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GASTROINTESTINAL

PHYSIOLOGY

By
H.Khorrami Ph.D.
http://khorrami1962.spaces.live.com
h"p://scribd.com/khorrami4  
khorrami4@yahoo.com
Secretions
Salivary Glands
•  3 pairs secrete into oral cavity
•  Each pair has distinctive cellular organization:
•  and produces saliva with different properties
•  Produce 1.0–1.5 liters of saliva each day:
•  70% by submandibular glands
•  25% by parotids
•  5% by sublingual glands
Salivary Glands
•  Parotid gland

•  Submandibular
Salivary Glands

Sublingual
Submandibular
1.PAROTID GLANDS – anterior & inferior to ear
clear, watery saliva & amylase
Stenson’s duct – enters opposite 2nd upper molar
MUMPS – viral inflammation & swelling
2. SUBMANDIBULAR GLANDS - body of mandible
Secretes serous fluid – serous cells
Wharton’s Ducts – open inferior to tongue near
frenulum
3. SUBLINGUAL GLANDS – floor of mouth
Multiple ducts posterior to submandibular duct
( Rivinus ducts)
Mucous secretions – mucos cells – thick & stringy
Gland   loca6on   histology   %  of  total   Nerve  
salivary   supply  
secre6on  
Paro6d   In  front  of   Purely   25%   9th  cranial  
ear   serous   Nerve  
Sub-­‐ Sub-­‐ Mixed   70%   7th  cranial  
mandibular   maxillary   S:M::4:1   nerve  
triangle  
Sub-­‐lingual   Floor  of   Mixed   5%   7th  cranial  
mouth   S:M::1:4   nerve  
Salivary gland
Saliva
•  99.4% water
•  0.6% includes:
•  electrolytes (Na+, Cl—, and HCO3—)
•  buffers
•  glycoproteins (mucins)- Glycoproteins, responsible for lubricating action
•  antibodies
•  enzymes
•  waste products(urea)
Composition of Saliva
•  In 24 hours-1-1.5 lit. pH=6.0-7.4
•  Water- 99%, Solid-1%
•  Organic compounds- salivary amylase, lingual lipase,
lysozyme, mucin, IgA, Kallikerin
•  Trace amount of urea, EDGF, NGF, Uric acid, FFA, blood
group antibodies .
•  Inorganic compounds
•  Cations, Na+,k+,Ca++(trace)
•  Anoins, HCO3,Cl,Br/I
Functions of saliva
Saliva plasma

•  Sodium= 15-20 meq/l •  Sodium= 145 meq/l


•  Potasium=20-25 meq/l •  Potasium=5meq/l
•  Bicarbonate= 40-60 meq/l •  Bicarbonate= 27 meq/l
•  Chloride=15-20 meq/l •  Chloride=110meq/l
Composition of saliva with flow rate
Salivary secretion
Functions of saliva
Digestion
- ptyalin (α-amylase)
- identical to pancreatic amylase
- cleaves α-1,4-glycosidic bonds of carbohydrates
- pH optimum 7
- functionally replaceable by pancreatic enzyme

- lingual lipase
- triglycerides
- lower acidic optimum – remains active throughout
the stomach and into the proximal duodenum

- dissolves dietary constituents

- increases the sensitivity of taste buds


Protective functions
•  Protect the mouth by cooling hot food
•  Dilute HCL/bile regurgitated in to the mouth
•  Wash away the food from teeth & destroy harmful bacteria
by:
•  Lysozyme-kills bacterias
•  Lactoferrin-binds to iron: bacteriostatic
•  IgA- act as antivirus & microbes
Lubrication
- mucus content
- facilitates swallowing
- necessary for speech
Innervation
Neural regulation of secretion
Lower Esophageal Sphincter (LES)
3. Composition of the Gastric Juice (cont’d)
e l l
s c
ucu
M 1. Mucus: Glycoprotein products found throughout entire GI tract.
Primary function as lubricant, but can also have many other
regionally specialized functions

c ell
ie f
h
C 2. Pepsinogen: Proenzyme made by chief cells. As it encounters
HCl in gland lumen, then continuing in the gastric lumen:
HCl (pH < 3)
Pepsinogen (42 kDa) Pepsin (35 kDa)
inactive proenzyme active protease

ell
talc
ie
ar
P 3a. Hydrochloric Acid: denatures food; activates pepsinogen;
dissolves bone; kills most bacteria

3b. Intrinsic Factor: Essential for absorption of Vitamin B12


Gastric Hcl Secretion
Gastric HCl Secretion Fig. 21-6
Lumen of
gastric gland

Na+ Pump
(Na,K-ATPase)
Proton Pump
(H,K-ATPase)
Na+
ATP
K+

HCl
Pancreatic juice
Endopeptidases
• Pepsin (stomach), cleaves at amino side of
aromatic A.A.'s
• Trypsin (pancreas), cleaves at COOH side of
basic A.A.'s, i.e., lys & arg
• Chymotrypsin (pancreas), cleaves at COOH
side of aromatic A.A.'s, also leu and met
• Enteropeptidase (duodenum) cleaves at
COOH side of Lys that is preceded by 4 Asp
and followed by non-Pro
Exopeptidases
•  Carboxypeptidase (pancreas), C-terminal
peptidase
•  Aminopeptidase (intestine), N-terminal
peptidase
Digestive enzymes
Intestinal Secretion
(intestine absorbs ~8.5-9 L/day, but it also secretes about 1.5 L/day)

NaCl Secretion
by the Intestine
K+

K Na, K,
2Cl 2Cl
Na+
Cl- op Cl- Na+
P
Na+
cl K+ K+
net turned on
secretion by cAMP

Na+ Na+

Surface receptors activate Gs protein


Secretory
Cholera toxin (from Vibrio cholerae) cells
alters Gs to prevent de-activation
Permanent activation of adenylyl cyclase
Chronic elevation of cAMP
Large pathological secretion
Fat Absorption: a problem of solvent association

Steps in the fat


absorption process
emulsification
~10,000-fold
increase in
surface area

micellar formation
hydrolysis
absorption

re-esterification

lipoprotein
formation/transport
Colipase (not an actual
enzyme) inserts between
bile salts to increase
access of lipase to fats
inside droplet or micelle.
Vitamins
Absorption of most fat-soluble vitamins (A, D, E, K) requires presence of fats
and bile salts, along with the lipid absorptive process.

Vitamin C, biotin, folic acid, nicotinic acid, riboflavin, and thiamine are
apparently absorbed by Na+-dependent facilitated transport — vitamin C
mainly in the ileum, the others mainly in the jejunum.

Vitamin B12, important for many functions throughout the body but especially
critical for normal maturation of red cells (erythropoiesis), requires intrinsic
factor for absorption. Intrinsic factor is a binding and protective agent for B12,
shepherding it through the small intestine to the ileum, where the complex
binds to apical receptors for internalization by endocytosis and ultimate transfer
to the bloodstream.

Bile salts
Almost all bile salts that pass through the small intestine are reabsorbed and
recirculated to the liver via the hepatic portal vein. Some are absorbed
passively in the jejunum, but most are absorbed actively in the ileum, with
dependence on Na+.
Ca2+ Absorption: mucosal regulation of a body need

AC
mRNA calbindins
Ca pumps
cAMP Na/Ca exch
intestinal PKA
lumen ?

ECaC
+
Ca-calbindin?
Ca++
lysosomes?
ves. transport?
++
Ca Ca++
S(5th) p. 707
Iron Absorption
tissue cells, e.g., liver &
erythrocyte precursors in
endocytosis? bone marrow

competitor:
lead transferrin
receptor

Fe-tannin
X
DMT1
ferroportin
Fe-citrate

Fe-ascorbate Hepcidin
(from liver,
when iron
stores are
enterocyte high)

Gastric acid is important for keeping elemental iron from precipitating. When acid is low,
as in atrophic gastritis, or with frequent use of acid inhibitors, absorption of elemental iron
by the duodenum is reduced.
The Large Intestine
The Large Intestine
Colon: net absorption of salt and water, but also some secretion of K+
(Colon participates with kidneys in regulating body K+.)

Na+

Cl-

H2O
NaCl Secretion by the Colon
(minor, except when pathological)
There is very little nutrient absorption by the colon,
however:

Short-chain fatty acids produced by colonic bacteria:


1) taken directly across apical membrane of colonocytes
2) many used by colonocytes as preferred metabolic substrate

Vitamin K and biotin: absorbed in small intestine from dietary


sources, but also produced by colonic bacteria and absorbed
across colonic epithelium
b. Secretion/Activation of Pancreatic Enzymes
CCK (cholecystokinin)
works on
acinar cells

#-Amylase
(Enterokinase)
Lipase
(from duodenal
secreted epithelial
by duodenal
(no activation needed) cells)
epithelium
Liver
•  https://www.youtube.com/watch?v=ioxyO2WPhLQ
The Enterohepatic Circulation
Bile Salt Bookkeeping Bile Salts (acids)
total bile salt pool = 2-4 gm
daily output = 20-30 gm/day Bile Pigments
synthesis = 0.3-0.5 gm/day
fecal loss = 0.3-0.5 gm/day

Transport back
into hepatic cells The UDP-glucuronylation
95% of bilirubin excretory pathway
bile pool Hb
breakdown

~99% of bile
secretion

fecal loss
(0.2 g/day)
Gastric emptying
Vomiting(emesis)
Exocrine pancreas
Protein digestion
Intestinal Nacl secretion