GIT PHYSIOLOGY

Dr Omar Sulaiman
Overview

 GIT ~ is a mucosa-line muscular tube extending

from mouth to the anus
 Primary functions : motility, secretion,
digestion, absorption and elimination
 Secondary functions: endocrine and
immunological roles
The Upper GIT

Hunger : increased Appetite : desire for

food-seeking behavior, certain foods that
salivation & directs choice of food.
rhythmical stomach Can be independent of
contractions hunger

Satiety : lack of desire

to eat. The feeling
Anorexia : aversion to
usually follows
food ingestion despite
ingestion of food &
sensations of hunger
depends on energy
stores
Food intake and its control

Food Intake

Central
Control Feedback
Control

Feeding Centre Satiety Centre Short Term Long Term

(ventrolateral (ventromedial (Mechanical (Chemical
nucleus) nucleus) feedback) feedback)
Feedback Control
Short Term (Alimentary Long Term (Nutritional
Feedback) Feedback)
 Mechanical feedback  Temperature: interaction
 Oral cavity between hypothalamus
&T°regulating system
 Inhibit feeding centre ±30
mins
 Blood concentration of
nutrients, including glucose,
 Stomach & duodenum
amino acids & lipid
distension
 Stored energy ~ negative
 Chemical content of food :
feedback
GI hormones & humoral
factors
 Suppress feeding
Salivation
 Oral hygiene and digestion
 Two secretions
2 stages of production
Stage 1: 1°Ssecretion in the acinus
– secretion of a solution ECF +
ptyalin(α amylase) & mucin
 dependent on the gland –
submaxillary & sublingual but not
parotid
Serous contains
ptyalin (α-amylase)&
enzymes that can
digest starch
Mucoid contains
mucin, which has
lubrication & oral
protective properties
Stage 2: 2°ionic modification in
the duct-active transport process,
reabsorption Na >K secretion,
generating -70mV, which passive
Cl reabsorption via Cl/HCO3
exchanger in the apical membrane
Mechanism & Nerve Supply for
Salivation
Composition of Saliva
Functions of Saliva
Swallowing

 From mouth to stomach ~ initiated voluntarily

but then proceeds through a reflex
 600 times a day coordinated with respiration
 3 phases : 1. Voluntary phase (closed mouth)
2. Pharyngeal phase
3. Oesophageal phase
Swallowing Phases

Oesophageal
Phase
6-10s.
Pharyngeal Phase Immediately after
Food bolus exerts oesophageal
pressure near the sphincter
opening of relaxation with
pharynx, each swallow,
Voluntary Phase stimulating pressure
Food is separated mechanoreceptors. increases,
into bolus by the These send promoting one-
tongue, propel it afferents to way passage. Two
posteriorly & medullary types of peristalsis
upwards against hard swallowing centres : Primary &
palate towards the Secondary
pharyn via CN V, IX & X
to elicit Peristalsis
Swallowing Reflex (Pharyngeal Phase)

Palatopharyngeal Vocal cords are Larynx pulled

Upper
folds move pulled together ~ anteriorly &
Soft palate rises ~ oesophageal
inwards (medially) epiglottis to tilt upwards ~
nasopharynx sphinter relaxes
~ channel for the over pharynx~ entrance to the
closed off, for 0.5-1 sec ~food
food bolus is trachea is closed esophagus is
preventing reflux enters upper
opened into the of ~ preventing stretched &
oesophagus
posterior pharynx respiration enlarged
Oesophageal Phase
Primary Peristalsis
 Continuation of oropharyngeal
swallowing
 Consists of a sequence of nerve
activation causing a ring of
contraction & high pressure : speed
~ 3-5 cm/s, LOS reached 6 sec later,
aided by gravity, faster with warm
liquids
 CN IX &X control peristalsis in
pharynx & upper 1/3 of esophagus ~
striated ms
 CN X controls smooth ms of lower
2/3 of oesophagus
Secondary Peristalsis
 Occurs in response to
oesophageal distension d/t
incomplete emptying into
stomach & reflux of stomach
contents back into oesophagus
 Involves intrinsic myenteric
circuits & pharyngeal reflexes
 Peristalsis until emptying into
stomach is complete
 No appreciable perception
Q: Describe the physiological factors that contribute to the competence and tone of the lower
oesophageal sphincter.
(10 marks)
 Intro:
Importance · Prevents regurgitation and aspiration
· Especially important supine, under anaesthesia

Barrier · Barrier pressure = sphincteric – intragastric

pressure
· Normal pressures (cmH2O): barrier 26, sphincter 36,
intragastric 10
· Reflux occurs when barrier pressure <13cmH2O
 Anatomical components:
Inner sphincter · Lower 2-4cm oesophagus. Not anatomically
distinct, not a true sphincter.
· Tonic contraction of circular muscle
· Provides 90% of basal pressure
· Innervation: CNX, abundant
Outer sphincter · Right crus of diaphragm loops contralaterally
around lower oesophagus. “Pinch cock”
mechanism
· Intermittent contraction
· Applies co-ordinated pressure during
inspiration, coughing
· Inervation: phrenic
Oblique entry · Oblique passage of oesophagus into stomach
· Gastric distension -> closure of orifice
· “Flap-valve” mechanism
Intra-abdominal · Sphincter is intra-abdominal
position
· External pressure assists closure
 Neural control:

Intrinsic · Meissner’s submucosal plexus

· Auerbach’s myenteric plexus: between circular and
longitudinal layers
· Myenteric reflex: distension > peristaltic wave
(sensed and controlled by the above).
E.g. reflex dilatation then contraction after swallowing.
· Myogenic reflex: distension -> contraction
· Swallowing: ↑VIP -> reflex relaxation

Extrinsic · PSNS: CNX via oesophageal plexus.

· SNS: cervical and thoracic SNS trunk via oesophageal
plexus.
· Complex modulation of intrinsic circuits
 Neural control:
Intrinsic · Meissner’s submucosal plexus
· Auerbach’s myenteric plexus: between circular and
longitudinal layers
· Myenteric reflex: distension > peristaltic wave (sensed and
controlled by the above).
E.g. reflex dilatation then contraction after swallowing.
· Myogenic reflex: distension -> contraction
· Swallowing: ↑VIP -> reflex relaxation
Extrinsic · PSNS: CNX via oesophageal plexus.
· SNS: cervical and thoracic SNS trunk via oesophageal plexus.
· Complex modulation of intrinsic circuits
Hormonal:
↑ LOS tone · Gastrin
· CCK
· Motilin
· Oestrogen
↓LOS tone · Secretin
· GIP
· VIP
· Progesterone
· PGE2
· Glucagon
· Severe illness ? exact cause
 Physical factors:

Intra- · ↑Abdo pressure -> ↓barrier pressure

abdominal
hypertension o Obesity, pregnancy
o Reverse Trendelenburg position
o Laparoscopy

Sphincter · e.g. hiatus hernia -> ↓LOS competence

dysfunction
Lower Oesophageal Sphincter
 Consists of a circular ring 3 cm above the
gastro-oesophageal junction.
 Normally constricted, protect the oesophagus
from acidic & proteolytic gastric secretions
 Relaxes for 5-10s when it meets the peristaltic
wave, permitting passage of food bolus.
 During drinking, there is rapid swallowing with
a relaxed LOS & no peristalsis until the last
swallow
Vomiting
 Forceful expulsion of gastric contents
 Active process
 Regurgitation is a passive process
Mechanical Stages of Vomiting

Closure of glottis: protects

Raising of larynx &
the airways & fixes the
Deep inspiration Hyoid bone: extends the
chest by holding
opening of UOS
diaphragm down

Strong contractions of
abd skeletal ms ~ increase Relaxation of LOS :
Elevation of soft palate:
IAP ~ diaphragm forced allows the stomach
seals off nasopharynx
up into thorax~ increase contents enter esophagus
ITP
Stomach
Storage of food: fundus
 Fundus as reservoir and contributes 1-1.5L capacity of a fully
relaxed stomach
 Suited to its function distensible:
~ muscular wall is thinner than others
~ maintain intragastric pressure over wide range of gastric
volumes
~ oblique layer of stomach muscle facilitates expansion
 Storage is facilitated by relaxation (vasovagal reflex) by
stomach
 Food entering through LOS results in decreased ms tone of
fundus & upper stomach walls, bulge outward
 Food can stay ~1 hour in the fundus
Gastric secretions and their control

 Two main components of 2L of stomach

secretions produced every day
 Non-acid secretion: alkaline material, which is
released by mucous cells, that coats the entire
mucosal surface
 Acid secretion: gastric juice released by parietal
and chief cells in the oxyntic region
A. Non-acid Secretion

 Alkaline secretion ~ mucus & bicarbonate

(HCO3)
 Adhere to stomach lumen
 Protective fluid barrier against acidic gastric
juice ~ autodigestion.
 Isosmolar ~ high HCO3 & pH 7.7 (alkali)
 Acid resistance trefoil proteins in the mucosa ~
resistance to tissue damage
B. Gastric Juice

 Composed of mucus, HCL, intrinsic factor,

pepsin & enzymes
 pH is low with increase in flow rate associated
with increase in acidity (~ pH1.0)
Mucus

 Secreted in the antropyloric region & surface mucus cells

located throughout stomach
 Roles as lubrication of food and protection against
autodigestion
 Gel ~ permits HCO3 to be trapped within ~ alkaline barrier to
H+ diffusion back to the epithelium
 pH gradient is established between the lumen (pH 1.5)&
epithelial surface (pH 6.5)
 PG & local irritation stimulate mucus production
 Pepsin partially degrades mucus, as a low pH is requires for
optimal pepsin activity
Hydrochloric Acid
 Secreted actively by parietal cells
 Functions: defense against ingested microorganisms, activation
of pepsinogen and stimulation of bile & pancreatic juice flow
 PG inhibit HCL secretion
 Gastrin ~ antral hormone
~ increases with protein
use

Signal-transduction
pathways for Ach & Rate of HCL ∞histamine Ach: from vagal nerve act
gastrin involve activation production by via M3 muscarinic
of protein kinase C, enterochromaffin cells receptor
cAMP & Protein kinase A

Ach & Gastrin direct

effects on parietal cells
acting via M3 & gastrin
receptor
Intrinsic Factor

 Produced by parietal cell

 Glycoprotein ~ essential for Vit B12 absorption in
the terminal ileum
 Def : Pernicious anaemia once liver storage
depleted (after 2-3 years)
Pepsin

 Chief cell secretes pepsinogen, the inactive

precursor of pepsin.
 Under acidic conditions (pH <2) ~ pepsinogen is
rapidly converted to pepsin
 Proteolytic enzyme that degrades proteins to
peptides.
 Stimulated by vagus or gastric enteric plexus
promotes the secretion of pepsinogen
Other Enzymes (in gastric juice)

 Gastric lipase : acts on butter fats

 Gastric amylase: starch digestion
 Gelatinize : liquefying some meat proteoglycans
Control of Gastric Secretion
 Occurs continuously at rest (basal) & response to food
 Stimulation associated with feeding involves neural,

hormonal and paracrine mechanisms

 Divided 3 phases:

1. Cephalic phase (20%) : stimuli involve brain

2. Gastric phase (70%) : stimulus is food/fluid in
stomach
3. Intestinal phase (10%): stimulus is food in
small intestine
* % of gastric secretion
Gastric Motility and Emptying

 Storage of food
 Mixing of gastric secretion with food to form a
mixture ~ Chyme
 Controlled release of chyme into the small
intestine
Gastric Motility
 Proximal stomach stores ood & presses it towards
the distal region via low-amplitude, slow peristalsis
waves
 3-4/min
 Initiated and regulated by pacemaker cells in the
middle of the stomach body
 During antral peristalsis, pyloric contraction causes
reflux of antral contents to more proximal ~
Retropulsion ~ breakdown of solid foods & churning
of food with secretions to form the semi-solid chyme
Pancreas
Exocrine (98%) Pancreatic Secretion

 2 components
 Aqueous alkaline fluid ~ secreted by duct cells
 Organic eg. Inactive digestive enzymes ~ secreted
by acinar cells
 It enters duodenum, pancreatic fluid regulates
the pH and digest fats, protein and nuclei acids
Alkaline secretion
 Isosmolar
 Main component ~ aqueous bicarbonate
(HCO3)
 Secreted by epithelial cells via intracellular
hydration of CO2
Enzyme secretion
 Acinar cells secrete following enzymes
Peptidases:
Digest proteins ~ peptides
Amylases:
Most abundant
Hydrolyse CHO to mainly
Secreted in precursor form to disaccharides
prevent pancreatic autodigestion
Eg. α-amylase
Eg. Trypsin, chymotrypsin &
carboxypeptidase

Lipases
Nucleases
Digest fat to release monoglycerides
and fatty acids Eg. Ribonuclease &
deoxyribonuclease which act on
Eg. Lipase, phospholipase & RNA and DNA
cholesterol esterase
Control of Pancreatic Secretion
Hormonal Control
 Secretin: most powerful
stimulation of ductal HCO3
secretion acts via 2nd
messenger cAMP, protein
kinase A & phosphorylation
CFTRCI
 Ach
 CCK: stimulate acinar cell
release of pancreatic enzyme
 Somatostatin inhibits all
pancreatic secretion
Neural Control
 Sympathetic stimulation:
globally inhibits secretion,
mainly through gland
arteriolar vasoconstriction
 Parasympathetic
stimulation: via vagal Ach,
increases both enzyme and
alkaline luid secretion
Phases of Pancreatic Secretion in
response to a meal
Questionssssssssss……
 Explain the role of portal circulation in hepatic
circulation
 Discuss the functions of liver as
1. Blood reservoir
2. Endocrine
3. Microcirculation
Q:Outline the protective and regulatory functions of the liver
(10 marks)
 1.Protective:
Innate immunity · Filter portal blood
· Kupffer cells: phagocytosis, cytokine secretion (IL-1, IL-6, TNF-
α)
· Synthesises complement (opsonization, lysis, chemotaxis)
· Synthesises acute phase reactants (CRP activates
complement, Ferritin, α1 antitrypsin)
Adaptive immunity · Kupffer cells: present antigens to T cells
H
· (Kupffer cells are macrophages lining the sinusoids)
Detoxification · Affects toxins and drugs
· Oral route via portal blood = first pass metabolism. Barrier
between gut and rest of body.
· Other routes via hepatic arterial blood
· Phase 1 reactions: oxidation, reduction, hydrolysis. By
CYP450. Usually inactivates.
· Phase 2 reactions: glucuronidation, sulfation, acetylation,
methylation. Usually solubilizes
· Large, lipid soluble metabolite -> bile, faeces
· Small, water soluble metabolite -> urine
 2.
Regulatory:
Macronutrient Carbohydrates:
concentrations · Islet β-cell = glucostat, liver = major effector
· Constitutive GLUT-2 = free glucose movement
· Direction of glucose flow controlled by hexokinase activity, not portal blood [glucose]
· Insulin -> ↑uptake, ↑trapping as G6P (↑hexokinase, glycogenesis, DNL, glycolysis)
· Glucagon, cortisol, SNS -> ↑release (↓hexokinase, ↑glycogenolysis, gluconeogenesis, lipolysis)
Proteins:
· Amino acid synthesis (↑insulin:glucagon) and breakdown (↓insulin:glucagon)
· Transamination (ALT, AST)
· Uptake and release into circulation as required
Lipids:
· Glucose -> fatty acid when glucose in excess (↑fatty acid synthase)
· Fatty acid -> ketones when ↑Acetyl-CoA:OAA ratio
· Synthesises apolipoproteins
Oncotic pressure · Synthesises and recycles albumin. Stable 40g/L
· Synthesises α and β globulins (not γ-globulin)
· Regulates plasma oncotic pressure, blood volume
· Minimizes transudation and oedema
Blood volume · Blood reservoir ~450mL
· ↓Blood vol -> ↑α1 vasoconstriction of sinusoids-> autotransfusion ~200mL
· ↑Blood vol -> ↓α1 vasoconstriction -> ↑capacitance (up to 1.5L in heart failure)
Red cell mass · Synthesises EPO: 10% in adult, near 100% in foetus
· Degrades EPO
Coagulation status · Synthesises all coag proteins except vWF
· Synthesises anticoag proteins C, S, AT3
· Synthesises plasminogen
ECF volume · Synthesises angiotensinogen (regulate ECF [Na+], ECF water, blood volume via Angiotensin 2,
aldosterone)
Calcium · Activates Vit D -> 25-OH-Vit D
homeostasis
GIT absorption · Continuous synthesis of bile
· Regulation of storage in and release from gallbladder is by CCK
· Bile = salts + acids + cholesterol + lecithin
· Transports lipid soluble substances into GIT for excretion
Q: Describe the factors influencing hepatic blood flow
(10 marks)
 Hepatic circulation:

· Total 1400mL/min = 100mL/min/100g = 30% of

Arterial cardiac output
supply
· Blood: 75% portal vein, 25% hepatic artery
· Oxygen: 50% portal vein, 50% hepatic artery
· Hepatic vein 1400mL/min
Venous
drainage

· Entrance to lobule via hepatic arteriole or portal

Flow vein
pattern
· Centripetal transit through sinusoid
· Exit from lobule via central vein
 Determinants of hepatic arterial flow:
Equations · Hepatic arterial flow = (mHAP – HVP) / hepatic arteriolar resistance
· HAP = mAP = 70mmHg
· HVP = CVP = 0-5mmHg
· R = (8 x length x viscosity) / (π x radius4)
Vascular · Myogenic autoregulation: ↓mAP -> ↓stretch -> reflex vasodilatation -
resistance > ↓R -> ↑Q
· Metabolic autoregulation: ↓pO2, ↑pCO2/H+/K+/adenosine ->
vasodilatation -> ↓R -> ↑Q
· Neural: SNS -> α1 vasoconstriction -> ↑R -> ↓Q
· Hormonal: adrenaline -> α1 constriction then β2 dilatation; overall
minimal change
· Anaesthesia: halothane inhibits hepatic arteriolar myogenic response
to hypotension
Hepatic arterial · mHAP = mAP = CO x TPR
pressure
· ↓CO -> ↓mAP -> ↓Q (e.g. hypovolaemia, bradycardia, cardiogenic
shock)
· ↓TPR -> ↓mAP -> ↓Q (e.g. sepsis, anaphylaxis)
Hepatic venous · HVP = CVP
pressure
· PPV: ↑HVP -> ↓Q
· Laparoscopy: ↑HVP -> ↓Q
· Heart failure: ↑HVP -> ↓Q
 Determinants of portal venous flow:
Equations · Portal venous flow = (PVP – HVP) / portal venous
resistance
· PVP = 5-10mmHg
· HVP as above (normal gradient <5mmHg)
· R = (8 x length x viscosity) / (π x radius4)
Vascular · Metabolic autoreg: ↑GIT activity -> ↓R -> ↑Q
resistance
· SNS/adrenaline -> α1 constriction -> ↑R -> ↓Q
· Cirrhosis: scarring -> ↑R -> ↓Q (and ↑pressure =
portal hypertension)
· Post-prandial splanchnic vasodilation -> ↓R -> ↑Q
Portal venous -
pressure

Hepatic · Hepatic vein thrombosis: ↑HVP -> ↓Q

venous
pressure
 Hepatic arterial buffer response:

Definition · Semi-reciprocal supply relationship

· Hepatic arterioles autoregulate, portal venules do
not ~ myogenic constrictive response
· Blood supply can reach 50%-50%

Mechanism · ↓Liver blood flow -> ↓adenosine removal ->

hepatic arteriolar dilatation
Q: Describe the pecularities of Hepatic Circulation
(10 marks)
Q: Describe the pecularities of Hepatic Circulation (10
marks)

 Hepatic circulation is a portal system. Blood has to pass through two capillary
networks—at first, the splanchnic and then the hepatic
 Although blood enters liver through two vessels (portal vein and hepatic artery),
yet the outflow from the liver is only through the hepatic vein. There is no vein
corresponding to the hepatic artery (contrast with pulmonary circulation).
 The pressure difference between portal vein and portal capillaries are not very
high, yet a large amount of blood passes through the liver. Mechanical factors,
mentioned above, help. Union between the radicles of the hepatic artery and portal
vein possibly adds motive force to the latter
 Filtration in the capillary area elsewhere takes place, because capillary pressure
(32 mm of Hg) is more than colloidal osmotic pressure (25-30 mm of Hg). But in
the liver, the osmotic pressure is same, while the capillary pressure is almost zero
 In the liver, blood comes into direct contact with the hepatic cells to some extent