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Flashcards in GI Tract Secretion Deck (42):
1

Acid Secretion in stomach

HCl
-kills bacteria (disinfects food @ pH 1.0, stomach @ pH of 2)
-begins protein digestion: denatures proteins and activates pepsinogen (active= pepsin)
-acid producing parietal cells also secrete intrinsic factor when secreting acid (vitamin B12 absorption)
-Energy consuming process: H/K ATPase pumps across the luminal surface against significant gradient (high amount of mitochondria in these cells.)

2

Mucosal defenses in the stomach

HCl secretion is risky so body has mechanisms to confine acidity to stomach as much as possible
-Mucus layer and alkaline (HCO3-) layer at the cell surface (surface mucus cells) protects the stomach lining-- prostaglandins can increase mucus production
-tight junctions prevent acid from infiltrating the layers of the wall
-rapid cell turnover maintains surface integrity

3

Parietal (oxyntic) cell

produces HCl and Intrinsic Factor

4

IF and Vit B12 absorption

-B12 is imp for RBC production
-B12 binds salivary R protein in stomach
-Pancreatic proteases remove R protein in duodenum
-IF from stomach binds B12 in duodenum
-IF/B12 complex binds to receptor in terminal ileum for absorption (the receptor is for IF)

5

Phases of HCl secretion

Interdigestive (basal) phase: between meals following circadian rhythm (highest in evening, lowest in morning b/f waking)

Cephalic phase: mostly neural regulation

gastric phase: initially neural followed by endocrin (gastrin) and neural regulation.

Intestinal phase: mostly endocrine regulation

6

Parietal Cell receptors

Acid secretion is stimulated by ACh, gastrin, and histamine

Histamine: H2 (increases adenylate cyclase-->cAMP)
ACh: M3 (muscarinic rec)
Gastrin: CCK-B

ACh and gastrin act by increasing intracell Ca.

Ca and cAMP activate protein kinases that phosphorylate H/K ATPase (direct path)

Indirect path: , ACh and gastrin stimulate the ECL (enterochromaffin-like) cells, resulting in secretion of histamine. This histamine then acts on the parietal cell

7

Peptic ulcer disease (PUD) RFs

-NSAID use (aspirin, ibuprofen) (COX inhibitor, need for PG production-->mucus secretion)
-tumors (Zollinger Ellison Syndrome)
ex. gastrinoma (in duodenum, produces lots of gastrin)
-Helicobacter pylori (stuck in mucus, activates immune system as part of activation epithelial cells)

8

H+ and HCO3- transport out of cell and consequence of acid secretion

-H/K ATPase
-primary active transport

HCO3- in exchange for Cl- (Cl/HCO3- anion exchanger)
-secondary active transport

(Cl then leaves cell via passive transport and H2O follows-- transcellular)

Consequence of acid secretion: pH of venous blood leaving the stomach is high (because of HCO3- transport): alkaline tide.

9

Phases of gastric acid secretion

-basal (inter-digestive phase): follows circadian rhythm (lowest secretion in morning, highest in evening)

-cephalic phase: initiated by sight/smell/taste/swallowing of food; vagus nerve (leads to 1. ACh release, 2. triggering of histamine release from ECL cells, 3. release of gastrin-releasing peptide from vagal and ENS, 4. inhib of somatostatin release from delta cells in stomach)

-gastric phase: entry of food into stomach (stomach distends--> vasovagal reflex and ENS reflex; partially digested proteins stimulate antral gastrin cells which release gastrin)

-intestinal phase: aa and partially digested peptides in proximal portion of SI stim acid sec by stimulating duodenal gastrin cells to secrete gastrin)

10

Protective barrier of gastric surface

Mucosal barrier and bicarbonate secretion protect mucosa from acid.

The barrier is also prevents diffusional dissipation of the enormous pH gradient

Barrier: surface epithelial cells, mucous (from goblet cells and mucous neck cells), bicarb

11

Chloride secretion in SI

via cells in crypts

(increased Cl secretion in crypt pushes antimicrobial peptide from paneth cells towards surface where it can act on bacteria)

12

Digestion

the process of breaking down food into an absorbable form

-some in mouth, stomach, but most in lumen or at surface of absorptive cells (enterocytes)

13

Absorption

process by which food molecs are transported across the enterocyte membrane (transcellular/cellular) or between cells (paracellular) and into blood or lymph

14

Largest source of carbs in our diet

plant starch amylopectin

amylase is thus the major enzyme in saliva and pancreatic secretions

Products of amylose/amylopectin digestion: maltose, maltotriose, and alpha-limit dextrin

(sucrose and lactose can be digested at surface of enterocyte)

15

Which type of sugars can be absorbed?

simple monomeric sugars**

(polymers cannot be absorbed)

16

isomaltase

(alpha dextrinase)
converts alpha-limit dextrins to glucose

enterocyte surface

17

maltase

maltose to maltotriose to glucose

enterocyte surface

18

lactase

lactose to glucose to galactose

enterocyte surface

19

sucrase

sucrose to glucose to fructose

enterocyte surface

20

trehalase

trehalose to glucose

enterocyte surface

21

Lactose intolerance

-missing brush border enzyme lactase
-causes gas and diarrhea due to colonic bacterial digestion of lactose
-areas where diary is not part of staple (Asia) have a higher prevalence

22

SGLT1 transporter

-requires sodium as a co-transporter
-transports glucose and galactose across the apical membrane of the enterocyte
-SGLT1 can operate in secretory diarrhea (increased cAMP/cholera) so is important in oral rehydration

Glucose binds transporter, Conformational change, facilitates binding of Na
Then conf change internalizes transporter
Na dissociates from transporter and moves into cellular space
Na away from transporter-->conformational change
Shift: facing outside again



-glucose and galactose use the same transporter as fructose on the basolateral surface (GLUT2, not Na dependent)

23

GLUT5 transporter

transports fructose across apical surface,
sodium independent

24

Regulation of carbohydrate consumption

-increased carb consump upregulates transporters and increases uptake of simple sugars
-decreased carb consumption downregulates transporters and decreases the uptake of simple sugars

25

Protein digestion

Stomach: Pepsin breaks down about 15% of proteins to small peptides

Small Intestine (lumen): Pancreatic proteases like trypsin, chymotrypsin, carboxypeptidase and elastase break down proteins to oligopeptides, di/tri-peptides and amino acids

Brush Border: Peptidases break down oligopeptides into amino acids, dipeptides, tripeptides

Intracellular peptidases: Peptidases in the enterocyte can break down di/tri-peptides into amino acids

26

Protein uptake pathways

sodium dependent:
utlilize Na/K ATPase gradient as major route for different classes of aa. water follows

sodium indep

specific carriers for small peptides (di- and tri-) linked to H+ uptake (co-transporter; example is PEPT1

Pinocytosis of small peptides by enterocytes (inf)

27

dietary fat

-30-40% of caloric intake
-build cell membranes, hormones, bile acids
-body cannot make LINOLEIC acid (omega 6 fatty acid) converted to arachidonic acid and alpha-linolenic (omega-3) acid "essential fatty acids"

-triglyc are most abundant fat in diet

28

Primary Bile acids

-produced in the liver from cholesterol-- cholic acid and chenodeoxycholic acid

29

secondary bile acids

formed by bacteria the intestines and colon

30

Bile salts

bile acids are complexed with glycine or taurine to make bile salts

-bile is recycled during a meal by uptake in the distal ileum-- enterohepatic circulation

31

lipid digestion

dietary fats--> lingual and gastric lipase--> pancreatic lipase (hyrolyses triglycerides into FFA)--> bile salts solubilize fat into micelles; FFA are transported to enterocytes --> triglycerides are resynthesized and chylomicrons form. Rleased into lacteal.

32

fat soluble vitamins

ADEK
absorbed along length of SI and are carried in micelles and form chylomicrons similar to dietary lipids

-water soluble vitamins either enter the enterocyte by simple diffisuion (biotin, folic acid) or specific transporters (B12)

33

fluid put into gut, fluid lost

9L put in, 100-200 mls lost
after the stomach, the SI contents become iso-osmotic with respect to the blood
-water/ions move paracellularly or transcellularly

-there is a net fluid secretion from cells in the intestinal crypts and net absorption from enterocytes on the villi
(*villi surface area > crypt surface area)

34

Sodium absoprtion

-absorbed all along intestine with MOST in jejunum 60-80%
-dependent on Na/K ATPase gradient
-water abs linked to Na abs
-Mech Na+/glucose & galactose or
Na+/amino acid cotransport, NaCl cotransport,
Na+/H+ exchange or passive diffusion

35

Chloride absorption

-passive in proximal intestines (due to loose TJs)
-offsets Na charge in intercellular space
-Distal ileum and colon (less leaky TJs), Cl exchanged for HCO3- that is offsetting the acids produced by bacteria

36

K absorption

-passive process
-paracellular in jejunum (low K in intercell space) but transcellular in colon
-K normally high in cells due to Na/K ATPase; a gradient develops as luminal water decreases on approach to colon, with passive flux of K into cells

severe diarrhea? K loss and hypokalemia

37

Ca and Mg absorption

-compete for uptake by the cells
-Ca enters enterocyte passively down its electrochemical gradient in proximal intestines
Uptake of Ca++ in intracellular calcium stores maintains the gradient
Ca++ ATPase pumps calcium out to the blood

38

Vitamin D in Ca absorption

Vit D is synthesized in the skin or absorbed by intestine
Vit D is 25-hydroxylated in liver
25-OH Vit D is 1-hydroxylated in kidney in presence of PTH
Vit D binds to cytoplasmic receptor, activating transcription/translation
Vit D stimulates the uptake of calcium by increasing Ca++ binding proteins and Ca++ ATPase molecules

39

Fe (iron) absorption

Regulated absorption in the proximal intestines
Transported across apical membrane as heme or Fe++ (receptor mediated)
Two possible fates:
- binds to apoferritin to form ferritin that stays in the cell and is lost when the cell dies
- binds to transferrin (carrier protein), leaves the cell and goes into the blood

40

Which part of the bowel has the lowest paracellular permeability to water?

colon
-trying to solidify waste and it needs to link water movement to transcellular ion movement

41

Diarrhea

-motility disorders
-osmotic diarrhea: caused by impaired digestion or defects in absorption:
lactase deficiency
ileal resection (bile salts not absorbed)
Celiac disease (gliaden induced destruction of villi)

secretory diarrhea:
may be caused by Vibrio cholerae. Increases cAMP levels in cells and this in turn activates the CF chloride channel, (and thus water) on the luminal surface

42

Oral rehydration therapy

antibiotics plus KHCO3 to prevent hypokalemia and metabolic acidosis, glucose (or amino acids) with NaCl to facilitate the absorption of electrolytes and water