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Gi Physiol Note

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0% found this document useful (0 votes)
18 views106 pages

Gi Physiol Note

Uploaded by

tg9tgf687b
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd

GASTROINTESTINAL

PHYSIOLOGY

Kazeem O. Ajeigbe Ph.D, FASLN


Associate Professor of Physiology
Federal University, Oye-Ekiti

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 1


OUTLINES
1. INTRODUCTION
o Overview of the alimentary tract
o Functional Anatomy of the tract
o Innervation of the GI tract
o Electrophysiology of GI smooth muscle
o Regulation of GI function

2. GI Motility 3. GI Secretion
-Chewing and Swallowing -Saliva
-Gastric motility -Gastric juice
-Small intestinal motility -Intestinal
juice
-Colonic motility -Pancreatic
juice
-Defeacation -Bile
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 2
4. DIGESTION & ABSORPTION
-Carbohydrate -Water
-Protein -Nutrients and electrolytes
-Fat

5. DISORDERS OF GIT
-Achalasia
-GERD
-Gastritis
-Peptic Ulcer
-Irritable Bowel syndrome
-Inflammatory Bowel Disease

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 3


From beginning to end:

Mouth

Oesophagus

Stomach

Small intestine
Duodenum (26 cm = 9.8’’)
Jejunum (2.5 m = 8.2 ft)
Ileum (3.5 m = 11.5 ft)

Large intestine (1.5 m = 4.9


ft)
Cecum
Ascending colon
Transverse colon
Descending colon
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 4
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 5
The general purpose of the alimentary
tract is to absorb H2O, electrolytes and
nutrients from ingested food and liquid.

This requires:
- Propelling of contents
- Digestion of contents
- Absorption of nutrients
- Large supply of blood flow (~
25% of total)
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 6
GI Blood Flow

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 7


As you
would
expect,
there is
extensive
blood flow
for nutrient
absorption

3/3/2023 -Arterial Blood supply


200 L MBBS/BPharm/BNSc Dr Kazeem to the intestines 8
Microvasculature of the intestine

Villi greatly increase the surface area of the small


intestine
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 9
Functional Anatomy of GI

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 10


Layers of GIT
The GI tract is composed of three basic functional
layers
1. Muscularis externa
-Outer longitudinal layer
-Inner circular layer

2. Submucosa

3. Mucosa
-Muscularis mucosae
-Lamina Propria
-Epithelium

Serosa is the outermost covering.. serves as a


protective layer
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 11
The morphology of the
epithelium varies
from one part of the GIT
to another

Muscularis mucosae is
thin innermost layer of
GI smooth ms

Nerves and blood vessels


travel in the submucosa

Longitudinal and circular


Ms fibers electrically
connected thru gap jnxs
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 12
Innervation of the GIT
INTRINSIC NERVES (also known as
enteric nervous system)

-Myenteric plexus
-Submucosa plexus

EXTRINSIC NERVES
-Sympathetic
-Parasympathetic
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 13
Regulation of GI Function

oNEURAL

oHORMONAL

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 14


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 15
Gastrin….
• Gastrin:
- produced from the stomach (G cells)
- release increased by stomach
distension, peptides, amino acids,
alcohol, caffeine, parasympathetic
innervation
- release inhibited by highly acidic pH
(< 2.0)

- functions: increases gastric (stomach)


secretions (primarily HCl); increases
histamine release; increases gastric
motility; opens pyloric sphincter (between
stomach and small intestine), relaxes
ileocecal sphincter, stimulates growth of
gastric mucosa.
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 16
Histamine..
– Produced by enterochromaffin-like cells
(ECL cells) of the stomach.
– Release is stimulated by gastrin.
– Action: increase HCl secretion from
parietal cells (major factor in HCl
secretion).

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 17


HOW IT WORKS AT THE RECEPTOR LEVEL

Combined neurocrine, endocrine and paracrine events in


Acetylcholine the activation of gastric HCl secretion
neural input

ACh
receptor
PARIETAL cell
histamine
receptor

H/K
P
ECL cell HCl
histamine- transduction-activation
secreting cell events
secretion
H/K
P

gastrin
receptor

release of
Gastrin histamine
hormonal input ECL cell =
enterochromaffin-like cell

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 18


HOW IT WORKS AT THE RECEPTOR LEVEL

Combined neurocrine, endocrine and paracrine events in


Acetylcholine the activation of gastric HCl secretion
neural input

ACh
receptor
PARIETAL cell
histamine
receptor

H/K
P
ECL cell HCl
histamine- transduction-activation
secreting cell events
secretion
H/K
P

gastrin
receptor

release of
Gastrin H-2 receptor blockers
histamine
hormonal input Tagamet
ECL cell =
Zantac
enterochromaffin-like
Pepcid cell
H/K ATPase pump inhibitors
Prilosec
Nexium
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 19
Aciphex
Somatostatin
o Produced by D cells of the stomach

o Secretion is stimulated by activation of


the sympathetic nervous system and by
acidic pH, and is inhibited by activation of
the parasympathetic nervous system,
continuously released, overridden by
gastrin and nerves

o Actions: inhibit gastrin and histamine


secretion (decreased acid release and
3/3/2023gastric motility); also directly
200 L MBBS/BPharm/BNSc Dr Kazeem inhibits acid
20
Secretin…
Produced by duodenum (enteroendocrine cells
of the small intestine); crypts of Lieberkühn

- stimulated by arrival of acidic chyme in


duodenum

- functions: stimulates bicarbonate secretion


from pancreas; inhibits gastric secretion
(decreases HCl production by inhibiting gastrin
release); decreases gastric motility (slowing
rate of gastric digestion and delivery to the
small intestine), increases hepatic bile
production, increases
3/3/2023 CCK,
200 L MBBS/BPharm/BNSc promotes growth21
Dr Kazeem
Cholecystokinin (CCK)…
produced by enteroendocrine cells of the
duodenum

- release stimulated by fatty acids


in duodenum (also amino acids, acidic
chyme)

- functions: causes gallbladder


contraction (bile to small intestine);
stimulates release of pancreatic
enzymes; decreases gastric motility and
secretion (increases somatostatin
release).
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 22
Integration of Neural &
Hormonal Function

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 23


GI
SECRETIONS
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 24
Associated glandular organs of the
alimentary tract produce secretions

Glands subserve two primary functions:


1. Digestive enzymes
2. Mucous glands produce mucus for
lubrication and protection of all parts
of the GIT

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 25


Principles involve
1. Mechanical stimulation:
Direct mechanical stimulation of
glandular cells by food cause the
local gland to secrete via tactile,
chemical irritation and gut wall
distension
2. Parasympathetic and sympathetic
stimulation:
Parasympathetic increases the rate of
secretion while sympathetic can have
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 26
Typical glandular cell for
formation and secretion of
enzymes

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 27


SALIVA
• Salivary glands produce about 1000 ml
of saliva per day
• Glands are: Parotid, submandibular
and sublingual
• Secretions could be serous and mucous
• Parotid secretes serous while
submandibular and sublingual produced
mixed secretions

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 28


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 29
Composition of Saliva

• Water
• Electrolytes
• Amylase
• Kallikrein
• Mucus etc

Saliva is hypotonic (Has higher K+ and


HCO3-; and lower Na+ and Cl-)

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 30


Functions of Saliva
• Carbohydrate digestion
• Provides lubrication and so aids
speech
• Its bactericidal (as it contains
thiocyanate, lysozymes and some
protein antibodies)

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 31


Regulation of salivary
secretion
• Parasympathetic signals from the
superior and inferior salivatory nuclei
in the medulla. Stimuli are taste,
tactile, and psychic. Salivary blood
vessels also dilates and increase
secretion

• Sympathetic stimulates β-receptors on


the acinar and ductal cell and caused
increased secretion
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 32
GASTRIC SECRETION

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 33


Oxyntic Gland Area - proximal 80%
of the stomach (body and fundus) -
secretes HCl and pepsinogen into
stomach lumen.
Pyloric Gland Area - distal 20% of
the stomach (antrum) - secretes
pepsinogen into the lumen, as well as
the hormone gastrin to the
bloodstream.
Gastric Mucosa Surface - secretes
mucus and HCO3- for protection from
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 34
Gastric gland
Mucous cells secrete mucous,
HCO3-, & trefoil peptides.

Chief cells secrete pepsinogen &


gastric lipase.

Parietal cells synthesize and secrete


hydrochloric acid & intrinsic factor.

ECL Cells secrete histamine.

Enteroendocrine cells (specifically G


cells) secrete gastrin

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 35


Composition of gastric juice

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 36


Mechanism of HCl
production

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 37


Regulation of HCl and
Pepsin

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 38


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 39
X X

One inhibitory and


three stimulatory
signals that alter
acid secretion by
parietal cells
in the stomach. X

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 40


Note:
Adverse effects associated with ulcer
treatment may include
1. Decrease absorption of calcium (risk of
osteoporosis)
2. Decrease absorption of B-12 leading to
homocysteine build up (vascular dementia,
anaemia and breast cancer)
3. Risk of ulcerative colitis and antibiotic
resistant infections…

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 41


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 42
Surface epithelium secretes a
mucus layer containing
bicarbonate for protection from
gastric acid.

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 43


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 44
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 45
Human…

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 46


Rat…

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 47


Protective and aggressive
factors in gastric mucosa

Diagrammatic
representation of
peptic ulceration

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 48


EXOCRINE PANCREAS

The exocrine cells in the pancreas play a central role


in the production of digestive enzymes

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 49


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 50
Formation…

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 51


Secretin stimulates HCO3-
secretion in the pancreatic ducts
when S cells detect that acid is
present in the duodenum

Secretin Receptors are Densely Expressed on Pancreatic


Ductular Cells in Humans

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 52


BILE
• Bile is produced in the liver
• Bile is stored in the
gallbladder
• Bile is secreted into the small
intestine.
• Bile salts are absorbed in the
small intestine and recycled
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 53
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 54
Bile formation by cells in the liver includes 6 components:
bile salts, lecithin, bicarbonate ions, cholesterol, bile pigments, and
trace metals.
The bile is funneled into the gallbladder and then delivered
into the duodenum upon stimulation from CCK

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 55


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DIGESTION & ABSORPTION

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 67


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 68
Digestion is the breakdown of ingested
food into absorbable form

The ingested food can be broadly


classified as

• Carbohydrate
• Protein
3/3/2023
• Fats
200 L MBBS/BPharm/BNSc Dr Kazeem 69
LUMINAL
• Mixing of chyme with enzymes
BRUSH BORDER
• Specific enzymes present on
the luminal surface of the
enterocytes

CYTOSOLIC/INTRACELLULAR
• Intracellular digestion in the
enterocytes
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 70
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 71
Proteins:
• All 3 phases, luminal, brush border and
cytosolic digestion may be involved

Carbohydrates:
• Only luminal and brush border digestion
– no intracellular digestion by the
enterocyte

Lipids:
• All digestion is luminal; triglyceride is re-
formed in the enterocyte!
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 72
Were digestive enzymes synthesized in their active
form, they would digest the very cells that make
them. Hence, inactive precursors (e.g., trypsinogen)
become activated (trypsin).

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 73


Digestion of Protein
Proteases stored in inactive form in
pancreas & secreted in response to neuro-
hormonal stimulation.

o Pancreatic trypsinogen converted to


active form by duodenal brush-border
enterokinase

o Trypsin activates all other luminal


peptidases.
o Digestion of oligopeptides in lumen and
small peptides at brush border.
o Uptake of free amino acids, di- and tri-
peptides by active transport mechanisms.
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 74
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 75
1. Lumen

2. Brush Border

3. Cytoplasm

Sites of Protein Digestion


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 76
Carbohydrate Digestion
• Polysaccharides digested in duodenal
lumen by pancreatic amylase to
produce oligosaccharides and
disaccharides.
• Brush border digestion of polymers by
specific amylases and disaccharidases
forms monosaccharides.
• Simple sugars taken up by active
transport processes into enterocytes.
• NO uptake of disaccharides or
oligosaccharides!
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 77
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3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 80
Fats Digestion
• Lipid digestion in luminal phase only.
• Digestion requires bile salts, pancreatic
lipase, co-lipase and phospholipids.
• Lipids emulsified by bile salts and
phospholipids.
• Triglyceride digested to form free fatty
acids and a monoglyceride.
• Digestion productions taken up by
diffusion

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 81


Bile salts and
phospholipids
convert large
fat globules
into smaller
pieces with
polar surfaces
that inhibit
reaggregation.

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 82


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 83
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ABSORPTION

General Features

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 86


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 87
By projecting
into the lumen,
the villi increases
the surface area
for absorption of
nutrients.

Microvilli [aka
brush
border] fringe the
villi to further
increase
surface area.
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 88
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 89
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 90
o Transepithelial transport - nutrients
must pass across the epithelial lining
of the small intestine

o Active transport - most nutrients


must be transported across
membrane using ATP of the cells

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 91


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3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 96
Carbohydrate Absorption
• Sugars enter blood stream by
facilitated diffusion or active transport
mechanisms.
• Glucose in the intestinal lumen
stimulates the release of GIP
(Gastrointestinal Inhibitory Peptide).
• GIP stimulates the release of insulin
from the pancreas in anticipation of
glucose in the portal blood.
• GIP inhibits gastric motility to facilitate
digestion and absorption from the GI
tract.
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 97
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 98
1. Sodium gradient for SGLT1 driven by Na+/K+ ATPase.
2. Basolateral GLUT2 transports monosaccharides to the blood.

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 99


Protein Absorption

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 100


Lipid Absorption

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 101


3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 102
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 103
• Free fatty acids and monoglycerides
reformed into triglycerides inside the
enterocytes.
• Triglycerides packaged together with
cholesterol and apo-lipoprotein
molecules to form very large
lipoproteins – CHYLOMICRONS.
• Chylomicrons secreted into lacteals –
terminal of lymphatic system - enters
systemic circulation in neck.
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 104
3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 105
TEST

3/3/2023 200 L MBBS/BPharm/BNSc Dr Kazeem 106

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