Pages From Physio Term 2

Gastrointestinal Physiology
Lt Col Nadia Noor

MBBS, MPHIL
Department of Physiology
Armed Forces Medical College
Parts of digestive system
A. Alimentary tract
B. Digestive glands
A. Alimentary tract: Extends from mouth to anus.

1. Mouth or buccal cavity with tongue & teeth
2. Oropharynx
3. Esophagus
4. Stomach
5. Small intestine
6. Large intestine
B. Digestive glands:
1. Salivary glands: Parotid, submandibular &
sublingual
2. Exocrine part of pancreas
3. Liver
4. Gall bladder
5. Other digestive glands in the wall of digestive tract
Gastrointestinal tract (GIT):

Extends from stomach to anus.
Alimentary tract
Functions of digestive tract
1. Ingestion of food.
2. Breaking of food into smaller particles.
3. Movement of food through the alimentary tract.
4. Secretion of various digestive juices.
5. Digestion of food.
6. Absorption of end product of digestion, water,
vitamins & minerals.
7. Excretion of unwanted substances (heavy metals,
toxins, bile pigments etc.) from the body.
Physiologic anatomy of GI wall
Wall of GIT is formed by 4 layers which are from within

outwards:
1. Mucus layer
2. Submucus layer
3. Muscular layer – outer longitudinal & inner circular
4. Serous layer
Gastrointestinal muscle as syncytium
Gastrointestinal smooth muscle is known as

functional syncytium, as the cell membrane of
two smooth muscle cells fuse at many points
which provide gap junctions.
These gap junctions allow free diffusion of ions, so

that action potential can travel easily from one cell
to another with least resistance.
Electrical activity of GI smooth muscle
The smooth muscle of GIT is excited by almost

continual slow, intrinsic electrical activity along the
muscle fiber membranes.
This activity is known as Basic electrical rhythm (BER).
It has two basic types of electrical waves:
1. Slow waves
2. Spike potential
Resting membrane potential of GIT= - 50 to - 60 mV

1. Slow waves
Slow, undulated changes in the resting membrane
potential of GI smooth muscle is called slow
waves.
Not true action potential.
Cause of slow wave

Interstitial cells of Cajal act as pacemaker for smooth
muscle cells of GIT due to presence of unique Na+
channels. Influx of Na+ through these channels
generate slow waves.
Importance of slow wave

Controls the frequency of rhythmic contraction of GI
smooth muscles.
2. Spike potential
It is the true action potential having both
depolarization & repolarization.
Spike potential lasts for 10 to 20 seconds.
Depolarization occurs due to influx of large amount of
calcium & also small amount of sodium by slow
Ca++-Na+ channel.
Neural control of GIT
GIT has mainly two types of nerve supply:

1. Intrinsic nerve supply
2. Extrinsic nerve supply
• Afferent sensory fibers also innervate the gut.

Intrinsic nerve supply of GIT
Intrinsic nerve supply of GIT is called enteric nervous

system.
Location- lies in the wall of GIT extending from

esophagus up to anus.
Number of neurons- about 100 million
Enteric NS is composed of 2 plexuses:

1. Myenteric plexus/ Auerbach’s plexus
2. Submucosal plexus/ Meissner’s plexus
Enteric nervous system
1. Myenteric plexus/ Auerbach’s plexus:

Location- outer plexus, lies between the outer
longitudinal & inner circular muscle layer.
Function- Controls GI movements.
2. Submucosal plexus/ Meissner’s plexus:

Location- inner plexus, lies in the submucosa.
Function- Controls GI secretions & local blood flow.
Myenteric & Submucosal plexuses
Differences between Myenteric &
Submucosal plexuses
Myenteric plexus Submucosal plexus

Controls GI movements. Controls GI secretions
& local blood flow.
Composed of both Composed of
excitatory & inhibitory excitatory neurons
neurons (inhibit sphincters). only.
Neurotransmitters secreted by ENS
1. Acetylcholine – excites GI activity

2. Norepinephrine, epinephrine – inhibit GI activity
3. Adenosine triphosphate
4. Serotonin
5. Dopamine
6. Cholecystokinin
7. Substance P
8. VIP (Vasoactive intestinal polypeptide)
9. Somatostatin
10. Enkephalin
11. Bombesin
Extrinsic nerve supply of GIT
Extrinsic nerves that control the GI functions are from

autonomic nervous system.
GIT has innervation from both -

1. Sympathetic nerve fibers
2. Parasympathetic nerve fibers
1. Sympathetic nerve fibers

Lateral horn cells of T5 – L2 segments of spinal cord
preganglionic fiber  sympathetic chain  celiac &
mesenteric ganglia  postganglionic fiber  GIT
Functions
a. Inhibit GI movements.
b. Decrease GI secretions.
c. Constricts sphincters.
Neurotransmitter – Norepinephrine
2. Parasympathetic nerve fibers

Parasympathetic supply to gut divides into cranial &
sacral divisions.
• Mouth & salivary glands – Facial &
glossopharyngeal nerves
• Esophagus, stomach, pancreas, small intestine &
upper part of large intestine – Vagus nerve
• Large intestine – Sacral 2,3,4 via pelvic nerve
All these preganglionic fibers synapse with the
postganglionic neurons in myenteric & submucosal
plexus.
Functions of parasympathetic nerve fibers

a. Accelerates GI movements.
b. Increase GI secretions.
c. Relaxes sphincters.
Neurotransmitter – Acetylcholine
Local hormones of GIT
1. Gastrin family – Gastrin, Cholecystokinin (CCK)

2. Secretin family – Secretin, Gastric inhibitory
peptide (GIP), Vasoactive intestinal polypeptide
(VIP), glucagon
3. Others – Somatostatin, pancreatic polypeptide,
neuropeptide, motilin, substance P, ghrelin etc.
Hormone Stimuli for Site of Physiological
Secretion secretion actions
Gastrin ↑ed by G cells of • Stimulates gastric
• Protein antrum acid & pepsin
• Distention secretion
• Vagal discharge • Stimulates growth
• Epinephrine of gastric mucosa
↓ed by • ↑ gastric motility
• Luminal acidity • Contracts lower
• Somatostatin esophageal
• Secretin, GIP, VIP sphincter
• Glucagon
• Calcitonin
Hormone Stimuli for Site of Physiological actions

Secretion secretion
Secretin • Acid S cells of • Stimulates pancreatic
• Fat small water & HCO3-
intestine secretion (hydrolytic
type)
• Stimulates biliary HCO3-
secretion
• Stimulates growth of
exocrine pancreas
• ↓ gastric secretion &
motility
• Constricts pyloric sphincter
Hormone Stimuli for Site of Physiological actions
Secretion secretion
Chole- • Protein I cells of • Stimulates pancreatic
cystokinin • Fat small enzyme secretion
(CCK) • Acid intestine (ecbolic type)
• Contracts gall bladder &
relaxes sphincter of Oddi
• Stimulates growth of
exocrine pancreas
• ↑ Intestinal motility
• Inhibits gastric emptying
• Constricts pyloric sphincter
Factors regulating gastrin secretion
Digestive juices
1. Saliva
2. Gastric juice
3. Pancreatic juice
4. Bile
5. Intestinal juice or Succus entericus
Salivary enzymes
Type of Enzymes Functions

enzymes
Amylolytic Salivary α-amylase Hydrolyzes boiled starches to
/ Ptyalin maltose
Lipolytic Lingual lipase Hydrolyzes neutral fat (TG) into
FA & MAG in stomach (10%)
Functions of saliva
1. Mechanical functions
2. Digestive functions
3. Defensive functions
4. Excretory function
5. Buffering action
Functions of saliva
1. Mechanical functions
i. Keeps the mouth moist & facilitates speech.
ii. Helps in mastication, formation of bolus &
swallowing.
iii. Acts as lubricant.
iv. Helps in taste.
v. Dilutes hot & irritant food, thus prevents injury of
mucus membrane.
vi. Provides protective coat for oral cavity & mucus
membrane.
Functions of saliva
• Salivary α-amylase (ptyalin) acts on boiled starch &
converts it into maltose.
α-amylase
Boiled starch Maltose
• Lingual lipase digests 10% of dietary lipids in
stomach.
Lingual lipase
Triglycerides FA + DAG
10%
Functions of saliva
3. Defensive functions
• Washes down the pathogens & food particles there
by prevent bacterial growth.
• Saliva contains thiocyanate ions & lysozyme that
has antibacterial activity.
• Salivary antibody (IgA) destroys bacteria.
Functions of saliva
• Excretes urea, heavy metals (Pb, Bi, As etc), iodine,
certain drugs like morphine, penicillin etc.
5. Buffering action
• Saliva contains HCO3-, PO4-3 that act as buffer.
Functions of gastric juice
2. Excretory functions
3. Functions of gastric HCl
4. Hemopoietic function
5. Functions of gastric mucin
6. Buffering action
• Pepsin (active form of pepsinogen) in presence of
HCl converts protein into proteoses, peptones &
polypeptides.
Proteoses
Pepsin
Protein Peptones
HCl Polypeptides
2. Excretory functions
• Excretes toxins, heavy metals, certain drugs etc.
3. Functions of gastric HCl

• Converts inactive pepsinogen into active pepsin.
• Acts as antiseptic agent against bacteria.
• Keep iron in ferrous state for absorption.
• Provides acid medium for the action of enzymes,
hormones etc.
4. Hemopoietic function
• Intrinsic factor of Castle helps in absorption of
vitamin B12, there by helps in maturation of RBC.
5. Functions of gastric mucin

• Lubricates irritant substances.
• Acts as protective barrier for gastric mucosa against
acid-pepsin digestion.
6. Buffering action
• Responsible for alkaline tide.
Alkaline tide
After a heavy meal, gastric HCl secretion increases.

This in turn increases the production of HCO3-. This
HCO3- enters the plasma & increases the pH of
blood. As a result, alkalinity occurs.
This is known as alkaline tide.
At the same time, alkalinity of urine is also increased.

This is called post prandial alkaline tide.
Functions of pancreatic juice
2. Neutralizing functions
Pancreatic enzymes
Type of Enzymes Inactive form Activated by

enzymes
Proteolytic 1. Trypsin Trypsinogen Enterokinase
Trypsin
2. Chymotrypsin Chymotrypsinogen Trypsin
3. Carboxy- Procarboxy- Trypsin
polypeptidase polypeptidase
4. Elastase Proelastase Trypsin
5. Ribonuclease (RNA ase)
6.Deoxyribonuclease (DNA ase)
Pancreatic enzymes

enzymes
Proteolytic 1. Trypsin Breaks down proteins into
2. Chymotrypsin peptides.
3. Carboxypolypeptidase Splits some peptides into
amino acids.
4. Elastase Digests elastin fibers.
5. RNA ase Splits RNA.
6.DNA ase Splits DNA.
Pancreatic enzymes

enzymes
Amylolytic Pancreatic Hydrolyzes starches (both boiled &
amylase unboiled) to disaccharides & few
oligosaccharides
Lipolytic Pancreatic lipase Hydrolyzes neutral fat (TG) into FA
& MAG
Cholesterol Hydrolyzes cholesterol esters
esterase
Phospholipase Splits FA from phospholipids
Regulation of salivary secretion
Salivary secretion is regulated by autonomic nervous

system having both parasympathetic &
sympathetic control.
Salivary secretion occurs in 2 conditions:

• Food is in the mouth (Unconditioned reflex)
• Sight, smell or thought of food (Conditioned reflex)
Parasympathetic control of salivary
secretion
Food in the mouth Sight, smell or thought of food
(Unconditioned reflex) (Conditioned reflex)
Higher center
Superior & inferior salivary nuclei of brainstem
Facial & glossopharyngeal nerve
Salivary glands
↑ Secretion of watery saliva

Neurotransmitter – Acetylcholine (ACH)
Parasympathetic control of salivary
secretion
Sympathetic control of salivary secretion
Lateral horn cells of T1,2 segments of spinal cord
Preganglionic fiber
Superior cervical ganglia of sympathetic chain
Postganglionic fiber
Salivary glands
Secretion of saliva rich in organic contents
Neurotransmitter – Norepinephrine (NE)

Regulation of gastric secretion
Gastric secretion is regulated by both nervous &

hormonal control.
It occurs in 3 phases:
1. Cephalic phase
2. Gastric phase
3. Intestinal phase
Cephalic phase of gastric secretion
• It occurs before food enters the stomach.

• It accounts for about 30% of gastric secretion.
Food in the mouth Sight, smell or thought of food
(Unconditioned reflex) (Conditioned reflex)
Cerebral cortex
Appetite center in amygdala & hypothalamus
Dorsal motor nuclei of medulla
Vagus nerve
Stomach
↑ Gastric secretion (30%)

Gastric phase of gastric secretion
• It occurs when food enters the stomach.

• It is regulated by:
a. Long vago-vagal reflex
Nervous control
b. Local enteric reflex
c. Gastrin – histamine mechanism - Hormonal control
Food in the stomach
Vago-vagal Local enteric reflex Gastrin – histamine

reflex mechanism
From stomach to
brain & then back
to stomach
↑ Gastric secretion (60%)

Gastrin – histamine mechanism
Protein in stomach
↑Gastrin released from G-cells
↑ Histamine release from enterochromaffin like (ECL) cells
↑ HCl release from oxyntic cells
↑ Pepsin release from peptic cell

Gastrin – histamine mechanism
Protein in stomach  Stimulates G-cells  ↑ Gastrin

release  Stimulates enterochromaffin like (ECL) cells
 ↑ Histamine release  Stimulates oxyntic cells 
↑ HCl release  Stimulates peptic cell  ↑ Pepsin
release
Intestinal phase of gastric secretion
• It occurs when food enters the upper part of small

intestine.
• It is regulated by:
a. Nervous mechanism
b. Hormonal mechanism
Intestinal phase of gastric secretion
a. Nervous mechanism – Inhibit gastric secretion by

entero-gastric reflex
b. Hormonal mechanism :
i. Gastrin (from duodenum) - ↑ gastric secretion
(about 10%)
ii. Secretin, GIP, VIP, somatostatin - ↓ gastric
secretion
Regulation of pancreatic secretion
Pancreatic secretion is regulated by both nervous &

hormonal control.
It occurs in 3 phases:
1. Cephalic phase
2. Gastric phase
3. Intestinal phase
Cephalic phase of pancreatic secretion
• It occurs before food enters the stomach.

• It accounts for about 20% of pancreatic secretion.
Cephalic phase of pancreatic secretion
Food in the mouth

Sight, smell or thought of food
Brain
Vagus nerve
Pancreas
↑ Pancreatic secretion (20%)

Gastric phase of pancreatic secretion
• It occurs when food enters the stomach.

• It accounts for about 5-10% of pancreatic
secretion.
Intestinal phase of pancreatic secretion
• It occurs when food enters the upper part of small

intestine.
• It accounts for most of pancreatic secretion.
• It is regulated by hormonal mechanism:

a. Secretin - ↑ Pancreatic secretion rich in water &
HCO3- (hydrolytic type)
b. Cholecystokinin - ↑Pancreatic secretion rich in
enzymes (ecbolic type)
Regulation of pancreatic secretion
Regulation of bile secretion
Bile secretion is regulated by :
1. Hormonal regulation
2. Nervous regulation
3. Enterohepatic circulation of bile salts
1. Hormonal regulation
• Secretin – ↑ Water & HCO3- rich biliary secretion
• Cholecystokinin (CCK) – Contraction of gall bladder
& relaxation of sphincter of Oddi
2. Nervous regulation
• Vagal stimulation (ACH) Causes weak secretion of bile
• Local enteric reflex
3. Enterohepatic circulation of bile salts

Choleretics
Substances which increase the secretion of bile from
liver are known as choleretics.
Effective choleretic agents are :

i. Acetylcholine
ii. Secretin
iii. Cholecystokinin
iv. Acid chyme in intestine
v. Bile salts
Cholagogues
Cholagogue is an agent which increases the release of
bile into the intestine by contracting gallbladder.
Common cholagogues are :

i. Bile salts
ii. Calcium
iii. Fatty acids
iv. Amino acids
v. Inorganic acids
Any ques?
Thank you
Gastrointestinal Physiology
Lt Col Nadia Noor

MBBS, MPHIL
Alimentary tract
Functions of digestive tract
1. Ingestion of food.
2. Breaking of food into smaller particles.
3. Movement of food through the alimentary tract.
4. Secretion of various digestive juices.
5. Digestion of food.
6. Absorption of end product of digestion, water,
vitamins & minerals.
7. Excretion of unwanted substances (heavy metals,
toxins, bile pigments etc.) from the body.
Movements of alimentary tract
1. Movement of mouth: Mastication/ Chewing

2. Movement of pharynx & esophagus: Deglutition/
Swallowing
3. Movements of GIT:
a) Movement of stomach
b) Movement of small intestine
c) Movement of large intestine
Basic functional movements of GIT
• Mixing movement- Keeps the intestinal content

thoroughly mixed at all times.
• Propulsive movement- Moves food forward along

the tract for proper digestion & absorption.
Movements of GIT
a) Movement of stomach:
• Mixing movement- Mixing
• Propulsive movement- Peristalsis
b) Movement of small intestine:
• Mixing movement- Segmentation
• Propulsive movement- Peristalsis
• Movements caused by muscularis mucosa
• Villi movement
c) Movement of large intestine:
• Mixing movement- Haustrations
• Propulsive movement- Mass movement
Swallowing/ Deglutition
Swallowing is a complicated process by which food

passes from the mouth through the pharynx & into
the esophagus.
Stages of swallowing/ deglutition:

1. Oral stage- voluntary, initiates swallowing process.
2. Pharyngeal stage- involuntary, moves food through
pharynx into esophagus.
3. Esophageal stage- involuntary, moves food from
esophagus to stomach.
Voluntary stage of swallowing
Food is moistens with saliva & chewed

↓
Food bolus is formed
↓
Tongue pushes the bolus posteriorly into the pharynx
This process is under control of several areas of

cerebral cortex, including motor cortex.
Pharyngeal stage of swallowing
Food bolus enters the posterior mouth & pharynx

↓
Stimulates the epithelial swallowing receptors
↓
Sensory impulse via V & IX cranial nerves (V, IX & X)
↓
Nucleus of tractus solitarius (& nucleus ambiguus) of
medulla of brainstem
↓
↓
Stimulates reticular substance of medulla & lower pons
(Swallowing/ deglutition centers)
↓
Motor impulse via V, IX, X & XII cranial nerves (V, VII & IX)
↓
Initiate a series of automatic contractions as follows:
1. Tongue blocks the oral cavity  Prevent the food

going back into the mouth.
2. Soft palate is pulled upward to block the posterior

nares  Prevent reflux of food into the nasal
cavities.
3. Palatopharyngeal fold on each side of the pharynx

are pulled medially to form a sagittal slit  Allows
passage of food into the posterior pharynx.
4. Vocal cords close  Protects the airway.
5. Larynx is pulled upward & epiglottis swings

backward to cover the laryngeal opening 
Prevent passage of food into the trachea.
6. Upper esophageal sphincters (pharyngo-esophageal

sphincter) relax  Allows passage of food from
pharynx into upper esophagus.
7. Contraction of the pharyngeal muscle from above

downwards  Propel food through the pharynx into
the esophagus by peristalsis.
Entire process occurs in less than 2 seconds.

Neuronal circuit of pharyngeal stage of
swallowing
Bolus enters the posterior mouth & pharynx

↓
Stimulates the epithelial swallowing receptors, around
the pharyngeal opening, especially on tonsillar pillars
↓
Sensory impulse via V & IX cranial nerves (V, IX & X)
↓
Nucleus of tractus solitarius (& nucleus ambiguus) of
medulla of brainstem
↓
Neuronal circuit of pharyngeal stage of
swallowing
↓
Reticular substance of medulla & lower pons
(Swallowing/ deglutition centers)
↓
Motor impulse via V, IX, X & XII cranial nerves (V, VII &
IX)
↓
Pharyngeal muscle & tongue
↓
Initiate a series of automatic involuntary pharyngeal
muscle contractions that pushes the food materials into
the esophagus
Esophageal stage of swallowing
• Food is rapidly conducted through the esophagus

into the stomach by peristalsis.
• Esophagus exhibits 2 types of peristalsis- primary &
secondary
• Primary peristalsis- peristaltic ring contraction of
esophageal muscle forms behind the food material
which is then swept down the esophagus at a speed
of 4 cm/sec & lasts for about 8-10 sec.
• Secondary peristalsis
When 10 peristalsis fails to move food into the stomach
↓
Distension of esophagus
↓
Impulse from intrinsic neural circuit of myenteric plexus
& partly from reflex generated in pharynx
↓
Vagus nerve
↓
↓
Medulla
Glossopharyngeal & vagus nerve Vagus nerve

↓ ↓
Upper 1/3rd of esophagus Lower 2/3rd of esophagus
Initiates secondary peristaltic waves

Before esophageal peristaltic wave approaches toward

stomach
↓
A wave of relaxation transmitted through the myenteric
inhibitory plexus
↓
Receptive relaxation of stomach & lower esophageal
sphincter (gastro-esophageal sphincter)
↓
Propulsion of food into the stomach
Swallowing/ Deglutition
Nervous system of GIT is called enteric nervous system.
Location- lies entirely in the wall of gut, beginning in the

esophagus & extending all the way to anus.
Number of neurons- about 100 million
Enteric NS is composed of 2 plexuses:

1. Myenteric plexus/ Auerbach’s plexus
2. Meissner’s plexus/ Submucosal plexus
1. Myenteric plexus/ Auerbach’s plexus:

Location- outer plexus, lies between the longitudinal &
circular muscle layers extending the entire length of
GIT.
Function- Controls GI movements.
2. Meissner’s plexus/ Submucosal plexus:

Location- inner plexus, lies in the submucosa.
Function- Controls GI secretions & local blood flow.
Myenteric & Meissner’s plexus
Neurotransmitters secreted by ENS
1. Acetylcholine
2. Norepinephrine
3. Adenosine triphosphate
4. Serotonin
5. Dopamine
6. Cholecystokinin
7. Substance P
8. VIP (Vasoactive intestinal polypeptide)
9. Somatostatin
10. Enkephalin
11. Bombesin
Stomach
• Functions of stomach
• Movements of stomach
• Chyme
• Peristalsis & peristaltic rush
• Law of gut
• Hunger contraction & hunger pangs
• Gastric/ Stomach emptying
Functions of stomach
A. Motor function
B. Secretory function
C. Digestive function
D. Absorptive function
E. Stimulatory function
F. Antiseptic function
G. Protective function
Motor functions of stomach
1. Storage function: Stores large quantity of food until

food can be processed in stomach, duodenum &
lower intestinal tract.
2. Mixing function: Mixes food with gastric secretions
until a semisolid mixture called chyme is formed.
3. Slow emptying function: Ensures slow emptying of
chyme from stomach into the small intestine at a
suitable rate for proper digestion & absorption by
small intestine.
Secretory functions of stomach
Cells Secretion
Peptic/ Chief/ Zymogenic cell Pepsinogen, gastric renin
Parietal/ Oxyntic cell HCl, Intrinsic factor of Castle
Mucus neck cell Mucin
G cell Gastrin
Entero chromaffin like cell (ECL Histamine
cell)
Digestive functions of stomach
Pepsin (active form of pepsinogen) in presence of HCl

converts protein into proteoses, peptones &
polypeptides.
Proteoses
Pepsin
Protein Peptones
HCl Polypeptides
Absorptive functions of stomach
1. Stomach absorbs small amount of water, alcohol,

certain drugs etc.
2. Stomach produces Intrinsic factor of Castle which
helps in absorption of vitamin B12 in terminal ileum.
Stimulatory functions of stomach
Stomach secrets gastrin which acts as a stimulator for

gastric juice secretion.
Antiseptic functions of stomach
Gastric HCl acts as an antiseptic agents against bacteria.

Protective functions of stomach
Gastric mucin acts as a lubricant and protects the

gastric mucosa from the action of HCl.
Physiologic anatomy of stomach
Chyme
Resulting mixture of food with gastric secretions that

passes down the gut is called chyme.
Appearance of chyme is like murky, milky semifluid or

paste.
Peristalsis
The anal ward movement of the gut contents is called

peristalsis.
• Basic propulsive movement of stomach & small

intestine
• Inherent property of syncitial smooth muscle tube
Peristalsis
Site- Stomach, small intestine, bile duct, glandular

duct, ureter & other smooth muscle tubes of the body.
Stimulus- Mainly by distension of gut, also physical or

chemical irritation of epithelial lining of gut or strong
parasympathetic stimulation.
Mechanism of peristalsis
Distension of gut by intestinal contents

↓
Stimulates the myenteric nerve plexus
↓
Contractile ring appears above the point of distension &
receptive relaxation below
↓
Contraction wave moves towards the distended part
(2-25 cm/sec in stomach & 1cm/sec in small intestine)
↓
Propels the luminal contents forward
Figure of peristalsis
Fig: Peristalsis
Factors affecting peristalsis
Factors promoting peristalsis

• Gastro-enteric reflex
• Gastrin, CCK, insulin, motilin, serotonin
Factors inhibiting peristalsis

• Secretin, glucagon
Peristaltic rush
In severe cases of infectious diarrhea, intense irritation

of the intestinal mucosa causes powerful & rapid
peristalsis. It is called peristaltic rush.
It is initiated by nervous reflexes of ANS & brain stem &

partly by local myenteric plexus reflexes.
Law of the gut
Distension of the gut

↓
Initiates peristalsis
↓
Contractile ring causes the peristalsis to begin from the
orad side of distended segment & to move forward
↓
Receptive relaxation of the gut below the distended
segment
↓
Push the intestinal contents in anal direction for 5-10 cm
Law of the gut
This complex pattern doesn’t occur in absence of

myenteric plexus. Therefore, it is called myenteric
reflex/ peristaltic reflex.
Peristaltic reflex plus the anal direction of movement of

peristalsis is called “Law of the gut”.
Hunger contraction
Intense, rhythmical contractions in the body of stomach

when stomach has been empty for several hours or
more is called hunger contraction.
• It is most intense in young, healthy people having

high degree of GI tone.
• It is also greatly increased in person having low blood

sugar.
Hunger pangs
Hunger contraction associated with mild pain in the

stomach pit are called hunger pangs.
• It begins 12-24 hours after the last ingestion of

food.
• It reaches to their greatest intensity in 3-4 days of

starvation & gradually weaken in succeeding days.
Gastric emptying / stomach emptying
The process of emptying of chyme from stomach into

the duodenum by intense, peristaltic contractions in
the stomach antrum is called gastric emptying/
stomach emptying.
Pyloric pump
Intense antral peristaltic contractions during stomach

emptying is called pyloric pump.
When pyloric tone is normal, this pyloric pump can

force up to several ml of chyme into the duodenum.
Factors regulating gastric emptying /
stomach emptying
Factors Description Action
A. Gastric 1. Gastric food ↑ Food volume stretches the stomach wall 
factors  volume elicit local myenteric reflex accentuates pyloric
Promote pump & inhibit pyloric sphincter  ↑ Emptying
emptying 2. Gastrin ↑ Activity of pyloric pump
3. Motilin Stimulates gastric motility.
B. Duodenal 1. Enterogastric • Strongly inhibit pyloric pump propulsive
factors nervous reflex contractions.
Inhibit • ↑ Tone of pyloric sphincter
emptying 2. Hormonal feedback from duodenum
a. Cholecystokinin (CCK) Inhibits pyloric pump & ↑ tone
of pyloric sphincter.
b. Secretin Inhibits gastric motility.
c. Gastro inhibitory peptide (GIP) Weakly ↓ GI motility.
Small intestine
• Segmentation contraction
• Peristalsis
Segmentation contraction
It is the basic mixing movement of the small intestine.
Mechanism
Distension of a portion of small intestine with chyme
↓
Stretching of the intestinal walls
↓
Elicits a local concentric contraction, spaced at intervals
along the intestine lasting for a fraction of min
↓
Mechanism of segmentation contraction
↓
Divides the intestine into spaced segments
↓
Relaxation of segmentation contraction
↓
Onset of a new set of segmentation contraction at new
point between the previous contractions
↓
Chop the chyme 2-3 times per minute
↓
Promote progressive mixing of food with small intestinal
secretions
Segmentation contraction
Small intestinal motility
Effect on motility Factors

Promoting motility 1. After meal
2. Gastrointestinal reflex
3. Gastrin
4. Cholecystokinin
5. Insulin
6. Motilin
7. Serotonin
8. Histamine
Inhibiting motility 1. Secretin
2. Glucagon
Large intestine
• Haustration
• Mass movement
• Defecation
• Defecation reflex
Haustration
It is the basic mixing movement of large intestine.
Mechanism
Distension of a portion of large intestine with intestinal
content
↓
Stretching of the intestinal walls
↓
Elicits a large circular constrictions, at which both
circular & longitudinal muscle contract
↓
Mechanism of haustration
↓
Cause the unstimulated portion of the large intestine to
bulge outward into bag like sacs, called haustrations
↓
Each haustration reaches its peak in about 30 seconds &
disappear during the next 60 seconds
↓
Fecal matter slowly dug into & rolled over & is gradually
exposed to the mucosal surface of large intestine
↓
Fluid & dissolved substances are absorbed until 80-
200ml of feces are expelled each day
Mass movement
It is the basic propulsive movement of large intestine.
It is a modified type of peristalsis which is initiated by

gastrocolic & duodenocolic reflexes.
Cecum & ascending colon- Propulsion by slow,

persistent haustral contraction.
Mechanism of mass movement
Distension or irritation of the colon,

usually in transverse colon
↓
Appearance of constrictive ring at the point of
distension or irritation
↓
Rapid disappearance of haustration, 20 or more cm
distal to constrictive ring
↓
Colon contracts as a single unit
↓
Mechanism of mass movement (cont)
↓
Propels the fecal material of this segment down the
colon
↓
Contraction develops progressively more force for about
30 seconds & relaxation occurs during the next 2-3
minutes
↓
Then another mass movement occurs
↓
Moves the fecal content farther along the colon
Mass movement (cont)
Velocity: 1-3 times/ day
Importance/ Significance
1. It helps to empty the content of proximal colon into
more distal part & finally into rectum.
2. It helps in desire of defecation.
Defecation
Expelling fecal matter through the anus from alimentary

tract is known as defecation.
Defecation reflex
The reflex mechanism that initiates defecation is called

defecation reflex.
It is of 2 types:
1. Intrinsic reflex - mediated by local enteric nervous
system in the rectal wall; it is relatively a weak reflex.
2. Parasympathetic reflex
Mechanism of defecation reflex
Feces enter the rectum
↓
Distension of rectal wall
Stimulates the myenteric plexus Stimulates the nerve endings of

rectum
↓
Signals transmitted to spinal cord
↓
Reflex parasympathetic signals via
pelvic nerves
Initiates peristalsis in descending colon,

sigmoid colon & rectum
↓
Mechanism of defecation reflex (cont)
↓
Descending colon, sigmoid colon & rectum force feces towards
the anus
↓
Relaxation of internal anal sphincter
↓
Voluntary relaxation of external anal sphincter
↓
Defecation takes place
Parasympathetic defecation reflex
Gastrointestinal reflex
The anatomical arrangement of the enteric nervous

system & its connection with sympathetic &
parasympathetic nervous systems supports three
types of gastrointestinal reflexes.
They are essential for gastrointestinal control.

Gastrointestinal reflex (cont)
Gastrointestinal reflexes are as follows:
1. Reflexes that are integrated entirely within the gut

wall enteric NS
These include reflexes that control GI secretions,
peristalsis, mixing contractions, local inhibitory
effects etc.
2. Reflexes from gut to prevertebral sympathetic

ganglia & then back to GIT
These include-
Gastrocolic reflex- transmit signals from stomach to
colon; to help in evacuation of colon.
Enterogastric reflex- transmit signals from colon & small
intestine to stomach; to inhibit stomach motility &
secretion.
Colonoileal reflex- transmit signals from colon to ileum;
to inhibit emptying of ileal contents into the colon.
3. Reflexes from gut to the spinal cord & brainstem &

then back to GIT
These include-
1. Reflex from stomach & duodenum to brainstem &
then back to stomach by the way of vagus nerve; to
control gastric motor & secretory activity.
2. Pain reflex; to inhibit entire GIT.
3. Defecation reflex- transmit signals from rectum to
spinal cord & then back again to colon & rectum; to
produce powerful colonic, rectal & abdominal
contractions required for defecation.
MCQ
1. Regarding enteric nervous system

a. contains about 100 trillion nerves
b. composed of myenteric & submucosal plexus
c. submucosal plexus is also known as Auerbach’s
plexus
d. Auerbach’s plexus lies in the submucosa
e. controls GI movements & secretion
MCQ
2. Neurotransmitters secreted by enteric nervous

system are
a. Acetylcholine
b. GABA
c. Cyclic AMP
d. ADP
e. Norepinephrine
MCQ
3. Swallowing
a. is a reflex response
b. is entirely a voluntary process
c. inhibits respiration
d. is also known as deglutition
e. center lies in cerebellum
MCQ
4. Functions of stomach are

a. intrinsic factor secretion
b. vitamin B12 absorption
c. chyme formation
d. gastrin production
e. food reservoir
MCQ
5. Motor functions of stomach include

a. storage of food
b. gastric emptying
c. gastric juice secretion
d. release of renin
e. peristalsis
f. HCL acid secretion
g. mixing movements
h. gastrin secretion
MCQ
6. Chief cells of stomach secrete

a. Lipase
b. Renin
c. Pepsinogen
d. HCL
e. Intrinsic factor
MCQ
7. Presence of food in stomach

a. increases pancreatic secretion
b. increases biliary secretion
c. stimulates gastrin release
d. enhances parietal cell activity
e. depresses gastric motility
MCQ
8. Peristalsis
a. is a reflex response
b. is initiated when gut wall is stretched
c. occurs in all parts of GIT
d. is a propulsive movement
e. is a mixing movement
f. is independent of extrinsic mechanism
g. moves at a rate of 200-250 m/ sec
h. increased by distension of intestine
i. increased by sympathetic stimulation
j. seen in ureter
MCQ
9. Movements of GIT
a. are enhanced by parasympathetic stimulation
b. including mixing & propulsion of food
c. are decreased in hyperthyroidism
d. are enhanced after any stressful condition
e. are associated with myenteric plexus
MCQ
10. Hormones/ Factors that inhibit gastric emptying are

a. gastrin
b. CCK-PZ
c. motilin
d. secretin
e. GIP
f. gastocolic reflex
g. enterogastric reflex
h. stretching of stomach wall
i. decreased duodenal pH
MCQ
11. Small intestinal motility is inhibited by

a. gastro enteric reflex
b. gastrin
c. secretin
d. glucagon
e. insulin
f. cholecystokinin
g. sympathetic activity
h. vagal activity
i. serotonin
MCQ
12. Physiology of digestion in large intestine include

a. synthesis of some vitamins
b. chemical digestion through bacterial action
c. chylomicrons move into lymph
d. chylomicrons are synthesized to triglycerides
e. formation of micelle
MCQ
13. Haustral movement occurs in

a. esophagus
b. stomach
c. colon
d. jejunum
e. cecum
MCQ
14. Regarding mass movement

a. is propulsive movement of large intestine
b. occurs 1-3 times/ day
c. is mixing movement of large gut
d. is associated with defecation reflex
e. is enhanced by sympathetic stimulation
MCQ
15. Functions of colon include

a. absorption of carbohydrate
b. storage of feces
c. absorption of electrolyte
d. prevention of back flow of fecal matter
e. emptying of food
Any ques?
Thank you
Renal Physiology
Lt Col Nadia Noor

MBBS, MPHIL
Physiologic anatomy of kidney
Number- 2 (two) in number
Location- lie on the posterior abdominal wall, outside
the peritoneal cavity.
Weight- 150 grams
Size- size of a clenched fist
Hilum- indented region on the medial side of each
kidney, through which pass the renal artery &
vein, lymphatics, nerve supply & ureter.
Kidney is surrounded by tough, fibrous capsule that
protects its delicate inner structure.
Kidney
Parts of a kidney
1. Outer cortex
2. Inner medulla

ü Medulla is divided into 8-10 cone shaped masses

of tissues called renal pyramids.
ü Base of each pyramid is located at the border
between cortex & medulla & terminates in papilla.
ü Each papilla drains into minor calyx.

Physiologic anatomy of kidney (cont)
ü 2-3 minor calices combine to form major calyx.
ü Major calices project into a funnel shaped space
called renal pelvis.
ü Renal pelvis continues with the upper end of
ureter.

Basic structure of kidney
Functions of kidney
1. Formation of urine
3. Regulatory function
4. Endocrine function
5. Synthetic function
6. Degradative function
7. Detoxifying function
8. Metabolic function
Functions of kidney
1. Formation of urine.
i. Excretion of metabolic waste products, such as-
a. urea (nitrogen containing end product of protein
metabolism)
b. uric acid (from nucleic acid metabolism)
c. creatinine (end product of muscle metabolism)
d. bilirubin (end product of Hb breakdown)
Functions of kidney (cont)
ii. Excretion of foreign chemicals such as toxin,

drugs, hormone metabolites, pesticides.
iii. Excretion of excess water & ions with
conservation of necessary substances (glucose,
amino acid).
3. Regulatory function
i. Regulation of water & electrolyte balances
ii. Regulation of arterial pressure
iii. Regulation of acid-base balance
iv. Regulation of body fluid osmolarity
4. Endocrine function
i. Renin
ii. Erythropoietin- stimulates the hematopoietic stem
cells of bone marrow to cause erythropoiesis
iii. 1, 25 Dihydroxycholecalciferol (active vitamin D)-
Regulate Ca++ & PO4-3
5. Synthetic function
i. Synthesis of glucose from amino acid by
gluconeogenesis during prolong starvation.
ii. Synthesis of ammonia which plays role in acid-
base balance.
6. Degradative function
Degradation of several polypeptide hormones, such
as insulin, glucagon & PTH.

7. Detoxifying function
Detoxification of certain drugs, chemicals.
8. Metabolic function
Stimulates AA oxidation, deamination &
gluconeogenesis.

Nephron
Nephron is the structural & functional unit of kidney.
Number – 1-1.2 million (8,00,000-10,00,000) in each

kidney
Nephrons cannot be regenerated.
Parts of nephron
Nephron has 2 parts:
1. Renal corpuscle
a. Glomerulus
b. Bowman’s capsule
2. Renal tubules
a. Proximal convoluted tubules (PCT)
b. Loop of Henle
c. Distal convoluted tubule (DCT)
d. Collecting tubule
e. Cortical collecting duct
f. Medullary collecting duct
Basic structure of nephron
Basic structure of nephron
Types of nephron
Cortical nephron Juxta medullary nephron

70-80 % 20-30 %
Glomeruli located in Glomeruli located deep in the
outer cortex. renal cortex near the medulla.
Have short loop of Henle. Have long loop of Henle.
Blood supply- Blood supply- Vasa recta
peritubular capillaries
Formation of dilute Formation of concentrated
urine. urine.
Types of nephron
Renal blood flow & renal fraction
Renal blood flow- 1100 ml/ min (1200-1300 ml/min);

22% (25%) of CO
RBF is more in renal cortex than renal medulla (1-2%).
Renal plasma flow- 650 ml/ min (700 ml/ min)
Renal fraction
The portion of CO that passes through the kidneys per
minute is called renal fraction.
It is about 20-25% of the CO.
Renal circulation
Renal artery  Interlobar artery  Arcuate artery 
Interlobular artery  Affarent arterioles 
Glomerular capillaries  Efferent arterioles 
Peritubular capillaries (In cortical & JM nephrons)/
Vasarecta (In JM nephrons)  Interlobular vein 
Arcuate vein  Interlobar vein  Renal vein
Renal circulation
Renal circulation
Renal circulation
Renal artery
Interlobar artery
Arcuate artery
Renal vein
Interlobular artery
Interlobar vein
Affarent arterioles
Glomerular capillaries Arcuate vein
Efferent arterioles Interlobular vein
Peritubular capillaries (In cortical & JM nephrons)/
Vasarecta (In JM nephron
Renal circulation
Glomerular capillary membrane
The glomerular capillary membrane of the kidney is

the basal lamina layer of the glomerulus.
Total area- 0.8 m2
Layers
1. A single layer of capillary endothelium
2. Capillary basement membrane
3. A layer of epithelial cells (podocytes)
Together these 3 layers make up the filtration barrier.
Layers of glomerular capillary
membrane
1. A single layer of capillary endothelium

• It has multiple small holes called fenestrae, which
is negatively charged.
• Allows particles up to 16 nm.
2. Basement membrane
• Composed of collagen & proteoglycans, which is
negatively charged.
• Allows particles up to 11 nm.
membrane
3. A layer of epithelial cells (podocytes)

• Line the outer surface of capillary basement.
• These cells have foot like projections
(pseudopodia) that are separated by filtration slit
pores, which are negatively charged & allows
particles up to 7 nm.
membrane
Neutral substances with MW < 4 nm can effectively

pass through the glomerular capillaries.
Thus all these 3 layers of glomerular capillary

membrane provide a barrier to filtration of plasma
proteins.
membrane
membrane
Dynamics of fluid exchange across
glomerular capillary
Forces causing filtration of fluid across the glomerular

capillary
Forces favoring filtration mm Hg

Glomerular hydrostatic pressure 60
Bowman’s capsule COP 0
Total outward force 60
Forces opposing filtration of fluid across the

Forces opposing filtration mm Hg

Glomerular capillary COP 32
Bowman’s capsule hydrostatic pressure 18
Total inward force 50
So, net filtration pressure = 60 - 32 - 18 = 10 mm Hg,
that favors filtration.
Forces causing filtration by the

Fig- Forces causing filtration by glomerular capillaries

Peculiarities of renal circulation

A. Peculiarities of renal blood flow (RBF)

1. RBF is very high, about 1200-1300 ml (20-25% of
total CO). This huge blood flow helps in rapid
filtration & poor reabsorption of waste products.

Peculiarities of renal circulation
A. Peculiarities of renal blood flow (RBF)

2. Blood flow in the kidney is not uniform. Bulk of
flow pass through the cortex; whereas slow,
sluggish flow through the medulla (1-2% pass
through vasa recta).
3. Renal blood flow is auto regulated despite marked
changes in arterial pressure (range 75-160 mm Hg).

Peculiarities of renal circulation (cont)

B. Vascular peculiarities
1. Renal circulation is a portal system. Blood has to
pass double capillary network, which is glomerular
capillary & peritubular capillary.
2. Glomerular capillary is the only capillary that
drains into arterioles.
3. GCHP is fairly high, about 60 mm Hg, that helps in
filtration.

Peculiarities of renal circulation (cont)

4. Peritubular capillary pressure is low, about 13 mm
Hg, that helps in reabsorption.
5. Glomerular capillaries are thick, but highly porous
than other capillaries.
6. Glomerular capillary membrane is (-)vely charged,
which repels plasma proteins during filtration.
7. Glomerular capillaries act as a filtration bed &
peritubular capillaries act as a reabsorption bed.

Functional importance of peculiarities of
renal circulation
1. High glomerular hydrostatic pressure (60 mm Hg)

causes high GFR, which helps in rapid filtration &
poor reabsorption of waste products.
2. Low hydrostatic pressure in peritubular capillaries
(13 mm Hg) helps in rapid reabsorption of fluid.
3. Autoregulation of renal blood flow & GFR despite
marked changes in arterial pressure (range 75-160
mm Hg) plays an important role in homeostasis.
Functional importance of peculiarities of
renal circulation (cont)
4. Low medullary blood flow (1-2 %) in comparison to
cortical blood flow preserves medullary
hyperosmolarity which is important for formation
of concentrated urine.
5. Vasarecta in juxtamedullary nephron acts as
countercurrent exchanger during formation of
concentrated urine.
6. Glomerular capillary membrane is (-)vely charged,
which repels plasma proteins during filtration.
Vasa recta in juxtamedullary nephron
Any ques?
Thank you
Renal Physiology
Lt Col Nadia Noor

MPHIL, MBBS
Urine formation- GFR
Urine formation
Urine formation results from:
1. Glomerular filtration
2. Tubular reabsorption - Reabsorption of substances
from renal tubules into the blood
3. Tubular secretion - Secretion of substances from
blood into the renal tubules
Urine formation
Renal handling of four hypothetical
substances
Glomerular filtration
1st step of urine formation
The process by which plasma is filtered in the

glomerular capillaries by all the functioning
nephrons of both kidneys is known as glomerular
filtration.
Glomerular filtration rate
The amount of glomerular filtrate formed by all the

functioning nephrons of both kidneys in each
minute is called glomerular filtration rate (GFR).
It is about 125 ml/ min or 180 L/ day.
Renal fraction
The amount of cardiac output that flows through the

renal arteries of both kidneys is called renal
fraction.
It is about 20-25% of the CO.
Filtration fraction
The fraction of renal plasma flow that is filtered

through the glomerular capillaries per minute is
called filtration fraction.
GFR
Filtration fraction= x 100
RPF
It is about 16-20%.
Glomerular filtrate
Ultra filtrate formed by all the nephrons of both

kidneys in each minute is called glomerular
filtrate.
It is about 125 ml/ min or 180 L/ day.
178.5 L (> 99%) of glomerular filtrate is reabsorbed,

only 1.5 L is excreted in each day.
Composition of glomerular filtrate
Composition of glomerular filtrate is identical to

plasma, except the cellular substances (especially
RBC), protein & substances bound to plasma
proteins (such as Ca++ & fatty acids) are absent.
In glomerular filtrate,
(-) ve ions (Cl-, HCO3-) are 5% more
(+) ve ions (Na+, K+) are 5% less- Donnan effect
Determinants of GFR
1. Net filtration pressure
2. Filtration coefficient (Kf)
Determinants of GFR
1. Net filtration pressure

It represents the sum of hydrostatic & colloid osmotic
forces across the glomerular membrane.
These forces are-
Forces favoring filtration mm Hg
Glomerular hydrostatic pressure 60
Bowman’s capsule COP 0
Determinants of GFR (cont)
Forces opposing filtration mm Hg

Glomerular capillary COP 32
Bowman’s capsule hydrostatic pressure 18
So, net filtration pressure = 60-32-18 = 10 mm Hg, that
favors filtration.
Forces causing filtration by the

Fig: Forces causing filtration by glomerular capillaries
Determinants of GFR (cont)
2. Filtration coefficient (Kf)

Kf is a measure of capacity of the capillary membrane
to filter fluid for a given NFP.
Kf = GFR
NFP
Kf ∝ GFR
Factors affecting GFR
1. Changes in RBF
2. Changes in glomerular hydrostatic pressure
3. Changes in glomerular capillary COP
4. Changes in Bowman’s capsule hydrostatic pressure
5. Changes in filtration coefficient (Kf)
6. Changes of systemic BP
7. Sympathetic stimulation
8. Effects of hormones & autacoids
9. Glomerular capillary permeability
10. Surface area of glomerular membrane
11. Age & sex
12. High protein intake & increase blood glucose
1. Changes in RBF
RBF ∝ GFR
2. Changes in glomerular hydrostatic pressure

i. Arterial pressure
Arterial pressure ∝ GFR
↑ Arterial pr (>180 mm Hg)  ↑GCHP  ↑GFR
ii. Afferent arteriolar resistance
↑ Afferent arteriolar resistance ↓GCHP ↓GFR
iii. Efferent arteriolar resistance (*)
In moderate constriction
↑ Efferent arteriolar resistance↑ Resistance to
outflow from glomerular capillaries ↑GCHP 
↑GFR
In severe constriction
↓ RBF ↑ Filtration fraction  ↑GCOP  ↓Net
filtration pressure  ↓GFR
3. Changes in glomerular capillary COP

↑ GCOP  ↓ GFR
4. Changes in Bowman’s capsule hydrostatic

pressure
↑ BCHP  ↓ GFR

5. Changes in filtration coefficient (Kf)

Kf is a measure of capacity of the capillary membrane
to filter fluid for a given NFP.
Kf = GFR
NFP
Kf ∝ GFR
6. Changes of systemic BP
Between 75 & 160 mm Hg arterial pressure, GFR
remains constant.
<70 mm Hg  ↓ GFR
>180 mm Hg  ↑ GFR
7. Sympathetic stimulation
↑ Sympathetic stimulation  ↑ Constriction of renal
arterioles  ↓ RBF  ↓ GFR
8. Effects of hormones & autacoids

Vasoconstrictors – E, NE, endothelin  constricts
vessels  ↓ RBF  ↓ GFR
Angiotensin II- constricts efferent arterioles (*)
Vasodilators – Endothelial derived NO, prostaglandin,

bradykinin  ↓ Resistance  ↑ RBF  ↑ GFR

Effects of hormones & autacoids on GFR

Hormones Effect on GFR
Norepinephrine ↓
Epinephrine ↓
Endothelin ↓
Angiotensin II ← (prevents↓)
Endothelial derived NO ↑
Prostaglandins ↑
9. Glomerular capillary permeability

Glomerular capillary permeability ∝ GFR
10. Surface area of glomerular membrane

Surface area of glomerular membrane ∝ GFR
11. Age & sex

GFR varies with age & sex. 10% less in female.
12. High protein intake & increase blood glucose

↑RBF  ↑GFR

Importance of GFR
1. Causes rapid filtration & poor reabsorption of

waste products by the kidneys.
2. All the body fluids are filtered & processed by the
kidneys many times [As plasma is 3 liters & GFR is
180 L/ day, so plasma is filtered & processed by the
kidneys 60 times/ day].
3. Allows the kidney to rapidly & precisely control the
volume & concentration of the body fluid.
Juxtaglomerular apparatus (JGA)
Initial segment of the distal tubule that comes in

contact with the afferent & efferent arterioles of
glomerular capillary plexus changes their
characteristics to form Juxtaglomerular apparatus
(JGA).
It consists of-
1. Juxtaglomerular cells (JG cells)
2. Macula densa
3. Lacis cell
Juxtaglomerular apparatus (JGA)
1. JG cells- modified epithelium lining the afferent &
efferent arterioles, which secret renin.
2. Macula densa- specialized epithelium of DT that
comes in contact with the afferent & efferent
arterioles; can sense the changes in NaCl conc in
tubular blood.
3. Lacis cell- agranular, present at the junction
between afferent & efferent arterioles; secret
renin.
Juxtaglomerular apparatus
Juxtaglomerular apparatus
Autoregulation of GFR
Intrinsic ability of the kidney that keeps the RBF & GFR
relatively constant despite marked changes in
arterial pressure ranges between 75 & 160 mm Hg
is called autoregulation of GFR.
Mechanism of autoregulation of GFR
A. Tubuloglomerular feedback
B. Myogenic autoregulation

Tubuloglomerular feedback
It has two components that act together to control

GFR:
1. Afferent arterial feedback mechanism
2. Efferent arterial feedback mechanism
These feedback mechanisms depend on the special

arrangement of juxtaglomerular complex which
consists of macula densa (modified epithelial cells
of DT) & juxtaglomerular cells (lining the afferent
& efferent arterioles).

Flowchart of tubuloglomerular feedback
↓ Arterial pressure
↓ GCHP
↓ GFR
↓ NaCl in macula densa
↑ Renin from JG cells
↓ Afferent arteriolar
resistance ↑ Angiotensin II
↑ Efferent arteriolar
↑ Glomerular blood flow resistance
↑ GCHP
↑ GFR towards normal
Myogenic autoregulation
Ability of the blood vessel mainly small arterioles to

resist stretching during increased arterial pressure
is referred to as myogenic autoregulation.
Flowchart of myogenic autoregulation
↑ BP
↑ Wall tension or wall stretch
Movement of Ca++ from ECF to vascular smooth muscle
Contraction of vascular smooth muscle
↑ Resistance of the vessel
Prevents excess ↑ in RBF & GFR
Protects the kidney from HTN induced injury
Renal clearance/ Plasma clearance
Virtual volume of plasma that is completely cleared of
a substance by the kidneys in each minute is called
renal clearance/ plasma clearance.
Importance of renal/ plasma clearance
i. Quantify the excretory function of the kidneys.
ii. Quantify the renal plasma flow (by clearance of
PAH).
iii. Quantify the basic function of kidney- GFR (by
clearance of inulin), tubular reabsorption &
tubular secretion.
Calculation of renal/ plasma clearance
Cs= Clearance rate of a substance
Us x V Ps= Plasma conc. of a substance
Cs= ;
Ps Us= Urine conc. of a substance
V= Urine flow rate
Thus renal clearance of a substance is calculated

from the urinary excretion rate (Us x V) of that
substance divided by its plasma concentration.
Measurement of GFR
Principle
If a substance is freely filtered (as freely as water),
neither reabsorbed, nor secreted by the renal
tubules, then the rate at which the substance is
excreted in urine (Us x V) is equal to the filtration
rate of that substance (GFR x Ps).
Thus, GFR x Ps = Us x V
Measurement of GFR (cont)
Therefore, GFR can be calculated as the clearance of

the substance as follows:
U x V
GFR = = C s
s
Ps
Here clearance of inulin is used to measure GFR.
Radioactive iothalamate & creatinine can also be
used to measure GFR.
Measurement of GFR by inulin clearance
So, Us x V
GFR = ;
Ps
Uinulin x V
=
Pinulin Pinulin - 1 mg/ ml

125 mg/ ml x 1 ml/ min
= ; V - 1 ml/ min
1 mg/ ml Uinulin – 125 mg/ ml
= 125 ml/ min
Measurement of GFR by inulin clearance
Inulin
Inulin is a polysaccharide (polymer of fructose).
• MW- about 5200.
• Found in roots of certain plants.
• Use- Administered intravenously to a patient to
measure GFR [10 gm of inulin dissolved in 100 ml
of normal saline is injected intravenously at the
rate 10 drops/ min]
Advantage/ criteria of Inulin
1. Freely filtered (as freely as water).
2. Neither reabsorbed, nor secreted by the renal
tubules.
3. Non toxic, biologically inert
4. Not produced or metabolized by the body.
5. Not stored in the kidney.
6. Easily & accurately measured.
Measurement of GFR by creatinine
clearance
Creatinine (product of muscle metabolism) is cleared

from the body almost entirely by glomerular
filtration.
Therefore, creatinine clearance can be used to
measure GFR.
24 hours urine is collected, then creatinine clearance

is calculated.
UCr x V
CCr = = GFR
PCr
Measurement of GFR by plasma
creatinine clearance
Creatinine clearance- In male- 90-140 ml/ min
In female- 80-125 ml/ min
Serum creatinine- In male- 0.6 - 1.2 mg/ ml
In female- 0.5 - 1.1 mg/ ml
Plasma creatinine concentration is inversely

proportional to GFR.
Advantage of creatinine clearance
1. No need of drug taking or infusion.
2. Daily creatinine production is remarkably constant.
3. Serum creatinine is little effected by protein intake.
4. It is related to age, sex & muscle mass.
5. Creatinine is not reabsorbed in the renal tubules.
6. Creatinine is filtered by the glomeruli into the renal
tubules.
Disadvantage of creatinine clearance
Small amount of creatinine is secreted into the renal

tubules, so the amount of creatinine excretion
slightly exceeds the amount filtered.
That’s why creatinine clearance is not a perfect marker
for estimating GFR.
Measurement of RPF
If a substance is completely cleared from the plasma,
then the clearance rate of that substance is equal
to the total renal plasma flow.
So the amount of substance in blood delivered to the
kidneys (RPF x Ps) is equal to the amount excreted
in urine (Us x V).
Thus, RPF could be calculated as follows:
Us x V
RPF = = C s
Ps
Measurement of RPF (cont)
P- aminohippuric acid (PAH) is used to measure RPF,

which is about 90% cleared from plasma.
PAH is filtered by the glomeruli & secreted by the
tubular cells, so its extraction ratio (EPAH) is high.
Arterial conc of PAH (PPAH) - Venous conc of PAH (VPAH)
EPAH=
Arterial conc of PAHPPAH
0.01 mg/ml – 0.001 mg/ml
=
0.01 mg/ml

= 0.9
UPAH x V
ERPF = = C PAH ERPF = Effective RPF
PPAH
= 5.85 mg/ ml x 1 ml/ min
0.01 mg/ ml
= 585 ml/ min
ERPF 585 ml/ min
Actual RPF= = = 650 ml/ min
EPAH 0.9
Use of clearance to quantify kidney
function
Clearance rate of other substances
Distribution of blood flow throughout
the body
Any ques?
Thank you
Renal Physiology
Lt Col Nadia Noor

MPHIL , MBBS
Tubular reabsorption & secretion
Tubular reabsorption
Substances reabsorbed from renal tubules
Substances secreted into renal tubules
Plasma load
Filtered load/ Tubular load
Regulation of tubular reabsorption
Fluid exchange across peritubular capillary
Transport maximum (Tm)
Renal threshold
Reabsorption of glucose, AA, Na, HCO3- & H2O
H+ secretion
Tubular reabsorption
Tubular reabsorption represents the net transport of

any substance from the tubular fluid to the
interstitial space of blood.
Substances reabsorbed from PCT
Completely
reabsorbed: (100%)
ü Glucose
ü Amino acid
ü Vitamins
ü Acetoacetic acid
Partially, but actively
reabsorbed:
ü Na+, K+ (65%)
ü Ca++ (<65%)
ü Mg++ (25%)
ü PO4-3 (75-80%)
Substances reabsorbed from PCT (cont)
Passively:
ü H2O (65%)- by osmosis
ü Cl- (50%)- by FD
ü Urea (40-50%)- by FD
A separate mechanism:
ü HCO3- (80-90%)
Substances secreted into the PCT
ü H+
ü Organic acid &
bases, i.e. K+, NH3,
bile salt, oxalate,
creatinine, urate,
PAHA (90%),
catecholamines
ü Drugs- penicillin,
salicylates
Substances reabsorbed from DLLH
DLLH:
ü H2O (20%)- by osmosis
ü Na+, Cl-, urea- small amount; by diffusion

Substances reabsorbed from ALLH
Thin ALLH:
ü H2O – Impermeable
ü Na+, Cl- - by diffusion
Thick ALLH:
ü Na+, K+, Cl- (25%)- by Na-2Cl-K CoT
ü Ca++ (25-30%), Mg++(65%)
ü HCO3- - by Na-HCO3- CoT
ü PO4-3 (small amount)
Substances secreted into the ALLH
Thin ALLH:
ü Urea- urea recycle
Thick ALLH:
ü H+
Substances reabsorbed from early DT
Early DT:
ü Na+, Cl- - by Na-Cl CoT
ü Ca++, Mg++ (<5%)
ü HCO3- - by Na-HCO3- CoT
ü PO4-3 (10%)

Substances secreted into the early DT
Early DT:
ü H+

Substances reabsorbed from late DT & CCT
Late DT & cortical CT:

ü H2O - + ADH
ü Na+, Cl- - + Aldosterone; by principle cells
ü K+(65%) - by intercalated cells
ü HCO3- - In exchange of H+
ü Urea- Impermeable

Substances secreted into late DT & CCT
Late DT & cortical CT:

ü K+- + Aldosterone; by principle cells
ü H+- by intercalated cells
ü NH3

Substances reabsorbed from MCD
Medullary CD:
ü H2O - + ADH
ü Na+, Cl- - + Aldosterone
ü Urea- by FD
ü HCO3-- In exchange of H+
Substances secreted into the MCD
Medullary CD:
ü H+

Substances reabsorbed & secreted in renal tubules
Segment Reabsorbed Secreted
1. PCT Completely reabsorbed (100%) • H+
• Glucose • Organic acid &
• Amino acid bases, i.e. K+,
• Vitamins NH3, Cr, urate,
• Acetic acid PAHA (90%),
Partially, but actively reabsorbed catecholamines
• Na+, K+ (65%) • Drugs-
• Ca++ (<65%) penicillin,
• Mg++ (25%) salicylates
• PO4-3 (75-80%)
Passively
• H2O (65%)- by osmosis
• Cl- (50%)- by FD
• Urea (40-50%)- by FD
A separate mechanism
• HCO3- (80-90%)

2. DLLH • H2O (20%)- by osmosis x
• Na+, Cl-, Urea (small amount)-
by FD
3. Thin ALLH • H2O - Impermeable • Urea – by urea
• Na+, Cl-- by diffusion cycle
4. Thick ALLH • H2O - Impermeable • H+
• Na+, Cl-, K+ - by Na-2Cl-K CoT
• Ca++ (25-30%)
• Mg++ (65%)
• HCO3- - by Na-HCO3 CoT
• PO4-3 (small amount)

5. Early DT • H2O - Impermeable • H+
• Na+, Cl- - by Na-Cl CoT
• Ca++, Mg++ (<5%)
• HCO3- - by Na-HCO3 CoT
• PO4-3 (10%)
6. Late DT, • H2O - + ADH • H+
CCT • Na+, Cl- - + Aldosterone ; by • K+- + Aldosterone;
principle cell by principle cell
• K+ (65%) – by intercalated • NH3
cell
• HCO3- - In exchange of H+ ;
by intercalated cells
• Urea – Impermeable

7. MCD • H2O - + ADH • H+
• Na+, Cl- - + Aldosterone ; by
principle cell
• HCO3- - In exchange of H+ by
intercalated cells
• Urea - by FD
Site of tubular reabsorption
1. Glucose - PCT
2. Amino acid - PCT
3. Na+ - PCT, LH, DT, CCT, MCD
4. K+ - PCT, thick ALLH, late DT, CT, CD (by intercalated
cells)
5. HCO3- - PCT, thick ALLH, early DT, late DT, CT, CD
6. H2O - PCT, DLLH, late DT, CT, CD (+ ADH)
Site of tubular secretion
1. H+ - PCT, thick ALLH, DT, CT, CD
2. K+ - PCT, late DT, CT (+ Aldosterone)
Plasma load
The total amount of substance present in plasma that
passes through the kidneys per minute is called
plasma load.
Plasma load= RPF x plasma conc. of substance
Plasma load of glucose= 650 ml/ min x 1mg/ ml
= 650 mg/ min
Filtered load/ Tubular load
The total amount of substance present in plasma that
is filtered through the glomerular capillaries per
minute is called tubular load/ filtered load.
Filtered load= GFR x Plasma conc. of a substance
Filtered load of glucose= 125 ml/ min x 1mg/ ml
= 125 mg/ min
Regulation of tubular reabsorption
1. Glomerulotubular balance
2. Hormonal factors
3. Nervous factors
Glomerulotubular balance
Intrinsic ability of the tubules to increase their

reabsorption rate in response to increased tubular
load (filtered load) is known as glomerulotubular
balance.
↑ Tubular load (filtered load)
↓
↑ GFR
↓
↑ Reabsorption rate in renal
tubules
↓
Prevents sudden change in GFR
on urine output

Hormonal factors regulating tubular
reabsorption
Hormone Site of action Effects

Aldosterone CT, CD ↑ NaCl, H2O reabsorption
↑ K+ secretion
ADH DT, CT, CD ↑ H2O reabsorption
Angiotensin II PT, thick ALLH, ↑ NaCl, H2O reabsorption
DT, CT ↑ H+ secretion
ANP DT, CT, CD ↓ NaCl reabsorption
PTH
PT, thick ALLH, ↓ PO 4
-3 reabsorption
DT ↑ Ca++ reabsorption
Nervous factors regulating tubular
reabsorption
Directly
Sympathetic stimulation
↓
↑ Reabsorption of Na (mainly) & water
Indirectly
Sympathetic stimulation
↓
↑ Renin
↓
↑ Angiotensin II
↓
↑ Reabsorption of Na & water
peritubular capillary
Forces opposing reabsorption of fluid across the

Forces opposing reabsorption mm Hg

Peritubular capillary hydrostatic pressure 13
Renal interstitium COP 15
Forces causing reabsorption of fluid across the

Forces causing reabsorption mm Hg

Peritubular capillary COP 32
Renal interstitium hydrostatic pressure 6
So, net reabsorption pressure = 38 – 28 = 10 mm Hg,
that favors reabsorption.
The maximum rate at which a substance can be

actively transported (reabsorbed or secreted) by
the renal tubules in each minute is called transport
maximum (Tm).
Limitation is due to saturation of carrier proteins or

enzymes of the transport systems.
Tm of glucose- 375 mg/ min
Renal threshold
It is the plasma concentration of a substance below

which the substance will not appear in urine, but
at or above which the substance will appear in
urine more than the normal minute amount.
Renal threshold for glucose= 200-220 mg/dl (180mg%)
>220mg/dl- Glucose appear in urine (Glycosuria)

Glucose reabsorption
Virtually all the filtered glucose (100%) is reabsorbed

from the proximal tubules (PT).
Glucose reabsorption
From tubular lumen into tubular epithelium:

By Na-glucose CoT (SGLT2 & SGLT1) in the luminal
membrane.
90% of filtered glucose- reabsorbed by SGLT2 in early

part of PT (S1 segment)
10% of filtered glucose- reabsorbed by SGLT1 in later
part of PT (S3 segment)
Glucose reabsorption (cont)
From tubular epithelium into interstitial fluid:

By glucose transporters (GLUT2 & GLUT1) in the
basolateral membrane by facilitated diffusion.
Glucose diffuse from the early part of PT (S1 segment)
- by GLUT2
Glucose diffuse from the later part of PT (S3 segment)
- by GLUT1
Glucose reabsorption in PT
Glucose reabsorption (cont)
Here energy is provided by Na-K pump which creates

an electrochemical gradient across the luminal
membrane that helps in reabsorption of glucose.
Amino acid reabsorption
Virtually all the filtered amino acid (100%) is

reabsorbed from the proximal tubules (PT).
Amino acid reabsorption (cont)
From tubular lumen into tubular epithelium:

By Na- amino acid CoT in the luminal membrane.
From tubular epithelium into interstitial fluid:

By facilitated diffusion in the basolateral membrane.

membrane that helps in reabsorption of AA.
Amino acid reabsorption in PT
Na+ reabsorption
Site of reabsorption:
• PT
• DLLH
• Thin ALLH
• Thick ALLH & early DT
• Late DT & cortical CT
Na+ reabsorption in PT
Following transporters are present in PCT for transport
of Na:
• Na- glucose CoT
• Na-AA CoT At the luminal membrane
• Na-H exchanger
• Na-K pump - At the basolateral membrane
Na+ reabsorption in PT (cont)
About 65% of the filtered Na+ is actively reabsorbed in
PT along with glucose & AA by Na- glucose & Na-
AA CoT respectively & in exchange of H+ by Na-H
exchanger.

membrane that helps in reabsorption of Na+ in PT.
Reabsorption of Na+ in PT
Reabsorption of Na+ in DLLH
Small amount of Na+ is passively reabsorbed in DLLH..

Na+ reabsorption in thick ALLH
Following transporters are present in thick ALLH for

transport of Na:
• Na-2Cl-K CoT
• Na-H exchanger At the luminal membrane
• Na-K pump - At the basolateral membrane
Na+ reabsorption in thick ALLH
About 25% of filtered Na+ is actively reabsorbed in the
thick ALLH along with Cl- & K+ by Na-2Cl-K CoT & in
exchange of H+ by Na-H exchanger.

membrane.
Reabsorption of Na+ in thick ALLH
Na+ reabsorption in early DT
About 5% of filtered Na+ is actively reabsorbed in the
early DT along with Cl- by Na-Cl CoT.

membrane.
Reabsorption of Na+ in early DT
Na+ reabsorption in late DT & cortical CT
Na+ is passively reabsorbed by the principle cells of

late DT & cortical CD under the influence of
aldosterone.
Here aldosterone stimulates the Na-K pump at the

basolateral membrane, which creates an
electrochemical gradient across the luminal
membrane that allows diffusion of Na+.
Na+ reabsorption in late DT & cortical CT
Na+ reabsorption in medullary CD
About 10% of the filtered Na+ is reabsorbed in the
medullary CD.
Reabsorption of HCO3-
HCO3- filtered - 4320 mEq/ day
HCO3- excreted - 1 mEq/ day
HCO3- is reabsorbed in-
• In early tubules (PT, thick ALLH & early DT)- 95%
• In late tubules (intercalated cells of late DT, CT & CD)
Reabsorption of HCO3-
HCO3- reabsorption in early tubules
In early tubules (PT, thick ALLH & early DT):
H+ is secreted into the tubular fluid by Na-H exchanger,
caused by concentration gradient derived from Na-K
pump that is present on the basolateral membrane.
At the lumen,
CA
Filtered HCO3- + H+ H 2CO3
CA
H 2CO3 CO2 + H2O
CO2 diffuse into the tubular cell.
CA
CO2 + H2O H2CO3
CA
H2CO3 HCO - + H+
3
HCO3- moves across the basolateral membrane or along
with Na+ by Na-HCO3 CoT in PT.
Reabsorption of HCO3- in early tubules
HCO3- reabsorption in late tubules
In late tubules (Intercalated cells of DT, CT & CD):

In the tubular epithelium,
CA
Dissolved CO2 + H2O H 2CO3
CA
H 2CO3 HCO - + H+
3
H+ is secreted into the tubular fluid by H-ATPase pump.
For each H+ secretion, one HCO3- is reabsorbed in
blood by Cl-HCO3 exchanger at the basolateral
membrane.
HCO3- reabsorption in late tubules
H+ secretion
H+ secreted- 4400 mEq/ day
• 4320 mEq/ day is secreted to reabsorb HCO 3-
• 80 mEq/ day is secreted to rid the body of non
volatile acids
H+ is secreted in-
• In early tubules (PT, thick ALLH & early DT)
H+ secretion
Secretion of H+ (4320 mEq) in exchange of HCO3-:

• In early tubules (PT, thick ALLH & early DT)
Secretion of excess H+ (80 mEq):

• By phosphate buffer
• By ammonia buffer
H+ secretion in early tubules
In early tubules (PT, thick ALLH & early DT):

caused by concentration gradient derived from Na-K
pump that is present on basolateral membrane.
At the lumen,
CA
Filtered HCO3 + H H 2CO3
- +
CA
H 2CO3 CO 2 + H2O
CO2 diffuse into the tubular cell.
CA
CO2 + H2O H 2CO3
H2CO3 HCO
CA
3
- + H+
For secretion of each H+ one HCO3- is reabsorbed in
blood.
H+ secretion in early tubules
H+ secretion in late tubules
In late tubules (Intercalated cells of DT, CT & CD):

In the tubular epithelium,
CA
CA
H 2CO3 HCO - + H+
3
H+ is secreted into the tubular fluid by H-ATPase pump.
For each H+ secretion, one HCO3- is reabsorbed in
blood by Cl-HCO3 exchanger at the basolateral
membrane.
H+ secretion in late tubules
H+ secretion by phosphate buffer
In late tubules (late DT, CT, CD):

CA
CA
H 2CO3 HCO 3
- + H+
caused by concentration gradient derived from Na-
K pump that is present on basolateral membrane.
This excess H+ combines with HPO4-- to form H2PO4-
which is excreted in urine as NaH2PO4 by carrying
excess H+.
H+ secretion by phosphate buffer
H+ secretion by ammonia buffer
In late tubules (late DT, CT, CD):

H+ is secreted into the tubular fluid by H-ATPase
pump.
This excess H+ combines with NH3 to form NH4+ which
is excreted in urine.
H+ secretion by ammonia buffer
Water reabsorption
Water is reabsorbed from the following segments by

the process of osmosis.
• PT
obligatory
• DLLH
• Late DT, CT & CD - + ADH; facultative
Water reabsorption
Obligatory water reabsorption:

Water is reabsorbed mainly from PT (65%) & also from
DLLH (20%), which is secondary to solute
reabsorption.
When solutes mainly Na+ is reabsorbed, an osmotic
difference is created across the tubular membrane.
This causes osmosis of water from the renal tubules.
Water reabsorption

Water reabsorption
Facultative water reabsorption:

Water is reabsorbed from late DT, CT & CD in presence
of ADH.

Water reabsorption
+ ADH
+ ADH
+ ADH

Diuresis
Excretion of large volume of urine is called diuresis.
Types of diuresis
1. Water diuresis
2. Osmotic diuresis
3. Pressure diuresis
Water diuresis
Excretion of large volume of dilute (hypotonic) urine is
called water diuresis.
Causes of water diuresis

i. Excess water intake
ii. Excess infusion
iii. Diabetes insipidus (Failure to produce ADH)
Water diuresis
↑ Water intake
↓
↑ ECF volume
↓
↓ Osmolarity
↓
Osmoreceptors in the hypothalamus is depressed
↓
↓ ADH secretion
↓
↓ Water reabsorption from DT and CD
↓
↑ Excretion of dilute urine
Osmotic diuresis
Excretion of large volume of concentrated (hypertonic/
isotonic) urine is called osmotic diuresis.
It occurs due to presence of excess amount of
osmotically active substance in the glomerular
filtrate.
Causes of osmotic diuresis
i. Diabetes mellitus
ii. Diuretics
iii. Mannitol infusion
Osmotic diuresis
↑ Osmotically active substance in the glomerular
filtrate (glucose, mannitol, NaCl)
↓
↑ Osmolarity of glomerular filtrate
↓
↓ Water reabsorption
↓
↑ Excretion of concentrated urine
Pressure diuresis
Excretion of large volume of dilute urine in response to
increase blood pressure (>200 mm Hg) is called
pressure diuresis.
Pressure diuresis
↑ BP (> 200 mm Hg)
↓
↓ Renin, ↓ Angiotensin II, ↓ Aldosterone
↓
↓ Reabsorption of Na & water from DT & CT
↓
↑ Urinary output
by way of
pressure diuresis & pressure natriuresis
Any ques?
Thank you
Renal Physiology
Lt Col Nadia Noor

MPHIL, MBBS
Normal urine
Normal urine
Normal urine is concentrated.
Osmolarity – 600 mOsm/ L
Specific gravity – 1002-1.028 gm/ ml
Kidney can excrete with an osmolarity as low as 50
mOsm/L or as high as 1200 mOsm/L.
Anti diuretic hormone (ADH)
Anti diuretic hormone (ADH)
v Also known as vasopressin.
v Peptide hormone of posterior pituitary gland.
Secreted by - Supraoptic (5/6) & paraventricular (1/6)
nucleus of hypothalamus.
Functions
1. ↑ H2O reabsorption from late DT, CT & CD.
2. Causes vasoconstriction & ↑ BP.
ADH
Control of ADH secretion
↓ ECF volume/ ↑ Body fluid osmolarity
Stimulate the osmoreceptors of supraoptic
& paraventricular nuclei of hypothalamus
Sends nerve impulse
Hypothalamo-hypophysial nerve tract
Post pituitary gland
Pituitary
Secret ADH stalk
↑H2O reabsorption from late DT, CT & CD
Mechanism of action of ADH
ADH
Binds with receptors on the luminal mem of tubular epi of CT & CD
Activates adenyl cyclase enzyme
Converts ATP into cAMP
cAMP causes phosphorylation of aquaporins
(special vesicles containing highly H2O permeable pores)
Insertion of aquaporins into the apical membrane
Provides many areas of high H2O permeability
Allows diffusion of H2O from tubular lumen into the tubular epi
Osmosis of H2O from tubular epi into the renal interstitium
Dilute urine
Dilute urine
When there is excess of water in the body, kidneys
excrete excess water by forming dilute urine.
Kidney can excrete dilute urine as much as 20 L/ day.
Osmolarity – as low as 50 mOsm/ L
Formation of dilute urine
Dilute urine is formed when there is -
Ø Excess water in the body (↑ ECF volume)
Ø ↓ Body fluid osmolarity
Ø Absence of ADH
Mechanism of formation of dilute urine
PCT
ü About 65% water and solutes are reabsorbed.
ü Osmolarity is same as that of plasma, 300 mOsm/ L.
DLLH
ü About 20% water is reabsorbed.
ü Small amount of NaCl & urea are also reabsorbed.
ü Isotonic to hypertonic (as high as 600 to 1200
mOsm/ L).
ALLH (thin)
ü Water impermeable.
ü NaCl is reabsorbed by passive diffusion.
ü Urea diffuse from medullary interstitium to ALLH for
urea cycle.
ü Hypertonic to isotonic.
ALLH (thick)
ü Na+, Cl-, K+ is actively reabsorbed by Na-2Cl-K Co-
transporter.
ü Other solutes (Ca++, Mg++, HCO3-, PO4-3) are also
reabsorbed.
ü Isotonic to hypotonic (100 mOsm/ L).
Early DT
ü Na+ & Cl- is actively reabsorbed by Na-Cl CoT.
reabsorbed.
ü Hypotonic.
Late DT, CT, CD

ü Water impermeable, in absence of ADH.
ü More solute reabsorbed.
ü More hypotonic (50 mOsm/ L).
Concentrated urine
Concentrated urine
When there is lack of water in the body, kidneys
conserve water by forming concentrated urine.
Kidney can excrete concentrated urine as low as 0.5 L/
day.
Osmolarity – 1200 - 1400 mOsm/ L
Formation of concentrated urine
Concentrated urine is formed when
Ø A person is dehydrated (↓ ECF volume)
Ø ↑ Body fluid osmolarity
Ø Presence of ADH
Factors required for formation of
concentrated urine
1. High level of ADH
2. High osmolarity of renal medullary interstitium-
produced by countercurrent mechanism
Mechanism formation of concentrated
urine
PCT
ü About 65% water and solutes are reabsorbed.
ü Osmolarity is same as that of plasma, 300 mOsm/ L.
DLLH
ü About 20% water is reabsorbed.
ü Small amount of NaCl & urea are also reabsorbed.
ü Isotonic to hypertonic (as high as 1200 to 1400
mOsm/ L)
urine (cont)
ALLH (thin)
ü NaCl is reabsorbed by passive diffusion.
ü Urea diffuse from medullary interstitium to ALLH
for urea recycle.
ü Hypertonic to isotonic.
urine (cont)
ALLH (thick)
ü Na+, Cl-, K+ is actively reabsorbed by Na-2Cl-K Co-
transporter.
reabsorbed.
ü Isotonic to hypotonic (100 mOsm/ L).
urine (cont)
Early DT
ü Na+ & Cl- is actively reabsorbed by Na-Cl CoT.
reabsorbed.
ü More hypotonic (50 mOsm/ L).
urine (cont)
Late DT, CCT

ü In presence of ADH, water is reabsorbed.
ü Urea not reabsorbed.
ü Hypotonic to isotonic (300 mOsm/ L).
MCD
ü In presence of ADH, water is reabsorbed.
ü Urea is reabsorbed by FD.
ü Isotonic to hypertonic (1200-1400 mOsm/ L).
Mechanism of formation of
concentrated urine
Hyperosmotic medullary interstitium
Responsible factors
1. Countercurrent mechanism
2. Urea recycle
Countercurrent mechanism
The mechanism by which hyperosmotic renal

medullary interstitium is created & maintained is
known as countercurrent mechanism.
It depends on the special arrangement of loop of

Henle & vasa recta, specialized peritubular
capillaries of renal medulla.
Hypothesis of countercurrent mechanism
A small difference in osmotic concentration at any

level between fluids in counter direction in two
parallel tubes connected in a hair pin manner can
be multiplied many times along the length of the
tube.
Aim of countercurrent mechanism
1. Helps in formation of concentrated urine, thereby
conserves water in our body.
2. Creates & maintains the hyperosmolarity of renal
medullary interstitium.
Types of countercurrent mechanism
1. Countercurrent multiplier mechanism
2. Countercurrent exchanger mechanism
Creation of hyperosmotic renal
medullary interstitium
1. Countercurrent multiplier mechanism
2. Urea recycle
Countercurrent multiplier mechanism
Repetitive reabsorption of NaCl by the thick ALLH &

continued inflow of new NaCl from the PT into the
LH multiply the concentration of medullary
interstitium. This is called the countercurrent
multiplier mechanism.
Ø Served by loop of Henle.
Aim
Ø Creates hyperosmolar renal medullary
interstitium.
Factors required for countercurrent
multiplier mechanism
1. Active transport of Na+ & co-transport of K+, Cl- &

other ions from thick ALLH into the medullary
interstitium.
2. Active transport of ions from the collecting ducts
into the medullary interstitium.
Factors required for countercurrent
multiplier mechanism (cont)
3. Facilitated diffusion of urea from the inner

medullary collecting ducts into the medullary
interstitium.
4. Diffusion of small amount of water from the

medullary tubules into the medullary interstitium.
Mechanism of countercurrent multiplier
mechanism
Step 1
Ø First the fluid flows down the LH.
Ø Its osmolarity is same as that of PCT, which is
about 300 mOsm/ L.
mechanism
Step 2
Ø Na+, K+ & Cl- are actively reabsorbed by Na-2Cl-K
CoT in the thick ALLH.
Ø It increases the medullary osmolarity &
establishes a gradient of 200 mOsm/ L.
mechanism (cont)
Step 3
Ø Osmosis of water from DLLH into the medullary
interstitium.
Ø Tubular fluid of DLLH & medullary interstitium
quickly reaches to an osmotic equilibrium (400
mOsm/ L).
mechanism (cont)
Step 4
Ø Additional flow of fluid into the LH from the PT.
mechanism (cont)
Step 5
Ø Causes further reabsorption of solutes from the
thick ALLH establishes a gradient of 200 mOsm/ L.
Ø This increases the medullary osmolarity, about
500 mOsm/ L.
mechanism (cont)
Step 6
Ø This is followed by further osmosis of water from
DLLH into the medullary interstitium.
Ø Tubular fluid of DLLH & medullary interstitium
quickly reaches to an osmotic equilibrium (500
mOsm/ L).
mechanism (cont)
Ø This cycle is repeated again & again (repeat steps 4-6)
until the medulla becomes hyperosmolar with an
osmolarity of about 1200-1400 mOsm/ L.
Countercurrent multiplier system in the
Loop of Henle
Urea recycle
Urea contributes 40-50% of the medullary osmolarity
(500 to 600 mOsm/ L) during formation of
concentrated urine.
Urea recycle
Urea is transported by facilitated diffusion.
Urea transporters (UT) :
1. UT-A3 (ADH dependent) - In medullary CD
2. UT-A1
3. UT-A2 - in thin ALLH
Requirements :
Ø Water deficit
Ø High level of ADH
Mechanism of urea recycle
Ø Urea is passively reabsorbed from the medullary

CD by UT-A3 (ADH dependent) & UT-A1.
Ø This is due to presence of high urea concentration
in the medullary CD.
Ø This gradient is created by reabsorption of H2O in
the cortical CT in presence of ADH.
Mechanism of urea recycle (cont)
Ø Urea is then passively reabsorbed from the

medullary interstitium into the thin ALLH by UT-
A2 & then back to the medullary CD.
Ø Thereby urea recirculation provides an additional
mechanism for forming hyperosmotic medullary
interstitium.
Contribution of urea recycle
Preservation of hyperosmotic renal
medullary interstitium
1. Low medullary blood flow (<5%)

Ø Minimize solute loss from the medullary
interstitium.
2. The vasa recta

Ø Acts as countercurrent exchangers.
Ø Minimize washout of solutes from the medullary
interstitium.
Countercurrent exchanger mechanism
Served by vasa recta, specialized peritubular

capillaries of renal medulla.
Aim
Ø Maintains the hyperosmolarity of renal medullary
interstitium.
Vasa recta
Ø It is an U shaped tubule with a descending limb,

hairpin bend & an ascending limb.
Ø It runs parallel to loop of Henle.
Ø It retains NaCl from the medullary interstitium &

removes water from it.
Ø Recycling of urea also occurs through vasa recta.
Vasa recta in juxtamedullary nephron
Mechanism of countercurrent exchanger
mechanism
Ø First blood descends into the medulla towards the
papillae by means of vasa recta.
Ø It becomes progressively more concentrated due

to solute entry from the medullary interstitium &
also loss of water into the interstitium.
Ø At the tip of vasa recta, the concentration is about
1200 mOsm/ L, same as that of medullary
interstitium.
mechanism (cont)
Ø Then blood ascends back towards the cortex.
Ø It becomes progressively less concentrated as

solute diffuse back into the interstitium & water
moves into the vasa recta.
mechanism (cont)
Ø Thus the U-shaped structure of vasa recta, acts as
countercurrent exchanger which minimizes the
solute loss & thereby maintains the hyperosmolar
medullary interstitium.
mechanism
mechanism
Obligatory urine volume
Minimal volume of urine that must be excreted each
day by the kidneys to rid the body of metabolic
waste products is called obligatory urine volume.
It depends on the maximum concentrating ability of

the kidney which is about 1200mOsm/ L.
Obligatory urine volume (cont)
A 70 kg adult male must excrete 600 mOsm solutes

each day.
Obligate urine volume is calculated as-
Obligate urine volume = 600 mOsm/ day
1200 mOsm/L

= 0.5 L / day (500 ml/ day)
Suggestive questions
1. What are the basic principles of formation of

concentrated urine?
2. What is countercurrent mechanism?
3. Mention the factors that contribute to formation
of concentrated urine.
4. What are the mechanism that produce
hyperosmotic medullary interstitium?
5. What is obligatory urine volume?
Suggestive questions
6. How is hyperosmolarity of medullary interstitium

maintained?
7. How is dilute urine formed?
8. Kidney excretes excess water by forming dilute
urine—explain it.
9. What is the role of urea in forming concentrated
urine?
10. What is the osmotic profile of filtrate in nephron?
Any ques?
Thank you
Renal Physiology
Lt Col Nadia Noor

MBBS, MPHIL
Micturition
The process by which urine is voided from the urinary
bladder is called micturition.
Innervation of urinary bladder
1. Sympathetic nerve supply – Nerve of filling
2. Parasympathetic nerve supply – Nerve of emptying
3. Somatic nerve supply
4. Sensory nerve supply
Type of nerves Nerve fibers Functions
1. Sympathetic Hypogastric • Relaxation of detrusor muscle
nerve (L1,2,3) • Constriction of internal urethral
sphincter
• Carries sensation of fullness & pain
• Nerve of filling
2. Para- Pelvic nerves • Constriction of detrusor muscle
sympathetic/ (S2,3,4) • Relaxation of internal urethral
Motor sphincter
• Nerve of emptying
3. Somatic Pudendal • Constriction of external urethral
nerves (S2,3,4) sphincter
4. Sensory Pelvic nerves • Detect stretch signals from
(S2,3,4) bladder & post urethra
• Initiate micturition reflex
Fig: Innervation of urinary bladder (Gyton)
Fig: Innervation of urinary bladder (Ganong)
Micturition reflex
Micturition reflex is an autonomic spinal cord reflex,

facilitated or inhibited by the higher centers of
brain, when strong enough causes micturition or a
conscious desire to micturate.
Mechanism of micturition reflex
When bladder starts to fill
↓
Stimulates the stretch receptors on the bladder wall &
posterior urethra
↓
Sensory signals
↓
Pelvic nerves
↓
Mechanism of micturition reflex (cont)
↓
Sacral 2,3,4 segments of spinal cord
↓
Motor impulse
↓
Pelvic nerve
↓
Contraction of detrusor muscle
↓
Progressive & rapid rise of pressure in the bladder
↓
↓
Pressure sustains for a period of time
↓
Micturition contractions relax spontaneously after a
fraction of a minute in a partially filled bladder
↓
Detrusor muscle stops contracting
↓
Fall of pressure back to baseline
Thus micturition reflex is a single complete cycle of -
1. Progressive & rapid increase of pressure
2. A period of sustained pressure
3. Return of pressure back to baseline
Micturition reflex becomes more frequent as the

bladder continue to fill.
When micturition reflex becomes powerful enough, it
initiates another reflex.
Impulse from the higher centers
↓
Inhibit the pudendal nerve
↓
Inhibit the voluntary constriction of external urethral
sphincter
↓
Micturition takes place
Cystometrogram in a normal human
The process by which the relation between intravesical
pressure & volume can be studied is called
cystometry.
It is done by inserting a catheter & emptying the
bladder, & then recording the pressure while the
bladder is filled with 50 mL increments of water.
A plot of intravesical pressure against the volume of

fluid in the bladder is called a cystometrogram.
Cystometrogram in a normal human
Ia- Initial slight rise
in pressure after 1st
increment of 50 ml
Ib- Long, nearly flat
segment after
further increments
(Law of Laplace;
P=2T/r)
II- Sudden, sharp
rise in pressure as
micturition reflex
is triggered
Fig: Cystometrogram in a normal human (Ganong)
Normal cystometrogram caused by
micturition reflexes
• 150 ml – First urge to void
• 400 ml – Marked sense of fullness
• 300-400 ml – Initiates micturition reflex
Normal cystometrogram caused by
micturition reflexes
Fig: Normal cystometrogram, showing acute pressure waves
(dashed spikes) caused by micturition reflexes (Gyton)
Control of micturition
Micturition is controlled by the facilitative & inhibitory
centers in the brain.
These are –
1. Brain stem – facilitatory areas in the pons & an
inhibitory areas in the midbrain
2. Cerebral cortex – both facilitatory & inhibitory
Control of micturition (cont)
Functions of higher centers on micturition:

1. Inhibit micturition reflex until micturition is desired.
2. Prevent micturition by tonic contraction of the
external urethral sphincter until a convenient time
is present.
3. Facilitate the sacral centers to initiate micturition
reflex & at the time inhibit the external urethral
sphincter to cause micturition.
Voluntary micturition
Voluntary contraction of the abdominal muscles
↓
↑ Pressure in the bladder
↓
Allows extra urine to enter the bladder neck & post urethra
↓
Stimulate the stretch receptors
↓
Initiate micturition reflex
↓
Simultaneous inhibition of external urethral sphincter
↓
Micturition takes place leaving 5-10 ml in bladder
Abnormalities of micturition
1. Atonic bladder
2. Automatic bladder
3. Uninhibited (spastic) neurogenic bladder
Atonic bladder
Destruction of the Damage to the sacral
sensory nerve fibers segment of spinal cord
Failure of transmission of stretch signals from bladder
↓
Micturition reflex cannot occur
↓
Loss of bladder control
↓
Bladder fills to capacity, but fails to empty periodically
↓
Overflows a few drops at a time through urethra
(Overflow incontinence)
Cause of atonic bladder
1. Destruction of the sensory nerve fibers.
2. Damage to the sacral segment of spinal cord
3. Damage to dorsal nerve fibers that enter the spinal
cord
For example, syphilis can cause constrictive fibrosis

around the dorsal root nerve fiber & destroy them.
This condition is called tabes dorsalis & the resulting
bladder is called tabetic bladder.

Automatic bladder
Damage to spinal cord above the sacral segment
↓
Initiate micturition reflex
↓
But no voluntary control, no inhibition or facilitation
from higher centers
↓
Periodic, but unannounced micturition
Uninhibited (spastic) neurogenic bladder
Partial damage to the spinal cord or brain stem
↓
Interrupts the inhibitory signals
↓
Continuous passage of facilitative impulses to sacral center
↓
Even a small amount of urine
↓
Elicit an uncontrollable micturition reflex
↓
Promotes frequent micturition
Any ques?
Thank you

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Gastrointestinal Physiology

Lt Col Nadia Noor

A. Alimentary tract: Extends from mouth to anus.

Gastrointestinal tract (GIT):

Wall of GIT is formed by 4 layers which are from within

Gastrointestinal smooth muscle is known as

These gap junctions allow free diffusion of ions, so

The smooth muscle of GIT is excited by almost

Resting membrane potential of GIT= - 50 to - 60 mV

Cause of slow wave

Importance of slow wave

GIT has mainly two types of nerve supply:

• Afferent sensory fibers also innervate the gut.

Intrinsic nerve supply of GIT is called enteric nervous

Location- lies in the wall of GIT extending from

Number of neurons- about 100 million

Enteric NS is composed of 2 plexuses:

1. Myenteric plexus/ Auerbach’s plexus:

2. Submucosal plexus/ Meissner’s plexus:

Myenteric plexus Submucosal plexus

1. Acetylcholine – excites GI activity

Extrinsic nerves that control the GI functions are from

GIT has innervation from both -

1. Sympathetic nerve fibers

2. Parasympathetic nerve fibers

Functions of parasympathetic nerve fibers

1. Gastrin family – Gastrin, Cholecystokinin (CCK)

Hormone Stimuli for Site of Physiological actions

Type of Enzymes Functions

3. Functions of gastric HCl

5. Functions of gastric mucin

After a heavy meal, gastric HCl secretion increases.

At the same time, alkalinity of urine is also increased.

Type of Enzymes Inactive form Activated by

Type of Enzymes Functions

Type of Enzymes Functions

Salivary secretion is regulated by autonomic nervous

Salivary secretion occurs in 2 conditions:

Superior & inferior salivary nuclei of brainstem

Facial & glossopharyngeal nerve

↑ Secretion of watery saliva

Lateral horn cells of T1,2 segments of spinal cord

Superior cervical ganglia of sympathetic chain

Secretion of saliva rich in organic contents

Neurotransmitter – Norepinephrine (NE)

Gastric secretion is regulated by both nervous &

• It occurs before food enters the stomach.

Dorsal motor nuclei of medulla

↑ Gastric secretion (30%)

• It occurs when food enters the stomach.

Food in the stomach

Vago-vagal Local enteric reflex Gastrin – histamine

↑ Gastric secretion (60%)

Neurotransmitter – Acetylcholine (ACH)

↑Gastrin released from G-cells

↑ Histamine release from enterochromaffin like (ECL) cells

↑ HCl release from oxyntic cells

↑ Pepsin release from peptic cell

Protein in stomach  Stimulates G-cells  ↑ Gastrin

• It occurs when food enters the upper part of small

a. Nervous mechanism – Inhibit gastric secretion by

Pancreatic secretion is regulated by both nervous &

• It occurs before food enters the stomach.

Food in the mouth