Jigjiga University

College of Veterinary Medicine

By
Dr MAHAMUD A.(DVM, MSc)
 RENAL PHYSIOLOGY
INTRODUCTION
➢ The urinary system consists of two kidneys, two ureters, the
urinary bladder and the urethra.
➢ The two kidneys remove waste products from the blood, help
the composition of plasma, and perform certain hormonal
functions.
➢ The system of tubules in each kidney coalesces into single
muscular tube, the ureter, which extends caudally to empty to
the urinary bladder, a distensible reservoir for the storage of
urine.
➢ when full the urinary bladder discharges urine through out the
urethra to the outside of the body.
3
Anatomical consideration of The Kidneys:
• The kidneys are paired reddish-brown organs that
filter plasma and plasma constituents from the
blood and then selectively reabsorb water and
useful constituents from the filtrate, ultimately
excreting excesses water and plasma waste
products.
• The kidneys are in the dorsal part of the
abdominal cavity on each side of the aorta and
caudal vena cava, just ventral to the first few
lumbar vertebrae.
• A fibrous connective tissue layer, called the renal
capsule, encloses each kidney, and around the renal
capsule is a dense deposit of adipose tissue, the
perirenal fat, which protects the kidney from
mechanical shock.
• On the medial side of each kidney is a small concave
depression area called the hilum, where the renal artery
and nerves enter and the renal vein and the ureter exit.
• The hilum opens into a cavity called the renal sinus,
which formed from the renal pelvis.
• The kidney is divided into an outer cortex and an
inner medulla that surrounds the renal sinus. The
medulla consists of a number of cone-shaped
renal pyramids, which appear triangular when
seen in a longitudinal section of the kidney. The
spaces between renal pyramids form renal column
or column of bertini.
• The cortex and renal Pyramids form the
parenchyma of kidney.
• This parenchyma consists of nephrons which are
functional units of kidney.
• In the renal sinus of the kidney is a large cavity called
renal pelvis.
• The edge of the pelvis contain cup like extensions called
major & minor calyces. Each minor calyx receives urine
from collecting ducts called Ducts of Bellini.
• From the major calyces urine drains in to pelvis. The
wide origin of the ureter in the kidney is the renal pelvis.
• The ureter exits the kidney and connects to the urinary
bladder.
Fig. 1.1 Structure of kidney (longitudinal section)
Fig 1.2 The Kidney
Blood supply to the kidneys: both kidneys receive between 15
and 20% of the body's systemic blood flow at rest.

• The renal artery branches into lobar and then interlobar

arteries →Arcuate arteries are branched into the cortex and
lead to interlobular arteries which distribute the blood to the
afferent arterioles → enters into the glomerular capillaries
then to the efferent arteriole → flows into more capillaries,
the peritubular capillaries, and the vasa recta → lead to
venules and the venous drainage of the kidney.
 Circulation of renal blood flow

Renal artery divides serially into – interlobar artery → arcuate → interlobular arteries →
afferent arterioles → capillary tufts of renal glomeruli into outer cortex → efferent arterioles
→ in juxtamedullary zone → arterioles become vasa recta (closely applied to loop of henle)
Venous drainage: Stelate veins → interlobular veins → arcuate veins → interlobar veins
Fig. 1.3 Renal circulation
Structure of Nephron:
• The basic histologic and functional unit of the
kidney is the nephron which consists of an
enlarged terminal end called the renal
corpuscle, a proximal tubule, a loop of Henle
(nephric loop), and a distal tubule.
• The distal tubule empties into a collecting
duct, which carries the urine from the cortex of
the kidney to a minor calyx.
❑The renal corpuscles, proximal tubules, and
distal tubules are in the renal cortex.
❑The collecting tubules and parts of the loops of
Henle enter the renal medulla
• 1. Bowmans capsule: It is a blind dilated end
of the nephron. It is a cup shaped structure. It
lies in cortex and contains a tuft of capillaries
called glomerulus.
– Bowman’s capsule & glomerulus together
constitute malpjigian capsule or Renal capsule.
– In the first step of urine formation, fluid passes
from the glomerular capillaries into the lumen of
Bowman's capsule across the filtration membrane.
– The glomerulus is supplied by an afferent arteriole
and is drained by an efferent arteriole
• 2. Renal tubule: It has the following parts.
1. PCT
2. Henles loop
3. DCT
4. Collecting tubule.
• i) PCT: The proximal tubule, also called the
proximal convoluted tubule, is approximately 14
mm long and 60 μm in diameter, and its wall is
composed of simple cuboidal epithelium. The
Bowmans capsule opens into it.
1 = Bowman's capsule, 2 = glomerulus, 3 = afferent arteriole, 4 = efferent arteriole, 5 = proximal convoluted tubule, 6 = distal
convoluted tubule, 7 = collecting duct, 8 = loop of Henle, 9 = peritubular capillaries
Fig 1.4 The structure of nephron
ii) The loops of Henle (nephric loops): These
are continuations of the proximal tubules.
• Each loop has a descending limb and an
ascending limb.
• The first part of the descending limb is similar
in structure to the proximal tubules.
• The descending limb posses squamous
epithelium.
Fig. 1.6 Flow of urine in nephron
• The limb then bends into U shaped structure.
The loops of Henle that extend into the
medulla become very thin near the end of the
loop. The thick part of the loop ( contains
cuboidal epithelium) returns toward the renal
corpuscle and ends by giving rise to the distal
tubule near the macula densa.
• The desert animals have larger Henle’s loop.
• iii) DCT: The distal tubules, also called the distal
convoluted tubules, are not as long as the proximal tubules.
It contains cuboidal cells. It begins near the pole of the
glomerulus and establish a close a close proximity to
glomerulus. This part of the DCT is called macula densa.

• iv)The collecting ducts are composed of simple cuboidal

epithelium, are joined by the distal tubules of many
nephrons, and are larger in diameter than other segments of
the nephron.
• Collecting Tubules → Ducts of Bellini → Minor
calyx →Major calyx →Pelvis →Ureters
→Urinary Bladder → Urethra → as urine to
outside.
Juxta Glomerular Apparatus & Macula Densa
JGA: complex structure including cellular
elements of glomerulus, distal tubule and
afferent & efferent arterioles.
➢ Macula densa cells- cells of the distal tubule
make contact with afferent arteriole in the
region of glomerulus.

➢ Some smooth cells of the afferent arteriole lie

in contact with macula densa, contain granules
of renin are known as Juxta glomerular cells.

➢ Have a role in GFR, B.P, Urine formation

regulation.
 Ureters, Urinary Bladder and Urethra

• Ureter- muscular tube that conveys urine from

the kidney to urinary bladder.
• Urinary bladder- a hollow muscular container
that lies in the pelvic cavity.
– It’s neck is continuous with urethra caudally.
– Has sphincters to control the flow of urine through the
urethra.
• Urethra- extends to the end of the penis in males.
– opens into the vestibule in females.
 RENAL PHYSIOLOGY
• Three fundamental mechanisms characterize kidney
function:
1. large quantities of water and solutes are filtered
from the blood.
2. This primary urine enters the tubule, where most of
it is reabsorbed, then it exits the tubule and passes
back into the blood.
3. Certain substances (e.g., toxins) are not only not
reabsorbed but actively secreted into the tubule
lumen. The non-reabsorbed residual filtrate is
excreted together with the secreted substances in the
final urine.
Functions of The kidneys
1. adjust salt and water excretion to maintain a constant
extracellular fluid volume and osmolality;
2. They help to maintain acid-base homeostasis;
3. they eliminate end-products of metabolism and foreign
substances
4. preserving useful compounds (e.g., glucose) by
reabsorption;
5. they produce hormones (e.g., erythropoietin) and
hormone activators (renin), and
6. have metabolic functions (protein and peptide
catabolism, gluconeogenesis, etc.).
 Physiology of Urine formation
Urine is formed in three steps:

1. Glomerular Filtration:

• Filtration is movement of fluid across the filtration

membrane as a result of a pressure difference.

• Blood enters through afferent arteriole → flows into the

glomerulus → filterable blood components (water,
nitrogenous wastes, nutrients & salts/ions) move toward the
inside of the glomerulus.
• While, non-filterable blood components such as blood cells along with
plasma proteins bypass the filtration process by exiting through the
efferent arteriole.

• The fluid entering the nephron becomes the filtrate.

• Filtration fraction: part of the plasma flowing through kidneys that is

filtered through the filtration membranes into the lumen of Bowman's
capsules to become filtrate.

• Approximately 99% of the filtrate volume is reabsorbed in the

nephron, and less than 1% becomes urine.

• Glomerular Filtration Rate (GFR): the amount of filtrate produced

each minute.
Factors affecting glomerular filtration rate are:
• filtration pressure
• constriction of arterioles
• renin and angiotensin
• aldosterone

Reabsorption Secretion

Excretion
Filtration
• The process of filtration is determined by two basic
features:

1. Semi-permeability of the filtration membrane:

• Filtration membrane- is semi-permeable to plasma in that

it:

• allows the passage of molecule with a molecular size of

less than 7nm in diameter.

• prevents the entry of blood cells and proteins into the

lumen of Bowman's capsule.

• allows other blood components to enter.

• Most proteins couldn’t pass it, and the filtrate contains only 0.03%
proteins. So filtrate contains H2O, glucose, amino acids,
electrolytes and wastes (everything that the blood plasma does)
except proteins.

• Filters several hundred times as much water and solutes as the usual
capillary membrane. This is due to:

a) capillary endothelium is perforated by thousands of small holes

called fenestrae.

b) basement membrane consists of a meshwork of collagen and

proteoglycan fibrillae that have spaces through which water and
small solutes can filter.
 c) Epithelial cells are not continuous but have podocytes separated
by gaps (slit pores) through w/ch the glomerular filtrate moves.

2. Presence of pressure gradient: three different pressures affect the

glomerular filtration.

• Hydrostatic pressure (blood pressure): forces water & small

sized dissolved substances out of the glomerular blood into
Bowman’s capsule.

• Interstitial pressure: created due to accumulation of much fluid

in Bowman’s capsule and that pressure creates a counter force
to the filtration process.
 • Colloidal pressure: created due to the presence of solutes in
blood. These solutes create a drag force against filtration.

2. Tubular Reabsorption:

• Reabsorption- the movement of substances from the filtrate

back into the blood.

• The filtrate leaves the lumen of Bowman's capsule and flows

through PCT, LH, and DCT, and then into the CT. As it passes
through these structures, many of the substances in the filtrate
undergo tubular reabsorption.
• Takes place in all tubular parts of the nephron.

• Inorganic salts, organic molecules, and about 99% of the filtrate

volume leave the nephron and enter the interstitial fluid by the
process of simple and facilitated diffusion, active transport, co-
transport and osmosis.

• The absorptive capabilities of various regions of the renal tubules

are:

i. PCT: the most active region for reabsorption.

• all glucose, lactate & amino acids by co-transport with Na+

ion reabsorbed.
 • 65 - 70% of Na+ ion by active transport.

• 65 - 70% of water by osmosis and solvent drag.

• 90% of bicarbonate.

• 50% of chloride by co-transported with Na ion.

• >90% of potassium.

• Almost all uric acid is reabsorbed but later returned to the filtrate.

ii. LH:

• Descending limb: water moves out freely by osmosis.

• Ascending limb: Na+, K+, Cl- move out by active transport &
water can’t leave the ascending limb.
 iii. DCT: Na+ and Cl- reabsorbed under hormonal control if
needed by the body.

• Na+ resorption is controlled by aldosterone & ADH.

3. Tubular Secretion:

• Secretion- the active transport of solutes into the nephron.

• Accomplished by the tubular lining cells.

• Released substances are from the blood in the peritubular

capillaries.

• Present in PCT, DCT & cortical CT, but not in the LH.
• is important for:

disposing of substances (toxins and drugs).

eliminating undesirable substances (urea & uric acid).

getting rid of excess ions to maintain electrolyte balance (K+

in exchange for Na+).

controlling acid-base balance to maintain blood pH (removal

of Cl-, H+ & ammonium ion in exchange for bicarbonates).
Mechanisms of Urine Concentration

• When large volume of water is consumed, the excess

eliminated without losing excessive electrolytes or
essential substances producing large volume of dilute
urine to maintain homeostasis.

• When water intake is restricted, kidneys produce small

volume of concentrated urine that contains sufficient
waste products to prevent their accumulation in the
circulatory system.
• Substances (glucose, a.a, Na+, Ca2+, K+, & Cl-) are actively
transported, and water moves by osmosis from lumens of the
PCT into the interstitial fluid (65% of the filtrate volume is
reabsorbed as water and solutes)→ excess solutes & water then
enter peritubular capillaries → filtrate enters LH (@ which 15%
reabsorbed) & then DCT → water diffuses into the interestitial
fluid @ the end of the DCT due to the permeability of its wall &
presence of ADH → filtrate flows into CT → water diffuses into
IF if ADH is present & another 19% of the filtrate is reabsorbed
→ 1% of the filtrate remains as urine.
Mechanisms used to produce concentrated urine:

1. ADH- high level of ADH → very high re-absorption of water in

DCT and CT → concentrated urine produced.

2. Counter current multipliers mechanism-

• Much water re-absorbed from descending LH & Na+ and Cl-

re-absorbed from ascending LH → high NaCl in the
interstitial space created → drag water from LH.

• During dehydration, CT leak urea to interstitial space →

increase osmolarity → increase water retention.
• Vasa recta (capillaries around LH): as blood circulates through
descending limb of vasa recta, NaCl diffuse into it from
interstitial fluid of medulla; as blood flows through ascending
limb of vasa recta, NaCl diffuses into interstial fluid of medulla.

Mechanism to produce diluted urine:

• Diluted urine- produced to remove excess water.

• formed by reducing the process of re-absorption in DCT and

CT (which have lower permeability to water).

✓ by blocking the activities of ADH &

✓ by reducing the Na+ re-absorption.

Characteristics and Composition of Urine:
A. Physical Characteristics
• Color - clear to yellowish due to urochrome.
▪ influenced by diet, drugs, and health state.
• Odor - slightly aromatic.
▪ influenced by diet, drugs, and health state.
• Volume of urine- varies from 1-1.8 lit/day.
▪ varies depending on water intake, state of mental & physical
activity, env’tal temp.
▪ decreased volume called oligouria & increased volume called
polyurea, anuria for urine abscence.
• PH - usually about 6 (acidic) & can vary with diet.
• Specific gravity- measured by Urinometer.

▪ 1.003-1.032 (havier than water).

B. Chemical Composition (characterstics)

• 95% water.

• 5% solutes - urea (breakdown of amino acids); uric acid;

creatinine.
Urine Flow through the Nephron and the Ureters
• Hydrostatic pressure averages 10 mm Hg in Bowman's capsule
and nearly 0 mm Hg in the renal pelvis.
• This pressure gradient forces the filtrate to flow from Bowman's
capsule through the nephron into the renal pelvis.
• B/c the pressure is 0 mm Hg in the renal pelvis, there is no
pressure gradient to force urine to flow to the urinary bladder
through the ureters.
• The circular smooth muscle in the walls of the ureters exhibits
peristaltic contractions that force the urine to flow through the
ureters..
• The peristaltic waves progress from the region of the renal pelvis
to the urinary bladder.

• Peristaltic contractions of each ureter proceed at a velocity of

approximately 3 cm/s.

• Can generate pressures in excess of 50 mm Hg.

• Pressure inside the bladder compresses the part at which

ureters penetrate the bladder obliquely, preventing backflow
of urine.

• Pressure in the urinary bladder increases slowly as its volume

increases to 400–500 ml.
Micturition Reflex (MR)
• Micturition (urination) is the elimination of urine from the
bladder.
• MR- is a reflexive process by which the UB empties itself when
it becomes filled.
• Bladder progressively fills until the tension in its walls rises
above a threshold value → stretch receptors are stimulated →
afferent action potentials conducted to the sacral segments of the
spinal cord → brain stem→ efferent AP cause the bladder to
contract & the internal urinary sphincter to relax → cause
conscious desire to urinate.
Regulation of urine formation

• Formation of urine is regulated by:

1. Nervous regulation

• kidneys are enervated by nerves from CNS.

• nerve impulses cause the renal blood vessels to become constricted or

dilated.

• may change the permeability of the glomerulus.

a) Sympathetic stimulation- causes constriction of afferent arterioles thus

decreasing GFR.

• causes release of epinephrine from adrenal medula → acts on alpha

receptors on vascular smooth muscle → starts the renin-angiotensin
mechanism by stimulating macula densa cells.
b) sympathetic nervous system- also directly stimulates the JGC to
release renin which begins the rennin-angiotensin mechanism.

• Renin acts on angiotensinogen (plasma protein made in the

liver) to release angiotensin I → converted to angiotensin II
by angiotensin converting enzyme → angiotensin II induce
production of aldosterone → causes the constriction of
arterioles.

• Constriction of efferent arterioles increases GFR whereas

constriction of the afferent arterioles will cause reduction in
GFR.
2. Hormonal regulation

a) Aldosterone: increases the Na-Cl absorption of the tubule and

also K+ elimination.

b) ADH: increase the reabsorption of water in the DCT and CT.

c) Parathormone: increases the tubular Ca++ reabsorption. It also

reduces reabsorption of phosphate.

d) Thyroxine: reduce reabsorption of water.

3. Intrinsic and extrinsic factors

a) Intrinsic factors (auto regulators):

• Are the first line of regulators when there is a change in filtration
pressure, rate of renal circulation and number of active
glomerulus.

• During these, juxta-glomerular cells and macula densa cells act

on the afferent and efferent arterioles to regulate the GFR.

• Kidneys maintain a relatively constant GFR regardless of

fluctuations in systemic blood pressure by regulating the
diameter of the afferent and efferent arterioles by:

• Myogenic mechanisms- responds to changes in the pressure

in the renal vessels.
 • Tubuloglomerular feedback mechanism- using of the macula
densa cells which release a vasoconstrictor if the GFR is too
high or permit vasodilation of afferent arterioles if the
filtration rate is too low.

b) Extrinsic factors:

• physical and mental status of the organism.

• cold condition.

• amount of water intake.

• using of drugs and diseases have an effect on the amount of

urine production.
Mechanism of acid-base balance

• If blood pH is altered due to metabolic causes,

hyper/hypoventilation may bring the pH back into the normal
range → respiratory compensation.

• However, in the case of an altered blood pH due to respiratory

causes, renal compensation corrects the problem.

• Renal compensation works by changing the secretion of H+ and

reabsorption of HCO3- by the kidneys.
Respiratory acidosis- is an abnormally high PCO2 in arterial
blood.

• Can result from slow breathing or hampered gas exchange

(pneumonia, cystic fibrosis, emphysema).

• Inadequate exhalation of CO2 → CO2 accumulates in the

blood → causes the blood pH to drop → rising PCO2.

• Kidneys provide renal compensation by increasing the

excretion of H+ and the reabsorption of HCO3-.
Respiratory alkalosis- is an abnormally low PCO2 in the arterial
blood.
• Can result from hyperventilation which may be caused by
several factors (oxygen deficiency due to high altitude, stroke,
or sever anxiety).
• During hyperventilation, CO2 is eliminated from the body
faster than it is produced → raising of blood pH → falling in
PCO2.
• Renal compensation brought the blood pH into the normal
range when the kidneys decrease the excretion of H+ and
reabsorption of HCO3-.