16 - Intestinal Absorption of Solutes and Amino Acids

Question 1

Lactose

Answer 1

Disaccharide

Glucose - Galactose

Question 2

Lactase

Answer 2

Enzyme on brush border

Breaks Lactose down to Glucose & Galactose

Lactase expression decreases upon weaning

Question 3

Lactose Intolerance

Answer 3

The inability to metabolize lactose.

No lactase (this is actually normal, without the mutation)

Lactose goes straight through to the colon. The bacteria in the colon eat the lactose and ferment it. This liberates H2, CO2, CH4!!

Question 4

Mutation on Chromosome 2

Answer 4

Conveniently prevents the shutdown of lactase production, even after weaning.

Arose independently in northern Europe and east Africa.

Question 5

Measuring Lactase Deficiency

Answer 5

Measure H2 in breath after giving lactose.

Question 6

Fluid absorption by the gut

Answer 6

9L absorbed per day.

Majority of fluids absorbed in small intestine.

Colon plays role in water & Na+ retention.

Question 7

Breakdown of fluid to absorb in the gut

Answer 7

2L intake

Endogenous secretions:
Saliva - 1.5L
Stomach - 2.5L
Bile - 0.5L
Pancrease - 1.5L
Intestines - 1.0L

Question 8

Breakdown of fluid absorption sites in the gut

Answer 8

Small intestine - 7L
Colon & rectum - 1.9L

Remains in feces - 0.1L

Question 9

Crypt-Villus Axis in Small Intestines - Absorption mechanisms

Answer 9

Electroneutral NaCl
Na+/H+ exchange
Parallel Na+/H+ and Cl-/HCO3- exchange

Solute-coupled Na+ transport
Na/Glucose
Na/Amino Acid

Question 10

Crypt-Villus Axis in Small Intestines - Secretion Mechanisms

Answer 10

Chloride Channels

Bicarb Exchange

Question 11

Surface-Crypt Axis in the Large Intestines - Absorption Mechanisms

Answer 11

Electrogenic Na+ (Apical ENaC)
Electroneutral NaCl
Short-Chain Fatty Acids
Potassium Channels

Question 12

Surface-Crypt Axis in the Large Intestines - Secretion mechanisms

Answer 12

Chloride Channels

Potassium Channels

Question 13

Luminal Water Content Control - What’s up with that?

Answer 13

Maintains fluidity
Allows digestive enzymes to get in contact with food particles
Facilitates diffusion of digested nutrients across absorptive epithelium

Provides for normal transit of intestinal contents.
Imbalance = Diarrhea or constipation

Defense against infection
Tourist diarrhea

Question 14

Jejunum - Transporters

Answer 14

Na+/H+ antiport at apical surface leads to acidic microclimate, but also takes sodium in.

Basolateral Na+/K+ antiport shuttles Na into the blood.

Also the H+ that was exported luminally has a bicarb that is exported basolaterally.

Net absorption of Sodium Bicarb + Sugar/AA

Question 15

Ileum - Transporters

Answer 15

Luminal Na+/H+ antiport is decreasing.

HCO3-/Cl- antiport is increasing.

Microclimate disturbed. Fat poorly absorbed.

Cotransport of Na+ and Sugars!

Net NaCl absorption.

Question 16

Colon - Transport

Answer 16

Na+ enters
K+ leaves

This is all controlled by aldosterone. The colon is the kidney of the GI system.

Na+/H+ exchange
Cl-/HCO3- exchange

KCl absorbed

Question 17

Colon - Luminal loss of potassium

Answer 17

Flow-dependent.
There are K+ channels on both ends of the cell, so it depends on the luminal gradient.

You lose potassium in diarrhea

Question 18

Crypt Cell - Transport

Answer 18

Basolateral:
Na+/K+ pump
Na+/K+/2Cl- import (essentially importing 1 NaCl and 1 KCl)

Apical:
Chloride channel

Question 19

Crypt Cell - Chloride Channels

Answer 19

CFTR
Gating this channel gates how much water is or isn’t secreted!

cAMP opens it!

Hormones modulate this (example: VIP)

Cholera toxin overproduces cAMP this way, permanently activating Adenylyl Cyclase.

Question 20

CLC-2

Answer 20

Another (smaller) chloride channel in the colon.

Therapeutic target.

Chronic constipation - Open CLC-2 via Lubiprostone (Amitiza)

Question 21

Lubiprostone

Answer 21

Opens CLC-2 channels to secrete more water in the colon.

Does not affect CFTRs

Question 22

Treat cholera

Answer 22

Keep up with fluid loss via IV fluids until immune system can kill the cholera itself.

Measure the rice-water stool and make sure you’re putting that much back in.

Question 23

Cholera Buzz Words

Answer 23

Oysters
Travelers
Imported Food

Question 24

How many cells make up a human?

Answer 24

10^13

Question 25

How many microorganisms do we harbor

Answer 25

10^14 (10 times as many as we have cells of our own!)

Question 26

Paneth Cells

Answer 26

Found at the base of the crypts

Provide innate immunity

Question 27

Paneth Cells

Answer 27

Specialized for regulated secretion.

Have TLRs that recognize PAMPS

Contain α-Defensins

Secreted in response to bacteria or cholinergic stimuli

Long-lived cells!

Defend & nurture stem cells!!

Lots of RER

Question 28

α-Defensins

Answer 28

Antibacterial proteins
Family of 6 proteins:
4 in PMNs
2 in Paneth cells (human defensins 5 & C, Cryptidin

Stored in zymogen granules:
Glycoprotein shell

Keep the lumen of the small intestine almost completely sterile.

Question 29

Second defense in small intestine (other than Paneth cells)

Answer 29

Peyer’s patches

Question 30

Peyer’s patches

Answer 30

Submucosal lymphoid follicles

Underlie mucosal domes

Question 31

Mucosal dome

Answer 31

Place in the mucosa with no villi
Overlie Peyer’s patches.
Contain M cells

Question 32

M Cells

Answer 32

Not many villi.

Have a big cavity on the basement membrane, containing macrophages, APCs and Lymphocytes.

Question 33

Transcytosis through an M-Cell

Answer 33

Pathogen transcytosed to the cavity where the antigens are directly presented to the immune cells (APCs, macrophages, lymphocytes).

Mediates early generation of immunity.

Almost pinocytosis-esque

Question 34

M-Cells - Vulnerability.

Answer 34

HIV and some other pathogens use M-Cells to their advantage and jump right on in.

Question 35

Intestinal Lymphocytes

Answer 35

High concentration Th cells (expressing CD4 & IL10)

Effector B cells differentiate into plasma cells, selectively secreting IgA via transcytosis

IgA absorbed to glycocalyx of enterocytes

Protects mucosa by immune exclusion

Question 36

IgA Pathway

Answer 36

IgA created by B cells has special selectins telling it to adhere at the gut.

IgA dimers bind to basolateral IgA receptors and transcytose into the lumen. Part of the receptor is cleaved off with the IgA, protecting it from digestion in the lumen.