Unit 6 - Intestinal Transport I: Fluid and Electrolytes

Question 1

what are the components and lengths of the SI?

Answer 1

starts distal to pyloric sphincter, extends 21 feet to cecum

• duodenum: 1 foot long (demarcated from jejunum by ligament of Treitz)
• jejunum: 8 feet long (proximal 2/5 of SI)
• ileum: 12 feet long (distal 3/5 of SI)

Question 2

compare absorptive SA of jejunum and ileum:

• simple cylinder
• mucosal folds of Kerkring
• villi
• microvilli

Answer 2

Jejunum:

• 10 cm2
• increase 7.5x
• increase 10x
• increase 20x (so total increase 1500x; 3x more SA than ileum)

Ileum:

• 10 cm2
• increase 2.4x
• increase 10x
• increase 20x (so total increase 480x)

Question 3

how is SA of SI amplified?

Answer 3

1. macroscopic folds of Kerckring
2. microscopic villi and crypts of Lieberkuhn
3. submicroscopic microvilli

Question 4

how is the SA of LI amplified?

Answer 4

1. macroscopic semilunar folds
2. crypts (but not villi)
3. microvilli

Question 5

how much of the total intestinal absorptive area is needed for absorption?

Answer 5

there are 7 million cm2, and only half is needed for absorption
-half can be removed surgically w/o compromising absorptive function

Question 6

what is celiac disease? (also non-tropical sprue)

Answer 6

malabsorptive syndrome where number and size of microvilli are reduced

• gluten destroys absorptive cells and decreases number of functional villi
• diarrhea and malnutrition result, causing fatal dehydration

Question 7

what is tropical sprue?

Answer 7

same as celiac disease, but caused by infectious agent

-present in tropical countries associated with diarrhea, malabsorption, and nutritional deficiencies

Question 8

what are villi and crypts of SI?

Answer 8

villi made of layer of absorptive enterocytes (columnar epithelial cells), and there are 2 villi next to each other with crypt between

Question 9

what is turnover of SI cells?

Answer 9

crypt cells migrate toward tip of villi, and are extruded 3-8 days later (250 g of cells lost daily, excreted or digested)

• need 1 week to replace intestinal mucosa
• rate of cell renewal is reduced due to radiation, malnutrition, and sprue

Question 10

what do undifferentiated cells of crypt do?

Answer 10

secrete NaCl from blood into lumen, and water follows osmotically

• crypt cells stop secreting as they migrate up the villus, and take on absorptive function, absorbing either NaHCO3 or NaCl
• mitotic figures can be seen at the base of the villi
• -these become goblet cells and enterocytes

Question 11

what do goblet cells do?

Answer 11

secrete mucous in response to ACh released from parasympathetic cholinergic nerve fibers
-mucous lubricates tissue during peristalsis, and forms protective barrier

Question 12

what is radiation sickness?

Answer 12

radiation targets dividing cells, and since there is high turnover of intestinal mucosa and goblet cells and enterocytes have common stem cell in base of grypts, radiation victims have intestinal bleeding, diarrhea, and malabsorption/dehydration

Question 13

what are the 2 parallel pathways for transfer of materials?

Answer 13

1. transcellular pathway: across brush border, thru cytoplasm, then across basolateral membrane
2. paracellular pathway (across shunt pathway): thru tight junction and extracellular space
   - very permeable to H2O and cations (Na, K), but not to anions
   - tight junctions are low resistance (high conductance) pathway

Question 14

what is the major membrane for absorption of nutrients? how does it do this?

Answer 14

brush border (AKA apical or lumenal membrane)

• has a glycoPRO matrix
• contains ectoenzymes (enterokinase, disaccharidases, peptidases) to complete digestive process

Question 15

what does the basement membrane contain?

Answer 15

capillaries and lacteals (also known as lamina propria)

Question 16

how does the paracellular pathway differ from jejunum to ileum to colon? what does this mean?

Answer 16

leaky in jejunum to tight in colon
-since shunt is permeable to H2O and cations, but not anions, when you drink water, the liquid is rapidly absorbed in jejunum by osmosis

Question 17

what is succus entericus?

Answer 17

intestinal secretions

Question 18

what happens if the jejunum is removed surgically?

Answer 18

ileum adapts to take over its function

Question 19

what are 2 exceptions that are absorbed only in ileum, instead of mainly in jejunum?

Answer 19

vitamin B12 (requires intrinsic factor from parietal cells) and ionized bile salts
-nonionized bile salts can be absorbed the entire length of SI

Question 20

what happens if the distal ileum is removed?

Answer 20

other parts of GIT cannot adapt, causing pernicious (macrocytic) anemia

Question 21

how is Na+ absorbed by jejunal absorptive cells?

Answer 21

Na has 2 mechanisms

1. Na+/glucose and Na+/AA cotransport from lumen into cell
2. Na+/H+ antiport on lumenal side to keep internal pH of enterocyte close to neutral
3. Na+/K+ pump on basolateral membrane

Question 22

how is HCO3- absorbed by jejunal absorptive cells?

Answer 22

HCO3- has “disappearing ball” mechanism

1. in cell, H2O breaks into H+ and OH
2. H+ from Na+/H+ antiport exits cell, and combines with HCO3- to make H2CO3
3. carbonic anhydrase breaks into H2O and CO2
4. CO2 crosses lumenal membrane, then combines with OH (from (1)) to make HCO3
5. HCO3 then somehow gets past basolateral membrane

Question 23

what is the membrane potential at rest and during absorption?

Answer 23

+5 mV at rest on serosal side, and rises to +15 mV after meal b/c electrogenicity of Na+/K+ pump

Question 24

where is there Na+/glucose or Na+/AA cotransport with Na+/K+ pumps?

Answer 24

jejunum (major) and ileum (minor)

Question 25

where are there Na+/H+ exchangers on both basolateral and luminal sides, plus an Na+/K+ pump on the basolateral side?

Answer 25

duodenum and jejunum (major)

Question 26

where are there parallel Na+/H+ and Cl-/HCO3- exchangers on the luminal side, with Na+/K+ pumps, water, and CO2 diffusion on the basolateral side?

Answer 26

ileum and proximal colon

Question 27

where are there Na+ channels on the luminal side, and Na+/K+ pumps on the basolateral side?

Answer 27

only in the colon

Question 28

what does amiloride block?

Answer 28

Na+/H+ exchangers and Na channels

Question 29

how is NaCl reabsorbed by ileal absorptive cells?

Answer 29

both enter via Na/H and Cl/HCO3 exchangers on lumenal side, then Na/K pump and Cl diffusion on basolateral side

Question 30

how are secretion and absorption related?

Answer 30

substances that promote secretion, inhibit absorption, and vice versa

Question 31

what are endogenous secretion stimulators?

Answer 31

• ACh (increase Ca+)
• histamine (increase Ca+)
• CCK
• secretin (increase cAMP)
• gastrin
• gastric inhibitory polypeptide
• motilin
• VIP (increase cAMP)

Question 32

what are exogenous secretion stimulators?

Answer 32

• Vibrio cholerae, salmonella, and E. coli (both increase cAMP)
• other microbial enterotoxins
• bile salts and FA
• laxatives

Question 33

what are endogenous absorption stimulators?

Answer 33

• alpha-adrenergic agonists
• dopamine
• enkephalins and other opiods
• somatostatin
• mineralcorticoids

Question 34

what are exogenous absorption stimulators?

Answer 34

nutrients

Question 35

how is NaCl secreted by crypt cell?

Answer 35

in jejunum, ileum, and colon

• cotransport for Na+/2Cl-/K+ on basolateral membrane (lost during maturation of crypt cells into absorptive cells)
• K+ ion channel sends K+ back into blood, or Na+ and K+ move down electrical gradients via electrodiffusion from serosa to mucosal solution or thru tight junctions

Question 36

what can block NaCl secretion?

Answer 36

loop diuretics like furosemide and bumetanide

Question 37

what do vipomas and cholera do?

Answer 37

increased VIP (vipomas) or increased AC (toxins) cause increased cAMP that causes increased secretion of NaCl and KCl (diarrhea, dehydration, and death)

Question 38

how are body stores of Fe regulated?

Answer 38

1 mg Fe++ absorbed daily as needed, otherwise bound to ferritin (storage)

• 20 mg Fe++ ingested daily, but most Fe+++, so only 5% is absorbed
• most ferritn-bound Fe++ is lost when cell exfoliates; a small amount as needed is released to transferrin and absorbed

Question 39

what happens if body Fe++ is low or high?

Answer 39

if low: number of brush border transporters increases

if high, number of brush border transporters decreases and the amount of ferritin increases

Question 40

what are the 2 pathways of Fe absorption?

Answer 40

heme: most efficient pathway
- Fe is freed within cell by heme oxygenase, and bound to intracellular mobilferrin

nonheme: Fe++ forms insoluble complexes with food, but more soluble at acid pH, so released by gastric acid
- absorbed via cotransport with H+

Question 41

what happens if patients are deficient in gastric acid?

Answer 41

absorb less Fe (especially nonheme), resulting in Fe-deficiency anemia

Question 42

what is the relationship between Fe++ and Fe+++?

Answer 42

Fe++ spontaneously oxidixes to Fe+++, but ascorbate and citrate in stomach help reduce it back
-Fe+++ is unaccepted by cell and excreted

Question 43

what is transferrin?

Answer 43

ferrous Fe++ binding PRO (beta1-globulin)

Question 44

how is duodenal absorption of Ca++?

Answer 44

Ca-ATPase actively transports Ca++ from serosal solution into cell (across brush border)

• stimulated by calbindin, which is stimulated by 1,25(OH)2D3
• Ca++ binds to calbindin, which also buffers it along with mitochondrial stores (ensures intracellular Ca++ doesn’t increase to toxic levels)
• extruded across basolateral membrane thru Ca++ pump and Na-Ca exchanger

passive paracellular absorption throughout SI (not just duodenum), which predominates (but not controlled by vit D)

Question 45

what stimulates all 3 steps of transcellular Ca++ absorption?

Answer 45

active form of vit D (1,25(OH)dihydroxyvitamin D)

Question 46

how does sunlight affect vit D?

Answer 46

7-dehydrocholesterol in skin absorbs UV rays to become vit D3 (cholecalciferol)

• liver transforms it to 25-OH-vitamin D3
• PTH stimulates kidney to transform this into 1,25(OH)2-vit D3 (AKA 1,25-dihydroxycholecalciferol)

Question 47

how is long-term regulation of Ca++?

Answer 47

increased Ca++ in plasma causes decreased PTH secretion, decreasing formation of 1,25-(OH)2-D3, causing decreased Ca binding PRO synthesis, which decreases Ca++ absorption