GI electrolytes Flashcards
Describe salt absorption in the digestive and interdigestive periods of the small intestine. (VILLI)
- Digestive period, there are glucose/sodium symporters (SGLT1) and amino acid/sodium symporters.
Sodium potassium ATPase keeps intracellular sodium low to drive these channels. (found in jejunum mostly and some ileum)
-chlorine and potassium absorption are passive and water follows salt. - Interdigestive period: there are constant secretions, CO2 is brought into the cell to make bicarb and proton via CA. This runs two antiporter, sodium/proton antiport, chloride/bicarb antiport. Sodium and cholride then get exported out of cell. (in ileum and proximal colon)
- cAMP, cGMP, calcium inhibit electroneutral absorption.
Describe Cl secretion in crypts?
Cl secretion occurs via CFTR channels in the crypts of both small and large intestines.
- it is promoted by calcium, cAMP, cGMP.
- secretion is usually low
- insignificant compared to absorption and bacterial toxins/hormones act here
Describe the three major types of diarrhea and the general mech for cholera.
- Osmotic diarrhea - some non absorbable substance is drawing water and electrolytes into gut lumen
- lactose intolerance - Invasive diarrhea - diarrhea becomes grossly bloody, stool will contain leukocytes and erythrocytes.
- Secretory diarrhea -
electrolytes and fluid are actively secreted into gut
-cholera
CHOLERA: an endotoxin is endocytosed, its alpha subunit binds to stimulatory G protein, activates adenyl cyclase which activates cAMP leading to increased CFTR activity.
describe the digestion and absorption of
- glucose/fructose
- protein
- Oligomer carbohydrates
- Peptide
- Triaglycerides
- Glucose and fructose have no digestion and are directly absorbed
- Proteins (luminal hydrolysis of polymers) to monomers (AA) and then absorbed
- Brushborder hydrolysis (there is sucrase, isomaltase, lactase attached to brush border): breaks down sucrose to glucose and fructose (you can’t absorb carbs past the monomer stage)
- Di or Tri peptide: is absorbed and then hydrolysis occurs intracellularly
- Triglycerides have luminal hydrolysis removing the glycerol and fatty acids. Then reabsorbing both and reassembling them in the cell.
Describe generally how starch is attacked by amylase? (which is inactivated in the stomach by the low pH)
Maltose (2), Maltotriose (3) come together and form an alpha 1,4 linkage. (alpha limit dextrin)
-this is formed by the amylase.
Glucoamylase will take a glucose off of the alpha limit dextrin. Then isomaltase (breaks alpha 1,6 bond), glucoamylase, sucrase can break it down into monomers.
What is the role of S cells?
When there is pH drop in the duodenum, S cells secrete secretin which tell the exocrine pancreas to increase bicarbonate secretions thus increasing pH.
Pancreas also has a more protein like secretion (enzymes) and that is more mediated by CCK.
What are Gliflozins?
They are SGLT2 inhibitors which specifically inhibit reabsorption of glucose reabsorption in the kidney tubule.
It leaves SGLT1 alone so there is still glucose uptake and allows glucose wasting in urine.
It is the only set of drugs that reduce cardiovascular complication in diabetes.
Describe lactose intolerance, its history.
Normal lactase expression in the small intestine is suppressed at the age of 5 when we should no longer need mothers milk. This suppression is due to the MCM6 gene.
Mutation in MCM6 has prevented lactose intolerance.
For those with lactose intolerance, they lack lactase in small intestine. Therefore the bacteria in the large intestine get the lactose and break it down (acetic acid, lactic acid) and a byproduct is H2/CO2 causing bloating. CO2 and H2 get into circulation and then get breathed out. This can then be measured in breath so for lactose intolerance, people produce more H2 in breath after ingestion of lactose.
What do chief cells do?
They are found in the stomach and secrete pepsinogen. With exposure to HCL pepsinogen is activated into pepsin.
Pepsin is active in very low pH (2) so it is inactive in duodenum)
How are peptides absorbed via a channel level?
The channel that absorbs di and tripeptides are PEPT1. It is a symporter of proton and peptides.
The protons are brought into the lumen by NHE (proton, sodium antiporter)
In the cell, tripeptidases, dipeptidases) break up the peptides into amino acids
What are the three D’s
Dermatitis
Dementia
Diarrhea
example: Pellegra which is due to niacin deficiency
How are nucleic acids digested by the duodenum?
RNase and DNase are made in the exocrine pancreas into the duodenum via pancreatic juice.
At brush border, phosphatase and nucleosidase convert nucleotides to pentose sugar, nitrogenous base and phosphate, which are then absorbed by duodenum and jejunum.
you start with large fat droplets from the stomach, now how do you digest and absorb lipids.
- Bile salts from bile duct coat and emulsify the fat droplets. This breaks them down into smaller droplets to increase surface area
- Pancreatic lipase and colipase break down the fats into monoglycerides and fatty acids which are now stored in “micelles”,
- Cholesterol is transported into cells
Monoglycerides and fatty acids leave the micelles and enter cells by diffusion. - Absorbed fat then combine with cholesterol and proteins to make chylmicrons.
- enter the golgi and are packaged to get exocytosed into the lacteal which is connected to the lymphatic system.
- End up in the central venous system (left subclavian vein then heads to liver)
- Chylomicrons carry TAGs, cholesterol esters (converted in the small intestine by ACAT) and fat solubble vitamins (ADEK). Cholesterol esters are formed by ACAT and are nonpolar allowing it to be packed in the center better with more space.
Describe the 3 types of salt absorptions in general terms
- Nutrient dependent sodium absorption: (using glucose and amino acids)
- SGLT1- glucose and sodium symport
- amino acid/sodium symport
- Na/K ATPase enhances sodium absorption. - Interdigestive phase: (using proton and bicarb)
- ileum-
- Sodium is brought in with exchange with proton
- Chloride is brought in with bicarbonate exchange.
- again Na/K ATPase is there
- carbonic anhydrase generates carbonic acid which supplies these two channels.
- Large intestine: just absorbs sodium, driven by the ATPase. In colon there is barely any electrolyte absorption.
Mineralcorticoids increase this sodium absorption (aldosterone)
What does VIP do?
It activates the same pathway as cholera toxin, constitutively activating cAMP which keeps CFTR always on.
Diarrhea.
It also relaxes smooth muscle.
