Phys Block 4 Gi

Front 1

salivary gland enzymes description

Back 1

ALPHA AMYLASE - inactive at pH<4.
75% starches acted on because little mixing in orad stomach.

LINGUAL LIPASE - active at acidic pH, therefore active in stomach.

hydrolizes TGs.

Front 2

bacteriocidic enzymes - saliva

Back 2

lactoferrin, IgA, lysozyme.

Front 3

Salivary electrolyte balance changes with regard to secretion rate

Back 3

Saliva ALWAYS HYPOTONIC to plasma (electrolyte balance changes, thought). Gets CLOSER to isotonic with increased sec. rate.

-LOW SEC. RATE --> Na>HCO3>K>Cl

-HIGH SEC. RATE...Cl>K

Front 4

Salivary Na reabsorption

Back 4

Na REABSORB --> Na enters lumenal side:
ENaC
Na-H exchanger
Na out basolat. side:
K/Na PUMP. *ATPase

Front 5

Salivary Cl reabsorb

Back 5

INTO APICAL -> Cl/HCO3 exchange
OUT Baslateral --> CFTR Cl channels... on both apical and BL sides, but more out via BL.

Front 6

Salivary HCO3 secretion

Back 6

Cl/HCO3 exchange apical.

Front 7

Salivary K secretion

Back 7

uptake BL side via Na/K PUMP

into Lumen via K/H exchanger.

Front 8

Salivary secretory regulation

Back 8

100% ANS (PSNS and SNS, although PSNS IS STRONGER)
NO GI PEPTIDE CONTROL

Front 9

Salivary PSNS mechanisms for secretions

Back 9

1. increase ion transport pathways
2. Contraction of Myoepi. cells
3. Metabolic vasodilation --> Increased O2 and Glucose utilization.
4. KALLIKREIN --> makes bradykinin ... vasodilate and increase cap. permeability (VIP??)

Front 10

Gastric Juice and Secreting Cells

Back 10

Parietal Cells - HCl and IF.
Chief Cells - Pepsinogen
Surface epithelial - Mucin
I

Front 11

IF = INTRINSIC FACTOR...

Back 11

ONLY INDESPENSIBLE SECRETION IN STOMACH.

Parietal Cells

Complexes vitamin B12, prevents proteolysis of B12.

Front 12

Stomach Glands and Location

Back 12

OXYNTIC - PROX 80%.
chief cells - PEPSINOGEN
parietal cells - ACID
mucous neck cells - PROLIF...up = surface epi
down = oxyntic/chief.

PYLORIC - DISTAL 20%.
G CELLS - gastrin
STEM CELLS - neck region

Front 13

Gastric acid secretion mech

Back 13

PARIETAL CELL
1. Generate H+ via (CA)
2. H+ into lumen via H/K exchange
Cl- into cell BL side via HCO3/Cl exchange.
3. Lumenal HCl.

Front 14

Gastric Juice Electrolytes changes with secretion rate

Back 14

GASTRIC JUICE = ISOTONIC WITH PLASMA; elec. balance varies WRT secretion:
1. Slow secrete = NaCl high, H,K LOW.
2. increase rates = increase H, decrease Na.

Front 15

Function of Gastric Mucosal Barrier

Back 15

prevent acid backflow. Because 1 million fold conc. difference WRT H+

Front 16

GASTRIC acid secretion stimuli and their receptors

Back 16

Ach = M3
Histamine = H2
Gastrin = CCKBeta

DIRECT - Ach, Gastrin, and Histamine stimulate Parietal H secretion.

INDIRECT - Ach and Gastrin stim. ECL cell to release HISTAMINE.

Front 17

Histamine

Back 17

from ECL cell

Stimulates parietal cell release of Gastric acid. (PARACRINE)

Release STIMULATED via Ach, gastrin

Release INHIBITED via PGs, somatostatin.

Front 18

MECHANISMS of gastric acid secretion via Ach, Histamine, and Gastrin.

Back 18

1. Gastrin and Ach --> increase Ca.
Gastrin - via Gq.
Ach - via direct channel stim
2. Histamine - Gs increase of cAMP.... inhibition via PG and Somatostatin via Gi.

Front 19

Neural regulation: Corpus versus Antrum of stomach

Back 19

Corpus - VAGUS:
1. stim parietal cell directly (Ach)
2. INDIRECT via ECL stim (Histamine) and D stim (INHIB SOMATOSTAT.)

ANTRUM:
Vagus - stim G and D cells.

Gastrin - same direct/indirect as vagus (D and ECL)

Front 20

Phases of gastric secretion

Back 20

1. CEPHALIC - 30% max. Initiated with THOUGHTS, and chemo/mechano receptors.
stim via SHAM feeding, inhib via VAGOTOMY.
2. GASTRIC - 50%, initiate with FOOD PRESENCE/STRETCH (vagal reflex, inhib with low pH) and AAs.
3. INTESTINAL PHASE (5%) CHYME - high pH stim., low pH inhib.
duod. has G cells (stim with AA/disention)

Front 21

INTESTINAL PHASE of gastric acid secretion: mediators

Back 21

STIMULATION OF PARIETAL ACID SECRETION via AAs etc:

1. Gastrin secreted from duod. G cells - acts on parietal cells in stomach.
2. inestinal endocrine cells serete ENTERO-OXYNTIN - stim parietal cells in stomach.
3. absorbed AAs - stim parietal cells in stomach.

Front 22

SECRETIN (WRT gastric acid)

Back 22

secreted in DUODENUM bc ACID:

inhib gastrin release (G cells)
inhib acid secretion (parietal cells)

Front 23

CCK/GIP wrt Gastric secretion

Back 23

CCK - released in duod. b/c FAs.
inhib. ACID SECRETION (only)

GIP - released in duod. b/c FAs AND GLUCOSE.
inhibits ACID SEC. AND GASTRIN RELEASE.

Front 24

SOMATOSTATIN (WRT gastric acid secretion)

Back 24

-inhib. gastrin release (antrum)
-inhib histamine release (corpus
-antagonizes histamine stim. of parietal cell.

Front 25

PEPSINOGEN (WRT gastric acid secretion) stimuli:

Back 25

1. acid sec. stimuli:
cholinergic (vagal via gastric/cephalic)
gastrin
acid on mucosa (contact, local cholinergic).
2. stimulate pepsinogen, inhib acid secretion:
Secretin (b/c duodenal acid).
CCK (duod. FAs).

NOTE ACID REQUIRED FOR PEPSINOGEN PRODUCTION.

Front 26

Zollinger Ellison Syndrome

Back 26

GASTRIN secreting PANC. TUMOR.

GERD, diarrhea, ulcers b/c acid, steatorrhea etc....

Front 27

Phys. Functions of EXOCRINE PANCREAS

Back 27

1. Enzymes - hydrolize carb, prot, lipids.
2. Buffer (HCO3) because panc. enzymes neutral/alkaline optima.

Front 28

Exocrine Pancreatic Cell makeup

Back 28

Acinar - 80% --> low volume sec, ENZYMES.
Ductal cells - minimal, high volume BICARB.
Islet cells - minimal.

Front 29

EXOCRINE pancreatic secretion regulation

Back 29

ANS:
SNS STIMulates
PSNS INhibit.

Front 30

EXOCRINE pancreas secretion electrolyte balance:

Back 30

ISOTONIC WITH PLASMA.
HCO3 and Cl- inversely proportional (HCO3 increases with increased rate of secretion).

Na>HCO3>Cl>K

Front 31

pancreatic DUCTAL CELL HCO3 secretion mechanism

Back 31

1. import HCO3-:
DIRECT - Na/2HCO3 exchange
INDIRECT - via CA... (OH- + CO2)... note H+ out via Na/H exchanger AND H pump.

2. HCO3 into LUMEN ... via Cl-/HCO3 exchange.

3. CL- gradient establishment via STIMULI:
a. Secretin (primary) - Gs, PKA phosphorylates CFTR Cl-channel.
b. Ach (M3) - Gq... cAMP -Ca - CaM kinase..

Front 32

Phases of Pancreatic secretion

Back 32

1.Cephalic - LO volume, HI enz.
20% max.
smell,site of food --> vagal... to ACINI and to DUCT cells... (ACINI = ENZ)... note stimulation of ancinus via Ach and stimulation of G cell -- gastrin -- Acinus via CCKA.
2.Gastric--LO Volume, HI enz. 5-10%
Distention of stomach --> vagal reflex --> gastrin and Ach.
3.Intestinal - hi V and E... 80%.
ACID IN DUOD --> secretin --> HCO3- (ductal)
FAT and PROTEIN -- CCK from duod. I cells --> ENZYME SECRETE.
acid, fat, and peptides--> chemoreceptors -->VASOVAGAL --> ACH.

Front 33

Inhibitors of Pancreatic secretion

Back 33

Somatostatin
Pancreatic polypeptide
* both inhibit CCK, secretin, and Ach...*

Front 34

CCK - WRT exocrine pancreas... stimuli:

Back 34

l-AA (Trp, Met, Phe), FA>8C

Front 35

Somatostatin stimuli: EXOCRINE PANCREAS

Back 35

pH responsive --> increase with lower pH...

Front 36

CELL TYPE that secretes CCK and Secretin

Back 36

ECL (enterochrommafin-like)

Front 37

Potentiation WRT Secretin, Ach, and CCK... mechanistic rationale

Back 37

CCK and Ach Potentiate secretin action on ductal cells...

Secretin DOES NOT potentiate Ach or CCk...

Secretin + Ach = potentiatition
Secretin + CCK = potentiate
Ach + CCK = additive.

This is because Secretin operates through the Gs mech, and other 2 work though Gq... common area downstream.

Front 38

Vagotomy WRT Pancreatic exocrine function

Back 38

60% block of pancreatic response to a meal... mainly due to INTESTINAL phase inhibitions...

Front 39

Bile function

Back 39

1. Fats
a) emulsify - allow digestion by lipases.
b) solubilize - micelles for absorption.
2. Eliminate toxic wastes

Front 40

Liver 3 major functions

Back 40

1. Biochem metabolism... everything.
2. Degrade/detox (drugs, toxins)
3. STORE iron, B12, A, D.

Front 41

What stimulates Gallbladder contraction?

Back 41

Vagus nerve.
CCK.

Front 42

Where is Bile Acid absorbed via ACTIVE TRANSPORT (SECONDARY)

Back 42

Ileum (Na/Bile acid cotransport)

Front 43

Primary and Secondary Bile Acids

Back 43

Cholic acid - deoxycholic acid
chenodeoxycholic acid- lithocholic

NOTE --> primary bile acids secreted by hepatocytes, secondary produced via bacteria in small intestine.
All can be conjugated via GLYCINE (pka 1.5) and TAURINE (pka 3.7) to increase solubility.

Front 44

Bile Acid Solubility Determinants

Back 44

-COOH pKa, and number of -OH's.

-Liver conjugates them with Glycine and Taurine (1.5, 3.7) to increase solubility.

Front 45

Lecithin

Back 45

30-40% component of Bile.

Phospholipid

Becomes solubilized in micelles, promotes micelle formation.

Front 46

Bilirubin

Back 46

-Heme breakdown product.
-Insoluble (carried by Albumin)
-Solubilized in Liver by conjugation to glucuronic acid to give bilirubin glucuronide... NOT FOUND IN MICELLES.

Front 47

Relative makeup of Organic components of Bile

Back 47

Bile acids - 50%
Lecithin - 30-40%
Cholesterol - 4% (Bile is primary excretory pathway).
Bile pigments - 2%

Front 48

Mechanism - hepatocyte Bile acid reabsorption and resecretion with Bile:

Back 48

Reabsorbed (from portal blood) with 100% efficiency via Na/BA coport.

BA out of hepatocyte into bile cananiculus via FACILITATED DIFFUSION. Electrolytes follow paracellularly, H20 follows them .... OSMOTIC FILTRATION.

Front 49

Excess Bile acids in colon result in what?

Back 49

Diarrhea... because they mess with Na/H20 reabsorption.

Front 50

Bilirubin glucouride reabsorption:

Back 50

most of it isn't ... most goes into feces.

Some unconjugated in distal intestine... results in reabsorption into portal circulation.

Some bilirubin taken up by liver, some goes to kidneys and is excreted.

Bilirubin converted to stercolbin and urobilinogen --> yellow color.

Front 51

How does BA return to liver effect Bile Volume?

Back 51

It increases Bile volume.

Front 52

SECRETIN effects on BILE SECRETION

Back 52

acts like it does with pancreatic duct cells.

causes duct cells to secrete HCO3- ...

Front 53

Bile Concentration in Gallbladder:

Back 53

Resorbs Cl-, Na, and HCO3... therefore water follows and concentrates bile.

Front 54

What is the charge of the gallbladder lumen? What does this tell us?

Back 54

-8mv; tells us that Na is the only electrolyte being ACTIVELY reabsorbed in bile concentration.

Front 55

Small intestine - Surface area expansion mechanism:

Back 55

1. Longitudinal folds - "Kerckring"
2. Villi - length decreases from duodenum to ileum...
3. Microvilli on enterocytes.

Front 56

Small intestine- Crypts

Back 56

1. 3 crypts/villi... located at the base of villi.
2. Secrete electrolytes (particularly Cl)
3. Proliferative

Front 57

When are digestion and absorption of nutrients usually complete?

Back 57

Before they arrive at the ileum.

Front 58

Most absorption is maximal proximally, and minimal distally... name 2 major exceptions:

Back 58

1. Bile acids active absorption at distal ileum.
2. B12 active absorption (endocytosis) at distal ileum.

Front 59

Animal starch versus Plant Starch

Back 59

1. animal - glycogen --> alpha 1-4 linked glucose with alpha 1-6 BRANCHES.
2. plant starch --> alpha1,4 glucose; no branch.

Front 60

Sucrose, Lactose, Maltose comp.

Back 60

Sucrose = glucose + fructose.
Lactose = glucose + galactose.
maltose = glucose + glucose.

Front 61

Cellulose

Back 61

BETA 1,4 linkages... not digested by pancreatic enzymes.

80% degraded by bacteria in GI.

Front 62

amylase with regard to carb. digestion

Back 62

hydrolizes INTERNAL alpha1,4 bonds... doesn't produce free glucose.

works in mouth --> SI.

Front 63

monosacharides absorbed by GI enterocytes.

Back 63

Glucose, Fructose, Sucrose.

Front 64

Glucose, Fructose, and Sucrose absorption mechanism in GI

Back 64

1. SGLT1 (secondary AT) --> Glucose and Sucrose.
2. GLUT5 (passive, therefore can't concentrate in enterocyte) --> FRUCTOSE.
3. GLUT5 --> passive ... transports all 3 out BL side of enterocyte.

Front 65

Lactose intolerance --> enzyme defiicency and location:

Back 65

Brush Border Lactase deficiency... most common carb. metabolism deficiency...
results in OSMOTIC DIARRHEA

Front 66

Pepsin + activation pathway...

How much protein does pepsin digest under ideal conditions??

Back 66

1. Digests PROTEIN in stomach...
2. Endoprotease.
3. Pepsinogen --> pepsin via GASTRIC ACID... note pepsin functions under ACIDIC CONDITIONS.
4. 10% of stomach protein under IDEAL conditions.

Front 67

Pancreatic proteases + activation.

What are their products?

Back 67

ZYMOGENS SECRETED:
trypsinogen, chymotrypsinogen, procarboxypeptidase A+B, proelastase.

Active Trypsin --> activates the rest.

Break down each other and proteins --> di/tripeps... or AAs.

Front 68

Enterokinase

Back 68

Brush border enzyme.

Activates Trypsin (from trypsinogen).

Front 69

Amino acid absorption mechanism/properties...

Back 69

1. Mainly absorb via Na secondary AT
2. Di/Tripeptides are absorbed quicker into blood than single AAs.
3. All blood uptake is AA (no di/tri).

Front 70

Amino acid uptake disorders and treatments...

Back 70

Hartnup's - neutral AA's not absorbed (e.g. phenylalanine.

Cystinuria - dibasic AA's not absorbed (e.g. cysteine, arginine)

can treat with dipeps (leucine-phenylalanine etc... because different transporter).

Front 71

where is CCK released in resonse to FAT??

Back 71

Duodenum (duodenal fat receptors).

delays stomach emptying.

Front 72

duodenal fat digestive enzymes (5)

Back 72

pancreatic lipase
colipase
cholesterol ester hydrolase
pancreatic PLA2
milk lipase

Front 73

pancreatic lipase

Back 73

most active at oil/water interface

hydrolizes 1 and 3 positions of TG

Front 74

colipase

Back 74

binds pancreatic lipase and prevents its inhibition by bile salts.

anchors pancreatic lipase at oil/water interface.

Front 75

cholesterol ester hydrolase

Back 75

removes FAs that are esterified to cholesterol

acts on TGs to release FFAs and Glycerol

BILE ACID ACTIVATED

Front 76

pancreatic phospholipase A2

Back 76

hydrolizes 2 postion of phospholipids.

produces lysophospholipids.

REQUIRES BILE SALTS for maximal activity.

Front 77

milk lipase

Back 77

in breast milk, helps digest TGs

Front 78

What TGs are MICELLE INDEPENDENT??

Back 78

Short chain and medium chained TGs

Front 79

FABP

Back 79

fatty acid binding protein

binds FAs in enterocytes

high affinity for long chained FAs and their monoglycerides.

transports to SER --> ultimately makes micelles...

Front 80

Steathorrea tx

Back 80

substitude with medium and short chained FAs in diet... because direct uptake...

Front 81

lipid hydrolysis problems:

Back 81

Pancreatic insufficiency --> CF, pancreatitis

Zollinger-Ellison syndrome --> gastric hypersecretion ... results in denaturation of pancreatic enzymes... (and also bile acid precip).