Digestion and absorption of fluids and electrolytes

Question 1

Net ion movement

Answer 1

Difference between movement:
From lumen into blood
From blood into lumen

Question 2

Segmental heterogeneity

Answer 2

differences in transport along the length of the intestines

Question 3

Surface heterogeneity

Answer 3

differences in transport from the top of a villus to bottom of a crypt

Question 4

cellular heterogeneity

Answer 4

differences in transport mechanisms in different cells within the same villus/ crypt

Question 5

Small intestine absorption and secretion

Answer 5

net absorption of Na, Cl, and K

net secretion of HCO-3

Question 6

Large intestine absorption and secretion

Answer 6

Net absorption of Na and Cl

Net secretion of K and HCO-3

Question 7

Intestinal epithelial cells are polar

Answer 7

contain an apical and basolateral surfaces

Question 8

transcellular movement

Answer 8

solute crosses two membranes in series

Question 9

Paracellular movement

Answer 9

solute moves passively between epithelial cells through tight junctions
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 10

resistance changes in paracellular movement

Answer 10

Overall, resistance increases as you move away from the mouth
Overall, resistance increases as you move down the crypt

Question 11

actions and examples of secretagogues

Answer 11

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

Question 12

actions and examples of absorptagogues

Answer 12

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

Question 13

Osmotic diarrhea

Answer 13

Osmotic Diarrhea
Dietary component that is not absorbed
Ex. lactose intolerance

Question 14

Secretory diarrhea

Answer 14

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 15

Sodium absorption

Answer 15

Most absorbed by:
Villous epithelium of small intestine
Surface epithelium of large intestine
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 16

Nutrient-coupled Na+ transport

Answer 16

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 17

What is the only type of Na transport not inhibited by cAMP or cAMP agonists?

Answer 17

nutrient-coupled

Question 18

Na-H Exchanger (NHE3)

Answer 18

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 19

Electroneutral NaCl Absorption (NHE3)

Answer 19

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 20

Electrogenic Na Absorption (ENaC)

Answer 20

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 21

Chloride absorption is often coupled to

Answer 21

Often coupled to Na+ absorption through intracellular gradient

Question 22

Passive transport of chloride

Answer 22

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 23

Active transport of chloride: CL-HCO3 Exchanger (DRA)

Answer 23

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

Question 24

Congenital Cl- diarrhea

Answer 24

absence of Cl-HCO3
extremely high [Cl-] in stool
high plasma [HCO3-]
Alkalotic
Cl- exchangers in blood cells and renal tubules unaffected ( different gene)

Question 25

Chloride secretion (CFTR)

Answer 25

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 26

K+ absorption happens where?

Answer 26

small intestine

Question 27

K+ passive transport

Answer 27

Solvent Drag Paracellular Pulled through tight junctions via the movement of water

Question 28

K+ Active transport

Answer 28

``` only in distal colon Transcellular K+ homeostasis Apical H-K pump Pumps H+ into lumen Basolateral Na-K pump ```

Question 29

K+ secretion happens where?

Answer 29

large intestine

Question 30

Passive K+ secretion

Answer 30

``` 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 31

Active K+ Secretion

Answer 31

``` 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 32

Calcium absorption: active

Answer 32

transcellular 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 33

Process of calcium active absorption

Answer 33

``` 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 34

Passive paracellular uptake of calcium absorption

Answer 34

``` 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 35

Iron exists as

Answer 35

Ferric (Fe3+) | Ferrous (Fe2+)

Question 36

Vitamin C

Answer 36

Ascorbic Acid (Vitamin C) - Complexes with Iron - Reduces Iron from ferric to ferrous - Increases absorption note: vitamin c needs to be in the GI tract at the same time as the iron in order to be able to do this

Question 37

Iron dysregulation

Answer 37

``` Results in: Anemia Iron depletion Hemochromatosis Iron overload Hereditary Hemochromatosis (HH) Body absorbs excess iron Women less susceptible to damage due to menstruation ```

Question 38

Excess iron becoming toxic in liver

Answer 38

``` 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 39

Heme Iron

Answer 39

Absorbed more efficiently 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 40

Nonheme Iron

Answer 40

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

Question 41

Active transcellular iron transport: divalent metal transporter

Answer 41

``` 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 42

Active transcellular iron transport: mobilferrin

Answer 42

binds Fe2+ in cytoplasm | Carries Fe2+ to the basolateral membrane

Question 43

Ferroportin transporter (FP1)

Answer 43

Translocates Fe2+ across basolateral membrane

Question 44

When Fe2+ reachs the interstitial fluid:

Answer 44

oxidized Fe2+ to Fe3+ Facilitates binding to Transferrin Carries through plasma

Question 45

When Fe3+ reaches the blood

Answer 45

Bound to transferrin | Stored in liver and reticuloendothelial system

Question 46

which ions are affectors of diarrhea

Answer 46

Na and Cl-

Question 47

Cholera mechanism of action

Answer 47

``` Cholera toxin binds apical receptors on crypt cells. Results in an increase of cAMP Results in secretion of Cl- by CFTR Na2+ and H2O follow Cl- into lumen Na2+ absorption inhibited by cAMP Result: Secretory Diarrhea ```

Question 48

Oral rehydration solution

Answer 48

on the fact that nutrient coupled-Na2+ absorption is not inhibited by cAMP stimulating secretagogues. Therefore, increasing glucose and/or amino acid concentrations in the lumen increases Na2+ reuptake. This increases intracellular [Na+] which is necessary for Na,K-ATPase function. Na,K-ATPase function is necessary for K+ and Cl- absorption as well. Solution contains varying concentrations of glucose, Na2+, Cl- and HCO3- Reverses dehydration and metabolic acidosis which were significant causes of mortality in the past. Direct result of research in nutrient coupled-Na2+ absorption.