Gastrointestinal physiology
Course outline
o Functional organization of GIT
o Movements of GIT
o Secretary functions of GIT
o Digestive and absorptive function of the
GIT
o Introduction to Energy and Metabolism
 The metabolic rate
 Salivary Secretion
 Energy balance
 Gastric secretion
 Feeding and its regulation
 Pancreatic secretion
 Body temperature regulation
 Intestinal secretion
 Bile secretion, jaundice
1
Introduction to GIT
 GIT consists of:
I.
alimentary canal or gastrointestinal tract (GIT)
 A muscular tube extending from the mouth to anus
 mouth, pharynx, esophagus, stomach, small intestine, and large intestine
II. Accessory organs and glandular organs
 teeth, tongue, gallbladder, salivary glands, liver, and pancreas
 Teeth aids mechanical breakdown of food
 Tongue assists chewing and swallowing and speech
 Other accessory organs produce and send secretions that facilitate chemical breakdown
of food
2
Introduction to GIT…
3
Basic functions of GIT
 GIT system carries out the following basic activities:
1.
Ingestion: food intake, which is controlled by the feeding and satiety center in the HT.
2.
Mastication or chewing: mechanical grinding of food with the aid of the teeth.
3.
Swallowing or deglutition: propulsion of food from the mouth to the stomach.
4.
Chemical digestion of food
5.
Secretion of enzymes, electrolytes (HCl, NaHCO3), mucous, and hormones
6.
Absorption of nutrients, water and electrolytes into the blood vessels
7.
Defecation: excretion of fecal matter
4
 FIG. Four processes of the digestive system
5
Histology of the Alimentary Canal
• From esophagus to the anal canal
walls of the GIT have
3.
same four layers
1. Mucosa:
 Secretion of mucus
 Moist epithelial layer
4.
 lines the lumen of alimentary canal
 Site of absorption
2. Submucosa: Consists of
 loose connective tissues,
 secretary glands
 lymph nodes
 blood vessels
 sub mucosal plexus (plexus of Meissner)
Muscularis externa:
 Longitudinal muscle
 Circular muscle
 myenteric plexus (plexus of Auerbach)
Serosa:
 outer most layer of GIT
 composed of connective tissue and
epithelium
6
Structure of the gastrointestinal tract
7
Regulation of GIT
 GIT regulated by the signals such as :
1. Neural regulation
o Parasympathetic Nervous System (PSNS)
o Sympathetic Nervous System (SNS)
o Enteric Nervous System (ENS)
2. Hormonal control
o GIT hormones
o Paracrine
o Neurocrine
 Stimulus: mechanical and chemical stimuli
o Stretch receptors (mechanoreceptors) and presence of substrate in the lumen
(chemoreceptors)
8
Regulation of GIT…
9
Regulation of GIT…
 ANS of the GIT comprises both extrinsic and intrinsic nervous systems.
1. Extrinsic control system by ANS (PSNS and SNS)
 Sympathetic NS = ↓GIT function (inhibitory effect)
 i.e. ↓motility, ↓secretion and cause contraction of sphincters
 Fibers originate in the spinal cord between T-8 to L-2.
 Receives sensory information from chemoreceptors and mechanoreceptors in GIT
 Preganglionic sympathetic cholinergic fibers synapse in the prevertebral ganglia.
 Postganglionic sympathetic adrenergic fibers leave the prevertebral ganglia and
synapse in the myenteric and submucosal plexuses.
o Direct postganglionic adrenergic innervation of blood vessels and some smooth
muscle cells also occurs.

Cell bodies in the ganglia of the plexuses then send information to the smooth
muscle, secretory cells, and endocrine cells of the GI tract
10
Regulation of GIT…
 Parasympathetic NS = ↑GIT function (excitatory effect)
 Preganglionic parasympathetic fibers synapse in the myenteric and submucosal
plexuses.
 Cell bodies in the ganglia of the plexuses then send information to the smooth
muscle, secretory cells, and endocrine cells of the GIT.

I.
Carried via the vagus and pelvic nerves
vagus nerve innervates esophagus, stomach, pancreas, & upper large intestine
o Reflexes in which both afferent and efferent pathways are contained in the vagus
nerve are called vagovagal reflexes
II. pelvic nerve innervates the lower large intestine, rectum, and anus.
11
Regulation of GIT…
12
Regulation of GIT…
2. Intrinsic control system by enteric NS ( minibrain / peripheral brain)
 The enteric nervous system coordinates digestion, secretion & motility to optimize nutrient
absorption, even in the absence of extrinsic innervation
 Its activity is modified by information from the CNS from local chemical and mechanical
sensors
 Submucosal plexus (Meissner’s plexus)
o Located in submucosa layer
o primarily controls secretion and blood flow
Excitatory: neurotransmitters (Acetylcholine)
o receives sensory information from chemoreceptors & mechanoreceptors in the GIT
 Myenteric plexus (Auerbach’s plexus)
o Located between circular and longitudinal muscle layers
o primarily controls the motility of the GIT smooth muscle
Excitatory : neurotransmitters (Acetylcholine & Substance P)
Inhibitory: VIP, nitric oxide
13
Regulation of GIT…
2. Intrinsic control system by enteric NS…
14
GIT Reflexes …
 Most GIT reflexes are initiated by luminal stimuli: distension, osmolarity, acidity, and
digestion products
 Types of the GIT reflexes are:
1. GIT local reflex
2. GIT short reflex
3. GIT long-looped reflexes
GIT short reflex
 Sensory information from GIT can be received, integrated and acted upon by the ENS
alone
 It also occurred when ENS works in conjunction with CNS. e.g. vagovagal reflex
15
GIT Reflexes …
GIT long-looped reflexes
 It involves a sensory neuron sending information to brain, which integrates signal & then sends
messages to GIT
 Gastrocolic reflex
o Stimulated by presence of acid levels in duodenum at a pH of 3-4 or in stomach at a pH of 1.5
o When stimulated, release of gastrin from G-cells in antrum of stomach is shut off.
o In turn, this inhibits gastric motility and secretion of HCl
o Emptying inhibitory factors include: duodenal acidic pH, duodenal distension, duodenal
hypertonicity, sympathetic stimulation, and intense pain.
o Emptying stimulatory factors include : parasympathetic stimulation, and increased volume and
fluidity of gastric contents
 Enterogastric reflex
o It involves an increase in motility of the colon in response to stretch in the stomach and
byproducts of digestion in the small intestine
o This reflex is responsible for the urge to defecate following a meal and helps to make room for
more food.
16
Hormonal control of GIT function
Gastrointestinal hormones, paracrine,
and Neurocrine
17
Hormonal control of GIT function
a) GIT hormone
 are released from endocrine cells in the GI mucosa into the portal circulation, enter the
general circulation, and have physiologic actions on target cells
 Four substances meet the requirements to be considered GIT hormones; others are
considered as “candidate” hormones.
 The four official GI hormones are:
1.
2.
3.
4.
Gastrin
cholecystokinin (CCK)
Secretin
glucose-dependent insulinotropic peptide (GIP)
18
Table: GIT hormonal and their action
Horm
ones
Site of
Secretion
G cells of
Gastrin gastric
antrum
CCK
Secreti
n
GIP
Stimulus (inhibition) for Secretion
Actions
•
•
•
•
•
•
•
Small peptides and aa
Distention of stomach
Vagus (via gastrin-releasing peptide)
Inhibited by H+ in stomach
Inhibited by somatostatin
↑ Gastric HCL secretion by parietal cells
Stimulates growth of gastric mucosa
I cells of
duodenum
and
jejunum
• Small peptides and amino acids
• Fatty acids and monoglycerides
• Triglycerides do not stimulate the release of
CCK b/c they cannot cross intestinal cell
membranes.
• Stimulates contraction of gallbladder &
relaxation of sphincter of Oddi for
secretion of bile
• Stimulate pancreatic enzyme & HCO3 secretion
• Stimulate growth of exocrine pancreas
• Inhibits gastric emptying
S cells of
duodenum
•
in duodenum
• Fatty acids in duodenum
• Stimulate pancreatic HCO3– secretion
• ↑ Biliary HCO3– secretion
• Inhibit Gastric H+ secretion by parietals
K cell of
Duodenum
jejunum
•
•
•
• Stimulate Insulin secretion
• Inhibit H+ secretion by parietals
H+
Fatty acids
amino acids
oral glucose
19
• In general the function of GI hormones includes:
1. Regulate the secretion and motility of GI tract
 Gastrin →HCL secretion, gastric empty
2. Trophic action
 Gastrin →stomach and duodenum mucosa
3. Regulate the release of other hormones
 GIP → insulin
 SS →GH, gastrin
20
Hormonal control of GIT function…
b) Paracrine
 are released from endocrine cells in the GI mucosa
 diffuse over short distances to act on target cells located in the GIT
 GIT paracrines are somatostatin and histamine
1. Somatostatin
 is secreted by cells throughout the GIT in response to H+ in the lumen
 Its secretion is inhibited by vagal stimulation.
 inhibits the release of all GIT hormones
 inhibits gastric H+ secretion
2. Histamine
 is secreted by mast cells of the gastric mucosa.
 increases gastric H+ secretion directly and by potentiating the effects of
gastrin and vagal stimulation
21
Hormonal control of GIT function…
C) Neurocrine
 are synthesized in neurons of the GIT, moved by axonal transport down the axon, and
released by action potentials in the nerves.
 GIT neurocrines are:
1. Vasoactive intestinal peptide (VIP)
 is released from neurons in the mucosa and smooth muscle of the GIT
 Produces relaxation of GI smooth muscle, including the lower esophageal sphincter
 Stimulates pancreatic HCO3– secretion and inhibits gastric H+ secretion
2. GRP (gastrin-releasing peptide)/(bombesin)
 is released from vagus nerves that innervate the G cells.
 stimulates gastrin release from G cells
3. Enkephalins (met-enkephalin and leu-enkephalin)
 secreted from nerves in the mucosa and smooth muscle of the GIT.
 stimulate contraction of GI smooth muscle, particularly the lower esophageal, pyloric,
and ileocecal sphincters
 inhibit intestinal secretion of fluid and electrolytes
22
Secretary function of GIT
 GIT secretions:
•
Salivary Secretion
•
Gastric secretion
•
Pancreatic secretion
•
Intestinal secretion
•
Bile secretion
23
Regulatory phases of GIT secretion
 Three phases of regulation of GIT secretion (stimulatory and inhibitory events) are named
for the location of stimulus that initiates response.
1. Cephalic (reflex) phase: prior to food entry
 Excitatory events include:
• Sight or thought of food
• Stimulation of taste or smell receptors
 Inhibitory events include:
• Loss of appetite or depression
• Decrease in stimulation of the parasympathetic division
24
Regulatory phases of GIT secretion…
2.Gastric phase: once food enters the stomach secretion is underway.
 Excitatory events include:
• Stomach distension
• Activation of stretch receptors (neural activation)
• Activation of chemoreceptors by peptides, caffeine, and rising pH
• Release of gastrin to the blood
 Inhibitory events include:
• A pH lower than 2 & Emotional upset that overrides the parasympathetic division
3. Intestinal phase: as partially digested food enters the duodenum
 Excitation
• low pH & partially digested food enters the duodenum and encourages gastric gland activity
 Inhibition
• distension of duodenum
• presence of fatty, or hypertonic chyme, and/or irritants in the duodenum →inhibition of
local reflexes and vagal nuclei →closing of pyloric sphincter →inhibition of gastric
25
secretion
Salivary secretion
•
•
•
•
Totally controlled by the PNS
Integrated at the salivatory centre in the medulla
salivatory nuclei control salivary glands
are stimulated by impulses from
Sensory impulses from the tongue (taste, touch)
Sensory impulses from oesophagus, stomach, SI
Impulses from the cerebral cortex (sight, smell)
Impulses from the feeding centre in the hypothalamus
26
Salivary secretion…
 3 major pairs of salivary glands that differ in the type of secretion they produce based their
acinar epithelial cells types:
1. parotid glands produce a serous, watery secretion
2. Submandibular glands produce a mixed (serous and mucous) secretion
3. sublingual glands secrete a saliva mucous in character
27
Salivary secretion…
 basic secretory units of salivary glands are clusters of cells called an acinar
 Initially acinar cells secrete a fluid that contains:
o water, electrolytes, mucus, enzyme & others w/c flow into collecting ductal cells.
 Within the ductal cells, the composition of the secretion is altered.
o i.e. Much of Na+ & cl-is actively reabsorbed, K+ and HCO3-is secreted
Fig: modification of saliva by ductal cells
28
Regulation of salivary secretion
 Saliva production :
 Increased (via activation of PSNS) by
food in the mouth, smells, conditioned
reflexes, and nausea.
 Decreased (via inhibition of PSNS) by
sleep, dehydration, fear, and
anticholinergic drugs (e.g., atropine)
29
Regulation of salivary secretion…
Appetite
Centre (HT)
+
+
Sight
Cortex Smell
Sound
Superior salivatory nucleus
Inferior salivatory nucleus
GPN
Medulla Ob.
Parotid
FN
+
Taste
Touch
Temperature
FN
+
VN
Lower esophagus
Stomach
Upper SI
FN=facial N, VN= Vagus, GPN=Glossopharyngeal N
SLG=sublingual gland, SMG=submandibular gland
SMG
SLG
Saliva
30
Salivary secretion…
 Daily secretion of saliva 1000 - 1500 ml/day
 Functions of salivary glands
 Formation of a bolus for swallowing
 Initiation of starch and lipid digestion
 Facilitation of taste
 Cleansing of the mouth and selective antibacterial action (lysozyme)
 Neutralization of refluxed gastric contents
31
Salivary secretion…
 Composition of saliva: Saliva is characterized by:
 High volume (relative to the small size of the salivary glands)
 High K +
 High HCO3- = along with phosphate provides a critical buffer
 Low Na+ and Cl– concentrations
 Hypotonic
 Presence of α-amylase, lingual lipase, and kallikrein)
 composition of saliva varies with the salivary flow rate
 At the lowest flow rates, saliva has the lowest osmolarity and lowest Na+, Cl–, and HCO –
concentrations, but has the highest K+ concentration.
 At highest flow rates (up to 4 mL/min), composition of saliva is closest to that of plasma
32
Gastric Secretion
 Gastric juice:
 HCl:
 Pepsinogen
 Electrolytes
 Intrinsic factor
 Mucus (mucus gel layer)
33
Gastric Secretion…
Table : gastric cell types and their secretions
Cell types
Part of stomach Production
Stimulus
Parietal cells
(Oxyntic cells)
Body(fundus)
HCl
intrinsic factors
Chief cells
G cells
Body(fundus)
antrum
pepsinogen
gastrin
Mucus cell
entire surface of Mucus & HCO3gastric mucosa
Vagus(Ach)
Gastrin
Histamine
Vagus(Ach)
Vagus(via GRP)
Small peptide
Inhibited by SS & prostaglandins
Vagus(Ach)
ECL cells
D cells
antrum
antrum
histamine
SS (somatostatin)
Poorly known
34
Mechanism of HCl Secretion….
Steps in HCl secretion
 Parietal cells secrete HCl into the lumen of the
stomach
1. Cl- enters parietal cells from ECF in exchange
for HCO3- and actively pumped into lumen
2. H+ is actively pumped into the lumen in
exchange for K+ by H+-K+ ATPase in the apical
membrane of the parietal cells
3. Origin of H+ is from CO2 in parietal cells
• H2O + CO2 → H2CO3 → H+ +HCO3
4.
Accumulation of osmotically-active H+ in the
cannaliculus generates an osmotic gradient
across the membrane that results in outward
diffusion of water
 The resulting gastric juice is 160 mM HCl
and 15 mM KCl
35
Mechanism of HCl Secretion…
 HCO3- is transported out of the basolateral membrane in exchange for cl-.
 The outflow of HCO3- into blood results in a slight elevation of blood pH known as the
"alkaline tide".
• This process serves to maintain intracellular pH in the parietal cell.
 Chloride and potassium ions are transported into the lumen of the cannaliculus by
conductance channels, and such is necessary for secretion of acid
 K+ is diffused into the lumen and Na+ enters the parietal cells
 K+ is thus effectively recycled.
 Parietal cells secrete 160 mmol/L of HCl, w/c is 1 to 3 million times greater than
concentration in the blood
36
Regulation of HCl secretion
 3chemical messengers stimulate the insertion
of H+/K+-ATPase into plasma membrane
thereby increasing HCl secretion:
1. Histamine : by activating H2 receptors
2. Vagus: two ways
o Direct(Ach):muscarinic (M3)
receptors
o Indirect (GRP) :
3. Gastrin: cholecystokininB (CCKB)
receptor
 Somatostatin: inhibits HCl secretion
o Direct: inhibit cAMP via Gi protein
o Indirect: inhibits release of histamine and
gastrin
 Prostaglandins: ↓cAMP via Gi protein
37
Regulation of HCl secretion…
fig: interaction of stimulating
chemicals
 ACh potentiates the actions of
histamine and gastrin in
stimulating H+ secretion
38
Regulation of HCl secretion…
 Fig: Cephalic and gastric
phases controlling acid
secretion of the stomach by
negative feedback loops
39
Release of Gastric Juice..
40
Regulation of HCl secretion…
 Other factors that
affects HCl secretion
 Distension
 Tactile stimulation
 Irritation
 Drugs (fig)
 Alcohol
Fig: Agents that stimulate and inhibit H+
secretion
41
Regulation of HCl secretion…
 Other factors that affects HCl secretion
 Distension
 Tactile stimulation
 Irritation
 Drugs
 Alcohol
42
Gastric Secretion…
Pepsin Secretion
 secreted an inactive precursor (pepsinogen)
 As exposure to low pH in lumen of stomach
activated(pepsin)
 Inactive form (zymogens)synthesis protect the
cell from proteolytic damage
 pepsin accelerates protein digestion
o Pepsin breaks down proteins into peptones &
polypeptides
 optimum pH is 1.5-3.5
43
Gastric Secretion…
Intrinsic factor
 It is glycoprotein secreted by parietal cells
 It is the only essential function of stomach as it is essential for vitamin B12 absorption.
 Atrophy of gastric mucosa leads to pernicious anemia.
44
Secretion of the Small Intestine
Mucosa of the SI secretes:
•
Digestive enzymes
•
Mucous: protective and lubricant
•
Electrolytes
Intestinal secretory out put = 2-3 L/d, pH,7.0
•
Hormones
Intestinal secretory glands:
1. Brunner’s gland: mucous glands, duodenal in distribution
2. Crypts of Lieberkun: mucous and electrolytes. Distributed in the SI below the
duodenum and in the LI.
3. Goblet cells: mucous glands
4. Enterocytes: digestive enzymes
5. Enteroendocrine cells: produce hormones
6. Enterochromaffin cells: serotonin producing cells
45
Secretory cells in the small intestine
Structural modifications of the small intestinal wall increase surface area
• Plicae circularis: deep circular folds of the mucosa and submucosa
• Villi – fingerlike extensions of the mucosa
• Microvilli – tiny projections of absorptive mucosal cells’ plasma
membranes
• The epithelium of the mucosa is made up of:
-Absorptive cells and goblet cells
-Enteroendocrine cells
-Interspersed T lymphocytes
• Cells of intestinal crypts secrete intestinal juice
• Brunner’s glands in the duodenum secrete
alkaline mucus
46
Pancreatic secretion…
Secrete digesting enzymes
 Trypsin and chymotrypsin: split whole and partially digested proteins into peptides
but do not cause release of individual amino acids
 pancreatic amylase: digest carbohydrates which hydrolyzes starches, glycogen, and
most other carbohydrates
 pancreatic lipase: digest fat capable of hydrolyzing neutral fat into fatty acids and
monoglycerides
 Composition pancreatic juice is characterized by:
 High volume
 Virtually the same Na+ and K+ concentrations as plasma
 Much higher HCO3– concentration than plasma
 Much lower Cl– concentration than plasma
 Isotonicity
47
Bile secretion and gallbladder function
Composition and function of bile
 Bile contains bile salts, phospholipids, cholesterol, and bile pigments
a. Bile salts
 are amphipathic molecules because they have both hydrophilic and hydrophobic portions.
 In aqueous solution, bile salts orient themselves around droplets of lipid and keep the lipid
droplets dispersed (emulsification).
 aid in intestinal digestion & absorption of lipids by emulsifying & solubilizing them in
micelles
b. Micelles
 Above a critical micellar concentration, bile salts form micelles.
 Bile salts are positioned on the outside of the micelle, with their hydrophilic portions
dissolved in the aqueous solution of the intestinal lumen and their hydrophobic portions
dissolved in the micelle interior.
 Free fatty acids and monoglycerides are present in the inside of the micelle, essentially
48
“solubilized” for subsequent absorption.
Bile secretion and gallbladder function….
2. Formation of bile
 Bile is produced continuously by hepatocytes.
 Bile drains into the hepatic ducts and is stored in the gallbladder for subsequent release
49
Reading assignment
 splanchnic circulation
50
GIT Motility
 Motility is a general term that refers to contraction and relaxation of the walls and
sphincters of the gastrointestinal tract.
 Motility grinds, mixes, and fragments ingested food to prepare it for digestion and
absorption, and then it propels the food along the GIT.
 All of the contractile tissue of the gastrointestinal tract is smooth muscle
o Except: pharynx, upper one-third of esophagus, and external anal sphincter are striated
muscle
51
GIT Motility…
 The smooth muscle of GIT is unitary smooth muscle, in which the cells are electrically
coupled via low-resistance pathways called gap junctions.
o Gap junctions permit rapid cell-to-cell spread of action potentials that provide for
coordinated and smooth contraction.
 The circular and longitudinal muscles of GIT have different functions.
o Depolarization of circular muscle leads to contraction (shortening)of a ring of smooth
muscle and a decrease in diameter of that segment of the GIT.
o Depolarization of longitudinal muscle leads to contraction (shortening) in the
longitudinal direction and a decrease in length of that segment of the GIT
52
GIT Motility…
 Contractions of GIT smooth muscle can be either phasic or tonic.
 Phasic contractions: periodic contractions followed by relaxation
o Found in esophagus, gastric antrum, and small intestine, all tissues involved in
mixing and propulsion.
o It is peristalsis and segmentation
o Peristalsis in the stomach is a consequence of conducted electrical events (slow
waves) that are generated in the muscle
 Tonic contractions: maintain a constant level of contraction or tone
without regular periods of relaxation
o It occurs in the lower esophageal sphincter, orad (upper) of stomach, and ileocecal
and internal anal sphincters.
53
Electrical activity of GIT smooth muscle
 Like all muscle, contraction in GIT smooth muscle is preceded by electrical activity
(action potentials)
 It is spontaneous and stimulated electrical activity of GIT smooth muscles
 Electrical slow waves:
 Slow waves are a unique feature of the electrical activity of GIT smooth muscle
 Slow waves are not action potentials but rather oscillating depolarization and
repolarization of the membrane potential of the smooth muscle cells.
54
Electrical activity of GIT smooth muscle…
 Mechanism of slow wave production
o Depolarizing phase of slow wave is caused by cyclic opening of Ca2+ channels,
which produces an inward Ca2+ current that depolarizes cell membrane
o During the plateau of slow wave, Ca2+ channels open, producing an inward Ca2+
current that maintains the membrane potential at the depolarized level.
o Repolarizing phase of slow wave is caused by opening of K+ channels, which
produces an outward K+ current that repolarizes cell membrane.
 Action potentials produced then initiate phasic contractions of the smooth muscle cells
55
Electrical activity of GIT smooth muscle…
 During depolarization phase of slow wave,
membrane potential becomes less negative and
moves toward threshold
 During repolarization phase, membrane potential
becomes more negative and moves away from
threshold.
 at the plateau ( peak of slow wave), membrane
potential is depolarized all the way to threshold,
then action potentials occur “on top of” the slow
wave.
 In figure A slow waves reach threshold and result
in bursts of six action potentials at the plateau.
 In figure B contraction (tension) occurs slightly
after the burst of action potentials.
Fig: Slow waves of GIT superimposed by action
potentials and contraction. A burst of action
potentials is followed by contraction.
56
Electrical activity of GIT smooth muscle…
 Frequency of slow waves
o Intrinsic rate (frequency) of slow waves varies along GIT, from 3 to 12 slow waves per
minute
 But it is constant and characteristic for each part of the GIT.
o It is lowest in the stomach (3 slow waves/min) & highest in duodenum (12 slow
waves/min)
o Frequency of slow waves sets frequency of action potentials and, therefore, sets frequency
of contractions
o Frequency of slow waves is not influenced by neural or hormonal input, although neural
activity and hormonal activity do modulate both production of action potentials and the
strength of contractions.
57
Electrical activity of GIT smooth muscle…
 Origin of slow waves
 slow waves originate in interstitial cells of Cajal, which are abundant in myenteric plexus
 Cyclic depolarizations and repolarizations occur spontaneously in interstitial cells of
Cajal and spread rapidly to adjacent smooth muscle via low-resistance gap junctions
 Interstitial cells of Cajal is pacemaker for GIT smooth muscle
 In each region of GIT, pacemaker drives frequency of slow waves, which determines the
rate at which action potentials and contractions occur.
58
Electrical activity of GIT smooth muscle…
 Relationship between slow waves, action potentials, and contraction.
 In GIT smooth muscle, even subthreshold slow waves produce a weak contraction.
 Thus, even without the occurrence of action potentials, the smooth muscle is not
completely relaxed but exhibits basal (tonic)contractions.
 However, if slow waves depolarize the membrane potential to threshold, then action
potentials occur on top of the slow waves, followed by much stronger (phasic)
contractions.
 The greater the number of action potentials on top of slow waves, the larger the phasic
contraction.
 In contrast to skeletal muscle (where each action potential is followed by a separate
contraction or twitch)
o in smooth muscle individual action potentials are not followed by separate twitches;
instead, the twitches summate into one long contraction
59
Electrical activity of GIT smooth muscle…
 Motor patterns in GIT and their functions during fasting and during digestion
Migrating motor complex (MMC)
 Are waves of electrical activity that sweep through the intestines in a regular cycle during
fasting.
 It triggers peristaltic waves, which facilitate transportation of indigestible substances into
colon
 It occurs every 90-120 minutes during interdigestive phase (b/n meals), and is
responsible for the rumbling experienced when hungry.
 Partially regulated by motilin
 They consist of four distinct phases:
1. Phase I :A prolonged period of quiescence
2. Phase II : Increased frequency of action potentials and smooth muscle contractility
3. Phase III: A few minutes of peak electrical and mechanical activity
4. Phase IV: Declining activity which merges with the next Phase I
60
Chewing and Swallowing
 Chewing and swallowing are the first steps in the processing of ingested food as it is prepared for
digestion and absorption
 Chewing has three functions:
1. It mixes food with saliva, lubricating it to facilitate swallowing
2. It reduces the size of food particles, which facilitates swallowing
3. It mixes ingested carbohydrates with salivary amylase to begin carbohydrate digestion.
 Chewing has both voluntary and involuntary components.
 Involuntary component involves reflexes initiated by food in the mouth.
 Sensory information is relayed from mechanoreceptors in mouth to brain stem, which
orchestrates a reflex oscillatory pattern of activity to muscles involved in chewing.
 Voluntary chewing can override involuntary or reflex chewing at any time.
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Swallowing
 Swallowing is initiated voluntarily in mouth, but thereafter it is under involuntary or
reflex control.
 Reflex portion is controlled by swallowing center in the medulla
 Sensory information (e.g., food in mouth) is detected by somatosensory receptors located
near the pharynx.
 This sensory information is carried to medullary swallowing center via vagus &
glossopharyngeal nerves.
 Medulla coordinates sensory information and directs motor output to striated muscle of
pharynx and upper esophagus
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Swallowing…
 Three phases are involved in swallowing: oral, pharyngeal, and esophageal.
 oral phase is voluntary, and pharyngeal and esophageal phases are controlled by reflexes
Oral phase
 It is initiated when the tongue forces a bolus of food back toward the pharynx, which
contains a high density of somatosensory receptors.
 Activation of these receptors then initiates the involuntary swallowing reflex in the
medulla.
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Swallowing…
Pharyngeal phase
 It is to propel food bolus from mouth through pharynx to esophagus in following steps
1. soft palate is pulled upward, creating a narrow passage for food to move into pharynx so
that food cannot reflux into nasopharynx
2. epiglottis moves to cover the opening to larynx, and larynx moves upward against
epiglottis to prevent food from entering trachea
3. upper esophageal sphincter relaxes, allowing food to pass from pharynx to esophagus
4. A peristaltic wave of contraction is initiated in pharynx and propels food through open
sphincter.
 Breathing is inhibited during the pharyngeal phase of swallowing
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Swallowing…
Esophageal phase
 esophageal phase of swallowing is controlled in part by swallowing reflex and ENS
 In esophageal phase, food is propelled through esophagus to stomach.
 Once bolus has passed through upper esophageal sphincter in pharyngeal phase, the
swallowing reflex closes the sphincter so that food cannot reflux into the pharynx.
 A primary peristaltic wave coordinated by swallowing reflex, travels down esophagus
propelling food along.
 If the primary peristaltic wave does not clear the esophagus of food, a secondary
peristaltic wave is initiated by continued distention of esophagus
 secondary wave mediated by ENS begins at site of distention and travels downward
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Functional movement of the GIT
 Two basic types of movements occur in the GIT:
1.
Propulsive
movements:
Ring
like
peristaltic
contractions sweep food along GIT
 It moves chyme forward along the tract at an
appropriate rate for digestion and absorption.
 Peristalsis is the basic propulsive movements
2.
Mixing movements : which keep the intestinal contents
thoroughly mixed at all times
 segmentation contractions
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Esophageal Motility
 Sphincters at either end of esophagus prevent air from entering upper esophagus and gastric acid
from entering lower esophagus.
 Both are closed, except when food is passing from pharynx into esophagus or from esophagus into
the stomach
 The path of food bolus through esophagus is as follows::
a)
upper esophageal sphincter relaxes to permit swallowed food to enter the esophagus.
b)
upper esophageal sphincter then contracts so that food will not reflux into pharynx.
c)
A primary peristaltic contraction creates an area of high pressure behind the food bolus
d)
•
peristaltic contraction moves down the esophagus and propels the food bolus along
•
If the person is sitting or standing, this action is accelerated by gravity
A secondary peristaltic contraction clears the esophagus of any remaining food.
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Esophageal Motility…
e) As food bolus approaches lower end of the esophagus, lower esophageal sphincter relaxes.
 This relaxation is vagally mediated, and the neurotransmitter is VIP
f) The orad region of the stomach relaxes (“receptive relaxation”) to allow the food bolus to
enter the stomach
 Gastroesophageal reflux (GER) : occur if the tone of lower esophageal sphincter is
decreased (intra-abdominal pressure is increased) and gastric contents reflux into
esophagus
 Achalasia: occur if lower esophageal sphincter does not relax during swallowing and food
accumulates in esophagus
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Gastric Motility
 The food that reached the stomach is no longer a food , called “food bolus”
General motor functions of the stomach:
1. Storage of large quantities of food (Reservoir)
 fundal receptive relaxation creates a storage reservoir, delaying solid food delivery to the
small intestine
2. Mixing and grinding: grinds food (churning) and mixes it with secretions
 Preparing the chyme for digestion in the small intestine
 It's not called bolus anymore since its mixed with digestive juices
3. Absorption of water and lipid-soluble substances (alcohol and drugs)
4. control the rate at which chyme empties into the intestine
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Gastric Motility…
 There are three components of gastric motility:
1. “Receptive relaxation
 When a meal is swallowed smooth muscle in stomach wall relaxes before the arrival of food
 allowing the stomach’s volume to increase to as much as 1.5 L with little increase in pressure
 vagovagal reflex that is initiated by distention of the stomach
2. Contractions (Mixing and Digestion)
 caudal region of stomach has a thick muscular wall and produces the contractions necessary
for mixing and digesting food
 These contractions (churning)break the food into smaller pieces and mix it with gastric
secretions to begin the digestive process
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Gastric Motility…
3). Gastric emptying
 Caudal region of stomach contracts to propel food into the duodenum
 Rate of gastric emptying is fastest when stomach contents are isotonic.
o If the stomach contents are hypertonic or hypotonic, gastric emptying is slowed
 Fat inhibits gastric emptying (i.e. ↑gastric emptying time) by stimulating release of CCK
 H+ in duodenum inhibits gastric emptying via direct neural reflexes
o H+ receptors in duodenum relay information to gastric smooth muscle via interneurons
in the GI plexuses
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Factors regulate gastric emptying
Duodenal factors that
inhibit emptying
Gastric factors that
promote emptying
Distention
Stimulate neural
reflex
Protein
stimulate
gastrin release
Increase motility of the
stomach
distension
fat
acid
Enterogastric
reflex
I cell
S cell
CCK
Secretin
hypertonicity
Decreased motility of the
stomach
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Small intestinal motility
 Motility of the small intestine
1. Mixes the luminal contents with the various secretions
2. Brings the contents into contact with the epithelial surface where absorption takes place
3. Slowly advances the luminal material toward the large intestine
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Small intestinal motility…
 There are two patterns of contractions in the small intestine:
1) segmentation contractions
 contraction and relaxation of intestinal segments
 chyme in the lumen of a contracting segment is forced both forward and backward in the intestine
 The rhythmic contraction and relaxation of the intestine, known as segmentation
2) peristaltic contractions.
 Each pattern is coordinated by ENS
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Small intestinal motility…
 There are two patterns of contractions in the
small intestine:
1) segmentation contractions
 contraction and relaxation of intestinal
segments
 chyme in the lumen of a contracting
segment is forced both forward and
backward in the intestine
 The rhythmic contraction and relaxation
of the intestine, known as segmentation
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Small intestinal motility…
2. Peristaltic contractions
 highly coordinated and propel the chyme through the small intestine toward the large
intestine
 Ideally, peristalsis occurs after digestion and absorption have taken place
 Contraction behind the bolus and, simultaneously, relaxation in front of the bolus cause
the chyme to be propelled caudally
 peristaltic reflex is coordinated by the enteric nervous system
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Small intestinal motility…
3. Gastroileal reflex
 mediated by the extrinsic ANS and possibly by gastrin
 The presence of food in the stomach triggers increased peristalsis in the ileum and
relaxation of the ileocecal sphincter
 As a result, the intestinal contents are delivered to the large intestine
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Large intestinal motility
 Fecal material moves from the cecum to the colon (i.e., through the ascending, transverse,
descending, and sigmoid colons), to the rectum, and then to the anal canal
 Haustra, or saclike segments, appear after contractions of the large intestine
1. Cecum and proximal colon
 When the proximal colon is distended with fecal material, the ileocecal sphincter contracts
to prevent reflux into the ileum.
a. Segmentation contractions in the proximal colon mix the contents and are responsible for
the appearance of haustra.
b. Mass movements occur 1 to 3 times/day and cause the colonic contents to move distally
for long distances (e.g., from the transverse colon to the sigmoid colon)
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Large intestinal motility…
2. Distal colon
 Because most colonic water absorption occurs in the proximal colon, fecal material in the
distal colon becomes semisolid and moves slowly. Mass movements propel it into the
rectum.
3. Gastrocolic reflex
 The presence of food in the stomach increases the motility of the colon and increases the
frequency of mass movements.
a. The gastrocolic reflex has a rapid parasympathetic component that is initiated when the
stomach is stretched by food.
b. A slower, hormonal component is mediated by CCK and gastrin
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Large intestinal motility…
4. Rectum, anal canal, and defecation: The sequence of events for defecation is as follows:
a. As the rectum fills with fecal material, it contracts and the internal anal sphincter relaxes
(rectosphincteric reflex).
b. Once the rectum is filled to about 25% of its capacity, there is an urge to defecate.
 However, defecation is prevented because the external anal sphincter is tonically
contracted.
c. When it is convenient to defecate, the external anal sphincter is relaxed voluntarily. The
smooth muscle of the rectum contracts, forcing the feces out of the body.
 Intra-abdominal pressure is increased by expiring against a closed glottis (Valsalva
maneuver).
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Large intestinal motility…
Pathway
1. Receptors for defecation reflex are stretch receptors
located in the wall of rectal rectum
2. Afferent information from the wall of rectum is
conveyed to sacral segment (S3) of spinal cord via
pelvic nerve.
3. Efferent input from spinal cord to rectum and internal
anal sphincter comes via pelvic nerve and to external
anal sphincter via somatic nerve (Fig).
4. Higher center, especially cortex influences spinal cord
center via corticospinal pathway.
5. Relaxation of internal anal sphincter is due to
inhibitory signals that originate in myenteric plexus in
response to peristaltic wave approaching anus.
 This allows the fecal matter to press onto the anal
canal
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Large intestinal motility…
Ileocecal sphincter
 Function: prevents back flow of faecal matter from the cecum to the ileum
 Factors regulating the sphincter
• Pressure and chemical irritation of ileum relax it and initiates peristalsis
• Pressure and chemical irritation of cecum inhibit peristalsis of ileum and closes the
sphincter
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Vomiting
 A wave of reverse peristalsis begins in the small intestine, moving the GI contents in the
orad direction.
 The gastric contents are eventually pushed into the esophagus.
 If the upper esophageal sphincter remains closed, retching occurs.
 If the pressure in the esophagus becomes high enough to open the upper esophageal
sphincter, vomiting occurs.
 The vomiting center in the medulla is stimulated by tickling the back of the throat, gastric
distention, and vestibular stimulation (motion sickness)
 The chemoreceptor trigger zone in the fourth ventricle is activated by emetics, radiation,
and vestibular stimulation.
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Digestive processes in the mouth
• Food is ingested
• Mechanical digestion begins (chewing)
• Propulsion is initiated by swallowing
• Salivary amylase begins chemical breakdown of starch
• The pharynx and oesophagus serve as conduits to pass food from the mouth to
the stomach
84
Digestive processes in the stomach
• Mechanical digestion : churning
• Chemical digestion : protein digestion
• Gastric juice : convert meal to acidic chyme
o HCl : kill bacteria, denature protein
o Pepsin: break down protein
85
Digestion in the Small Intestine
• As chyme enters the duodenum:
• Carbohydrates and proteins are only partially digested
• Almost no fat digestion has taken place
• Digestion continues in the small intestine
• Chyme is released slowly into the duodenum
• Because it is hypertonic and has low pH, mixing is required for proper
digestion
• Virtually all nutrient absorption takes place in the small intestine
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Digestion in the Small Intestine…cont’d
 Carbohydrate: start digestion in mouth by salivary amylase in duodenum by pancreatic
amylase.
a. α Amylases (salivary and pancreatic) hydrolyse 1,4-glycosidic bonds in starch, yielding
maltose, maltotriose, and α-limit dextrins
b. Maltase, `α- dextrinase, and sucrase in the intestinal brush border then hydrolyse the
oligosaccharides to glucose.
c. Lactase, trehalase, and sucrase degrade their respective disaccharides to
monosaccharides
• Lactase degrades lactose to glucose and galactose
• Sucrase degrades sucrose to glucose and fructose
87
Digestion in the Small Intestine…cont’d
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Digestion in the Small Intestine…cont’d
 Proteins: start digestion in stomach by pepsin turns proteins into peptides
 Pancreatic proteases include : trypsin, chymotrypsin, elastase, carboxypeptidase A, and
carboxypeptidase B.
 are secreted in inactive forms that are activated in the small intestine as follows:
a) Trypsinogen is activated to trypsin by a brush border enzyme, enterokinase.
b) Trypsin then converts chymotrypsinogen, proelastase, and procarboxypeptidase A and B
to their active forms. (Even trypsinogen is converted to more trypsin by trypsin)
c) After their digestive work is complete, the pancreatic proteases degrade each other and
are absorbed along with dietary proteins
89
Digestion in the Small Intestine…cont’d
Fig. Activation of proteases in the stomach (A) and small intestine (B). Trypsin autocatalysis its own activation and the
90
activation of the other proenzymes.
Digestion in the Small Intestine…cont’d
Fig. Digestion of proteins in the stomach (A) and small intestine (B)
91
Digestion in the Small Intestine…cont’d
Fats: start in mouth by lingual lipase
 Lingual lipases digest some of the ingested triglycerides to monoglycerides and fatty
acids.
 However, most of the ingested lipids are digested in the intestine by pancreatic lipases
o Bile acids emulsify lipids in the small intestine, increasing the surface area for digestion
o Pancreatic lipases hydrolyse lipids to fatty acids, monoglycerides, cholesterol, and
lysolecithin
o The enzymes are pancreatic lipase, cholesterol ester hydrolase, and phospholipase A2.
o The hydrophobic products of lipid digestion are solubilized in micelles by bile acids.
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Digestion in the Small Intestine…cont’d
Fig. Digestion of lipids in the small intestine
93
Absorption in the Small Intestine
94
Absorption in the Small Intestine
 Absorption is the passage of the end products of digestion from the GI tract into
blood or lymph occurs by diffusion, facilitated diffusion, osmosis, and active
transport.
Essentially all carbohydrates are absorbed as monosaccharides and they are
absorbed into blood capillaries.
Most proteins are absorbed as amino acids by active transport processes.
Dietary lipids are all absorbed by simple diffusion
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Small Intestine: Microscopic Anatomy
• Structural modifications of the small
intestine wall increase surface area
• Plicae circulares: deep circular folds of
the mucosa and sub mucosa
• Villi – fingerlike extensions of the mucosa
• Microvilli – tiny projections of absorptive
mucosal cells’ plasma membranes
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Summary of Digestion and Absorption
Nutrient
Digestion
Mechanism of Absorption
Carbohydrates
To monosaccharides
(glucose, galactose,
fructose)
• Na+-dependent cotransport (SGLT1) (glucose, galactose)
• Facilitated diffusion (fructose)
• transported from cell to blood by facilitated diffusion (GLUT2)
Proteins
To amino acids,
dipeptides,
tripeptides
 Na+-dependent cotransport (amino acids)\
 H+-dependent cotransport (di- and tripeptides)
 After the dipeptides & tripeptides are transported into intestinal cells,
cytoplasmic peptidases hydrolyze them to amino acids.
 amino acids are then transported from cell to blood by facilitated diffusion
Lipids
To fatty acids,
monoglycerides,
cholesterol
•
•
•
•
Micelles form with bile salts in intestinal lumen
Diffusion of fatty acids, monoglycerides, and cholesterol into cell
Re-esterification in cell to triglycerides and phospholipids
Chylomicrons form in cell (requires apoprotein) and are transferred to lymph
Fat-soluble
vitamins
Micelles with bile salts
Water-soluble
vitamins
Na+-dependent cotransport
Vitamin B12
Intrinsic factor–vitamin B12 complex
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Absorption of monosaccharides
98
Absorption of proteins
Fig. mechanism of absorption of amino acids, dipeptides, and tripeptides in the small intestine
99
Absorption of lipids
Fig. Mechanism of absorption of lipids in the small intestine.
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Water Absorption
• 95% of water is absorbed in the small intestines by osmosis
• Water moves in both directions across intestinal mucosa
• Water uptake is coupled with solute uptake, and as water moves into mucosal cells,
substances follow along their concentration gradients
101
Energy and Metabolism
Metabolic rate
• Even at complete rest, considerable energy is required to perform all chemical reactions of
the body.
• This minimum level of required to exist is called the basal metabolic rate (BMR) and
accounts for about 50 to 70 % of the daily energy expenditure in most sedentary
individuals.
• BMR normally averages about 65 to 70 Calories per hour in an average 70 kilogram man.
• Much of the BMR is accounted for by essential activities of the central nervous system,
heart, kidneys, and other organs.
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Energy balance
Energy intake and output are balanced under steady-state conditions
• Intake of carbohydrates, fats, and proteins provides energy to perform various body functions or stored for
later use.
• Average physiologically available energy as Calories in each gram of these three foodstuffs:
o 1 gram of carbohydrate liberates 4 Calories
o 1 gram of fat liberates 9 Calories
o 1 gram of protein liberates 4 Calories
• .
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Energy balance..
• Daily requirement
o Average daily requirement for protein is 30 to 50 grams.
o Carbohydrates and fats act as "protein sparers" when diet contains an abundance of carbohydrates and
fats.
o In starvation, after the depletion of carbohydrates and fats, protein stores are consumed rapidly for energy
Energy balance between caloric intake and energy output:
 The average adult must take in about 2000 kcal/d. Caloric requirements above the basal level depend on the
individual's activity.
 Another 500 to 3000 additional kcal per day are required to meet the energy demands of daily activities
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Feeding and its regulation
• Food intake is regulated by two centers present in hypothalamus: Feeding center and Satiety center
Feeding center
• It is in the lateral hypothalamic nucleus
• Stimulation leads to uncontrolled hunger and increased food intake (hyperphagia), resulting in obesity.
• Destruction of feeding center leads to loss of appetite (anorexia) and refuse to take food.
• Normally, feeding center is always active, has the tendency to induce food intake always
Satiety center
• It is in the ventromedial nucleus of the hypothalamus.
• Stimulation of this nucleus causes total loss of appetite and cessation of food intake.
• Destruction of satiety center leads to hyperphagia and animal becomes obese called 'hypothalamic obesity.
• It plays an important role in regulation of food intake by temporary inhibition of feeding center after food
intake.
105
Regulation of food intake
• Regulation of food intake by several mechanisms
Glucostatic mechanism
• Food intake increases blood glucose level which stimulates satiety centre to inhibit feeding centre and stop
food intake
• After 3 hours of food intake, blood glucose level falls which causes no inhibition of feeding center by satiety
center.
• Hence appetite increases leading to food intake
Lipostatic mechanism
• Leptin secreted by adipocytes (cells of adipose tissue)
• It plays an important role in controlling the food intake as it enter brain and inhibits feeding centre
• Leptin inhibits release of Neuropeptide Y and stimulate release of Pro-opiomelanocortin (POMC) in
hypothalamus
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Regulation of food intake
Peptide mechanism
• Release of several GIT hormones which regulate food intake
• Ghrelin is secreted in stomach during fasting.
• It directly stimulates the feeding center and increases the appetite and food intake.
• peptides which increase the food intake : ghrelin, Neuropeptide Y (NPY)
• Peptides, which decrease the food intake: Leptin, α-MSIF (Melanocyte stimulating hormone), Peptide YY
Hormonal mechanism
• Hormones which inhibit the food intake: Somatostatin, Oxytocin, Glucagon, Pancreatic polypeptide,
Cholecystokinin
107
Body temperature regulation
• Thermostatic mechanism of food intake due to interaction within hypothalamus between
temperature-regulating system and food intake regulating center.
• Food intake is inversely proportional to body temperature
 In fever, the food intake is decreased:
Probably by action of preoptic thermoreceptors on feeding center
Cytokines also have been suggested to play a role in decreasing the appetite during
fever.
 Increased food intake in a cold animal to:
Increase its metabolic rate
Provide increased amount of fat for insulation
108
Obesity and balanced diet
• Obesity is defined as an excess of body fat.
• Body mass index (BMI) is calculated as Weight in kg/Height in m²
• In clinical terms, a BMI between 25 and 29.9 kg/m² is called overweight, and a BMI greater than
30 kg/m² is called obese.
• Obesity is usually defined as 25 per cent or greater total body fat
• Total body weight is estimated with various methods, such as
o measuring skin-fold thickness,
o bioelectrical impedance, or
o underwater weighing.
• These methods rarely used, hence in clinical practice BMI is commonly used to assess obesity
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Causes of obesity
• Excess energy intake than that of energy output
o for each 9.3 calories of excess energy, approximately 1 gram of fat is stored mainly in
adipocytes in subcutaneous tissue and in the intra-peritoneal cavity ,liver and other
tissues
o excess energy intake in children led to hyperplastic obesity (increased numbers of
adipocytes and only small increases in adipocyte size),
o Obesity in adults, results in increase adipocyte size (hypertrophic) and new adipocytes
can differentiate from fibroblast-like pre-adipocytes (hyperplastic).
• Decreased physical activity (sedentary life).
• Abnormal feeding regulation due to environmental, social, and psychological factors.
110
Causes of obesity…
• Neurogenic abnormalities
o Lesion of ventromedial nuclei of the hypothalamus
o Functional organization of the hypothalamic or other neurogenic feeding centers
o Increased formation of orexigenic neurotransmitters such as NPY and decreased
formation of anorexic substances such as leptin, a-MSH.
• Genetic factors cause 20 to 25 per cent of obesity
o Genes causing abnormalities of pathways that regulate feeding centers; and energy
expenditure and fat storage.
o Three monogenic causes of obesity include mutations of MCR-4 gene, congenital leptin
deficiency, mutations of the leptin receptor.
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THANY YOU
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