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Debre-Tabor University

COLLEGE OF MEDICINE AND HEALTH SCIENCES

Physiology of Gastrointestinal system


By: Derib A. (BSc, MSc in Medical Physiology)

February 12, 2024 By Derib A. 1


Gastrointestinal System

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Learning objectives:
 Describe physiological importance of GI system

 Identify the different functional layers of GIT

 Describe the different activities of GIT

 Understand the regulation of GIT activities

 Mention secretory products of the GI system.


 Elaborate digestion and absorption of food products

 Describe the role played by accessory organs

February 12, 2024 By Derib A. 3


Overview of Gastrointestinal System
• Food is essential for production of energy, growth and
repair of tissues.
• ~1 kg of solid food and 1- 2 liters of fluid consume in
each day.
• ~30 kcal/kg/day.
• The food that we ingest must be broken down into simple
molecules for efficient absorption.
• GI system is responsible for digestion and absorption of
these materials.
• Passage of digested food from GIT lumen into blood or
lymph vessels is called absorption
February 12, 2024 By Derib A. 4
Overview of GI system…
• GI tract extends from the mouth to anus
• Composed of several organs with distinct functions.
• Specialized independently controlled thickened
sphincters that assist in gut compartmentalization.
a)Alimentary Canal:
• About 8-10 meters long
b) Accessory organs:
• Salivary glands
• Liver and gall bladder
• Pancreas
February 12, 2024 By Derib A. 5
Functional structure of the GI system
Main GI-Organs Accessory Organs
1. Mouth 1. Salivary
2. Pharynx glands
3. Esophagus 2. Pancreas
4. Stomach 3. Liver &
5. Small 4. Gallbladder
intestine
6. Large
intestine
7. Rectum
(Anus)

Fig.1: GIT-organs and its accessories


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Important roles of GI-System:
 Roles in homeostasis

– overall function of GIT that sustains life


– provides the body with a continual supply of
nutrients, water and electrolytes.
– Remove undigested /waste out of the body

 In fluid balance, and

 In microbial defense

February 12, 2024 By Derib A. 7


Role of GIS in homeostasis:
• GIT is involved in day to
day intake & excretion
of food substances (it
breaks, digests, absorbs,
and eliminates nutrients,
and finally supplies
energy (ATP).
• It, therefore,
guarantees
perpetuation and
survival of life

February 12, 2024 By Derib A. 8


GIS in Fluid balance
A. Secretion
~ 7 L of fluid are secreted (added) from
different organs into the lumen daily
~ 2 Liters of fluid is drunk daily
Total= 9 L of fluid is added into GIT/day

B. Absorption
~ 8.5 L absorbed by Small intestine
~ 400 ml is absorbed by LI

C. Excretion: only ~ 50 -100ml of fluid


is excreted daily with feces

• Any factor that affects fluid balance of


the GIT, has a direct effect in
disturbing circulatory dynamic like a
decrease in blood volume

February 12, 2024 By Derib A. 9


GIS and its Natural Defense:

 Non-immunologic defense
Mucosal barrier
HCl
Mucin
Peristalsis: disturb localization of MOs
 Immunologic (GALT): GUT associated lymphoid tissue
– Intestine possess the largest mass of lymphoid
tissue in our body

February 12, 2024 By Derib A. 10


Microbial defense by GIS
a. Mouth: Saliva
contains lysozymes
and IgA that attacks
microbes
b. Stomach: HCl
has bactericidal
actions
c. Small intestine
Immuno-competent
cells (Payer's
patches) attack
microbes in SI wall
d. Macrophages: In
SI, developed from
monocytes, destroy
microbes by
Phagocytosis

February 12, 2024 By Derib A. 11


Histological layers of the GIT

February 12, 2024 By Derib A. 12


Histological layers..
 Mucosa
 Contains: epithelium, lamina propria, muscularis mucosa
 Protection, secretion & absorption from luminal surfaces
 Submucosa
 contains blood vessels, lymph nodes and some nerve
fibers.
• Between submucosa and circular muscles, a nerve plexi
called messiner’s plexus
– involved in GI secretions

February 12, 2024 By Derib A. 13


Histological layers..
 Muscularis Externa
• Contains circular & longitudinal smooth muscle layers
– Contraction of circular muscles decreases lumen diameter
– Contraction of longitudinal muscle decreases length of GIT.
• Between them is found Myenteric plexus
– involved in GI motility.

 Serosa: outer most protective layer


– consists of adipocytes and connective tissue

February 12, 2024 By Derib A. 14


Histological layers of
the GIT

February 12, 2024 By Derib A. 15


Blood flow to the GIT

GIT blood flow is classified under


splanchnic circulation which
includes: GIT, Liver, Spleen,
pancreas etc

Venous blood collected from


these regions pass through the
portal circulation and end in
the liver > liver sinusoids >
hepatic vein> inferior VC

Adv. of portal circulation:


Potentially harmful agents
that come with blood are
destroyed by macrophages of
the liver (Reticuloendothelial
cells)

February 12, 2024 By Derib A. 16


Blood flow to the GIT…

• GI system receive 30% of CO= 1.5L/min


• Blood from GIT below esophagus drains into hepatic
portal vein.
• Blood in portal vein is more oxygenated than systemic
veins;
– 80-90% saturated
– Provide 70% of oxygen requirements of the liver
• Blood from hepatic artery is oxygenated but nutrient-
poor compared to hepatic portal vein.

February 12, 2024 By Derib A. 17


Regulation of Gastrointestinal activities
• Three principal control mechanisms:
I. Neural

II. Endocrine

III. Paracrine

February 12, 2024 By Derib A. 18


Hierarchical Neural control of GI functions
February 12, 2024 By Derib A. 19
I. Neural control of GIT functions

 Neural innervations of  Sensory stimulation


the GIT include: occurs by:
a. Stretch or
a. Afferent sensory fibers Irritants
b. Excessive
b. ANS (PNS, SNS)
distention
c. Chemical stimuli
c. Enteric nervous system
of the food

February 12, 2024 By Derib A. 20


Neural innervations of GIT:
1. Autonomic innervations
(extrinsic regulation):
– have generally
a modulatory role
A. Parasympathetic:
- Usually excitatory (Ach is NT)
- Carried via vagus and
pelvic nerves
- Causes strong contractions
on longitudinal muscles
- At sphincters: cause dilation
of circular SM

February 12, 2024 By Derib A. 21


B. Sympathetic:
- Usually inhibitory (NE as NT)
-Fibers originate in the spinal cord
b/n T-8 and L-2.
-Exerts its effects in two ways:
1.Direct effect of secreted NE
2.Inhibitory effect of NE, on the
neurons of entire ENS (major)

-Constrictor at sphincters
-Reduce intestinal blood flow!!

February 12, 2024 By Derib A. 22


How PNS cause SM contraction?

• Post-ganglionic fibers release Ach

• Ach bind Muscarinic (M3) receptors on SM cells

• Binding activates Gq subunit of GPCR, this in turn


activate PLC
• PLC converts PIP2 to IP3 and DAC

• IP3 cause Ca2+ release from ER

• Ca2+ bind Calmodulin that activate MLCK


• Activated MLCK phosphorylate Myosine ATPAse…..
Actin bind myosin……contraction
February 12, 2024 By Derib A. 23
C. Enteric NS (Intrinsic regulation)
– The primary neural mechanism that controls GI
function.
– Consists ≈ 100 million neurons
– Located solely within GI tissues = little brain
– Coordinates and relays information from ANS to GIT
- Communicate with ANS

– Several neurotransmitters: Ach, substance P, Nitric


oxide……
– Work exclusively of ANS

February 12, 2024 By Derib A. 24


 Two Enteric NS innervations
I. Myenteric plexus
 Auerbach’s plexus, or Outer
plexus
 Lies b/n longitudinal and
circular muscle layers
 Controls mainly GI movements
II. Submucosal plexus
 Meissner’s plexus or Inner
plexus
 Lies with in the submucosa.
 Controls mainly GI secretion
and local blood flow.

February 12, 2024 By Derib A. 25


Neural innervations of GIT…

2. Somatic innervations:
• Voluntary muscle fibers at the

 upper esophagus and lower end of the GIT are


controlled by somatic nerves that are voluntary in
action.

February 12, 2024 By Derib A. 26


II. Endocrine Regulation of GIT

 Affects the motility and secretary


activities of the GIT

February 12, 2024 By Derib A. 27


GI hormones

February 12, 2024 By Derib A. 28


GI hormones and their effects

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III. Paracrine regulation:

February 12, 2024 By Derib A. 30


Paracrine regulation

Paracrines
 Are released from endocrine cells in the GI mucosa
 Diffuse over short distances to act on target cells.

 Common GI paracrine are

 somatostatin and histamine

February 12, 2024 By Derib A. 31


A. Somatostatin:
•Secreted by cells throughout the GI tract in response to
H+ in the lumen.
•Its secretion is inhibited by vagal stimulation
•Inhibits the release of all GI hormones.
•Inhibits gastric H+ secretion
B. Histamine:
– Secreted by ECL cells of gastric mucosa.
– Increases gastric H+ secretion directly and by
potentiating the effects of Gastrin and vagal
stimulation
February 12, 2024 By Derib A. 32
Neurocrine regulation
• Neurocrines: Hormones synthesized in GI neurons
A. VIP: Vasoactive intestinal peptide
• Released from neurons in the mucosa and smooth
muscle of GIT
• Produces relaxation of GI smooth muscle
• Stimulates pancreatic HCO3– secretion
• Inhibits gastric H+ secretion.
B. GRP (bombesin): Gastrin Releasing Peptide
• Released from vagus nerve that innervate G cells.
• Stimulates gastrin release from G cells.
February 12, 2024 By Derib A. 33
Main activities of Digestive Tract
1. Ingestion
2. Motility

3. Secretion

4. Digestion

5. Absorption

6. Excretion
February 12, 2024 By Derib A. 34
Processes carried out by the GIT:

The law of the gut------- mouth to Anus


February 12, 2024 By Derib A. 35
I. Ingestion

 Voluntary intake of food and


drink.

 Controlled by Feeding center


and satiety center in the
hypothalamus.
 Amount of food - hunger
 Type of food - appetite

February 12, 2024 By Derib A. 36


Mastication (Chewing)
 Mouth is responsible for mechanical digestion of
solid food by mastication.
 Chewing (mastication)
1. Mixes food with saliva, lubricating it to facilitate
swallowing.
2. Reduces the size of food particles,
which facilitates swallowing
3. Mixes ingested CHO with salivary amylase to
begin CHO digestion.

February 12, 2024 By Derib A. 37


Swallowing (Deglutition)

 Initiated
voluntarily in the
mouth.

 The reflex portion


is controlled by the
swallowing
center.

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Swallowing reflex
• Tongue pushes the bolus to the
back side of mouth
• The soft palate elevates and
prevents the nasal passages
• Epiglottis moves back and
covers the glottis and prevents
food from entering trachea.
• UES relax and food descends
into esophagus.
• The reflex is controlled by
swallowing center in the
Medulla
February 12, 2024 By Derib A. 39
Phases of swallowing reflex

1. Oral (Voluntary) phase: bolus is pushed by tongue


towards the pharynx voluntarily
2. Pharyngeal phase: Passage of food through pharynx into
esophagus.
•Soft palate is pulled upward to close posterior nares, to
prevent reflux of food into the nasal cavities.
•UES relaxes while Epiglottis closes to keep swallowed
material out of the airways
3. Esophageal phase:
•Food moves downward to Esophagus, propelled by
peristaltic waves, and aided by gravity
February 12, 2024 By Derib A. 40
a) The tongue pushes the food bolus to the back of the mouth.
b) Soft palate elevates to prevent food from entering nasal passages
c) Epiglottis covers the glottis to prevent food from entering the
trachea and the upper esophageal sphincter relaxes.
d) Food
Februarydescends
12, 2024 into the esophagus.
By Derib A. 41
II. GI MOTILITY
• Motor activity of the GIT
• Coordinated pattern of smooth muscle contraction and
relaxation with in the GIT
• Performs several functions:
– Segmental contractions
– Propulsion
– Act as reservoirs (sphincters)
– Prevent retrograde movement of contents (toward
anal direction)
– Dispose of residues
February 12, 2024 By Derib A. 42
Types of movements in the GIT
• Two types

1.Propulsive movements: Peristalsis


• Cause food to move forward along the GIT at an
appropriate rate for digestion and absorption
• Occurs from esophagus up to the rectum.

2. Mixing movements
• Keep GI contents thoroughly mixed at all times

February 12, 2024 By Derib A. 43


Propulsive movements-peristalsis
 Stimuli for peristalsis
• Distention of the GIT
• Chemical or physical irritation of the GIT
• Strong parasympathetic stimulation

Peristalsis is always from orad to caudal direction


February 12, 2024 By Derib A. 44
Motility in the Esophagus
• At rest, upper and lower esophageal sphincters are
closed.

• Thus no backflow of gastric contents occur except


during belching or vomition.

• Movement of food in the esophagus is initiated


voluntarily and then it becomes involuntary
– Upper 1/3 skeletal, both middle 1/3, and lower 2/3
consists of smooth muscles

February 12, 2024 By Derib A. 45


Motility in the stomach
• Motility of stomach contents are accomplished by:
A. Mixing B. Peristaltic waves
A. Mixing processes
- Back and forth movement of chyme against closed
pyloric sphincter
- Mixing contractions are beneficial to mix chyme with
gastric juice
- Pacemaker cells are located at funds region and fire
spontaneously causing generation of slow waves called
basic electrical rhythm
- Slow waves result in tonic, weak contractions of the
stomach walls (3 wave/min)
February 12, 2024 By Derib A. 46
Motility of the stomach..

B. Peristalsis
 Initiated near fundal-
corpus border and
proceed caudally,
producing a peristaltic
wave that propels the
food towards the
pylorus.

February 12, 2024 By Derib A. 47


Gastric emptying and the role of pylorus
• When stomach is filled • Moreover, the rate of
with food, pylorus emptying from stomach is
remains closed for a delayed by factors like
long time except for hyper tonicity, acidity
intermittent opening (pH<3), and chyme
that allows small food osmolarity in the
(1-3 mm) particles to duodenum.
pass to duodenum. • These factors induce
closure of the pylorus.
• NO causes relaxation of
pylorus, while CCK • Liquids empty faster than
causes contraction and solids from stomach
delays gastric emptying

February 12, 2024 By Derib A. 48


Gastric Emptying and delaying…
A. Neural factor
B. Hormonal factors
 Parasympathetic: increase rate
-CCK, Secretin and
of emptying by opening pyloric GIP delay emptying
sphincter (dilatation) (contract pylorus)
 Sympathetic: constriction of
pyloric sphincter through its
-Gastrin stimulates
Adrenergic receptors, delay emptying stomach emptying by
 Enterogastric reflex: increasing rate of
• When fat or protein chyme reaches stomach motility.
duodenum, receptors detect and send
impulses to enteric nerves of stomach
that cause inhibition of stomach
motility and secretion, delays
emptying.
February 12, 2024 By Derib A. 49
Neural pathway

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Hormonal factors

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Rate of emptying of CHO, protein and fat

The rate at which stomach


empties depends on
fluidity of the chyme and its
contents.
 Liquids empty faster than
solids.
 Moreover, the following
steps take place for organic
chyme when emptying
stomach:

CHO> protein> fat

February 12, 2024 By Derib A. 52


Gastric emptying, physiological advantage
1. It gives ample time for nutrients (e.g., like fat)
to remain longer in the stomach and be digested
by gastric juices.

2. The delay prevents acids (HCl) not to be damped into


duodenum at higher rates to cause duodenal ulcers.

3. The delay also gives time for pancreatic secretions to


reach duodenum and neutralize the acid.
4. Prevent overwhelming of the SI with chyme.
 Digestion & absorption affected, nutrients excreted

February 12, 2024 By Derib A. 53


Motility in Small intestine
1. Segmentation:
•Involves ring like (rhythmical)
contraction and relaxation in short
distances.
•Provides a sustained small divisions
and mixes chyme by bringing it into
contact with intestinal wall.
•Small ring like contractions help
chop, cut and mix the chyme with
intestinal juice
•Also such motility allows contents to
stay longer and promote increased
absorption of chime
•No forward movement

February 12, 2024 By Derib A. 54


2. Peristalsis:

Orad caudad

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III. Secretory function of GI System

• Salivary Secretions

• Gastric Secretions

• Pancreatic Secretions

• Hepato-biliary Secretions

February 12, 2024 By Derib A. 56


GIS Secretions:
•~ 6-8 L/day

•GI secretions play a role to:


– Lubrication (water and mucus)
– Digestion (enzymes)
– Protect (mucus)
– Sterilize (HCl)
– Neutralization (HCO3-)

February 12, 2024 By Derib A. 57


Average amounts of daily input in to the GIT

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Salivary glands and their secretions

A. Parotid 25%:
• Secrete mainly serous watery
fluid rich in ptyline
B. Submandibular 70%:
• Produce both serous and
mucous fluid.
C. Sublingual ~5%:
• Secrete mainly thick mucous
with little serous fluid.

February 12, 2024 By Derib A. 59


Composition and functions of saliva
Total secretion = 1-1.5 L/day
• H2O (99.5%): facilitates taste and dissolution
• Electrolytes (0.5%): Na+, Cl-, K+, HCO3-, etc.
• Mucin: for lubrication
• Enzymes: alpha- amylase, lingual lipase
• Lysozymes, thiocyanate, Glycoproteins, albumin,
globulin, IgA, mucus, etc.
Function of saliva
- lubrication, speech
- digestion
- mixing
- bacterial attack Reduce dental carries
February 12, 2024 By Derib A. 60
Reflex control of salivation
• Nervous control
 Sight, smell and test or thinking of food  Receptors
in oral cavity or smell  Sensory fibers from the
tongue to nuclei in brain stem (MO) called Salivatory
nuclei  Parasympathetic fibers act on salivary glands
to increase salivary secretion.

 Salivation can also be controlled by higher centers like


hypothalamus which has nerve connections
with salivatory nuclei.

 Higher centers like appetite area in the hypothalamus


are also involved in reflex control.

February 12, 2024 By Derib A. 61


Gastric Secretion
• 2.5L of gastric secretions are produced/day
• Secretion: water, HCl, pepsin, mucus, IF, electrolytes,
gastrin
• Functionally, the gastric mucosa is divided into
oxyntic gland area and pyloric gland area.
• Oxyntic gland mucosa secretes acid and is located in
the proximal 80% of the stomach.
– includes the body and the fundus.

• The distal 20% of gastric mucosa, pyloric gland


mucosa synthesizes and releases gastrin hormone.
February 12, 2024 By Derib A. 62
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Gastric secretion.…
• Gastric glands has a variety of secretory cells
 Mucous neck cells or goblet cells: secrete mucus
 Parietal (oxyntic) cells: secrete HCl and IF (Intrinsic factor)
 IF: VB12 absorption from the small intestine
 Chief (peptic) cells: produce pepsinogen
 Pepsinogen is activated to pepsin by:
– HCl in the stomach
– Pepsin itself by a positive feedback mechanism
 Enterochromaffin like cells: secrete histamine
 G cells: secret gastrin hormone
 D cells: Somatostatin
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Mechanism of Gastric acid (HCl) secretion

• H+ from dissociation of H2O in the cytoplasm of parietal


cells are continuously pumped actively through the
membrane of the cell into lumen.
• Intracellular CO2 and OH- combine to produce HCO3-
• Cl- are transported from blood into parietal cells and finally
into the lumen of the gland by facilitated diffusion.
• HCO3- in exchange to Cl- is transported in reverse
direction (from the cytoplasm into blood, charge balance).
• Finally, H+ and Cl- combine in the lumen to produce HCl

February 12, 2024 By Derib A. 67


Mechanism of Gastric Acid Secretion:

February 12, 2024 By Derib A. 68


(Cont…) Mechanism of Gastric Acid Secretion:

• HCl has a pH of about 2.


• This highly acidic environment serves to:
 Provide hostile env’t to bacteria and other pathogens
-Kills ingested bacteria
 Denature proteins and cause it to unfold, thereby
increasing surface area that pepsins can function
-Provides the optimum pH for pepsin action.
 Aid protein digestion (activate pepsinogen to pepsin)

February 12, 2024 By Derib A. 69


Regulation of Gastric Acid
 Neural
Secretion:  Hormonal
 Paracrine

February 12, 2024 By Derib A. 70


Pepsinogen secretion:
 Pepsin is a proteolytic enzyme that begins protein
digestion.
 Pepsin is secreted by chief cells in the form of inactive
precursor called pepsinogen
 During cephalic stage of digestion, vagal stimulation
directly stimulate chief cells to release pepsinogen.
 During gastric phase of digestion, low pH activates
pepsinogen secretion.
 Low pH of stomach also converts pepsinogen into pepsin.

February 12, 2024 By Derib A. 71


Activation of pepsinogen:

February 12, 2024 By Derib A. 72


Gastric Mucosal Barrier
• Protection of the stomach wall from acidic attach is
accomplished by:
a. Production of thick mucous
b. HCO3- secretion
c. Efficient blood supply
d. Efficient renewal of the epithelial cells
e. Tight junctions

 Ulcer can develop if the mucous layer and HCO3-


production is minimized.

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February 12, 2024 By Derib A. 74
Pancreatic secretions
• Pancreas: Glandular organ with exocrine & endocrine
roles
 Exocrine function
• Exocrine cells (acinar cells) secret pancreatic juices
that break down different categories of foodstuff
• The pancreatic juice secretes 1.5L fluid/day
– Colorless, viscous and alkaline (pH = 8.0) fluid
– Rich in HCO3- to neutralize acid and provide
optimum pH for action of pancreatic enzymes
• Failure to neutralize the chyme as it enters intestine will
result in duodenal ulcers.
February 12, 2024 By Derib A. 75
Pancreas

February 12, 2024 By Derib A. 76


Pancreatic secretions…Cont’d
1.Acinar cells: in
response to CCK
secrete inactive
digestive enzymes
 Trypsinogen
 Chymotripsinogen
 Carboxypolypeptidase
 Pancreatic lipase
 Pancreatic Alpha
amylase

2. Ductile cells: Secretin


stimulates secretion of
watery HCO3-

February 12, 2024 By Derib A. 77


February 12, 2024 By Derib A. 78
(Cont…) Pancreas, Composition
1. Water
2. Electrolytes (HCO3-, Na+,
K+, Cl- )
3. Digestive enzymes:
(inactive pro-enzymes)
 Pancreatic Amylase
 Pancreatic lipase
 Proteases
 Nucleases etc…

February 12, 2024 By Derib A. 79


Pancreatic digestive Enzymes
 Proteolytic: trypsin, chymotrypsin and carboxy-
polypeptidase
 For protein digestion

 Amylolytic: pancreatic amylase


 Lipolytic: pancreatic lipase, cholesterol esterase and
phospholipase
 Nuclease digestive enzymes

NB: Many of the enzymes synthesized and stored in acinar cells as


pro-enzymes.

February 12, 2024 By Derib A. 80


Activation of pancreatic secretions in
the duodenum
• All the inactive proenzymes flow
through the common bile duct to
reach to duodenum.
• The enzyme “enterokinase”
located on the wall of duodenum
1st activates trypsinogen to
Trypsin.
• Once Trypsin is formed it
activates all the protein enzymes
to their active forms.
• Inside the pancreas, trypsin
inhibitor enzyme prevents the
activation of proenzymes to
Trypsin.
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February 12, 2024 By Derib A. 82
Regulation of pancreatic secretions

Stimuli for
secretion
 Secretin

 Cholecystokinin

 Acetylcholine

-Vagovagal stimuli

February 12, 2024 By Derib A. 83


Fig. Hormonal
regulation of pancreatic
enzyme secretion

February 12, 2024 By Derib A. 84


Fig. Hormonal
regulation of
pancreatic bicarbonate
secretion

February 12, 2024 By Derib A. 85


Hepatobiliary Function
Liver:
• The largest internal organ
• Weighing 1.3 kg(2%).
• Dual blood supply (potral, hepatic artery)
• Receives and processes nutrient-rich venous
blood
• Unique capacity to regenerate

February 12, 2024 By Derib A. 86


The basic histological structure of liver:

February 12, 2024 By Derib A. 87


Functions of Liver
• Nutrient and vitamin metabolism

• Formation and secretion of bile

• Bilirubin metabolism

• Synthesis of plasma proteins & clotting factors

• Storage of fat and some vitamins

• Drug metabolism/Xenobiotic transformation


February 12, 2024 By Derib A. 88
Functions of liver…
1. Carbohydrate Metabolism
• Glycolysis, glycogenesis, gluconeogenesis, glycogenolysis
– Turn proteins and triglycerides into glucose
– Turn excess glucose into glycogen & store in the liver
– Turn glycogen back into glucose as needed
2. Lipid Metabolism
• β-oxidation, formation of phospholipids, lipoproteins,
synthesis of cholesterol and conversion of CHO into fat
3. Inactivation of drugs & hormones: Sulfonamides, penicillin,
thyroid hormones, steroids
4. Remove waste products: Bilirubin and cholesterol

February 12, 2024 By Derib A. 89


Functions of liver...
5. Protein Metabolism
• Deamination of amino acids, removes amine group (NH2)
from amino acids.
• Converts toxic ammonia into urea for excretion.
6. Synthesize plasma proteins: blood clotting & immune system
7. Secretion of bile and its salts: digestion of fat
8. Stores fat soluble vitamins: (A, B12, D, E, K), iron, copper
9. Filtration of blood: phagocytosis of worn out blood cells &
bacteria.
• Removes blood clots and toxins from portal circulation
10. Activates vitamin D
February 12, 2024 By Derib A. 90
Biliary Secretions:
 General features of Bile:
 Alkaline fluid (pH= 8) secreted by hepatocytes.
 Bitter-tasting, dark green to yellowish brown fluid.
 250-1100 ml of bile secreted daily.
 Stored in the gallbladder during interdigestive period
 Upon eating discharged into the duodenum.
Functions of bile
• Digestion and absorption of fats
• Excretion of water-insoluble subs.: cholesterol
and bilirubin

February 12, 2024 By Derib A. 91


Constituents of Bile:
1. Bile salts (bile acids), ~11%
2. Bile pigment (bilirubin), ~1%
3. Other organic constituents: ( ~3%)
Cholesterol, Lecithin, protein etc
4. Electrolytes (Na+, K+, Ca2+, Cl-, and greater
HC03- than plasma) ~1%.
5. H2O (~ 84%)

February 12, 2024 By Derib A. 92


February 12, 2024 By Derib A. 93
Regulation of bile entry in to the small intestine:
February 12, 2024 By Derib A. 94
Storage of bile
• Stored in the gall bladder.
• 30 - 60 ml
• The liver bile less conc. than gall
bladder bile.
• As bile remains in the gall bladder,
water, Na+, Cl- and other small
electrolytes are continually
absorbed by gall bladder mucosa
– conc. bile 12 - 20 times.

February 12, 2024 By Derib A. 95


Gallstone Formation:
• Gallbladder stores bile between meals, concentrates bile.
• Water & electrolytes reabsorbed.
• Bile salts, bile pigments, and cholesterol become
increasingly concentrated.
• These substances precipitate and form solid crystals.
• When they become larger, they form gallstones.
• Gallstones may then block the flow of bile causing
obstructive jaundice.

February 12, 2024 By Derib A. 96


Formation of gallstones:

February 12, 2024 By Derib A. 97


Cholelithiasis
February 12, 2024 By Derib A. 98
IV. Digestion and Absorption
function of GI system

February 12, 2024 By Derib A. 99


DIGESTION
 Breakdown of food
molecules for
absorption into
circulation
Types of digestion
1.Mechanical
digestion
2.Chemical digestion

100
Digestion in stomach
 Protein digestion - about 10%
 Fat digestion - minimal

101
Absorption in stomach
 Stomach is a poor absorptive area because
– It lacks villus and presence of tight junctions
between the epithelial cells.

 Substances absorbed are:


Small quantities of H2O
Alcohol
Drugs (Aspirin, Morphine)

 No nutrient absorption.
102
Digestion and absorption in the Small
intestine
• SI is specialized for
completion of digestion and
absorption of nutrients.
a. Duodenum: mainly
secretory (mucous,
hormones, enzymes)
b. Jejunum: mainly absorptive
c. Ileum : mainly absorptive

103
Digestion and absorption in the SI….

• Digestion occurs in the GI lumen by secreted enzymes


and on the surface of enterocytes by membrane-bound
enzymes.
• Absorption occurs by
– simple and facilitated diffusion
– Active transport
– Endocytosis and paracellular transport.
• Surface area of SI is greatly increased by extensive
folding and projection of fingerlike villi covered with
microvilli.

February 12, 2024 By Derib A. 104


Functional histology of Small Intestine

February 12, 2024 By Derib A. 105


Carbohydrate Digestion and Absorption
• Carbohydrates provide ~45% of the total energy needs
– require hydrolysis to monosaccharides before
absorption

(salivary and pancreatic)

February 12, 2024 By Derib A. 106


Digestion of Carbohydrates

• Mouth: Salivary amylase


• Esophagus & stomach: nothing
happens

• Duodenum: Pancreatic amylase


• SI(Brush border enzymes):
(maltase, sucrase & lactase) act
on disaccharides and produce
monosaccharides (fructose,
glucose & galactose)
107
February 12, 2024 By Derib A. 108
Absorption of monosaccharides: Na+ Coupled
Transport

Apical Basolateral
February 12, 2024 By Derib A. 109
Digestion of proteins
Involved Enzymes
*Pepsin in the stomach
• Enzymes acting in the small intestine
* Pancreatic enzymes
– trypsin, chymotrypsin and
carboxypeptidase
* Brush border enzymes
– aminopeptidases, carboxypeptidases,

and dipeptidases
110
February 12, 2024 By Derib A. 111
Absorption of Proteins
• Digestive products of protein can be absorbed as amino
acids, dipeptides, and tripeptides
A. Free amino acids
 Absorbed by Na+ dependent 2ry active transport
 Amino acids are then transported from cell to blood by
facilitated diffusion.
B. Dipeptides and tripeptides
 Absorbed by H+ dependent cotransport
 After dipeptides and tripeptides are transported into
intestinal cells, cytoplasmic peptidases hydrolyze them
to amino acids.
C. Larger peptides: endocytosis
112
Absorption of proteins

Lumen

Endocytosis

K+ Na+

Pump
Exocytosis

February 12, 2024 By Derib A. 113


Digestion of Fats:

Cholesterol esters
Phospholipids
Cholesterol esterase
Phospholipase A2
Cholesterol Phosphate + Fatty acids

February 12, 2024


Absorption
By Derib A. 114
Emulsification of Lipids:
•Lipids must be broken down into small droplets or
emulsified into fat globules by bile acids before being
digested.
•This increases the surface area for digestion.

February 12, 2024 By Derib A. 115


February 12, 2024 By Derib A. 116
Absorption of lipids
 Micelle formation
 The emulsified products of lipid digestion must form
micelles with bile salts before they can be absorbed.
 Micelles: small spherical aggregates containing lipids
coated with bile salts.
 Micelles bring the products of lipid digestion into
contact with absorptive surface of intestinal cells.
 Then, fatty acids, monoglycerides, and cholesterol
diffuse across the luminal membrane into the cells.
February 12, 2024 By Derib A. 117
Fat absorption…
 Micelles release MGs and
FFAs into the cells via simple
diffusion.
 Inside the cell,
 Monoglycerides + FFA 
triglycerides
 Coated with lipoproteins =
chylomicrons
 Chylomicrons exit the
epithelial cell by exocytosis,
 Enter to lacteal → Thoracic
duct → Circulation.

February 12, 2024 By Derib A. 118


Summary on Absorption in SI

February 12, 2024 By Derib A. 119


Large intestine
Functions of the large intestine
1. Water absorption.
2. Electrolyte absorption; mainly NaCl.
3. Mucous & HCO3- Secretion.
4. Storage, transport, and evacuation of feces.
5. Absorption of some drugs (suppositories).
6. Microbial fermentation.
• Microbes in the large intestine produce enzymes capable of
digesting cellulose.
• In addition, microbes in the colon stimulates synthesis of some
vitamins (Vit. K, and B-groups).

February 12, 2024 By Derib A. 120


Absorption in the large intestine
• Na+ absorption takes place •
The resulting secretion of
by active transport from HC03- helps in
colon. neutralization of acids
– Aldosterone helps in generated by microbial
absorption fermentation in the colon.
• K+ is secreted in the large • Vitamins and drugs are
efficiently absorbed from
intestine LI.
– creates a major problem • Metabolism and death of
of K+ depletion during colon bacteria provide a
severe diarrhea. useful source of several
vitamins (Vit. K, Vit. B
• Cl- is absorbed in exchange etc.)
for HC03-.
February 12, 2024 By Derib A. 121
Part V. Excretion function of the GIT

February 12, 2024 By Derib A. 122


Defecation
• At intervals, usually after meals, involuntary muscles
within the walls of large intestine propel solid waste
material, called feces or stool toward the rectum.
• This material is then eliminated by both voluntary
and involuntary muscle actions by a process called
defecation.

• Defecation reflex
– The act of removing undigested waste products
through the anus

February 12, 2024 By Derib A. 123


Components of Defecation reflex
• Stimulus: undigested material distending the rectum.
• Receptor: stretch receptors in rectum.
• Afferent: sensory nerves sending signals to sacral segment
of spinal cord
• Centre: sacral segment of spinal cord
• Efferent: parasympathetic nerve to smooth muscle of rectum
and internal anal sphincter.
• Defecation reflex cause
 internal anal sphincter to relax
 rectum and sigmoid colon muscles to contract.
 external anal sphincter to relax
February 12, 2024 By Derib A. 124
February 12, 2024 By Derib A. 125
 Defecation signals
entering spinal cord
initiate other effects,
such as
 Taking a deep breath
 Contraction of the
abdominal wall
muscles and
 Relaxation of pelvic
floor to relax
downward

February 12, 2024 By Derib A. 126


Feaces and its composition:
• Normal feces is composed of 75% water and 25% solids
• Daily excretion amounts ~250g of stool.
• The bulk of fecal solids are bacteria and undigested
organic matter and fibers (cellulose)
• The brown color is mainly due to stercobilin and also
urobiloinogen produced by bacterial degradation of
bilirubin
• The odor results from gases produced by bacterial
metabolism from flatus (scatol, inodle, H2S etc).

February 12, 2024 By Derib A. 127


The
EndYOU!!!
THANK

February 12, 2024 By Derib A. 128

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