16 - Intestinal Absorption of Solutes and Amino Acids Flashcards
Lactose
Disaccharide
Glucose - Galactose
Lactase
Enzyme on brush border
Breaks Lactose down to Glucose & Galactose
Lactase expression decreases upon weaning
Lactose Intolerance
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!!
Mutation on Chromosome 2
Conveniently prevents the shutdown of lactase production, even after weaning.
Arose independently in northern Europe and east Africa.
Measuring Lactase Deficiency
Measure H2 in breath after giving lactose.
Fluid absorption by the gut
9L absorbed per day.
Majority of fluids absorbed in small intestine.
Colon plays role in water & Na+ retention.
Breakdown of fluid to absorb in the gut
2L intake
Endogenous secretions: Saliva - 1.5L Stomach - 2.5L Bile - 0.5L Pancrease - 1.5L Intestines - 1.0L
Breakdown of fluid absorption sites in the gut
Small intestine - 7L
Colon & rectum - 1.9L
Remains in feces - 0.1L
Crypt-Villus Axis in Small Intestines - Absorption mechanisms
Electroneutral NaCl
Na+/H+ exchange
Parallel Na+/H+ and Cl-/HCO3- exchange
Solute-coupled Na+ transport
Na/Glucose
Na/Amino Acid
Crypt-Villus Axis in Small Intestines - Secretion Mechanisms
Chloride Channels
Bicarb Exchange
Surface-Crypt Axis in the Large Intestines - Absorption Mechanisms
Electrogenic Na+ (Apical ENaC)
Electroneutral NaCl
Short-Chain Fatty Acids
Potassium Channels
Surface-Crypt Axis in the Large Intestines - Secretion mechanisms
Chloride Channels
Potassium Channels
Luminal Water Content Control - What’s up with that?
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
Jejunum - Transporters
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
Ileum - Transporters
Luminal Na+/H+ antiport is decreasing.
HCO3-/Cl- antiport is increasing.
Microclimate disturbed. Fat poorly absorbed.
Cotransport of Na+ and Sugars!
Net NaCl absorption.
Colon - Transport
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
Colon - Luminal loss of potassium
Flow-dependent.
There are K+ channels on both ends of the cell, so it depends on the luminal gradient.
You lose potassium in diarrhea
Crypt Cell - Transport
Basolateral:
Na+/K+ pump
Na+/K+/2Cl- import (essentially importing 1 NaCl and 1 KCl)
Apical:
Chloride channel
Crypt Cell - Chloride Channels
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.
CLC-2
Another (smaller) chloride channel in the colon.
Therapeutic target.
Chronic constipation - Open CLC-2 via Lubiprostone (Amitiza)
Lubiprostone
Opens CLC-2 channels to secrete more water in the colon.
Does not affect CFTRs
Treat cholera
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.
Cholera Buzz Words
Oysters
Travelers
Imported Food
How many cells make up a human?
10^13
How many microorganisms do we harbor
10^14 (10 times as many as we have cells of our own!)
Paneth Cells
Found at the base of the crypts
Provide innate immunity
Paneth Cells
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
α-Defensins
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.
Second defense in small intestine (other than Paneth cells)
Peyer’s patches
Peyer’s patches
Submucosal lymphoid follicles
Underlie mucosal domes
Mucosal dome
Place in the mucosa with no villi
Overlie Peyer’s patches.
Contain M cells
M Cells
Not many villi.
Have a big cavity on the basement membrane, containing macrophages, APCs and Lymphocytes.
Transcytosis through an M-Cell
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
M-Cells - Vulnerability.
HIV and some other pathogens use M-Cells to their advantage and jump right on in.
Intestinal Lymphocytes
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
IgA Pathway
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.
