15 - Gastric Physiology, Acid Secretion, and Digestion Flashcards
Pancreas
Mixed endocrine-exocrine organ
Primarily exocrine
Acini = 84% Ducts, 5% of pancreatic mass
Islets (endocrine pancreas) = 1% of pancreatic mass
Both ducts and acini of the exocrine pancreas are secretory
Exocrine cells of the pancreas
Polarized
Secrete from apical surfaces
Respond to signals delivered to basolateral surfaces
Acinar cells
Secrete enzymes
Duct Cells
Secrete water, bicarb, sodium
Centroacinar cells
Cells that project back into the acini
Mechanism for creating bicarb that is eventually shuttled into the lumen of the duct
CO2 + H2O = HCO3- and H+
H+ moves into bloodstream in exchange for sodium
Sodium moves into the bloodstream in exchange for potassium via the Sodium/Potassium pump (sodium is kind of just a middle man)
Bicarb moves into the lumen in exchange for chloride.
Secretin
H+ stimulates secretin’s production.
Produced by S Cells
Stimulates cAMP (works with nerves, works without nerves)
Duct cells put out a lot of water and bicarb.
Cholecystokinin (CKK)
Produced by I cells
Stimulates duct cells to release intracellular calcium (via IP3 cascade, working together with nerves)
Calcium is the signal for pancreatic enzyme release.
What is the ideal pH fro pancreatic enzymes to work?
Neutral!
This means the pancreas has to secrete bicarb along with its enzymes so that the acidic pH of the gut can be combatted!
Secretin response to acid
Acid induces secretin-releasing peptides (S-RPs) to be released.
Vagal stimulation also induces this.
S-RPs stimulate S cells
S cells release secretin
Secretin’s effect on the duct
Secretin stimulates receptors on the duct cells.
Duct cells increase cAMP production.
Carbonic anhydrase catalyzes the production of H+ and HCO3- from CO2 and H2O
Luminal Cl- channel (CTFR) opens, and is coupled to a Cl-/HCO3- antiport channel.
Basolateral Na+/H+ antiport, Na+/K+ ATPase & H+ ATPase (exporting H+
Overal trend. When the gut gets more acidic (via parietal cells), the blood
Gets more alkaline
When the gut gets more basic (via pancreatic secretion), the blood
Gets more acidic
What amplifies the absorptive surface of the gut?!
Length Plicae Villi Microvilli Glycocalyx
How big is the surface area of the intestines?
A tennis court!!!
300 square meters
Small intestinal mucosa crypt-villus organization
Crypt-villus axis is continuous (Cores of villi contain lamina propria)
Stem cells are found near the base of the crypts (generate crypt epithelial cells that line the villi)
Enterocytes mature at the crypt-villus junction
Old cells are extruded from villus tips.
It’s like an escalator.
Core of microvilli
Microfilaments
External plasma membrane surface of microvilli
Studded
Studs are clathrin, enzymes and transporters.
Terminal Web
Microfilaments in microvilli enter the cells and are linked by myosin. This is called the terminal web.
Beneath the terminal web
Intermediate Filaments (providing structure)
Celiac Pathogenesis
Gluten triggers a hypersensitivity reaction against the gut.
Crypt cells turn over crazy quicksies.
The intestines are now lined with crypt cells without the microvilli and junk!!!!!! Can’t absorb!!!!!!!!
Steatorrhea
Fat-soluble vitamin deficiencies!
5 patterns of digestion-absorption
No digestion (glucose transport)
Luminal hydrolysis of polymer to monomers (protein to AA, AA transport)
Brush border hydrolysis of oligomer to monomer (Sucrose to fructose & glucose, glucose & fructose transport)
Intracellular hydrolysis (peptide uptake, breakdown to AA, AA export)
Luminal hydrolysis followed by intracellular resynthesis (triglyceride to glycerol & fatty acids, uptake of those components, triglyceride resynthesis, triglyceride export)
Where are carbohydrates, proteins & lipids maximally absorbed?
Duodenum
Less absorbed further downstream, no more absorption once you hit the ileum.
Where are calcium, iron and folate actively absorbed?
Duodenum
Calcium also continues to be absorbed throughout small intestine.
Where are bile acids maximally absorbed?
Ileum
Less-so in the jejunum and the ascending colon
Where is B12 (cobalamin) absorbed?
ONLY IN THE ILEUM
What MUST you do (nutritionally) if you’ve had to remove your ileum?
B12 injections. Can’t absorb it anymore.
Carbohydrate digestion
Luminal & Surface enzymes & transporters
Luminal digestion, terminating on the microvilli with immediate capture.
Carbohydrate Digestion - Luminal Enzymes
Amylase
Carbohydrate Digestion - Brush Border Enzymes
Glucoamylase
Lactase
Sucrase-Isomaltase
Carbohydrate breakdown products - Apical Transporters
SGLT1 (RIGHT NEXT TO Glucoamylase & Lactase)
GLUT5 (RIGHT NEXT TO Sucrase-Isomaltase
Carbohydrate breakdown products - Basolateral Transporters
GLUT2
SGLT1
Located on apical membrane. Sodium, sugar co-transporter
Na+ : Sugar
2 : 1
Doesn’t absorb L-glucose or fructose. D-form only!!
GLUT5
Apical transporter
Mainly in jejunum
Absorbs fructose
GLUT2
Basolateral membrane throughout small intestine
Intestinal epithelial cells - Na/K pump
Sodium into blood
Potassium into cell.
Continues the momentum of the sodium that was co-imported with sugars by SGLT1
5 Pancreatic Peptidases
Trypsinogen Chymotrypsinogen Proelastase Procarboxypeptidase A Procarboxypeptidase B
Trypsinogen
Cleaved by Enterokinase (enteropeptidase) on the brush border of the jejunum. Becomes Trypsin there.
Trypsin
Cleaves the inactive forms of all 5 pancreatic peptidases.
Chymotrypsinogen
Cleaved to Chymotrypsin by Trypsin
Proelastase
Cleaved to elastase by Trypsin
Procarboxypeptidase A
Cleaved to Carboxypeptidase A by Trypsin
Procarboxypeptidase B
Cleaved to Carboxypeptidase B by Trypsin.
Endopeptidases
Trypsin
Chymotrypsin
Elastase
Karate chops peptides into smaller ones (2 - 6 amino acids each)
Exopeptidases
Carboxypeptidase A
Carboxypeptidase B
Nibble peptides from the ends (single amino acids)
Protein Digestion
In lumen and at brush borders
Same deal as complex carbohydrates via pepsinogen/pepsin in stomach, then trypsin, chymotrypsin, elastase, carboxypeptidase A, carboxypeptidase B in the lumen of jejunum, then brush border peptidases finish off the oligopeptides, like maltotriose and junk
Amino acid absorption
Sodium-coupled transport at apical membrane
Protein Digestion - Luminal
Yields oligopeptides (and AAs that are absorbed)
PepT1
H+/Oligopeptide cotransporter
Those peptides are digested in the cytosol
Fat absorption
Hydrolysis & resynthesis
In lumen, bile salts detergentrify the emulsion droplets and enzymes break down the triglycerides, forming a mixed micelle.
Triglycerides hydrolyzed to glycerol and fatty acids.
Those components are absorbed
Triglycerides reassembled in Endoplasmic Reticulum (Technically “outside” the cell).
They meet up with apoproteins from the RER.
These complexes are processed and packaged in the golgi, and exported as a chylomicron.
Released via Exocytosis!
Acid microclimate disequilibrium zone
Acidic region of the lumen adjacent to the microvilli, maintained by Na+/H+ pump.
This allows for monoglycerides and fatty acids to move across the membrane easily.
Chylomicron Absorption
Lymphatics have discontinuous walls that allow for absorption. This dumps into the thoracic duct, and back into circulation.
Vitamin B12
Eat B12 bound to food.
Stomach acid dissociates B12 from food.
Haptocorrin (made by gastric and salivary glands) binds to B12 to protect it from stomach acid.
Haptocorrin-B12 and Intrinsic Factor travel to the duodenum.
Trypsin, chymotrypsin and elastase digest Haptocorrin, allowing B12 and IF to complex.
Terminal ileum contains IF-B12 receptors. Endocytose complex
Lysosomes fuse and digest IF, allowing B12 to enter the cytoplasm.
B12 enters secretory vesicles containing Transcobalamine II, which complexes with B12 and is secreted into the interstitial space.
Histo - Active Gastritis
Neutrophil Infiltration
Histo - Chronic Gastritis
Plasma Cells
Lymphocytes
Rare Eosinophils
Histo - Hemorrhagic Gastritis
Fresh Blood
Histo - Erosive Gastritis
Destruction of parts or entire mucosa
Histo - Granulomatous Gastritis
Granulomas
Histo - Eosinophilic Gastritis
Eosinophils
Histo - Lymphocytic Gastritis
Intraepithelial Lymphocytes
Oft associated with celiac disease
If not, lymphoma of the stomach
Histo - H. Pylori
“Chronic Active Gastritis”
Neutrophils
Plasma Cells
Lymphocytes
Rare Eosinophils
Autoimmune Gastritis
Autoantibodies to Parietal Cells
Rarely AutoAb to Intrinsic Factor
Body predominant inflammation (Lymphs, Plasma Cellz)
Antrum spared
Atrophy (loss of oxyntic glands)
Autoimmune Gastritis - Atrophy
Loss of parietal cells in oxyntic glands causes Hypergastrinemia!!!
Hypergastrinemia causes ECL hyperplasia
