

•Throughout colon
•Basally low
•Activated by aldosterone and cAMP
•Pump-leak model
–Basolateral membrane
•Na/K pump
–Creates low intracellular [Na+] which drives the cotransporter
•Na/K/Cl cotransporter
–Brings in K+ for secretion and Na+ to drive pump
•K+ Channel
–Contributes to K+ recycling
–Apical membrane
•K+ Channel

Question 23

HOw and where is Ca+ absorption potentiated?

WHat is it under the control of?

Answer 23

•Active Transcellular Uptake
–Only in duodenum
•Small surface area and high speed of flow reduces uptake
–Villous Epithelial Cells
•Under control of Vitamin D
–Influences all steps
–Induces synthesis of Calbindin

Question 24

Ca+2 absorption is a process, what are the 3 steps?

Answer 24

–1) Uptake through Ca2+ Channels
•Moves across apical membrane
•Driven by the electrochemical gradient
–2) Binding to Calbindin
•Intracellular, cytosolic protein which buffers Ca2+
–3) Extrusion through Ca2+ Pumps and Na-Ca Exchanger
•Moves across basolateral membrane
•Into interstitial fluid

Question 25

Ca+2 absorption also occurs by passive paracellular uptake what is special about this method?

Answer 25

–Higher concentration than active uptake
–NOT under the influence of Vitamin D
–Throughout small intestine
•Jejunum and Ileum
–Enhanced by low plasma concentration
•Lactation

Question 26

WHat is often complexed with ferrous iron?

Answer 26

Asorbic acid (vitamin C)

»Complexes with Iron
»Reduces Iron from ferric to ferrous
»Increases absorption

Question 27

What can iron dysregulation result in?

Answer 27

Anemia

Hemochromatosis (iron overload)

•Hereditary Hemochromatosis (HH)
–Body absorbs excess iron
»Women less susceptible to damage due to menstruation

Question 28

What does iron dysregulation result in?

How can it be detected?

What is the treatment

Answer 28

•Excess iron can become toxic in liver
•Results in:
–Cirrhosis
–Hepatomas
–Pancreatic Damage
–Bronze pigmentation
–Pituitary and Gonadal failure
–Arthritis
–Cardiomyopathy
•Detection:
–Elevated iron and transferrin saturation
–Elevated ferritin
–Liver biopsy
•Treatment
–Remove blood from patient (phlebotomize) every few months to normalize iron and ferritin.

Question 29

Dietary Iron takes two forms, the Heme iron form is absorbed more efficiently, how is it transported and where does that occur?

Answer 29

•Active Transcellular Transport Only
–Occurs only in duodenum
–Binds brush border protein
–Endocytotic mechanism
»Transported to cytoplasm
»Heme oxygenase
•Releases free Fe3+
•Enterocyte reduces Fe3+ to Fe2+
•Then handled the same as free iron (see below)

Question 30

Non- Heme iron transport?

Answer 30

–Absorbed less efficiently
•Exists as either ferric or ferrous iron
–Active Transcellular Transport Only
•Occurs only in duodenum

Question 31

Describe the DMT1 transporter for active transcellular iron transport?

What does DMT1 cotransport?

Is it specific for iron?

Ferric Reductase Dcytb does what to iron?

Answer 31

•Transporter (DMT1)
–Cotransports Fe2+ and H+ into cytoplasm
•Inward directed H+ gradient
–Not specific for Iron
•Many divalent metals including toxic (Cd2+, Pb2+)
•Not Ferric iron
•Ferric Reductase Dcytb
–Reduces ferric iron to ferrous iron
•Cytochrome
–Apical extracellular surface
–Required for uptake in DMT1

Question 32

What are the other 2 transporters? Hint, one carries iron to the basolateral membrane and the other translocates it.

Answer 32

•
•2) Mobilferrin
–binds Fe2+ in cytoplasm
–Carries Fe2+ to the basolateral membrane
•3) Ferroportin Transporter (FP1)
–Translocates Fe2+ across basolateral membrane

Question 33

What happens when Fe2+ reaches the interstitial fluid?

When it reaches the blood what it it bound to and where is it stored?

Answer 33

•When Fe2+ reaches the interstitial fluid:
–oxidized Fe2+ to Fe3+
–Facilitates binding to
•Transferrin
–Carries through plasma
•When Fe3+ reaches the blood:
–Bound to transferrin
–Stored in liver and reticuloendothelial system