RENAL

PHYSIOLOGY
Arba Minch University
College of Medicine & Health Sciences
School of Medicine
Physiology Unit
By:
Tariku A. (MSc)

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 Objectives
At the end of this lesson the students are expected to:
1. List functions of the renal system.
2. Discuss the components of renal system.
3. Explain the functional structures of the nephron.
4. Discuss blood flow through the kidney.
5. Explain the urine formation processes.
6. List the renal system abnormalities.

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 Outlines
• Components of the renal system
• Functions of the kidney
• Functional structure of the kidneys
• Blood supply & innervations of the kidneys
• Nephron: functional parts
– glomerulus, renal tubules & collecting duct
• Processes of urine formation
• Renal system abnormalities

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 Overview
• The kidneys represent the primary organs of
homeostasis in the regulation of both volume &
composition of body fluids & the excretion of
metabolic waste products in urine.
• The kidneys are large, bean-shaped organs which lie
on the dorsal side of the visceral cavity.
• They are protected by a tough fibrous coat called the
renal capsule.
• Adipose (fatty) tissue surrounds the renal capsule &
cushions the kidney.
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 Components of renal system
The renal system composed of
• Kidneys: formation of urine
• Ureters: transport urine
from the kidneys to the
bladder
• Urinary bladder: provides
a temporary storage
reservoir for urine
• Urethra: transports urine
from the bladder out of the
body
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 Kidneys
• Bean-shaped, retroperitoneal,
located in the abdominal
cavity at the lumbar region.
• The right kidney is crowded
by the liver & lies slightly
lower than the left.
• Renal hilus: inlet/out let of
ureters, arteries, veins,
lymphatics and nerves
• At the top of each kidney
there is adrenal gland
(suprarenal gland).

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 Kidneys…
• On a longitudinal section of
kidney there are 2 distinct
regions, cortex & medulla.
• The outer cortex surrounds
darker triangular structures
called pyramids which form
the medulla.
• The inner part of the kidneys,
the renal pelvis collects the
urine from the calyces
draining it into the ureter.

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 Nephron
 The basic functional unit of the kidneys.
 Each kidney is made up of approximately 1 million
nephrons, consisting:
 Renal corpuscle
• Glomerulus
• Bowman’s capsule
 Renal tubules
• Proximal convoluted tubule
• Loop of Henle
• Distal convoluted tubule
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 Nephron…

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 Types of Nephrons
Cortical nephrons Juxtamedullary nephrons
• 85% of nephrons, • Few in number, are located
located in the cortex in the medullary region
• Have short loop of Henle • Have long loops of Henle

• Supplied with that deep the medulla, have

peritubular capillaries extensive thin segments

• Involved in the • Supplied with vasa recta

formation of diluted
urine. • Involved in the production
of concentrated urine

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 Types of Nephrons …

Corticla nephrons

Juxtamedullary nephron

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 Functions of the Urinary System
1. Regulate:
 ABP by controlling blood volume & RAAS, RBC formation
by producing EPO, Electrolytes concentration (Na+, K+,
Ca2+, PO43-), ECF & blood volume, Acid-base balance, and
Osmolality of the body fluid (300 Mosm/l) maintain the
proper balance between water & salts.
2. Endocrine function: EPO, Calcitriol, PGE1 & PGE2.
3. Filter 200 liters of blood daily to eliminate toxins,
metabolic wastes & excess ions.
4. Drug metabolism & detoxification of certain
chemicals.

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 Functions of the Urinary System…
5. Excretion: by forming urine, the kidneys help excrete
wastes substances that have no useful function in the body.
• Some wastes excreted in urine result from metabolic
reactions in the body. These include:
– ammonia & urea from the breakdown of amino acids
– bilirubin from the breakdown of hemoglobin
– creatinine from the breakdown of creatine phosphate in
muscle fibers and
– uric acid from the breakdown of nucleic acids.
• Other wastes excreted in urine are foreign substances from
the diet, such as drugs & environmental toxins.

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 Functions of the Urinary System…
1. Filtration of the blood
– Occurs in the glomerulus of the kidney nephron.
– Contributes to homeostasis by removing toxins
or waste.

2. Reabsorption of vital nutrients, ions & water

– Occurs in most parts of the kidney nephron.
– Contributes to homeostasis by conserving
important materials.

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 Functions of the Urinary System…
3. Secretion of excess materials
– Assists filtration in removing material from the blood.
– Contributes to homeostasis by preventing build-up of
certain materials in the body (drugs, waste, etc).

4. Activation of Vitamin D
– Vitamin D made in the skin is converted to Vitamin D3
by the kidney.
– Active Vitamin D (D3) assists homeostasis by increasing
calcium absorption from the digestive tract &
reabsorption from renal tubules.
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 Functions of the Urinary System…
5. Release of Erythropoietin (EPO) by the kidney
– EPO stimulates new RBC production.
– New RBC’s assist homeostasis by insuring
adequate Oxygen & Carbon dioxide transport.
6. Release of Renin by the kidney
– Renin stimulates the formation of a powerful
vasoconstrictor called Angiotensin II
– Angiotensin II assists homeostasis by causing
vasoconstriction which increases blood pressure.

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 Functions of the Urinary System…
7. Release of Prostaglandins
– Prostaglandins dilate kidney blood vessels.
– Dilated blood vessels contribute to homeostasis
by maintaining blood flow in the kidneys.

8. Secretion of H+1 & reabsorption of HCO3-1

– Eliminates excess hydrogen ions & conserves
buffer material such as bicarbonate.
– Contributes to homeostasis by controlling
acid/base conditions in body fluids
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 Kidney Structures

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 Kidney Structures…
 Capsule
– The outer membrane that encloses, supports and
protects the kidney

 Cortex
– The outer layer of the kidney that contains most of the
nephron, main site for filtration, reabsorption & secretion

 Medulla
– Inner core of the kidney that contains the pyramids,
columns, papillae, calyces, pelvis and parts of the nephron
not located in the cortex.

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 Kidney Structures…
 Renal Pyramids
– Triangular shaped units in the medulla that house the loops of
Henle and collecting ducts of the nephron.
– Site for the counter-current system that concentrates salt
and conserves water and urea.
 Renal Column
– A passageway located between the renal pyramids found in
the medulla and used as a space for blood vessels.

 Nephron
– The physiological unit of the kidney used for filtration of
blood and reabsorption and secretion of materials.

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 Kidney Structures…
 Renal Papilla
– tip of the renal pyramid that releases urine into a calyx

 Calyx
– A collecting sac surrounding the renal papilla that transports
urine from the papilla to the renal pelvis

 Renal Pelvis
– Collects urine from all of the calyces in the kidney

 Ureter
– Transports urine from the renal pelvis to the bladder

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 Blood supply to kidneys
• The kidneys receive approximately 20% of the
cardiac output (about 4 ml/min/g) one of the
highest blood flow values.
• The profile of the vascular blood pressure in the
renal circulation is characteristic, with a high
capillary pressure:
– that reflects the need to support the filtering capacity of
the kidneys.

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 Blood supply to kidneys…
• Renal Artery
– Transports oxygenated
blood from the heart
and aorta to the kidney
for filtration.
• Renal Vein
– Transports filtered and
deoxygenated blood
from the kidney to the
posterior vena cava and
then the heart.

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 Blood supply to kidneys…
 Renal blood flow/RBF
– The amount of blood flow to kidney per minute.
– Arterial flow into and venous flow out of the kidneys
follow similar paths.

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 Blood supply to kidneys…

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 Capillary Beds of the Nephron
• Every nephron has two
capillary beds
– Glomerulus
– Peritubular capillaries
or Vasa recta

• Each glomerulus is:

– Fed by an afferent
arteriole
– Drained by an
efferent arteriole

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 Characteristics of the RBF
1. RBF = 1200 ml/min, or 20% of
the CO. 94% to the cortex.
2. Two capillary beds: glomerulus
and peritubular capillaries.
3. High hydrostatic pressure in
glomerular capillary (about 60
mmHg) & low hydrostatic
pressure in peritubular capillaries
(about 13 mmHg).
4. It is unique that glomerular
capillaries are found b/n 2
arterioles.

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 Nerve supply to the kidneys
• Kidneys receive sympathetic nerve supply from the
last thoracic & upper 2 lumbar segments of the spinal
cord which relay in the paravertibral and mesentric
ganglia.
• Sympathetic stimulation results in
Constriction of arteries & arterioles →↓RBF (α-AR effect)
 ↑Na reabsorption in renal tubules (α-AR effect)
 ↑Renin secretion by JG-cells (β-AR effect)
Dilation of efferent arterioles (β-AR effect)

• Parasympathetic supply from vagus nerve

– function is not clear so far
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 Process of urine formation
- The mechanism by which
nephrons clear the plasma of
unwanted substances is:
1. Filters the plasma through
the fenestrated glomerular
membrane into renal tubules.
2. Reabsorption of needed
substances , as the filtrate
flows through the tubules.
3. Secretion of unwanted
substances into the renal
tubules.
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 Process of urine formation…

GFR  125 ml/min, 180L/day, about 1% is excreted

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 Process of urine formation…

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 Glomerulus and Bowman’s capsule

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 Glomerular Filtration
• Filtration of fluid through the glomerular capillaries.
• The kidneys filter the body’s entire plasma volume
60 times each day. The filtrate contains:
– all plasma components (except protein); water,
nutrients, and essential ions to become urine
(Plasma proteins are not filtered and are used to
maintain oncotic pressure of the blood).
• Glomerulus is more efficient than other capillary
beds because:
 Its filtration membrane is significantly more permeable.
 Glomerular blood pressure is higher ;it has a higher net
filtration pressure.

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 Glomerular filtration…
• Mechanism: bulk flow
• Direction of movement :
- from glomerular capillaries to capsule space
• Driving force:
- Pressure gradient (net filtration pressure, NFP)
• Types of pressure:
• Favoring Force: Capillary Blood Pressure (BP)
• Opposing Force: Blood colloid osmotic pressure(COP),
and Capsule Pressure (CP)

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 Filtration Membrane

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 Glomerular membrane
– Made up of 3 layers
1. Endothelial layer
2. Basement membrane
3. Epithelial cell (podocytes)
– Thickness: 1 µm
– Fenestrated, highly
permeable
– Allows the passage of all
components of plasma
except plasma proteins
and blood cells

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 Glomerular Filtration Rate (GFR)
• The amount of fluid filtered per minute in all nephrons of
both kidneys. [GFR = 125 ml/min, or 180 L/day].
• Filtration fraction (FF): the fraction of RPF (renal plasma
flow) that becomes glomerular filtrate
RBF = 1200 ml/min RPF = 55% of RBF, 650 ml/min
FF = GFR/RPF, 125/650 = 19%
• Filtration pressure (FP): the net pressure forcing fluid to
be filtered through the glomerular membrane. Determined by
1. Glomerular capillary pressure (60 mm Hg)
2. Glomerular capillary colloid osmotic pressure (32mm Hg)
3. Capsular hydrostatic pressure (18 mm Hg)
FP = GCP – (GCCOP + CHP) = 60 – (32 + 18) = 10 mm Hg

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 Glomerular Filtration Pressure

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 Factors affecting GFR
1. Filtration pressure
2. Permeability of the glomerular capillary membrane
3. Diameter of afferent arterioles: dilation ↑ GFR
- Caffeine & diuretics dilate AA & ↑ GFR.
- Sympathetic stimulation constricts AA and ↓ GFR.
4. Diameter of efferent arterioles: dilation ↓ GFR
↓RBF→↓GFR →↑Renin →↑Ang-II →EA constriction → ↑GFR
5. Concentration of plasma proteins:
↑Proteins → ↑PCOM →↓GFR
6. Renal blood flow: ↑RBF → ↑GFR
7. Arterial blood pressure: ↑ABP (limits) → ↑GFR

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 Diameter of AA vs. GFR

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 The Juxtaglomerular apparatus
• Initial portion of the DT passes in the angle between the
AA & EA.
• Epithelial cells that come in contact with the arterioles are being
modified & become secretory & collectively called macula densa.
– secret PG - E1 & E2, vasodilator action on AA & EA

• The smooth muscles of AA & EA at the contact site become

thickened and granulated called JG cells
– responsible for the secretion of renin & erythropoietin

• The whole complex of macula densa and JG cells or granular cells

is called JG-complex

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 Juxtaglomerular Apparatus (JGA)

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GFR regulation : Adjusting blood flow
• GFR is regulated by three mechanisms
1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation
• All three mechanism adjust;
 Renal blood pressure & resulting blood flow

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 Autoregulation of GFR
• When the GFR is increased:
– tubular fluid will pass with minimum reabsorption of the required
substances.

• When the GFR is decreased:

– tubular fluid will pass with maximum reabsorption of unwanted
substances.

• Therefore, the glomerular filtrate must flow into the tubular

system at an appropriate rate to:
- allow unwanted substances to pass into the urine
- reabsorb nutritionally important substances
• GFR shows only little change with a broad change in ABP b/n
80 – 220 mm Hg.
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 Autoregulation of GFR …
There are two autoregulation mechanisms of GFR
1. Afferent arteriole vasodilator feedback mechanism
↓GFR →Tubular fluid flows slowly →↑Na+, Cl- reabsorption
→Detected by the macula densa, secret PG-E1 & E2
→Dilation of AA → ↑GFR

2. Efferent arteriole vasoconstrictor Feed.b mechanism

↓GFR →Tubular fluid flows slowly →↑Na+, Cl- reabsorption
→Detected by the macula densa, secret PG-E1 & E2
→Stimulate JG-cells to secret renin → ↑Ang-II →
vasoconstriction of EA → ↑GFR

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 Neural regulation of GFR
• Sympathetic nerve fibers innervate afferent and
efferent arteriole
 Sympathetic stimulation is low but can increase during
hemorrhage and exercise
 Sympathetic stimulation constricts AA and ↓GFR

• Vasoconstriction occurs as a result which

 Conserves blood volume (hemorrhage) and
 Permits greater blood flow to other body parts
(exercise)

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 Hormonal regulation of GFR
 Several hormones contribute to GFR regulation
1. Angiotensin II
• produced by renin (released by JG-cells) is a potent
vasoconstrictor. ↓ GFR.
2. ANP
• released by atria when stretched, ↑ GFR by increasing
capillary surface area available for filtration.
3. NO: a potent vasodilator, ↑ GFR
4. Endothelin: a potent vasoconstrictor, ↓ GFR
5. Prostaglandin E2
• a potent vasodilator on AA, ↑ GFR

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 Regulation of renin-angiotensin system

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 Renin Release

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 Tubular reabsorption & secretions
 Proximal convoluted tubule (PCT)
- Composed of cuboidal cells with numerous microvilli and
mitochondria. [15 mm long & 55 µm in diameter].
- Reabsorbs water and solutes from filtrate and secretes
substances into it.
 Loop of Henle
– a hairpin-shaped loop of the renal tubule (U-shaped tubules), lie
b/n PCT and DCT , has descending & ascending limbs with 2
segments: thin & thick segments
 Distal convoluted tubule (DCT)
– Cuboidal cells without microvilli that function more in secretion
than reabsorption. 5 mm long, 35 µm in diameter.

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 Tubular reabsorption & secretions…

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 Function of proximal tubules
1. Reabsorption of nutrients.
2. Reabsorption of Na+ (70-75%).
3. Almost total reabsorption of K+.
• Fluid in the Loop of Henle is free of K+. K+ is secreted in
the DT.
4. Passive reabsorption of Cl-, HCO3-
• Obligatory reabsorption of H2O (70-75%) along with
Na, K, Cl, HCO3 independent of ADH.
5. Reabsorption of urea.
6. Secretion of H+, NH4, creatinin sulphate and drug
metabolites.
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 Function of proximal tubules…

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 Glucose reabsorption in the PCT
 Glucose is reabsorbed along with Na+ in the
early portion of the proximal tubule.
Glucose is typical of substances removed from
the urine by secondary active transport.
Essentially all of the glucose is reabsorbed, and no
more than a few milligrams appear in the urine per
24 hours.

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 Na+ reabsorption in the PCT
• Paracellular transport of • Trans-cellular transport
Na+ involves: of Na+ involves:
– Passage of Na+ through – Antiport carriers
the tight junction b/n Na-H ATPase, Na-K ATPase
cells – Symport carriers
– Passive diffusion of Na+ Na-Glu, Na-aa, Na-HCO3-
through Na-channels

Transcellular Pathway

Lumen Cells Plasma

- Active/carrier mediated
Paracellular Transport
- Passive transport

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 Na+ reabsorption in the PCT…

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 Secondary active transport
Tubular Tubular
lumen Tubular Cell Interstitial lumen Tubular Cell Interstitial
Fluid Fluid
Co-transport Counter-transport
(symport) (antiport)
out in out in

Na+ Na+

glucose H+

Co-transporters will move one Counter-transporters will move

moiety, e.g. glucose, in the one moiety, e.g. H+, in the
same direction as the Na+. opposite direction to the Na+.
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Tubular reabsorption & secretion (cont’d)
 Loop of Henle
Descending limb
• passive reabsorption of H2O
Ascending limb
• active reabsorption of NaCl
• impermeable to H2O

 Distal tubules (diluting segment)

• active reabsorption of NaCl
• impermeable to H2O & urea
• late DT is permeable is to H2O
ADH dependently
 Collecting ducts
• reabsorption of Na, Ca and H2O hormone dependently
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 Tubular transport maximum (Tm)
• The maximum amount of substance (mg) transported
(reabsorbed/secreted) by tubules per minutes.
• TmG (Tmax of glucose =350 mg/min)
– the maximum amount of glucose in mg that can
be reabsorbed by the renal tubules per minute
• it means glucose that is filtered in the
glomerulus is reabsorbed.

• Determination of TmG is used as a renal function test

– b/c it measures the reabsorptive power of the
kidneys.
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 Tubular transport maximum (Tm)…
• Renal threshold for glucose is 180 mg/dl
– When BGC > 180 mg/dl, small amount start to
be appeared in urine

– When the TLoad of glucose is 400 mg/min, the

amount excreted in urine is 400-350=50 mg/min.

• Tm for creatinin is 16 mg/min

• TmPAHA = 80 mg/min

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 Tubular load (TLoad) of substances
• The rate of a particular substance filtered through the glomeruli
into the tubules per minute
• It equals GFR times the concentration of the substance in the
filtrate.

TLoad of a subs (freely filtered) = Conc. In the filtrate X GFR

• TLoad of Glucose = 100 mg/dl X 125 ml/min = 125 mg/min

• TLoad of Na+ = 142 meq/1000 ml X 125 ml/min=18 meq/min

• TLoad of Cl- = 13 meq/min

• TLoad of Urea = 33 mg/min

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 Renal plasma clearance
• A measure of the volume of plasma that is completely cleared of
a given substance per minute.
• A measure of the efficiency of the kidneys with which the
plasma is cleared of a given substance
• It is the ratio of the renal excretion rate of the substance to
its concentration in plasma
• It can be calculated using the following formula:
Ux V
Cx = ____
Px
Where:
Cx = Clearance of the subs (ml/min)
Ux = Concent. Of the subs. In urine (mg/ml)
V = Volume of UO (ml/min)
Px = Concent. of the subs in plasma (mg/ml)
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 Importance of renal plasma clearance
1. Measurement of GFR
• GFR can be determined by inulin clearance test.
• The plasma clearance value of inulin (Cin) = GFR
• Inulin is a fructose polysaccharide, freely filtered in the
glomerulus, neither reabsorbed nor secreted by the renal
tubules
2. Measurement of RBF and RPF
• RBF/RPF is measured by PAHA, completely cleared
3. Indicator of the renal handling of different substances
- reabsorption or secretion in the renal tubules
Examples:
Plasma clearance of glucose = 0 , Inulin= 125 ml/min,
GFR Urea < GFR, partially reabsorbed
Cx > GFR, Partially secreted
4. Gives quantitative information about renal diseases
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 Function of Loop of Henle
in the process of urine formation
Create & maintain osmotic gradient in the renal
medullary interstitium
It involves in the formation of concentrated urine
up to 1200 Mosm/l
It acts as a counter-current multiplier system
which creates
 osmotic gradient in the renal medullary
interstitium as well as in the tubule.

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 Function of Loop of Henle…
 A counter-current system
is any system where there are two currents flowing
parallel, opposite and adjacent to each other.
 Counter-current multiplier
operates actively to create an osmotic or chemical
gradient in the renal interstitial space by the Loop of
Henle and vasa recta
 Counter-current exchanger
operates passively to maintain an osmotic or chemical
gradient

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 Countercurrent system
The U-shaped loop forms
the counter-current system,
which means fluid passes
in opposite direction
through 2 loops, Loop of
Henle and vasa recta
It has also a counter-
current multiplier function,
b/c it acts to increase
(multiply) the osmolality of
fluid in the loop of Henle as
well as in the medullary
interstitium.

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 Counter-current multiplier system…
 Osmolality of tubular fluid
& interstitial fluid increases
progressively as we go deep
into the renal medulla from
the cortex.
 Formation of multiple
stratification of osmolality
by the flow of fluid in
opposite directions in the
LH and in VR.

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 Countercurrent Mechanism…
 Descending limb of Loop of Henle
• Permeable to water, but impermeable to Na+, K+, Cl-, urea
• Water flows out down the osmotic gradient
• Osmolality of tubular fluid increases progressively up to
1200 mosm/L
 Thick segment of the ascending limb of Loop of Henle
• Impermeable to water & urea, but active reabsorption of
electrolytes (Na+, Cl- and K+)
• The osmolaltiy of tubular fluid is progressively decreases
up to 150 mosm/l

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 Countercurrent system
Function of vasa recta as a
counter current exchanger
maintains hyper-osmolarity
of medullary interstitium
through:
a. Uptake of NaCl & urea &
removal of water from the
descending limb
b. Removal of NaCl & urea &
uptake of water in the
ascending limb
c. Slaggish flow of blood in it

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Hyperosmotic Gradient in the Renal Medulla Interstitium
 Causes of hyperosmolality in the medullary interstitium
1. Counter-current arrangement of the ascending &
descending limb of the LH
2. Both passive & active reabsorption of Na, Cl & K in the
ascending limb of LH
3. Active reabsorption of Na+ and passive reabsorption of
urea from CD
 Importance of medullary hyperosmolarity
• It is essential for the formation of concentrated urine.
This is b/c it leads to passive reabsorption of water from the
CD (ADH).

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Formation of concentrated and diluted urine
Importance:
1. When there is excess water in the body and body
fluid osmolarity is reduced:
 the kidney can excrete urine with an osmolarity as low
as 50 mOsm/liter,
 a concentration that is only about 1/6 the osmolarity of
normal extracellular fluid.
2. Conversely, when there is a deficient of water and
extracellular fluids osmolarity is high:
 the kidney can excrete urine with a concentration of
about 1200 to 1400 mOsm/liter.

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 The basic requirements for formation of
concentrated or diluted urine
1. Controlled secretion of antidiuretic hormone (ADH)
• which regulates the permeability of the distal
tubules and collecting ducts to water
2. High osmolarity of the renal medullary interstitial
fluid
• which provides the osmotic gradient necessary
for water reabsorption to occur in the presence
of high level of ADH.

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 Water reabsorption
Obligatory water reabsorption
Facultative (selective)
water reabsorption • Using sodium & other
• Occurs mostly in solutes.
collecting ducts • Water follows solute to the
• Through the water interstitial fluid (transcellular
and paracellular pathway).
poles (channel)
• Largely influenced by sodium
• Regulated by the
reabsorption
ADH

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 The Role of ADH
• There is a high osmolarity of the renal medullary interstitial
fluid, which provides the osmotic gradient necessary for
water reabsorption to occur.
• Reabsorption of water in the DT & CT is determined by the
hormone ADH.
• Osmoreceptors in the hypothalamus detect the low levels
of water (high osmolarity), so the hypothalamus sends an
impulse to the pituitary gland which releases ADH into the
bloodstream.
• ADH makes the wall of the DT and CT more permeable to
water.
• Therefore, when ADH is present more water is reabsorbed
and high amount of electrolytes are excreted.

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 Formation of Water Pores:
Mechanism of Vasopressin Action

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 Mechanism of formation of concentrated urine
When there is a shortage of H2O in
the body

↓ECF volume, ↑Osmolality

Stimulates osmoreceptors in the HT

↑ADH secretion

ADH ↑ H2O reabsorption in the DT & CD

↑Excrition of solutes

Concentrated (1200 mosm/l), in

small volume of urine is produced

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 Mechanism of formation of diluted urine
When there is excess H2O in
the body

↑ECF vlume, ↓Osmolality

↑Aldosterone secretion
↓ADH secretion

↑NaCl reabsorption in the DT &

CD

↑H2O excretion
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Diluted urine (50-100 mosm/l)
83
 The Effects of ADH on the distal collecting duct and
Collecting Ducts

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 Water handling of the renal tubules

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Tubular reabsorption of H2O and electrolyte

1. Reabsorption of H2O in the DT and CD is

dependent on the presence of ADH
2. Reabsorption of Na+ in the DT and CD is
dependent on aldosterone
3. Reabsorption of Ca2+ in the DT and CD is
dependent on the presence of PTH and calcitriol

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 Regulation of [Na+] and osmolality
↑[Na+] and ↑Osmolality ↓[Na+] or ↓Osmolality &
↑[K+]
Stimulates osmoreceptors in
the SON of HT Stimulates adrenal cortex

↑ADH secretion ↑Aldosterone secretion

↑H2O reabsorption in the ↑Na+ reabsorption

DT and CD ↑K+ excretion in DT and CD

↓[Na+] and ↓Osmolality ↑[Na+] &↑Osmolality ↓[K+]

back to normal back to normal
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 Diuretics
• Drugs that increase the urine output. Of 3 classes
1. Drugs increasing solute excretion
a. Na+ reabsorption inhibitors
Mercurials, thiazides, frusemide
b. Na-H pump inhibitors: acetazolamide, NH4Cl
c. Osmotic diuretics: mannitol, dextran, glucose
2. Drugs increasing GFR
- cardiac glycosides, plasma expanders, xanthenes derivatives
3. Drug inhibiting release of ADH
- water, ethanol alcohol

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 Normal urine & blood values
• Urine pH ~ 6.0
• Blood pH = 7.4
• Blood [HCO3-] = 24 mM
• Blood PCO2 = 40 mmHg
• Plasma osmolality = 300 mOsm/kg water
• Urine osmolality = 600 mOsm/kg water
– depends upon hydration status
– note that this can vary between 50-1200
depending on water intake etc.

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 Physical Characteristics of Urine
• Color and transparency
– Clear, pale to deep yellow
• Concentrated urine has a deeper yellow color
– Drugs, vitamin supplements, & diet can change the color
– Cloudy urine may indicate infection of the urinary tract
• Odor
– Fresh urine is slightly aromatic
– Standing urine develops an ammonia odor
– Some drugs and vegetables alter the usual odor
• pH
– Slightly acidic (pH = 6) with a range of 4.5 to 8.0
– Diet can alter pH
• Specific gravity
– Ranges from 1.001 to 1.035
– Is dependent on solute concentration
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 Chemical Composition of Urine
• Urine is 95% water and 5% solutes
• Nitrogenous wastes include:
- urea, uric acid, and creatinine
• Other normal solutes include:
– Sodium, potassium, phosphate, and sulfate ions
– Calcium, magnesium, and bicarbonate ions
• Abnormally high concentrations of any urinary
constituents may indicate pathology.

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 Ureters
• Slender tubes that convey urine from the kidneys
to the bladder.
• Enter the base of the bladder through posterior wall
– As bladder pressure increased (increased urine
volume in bladder) distal ends of ureters are
closed off & prevent backflow of urine into ureters
• Ureters have a trilayered wall
– Epithelial mucosa
– Smooth muscle
– Fibrous connective tissue
• Ureters actively propel urine to the bladder via
response to smooth muscle stretch.

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 Urinary Bladder
• Smooth muscular sac that temporarily stores urine.
It lies on the pelvic floor posterior to the pubic
symphysis.
 Males – prostate gland surrounds the neck inferiorly
 Females – anterior to the vagina and uterus

• Trigone – triangular area outlined by the openings

for the ureters & the urethra. Clinically important
because infections tend to persist in this region.
• The bladder wall has 3 layers; epithelium, a thick
muscular layer (detrusor muscle), a fibrous layer.
• It is distensible and collapses when empty.
Accommodates as high as 1.5 L of urine.
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 Urinary Bladder…

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 Urethra
• Muscular tube that drains urine from the bladder
& moves urine out of the body
• Sphincters keep the urethra closed when urine is
not being passed
 Internal sphincter
– involuntary sphincter at the bladder-urethra junction
 External sphincter
– voluntary sphincter surrounding the urethra as it
passes through the urogenital diaphragm
• Levator ani muscle
– voluntary urethral sphincter

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 Urethra …
• The female urethra is tightly bound to the anterior
vaginal wall.
– Its external opening lies anterior to the vaginal opening and
posterior to the clitoris
• The male urethra has three named regions
 Prostatic urethra
– runs within the prostate gland
 Membranous urethra
– runs through the urogenital diaphragm
 Spongy (penile) urethra
– passes through the penis and opens via the external
urethral orifice
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 Micturition reflex
1. Stimulation of stretch receptors
by large volume of urine (200-
400 ml)
2. Sensory impulse transmitted to
the spinal cord through PNS
3. Motor impulse stimulates
smooth muscle lining bladder &
4. Relax internal urethral sphincter
(IUS)
5. Stretch receptors also send
impulse to higher centers
(Pons, HT and cerebral cortex)
6. Motor impulse from higher
centers promote readiness to
urinate
7. Identify places for urination
8. Relax external urethral sphincter

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 Regulation of acid-base balance
• Normal blood pH: 7.35 – 7.45
- pH < 7.35 is called acidosis, >7.45 is called alkalosis
- Acidosis & alkalosis disturb the function of cells, hormones,
enzymes.
• The body has 5 pH regulatory mechanisms that
control the normal range:
1. The chemical buffer system: has 3 components
– Bicarbonate system: H2CO3 & NaHCO3
– Phosphate buffer system: NaH2PO4/Na2HPO4
– Hb & protein buffer system that can trap H+ or OH-

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 Regulation of acid-base balance…
2. The respiratory buffer system:
– Regulates pH by controlling PCO2

3. The renal buffer system:

– Regulates pH by controlling the concentration of HCO3-
and H+
– The kidneys regulate the concentration of H in the
blood by excreting a variable amount of H in the urine.
– They also conserve blood bicarbonate ions (HCO3), an
important buffer of H.
– Both activities help regulate blood pH.

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 Pathopysiology of kidneys
 Renal failer
 a decrease or cessation of glomerular filtration
• Acute renal failure
• Chronic renal failure
 Renal stone/ calculi
– Nephrolithiasis/ Kidney stone/Urolithiasis
 Glomerulonephritis
 Nocturnal enuresis
 Urinary tract infections

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 Acute Renal Failure
• Pathophysiology
 Prerenal Acute Renal Failure
• Dysfunction before the level of kidneys
– Most common and most easily reversible
 Renal Acute Renal Failure
• Dysfunction within the kidneys themselves
 Postrenal Acute Renal Failure
• Dysfunction distal to the kidneys

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 Acute Renal Failure …

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 Chronic Renal Failure
• Chronic Renal Failure
– Permanent Loss of Nephrons
– End-Stage Renal Failure, 90% of the nephrons
have been lost.
• Pathophysiology
– Similar to Renal ARF
• Microangiopathy
• Glomerular injury
• Tubular cell injury
• Interstitial injury
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 Renal Stone/Calculi
• Pathophysiology
– Results when “too
much insoluble stuff”
accumulates in the
kidneys.
– Stone types:
• Calcium salts
• Struvite stones
• Uric acid
• Cystine

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 Nephrolithiasis/Kidney stone/Urolithiasis
- Crystalline structures made up of renal excreta in
urine.
- Mechanism of renal stone formation; 3 theories
1. The saturation theory:
- ↑Stone components. e.g. Ca salt
2. The inhibitor deficiency theory:
- ↓Inhibitor components
3. The matrix theory:
- organic materials produced by renal epithelial
cells serve as a nucleus for the formation of
renal stone.

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 Nephrolithiasis…
 Types of kidney stone:
1. Ca-stone (Ca-oxalate, Ca-phosphate):
- Causes: hypercalcemia, ↑↑PTH, Vit-D over dose
2. Magnisium ammonium phosphate stone
(Struvite stone)
- Cause: UTI
3. Uric acid stone
- Causes: ↑Urine acidity (pH 5.5), Gout due to high protein diet
4. Cyctine stone
- Cause: Cyctinurea due to genetic defect in aa metabolism

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 Glomerulonephritis
• An inflammation of the glomeruli of the kidney.
• One of the most common causes is an allergic
reaction to the toxins produced by streptococcal
bacteria that have recently infected another part of
the body, especially the throat.
• Because inflamed & swollen glomeruli allow blood
cells & plasma proteins to enter the filtrate,
– the urine contains many red blood cells (hematuria) &
large amounts of protein.

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 Urinary Incontinence
• Lack of voluntary control over micturition.
• Under about 2–3 years of age, urinary incontinence is
normal because neurons to the external urethral
sphincter muscle are not completely developed.
• Infants void whenever the urinary bladder is sufficiently
distended to trigger the reflex.
• In stress incontinence, the most common type of
urinary incontinence, physical stresses that increase
abdominal pressure, such as coughing, sneezing,
laughing, exercising, straining, lifting heavy objects,
pregnancy, or simply walking, cause leakage of urine
from the urinary bladder.
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 Nocturnal enuresis
• Discharge of urine during sleep, resulting in bed-wetting.
• Occurs in about 15% of 5-year-old children and generally
resolves spontaneously, afflicting only about 1% of
adults.
• Possible causes include:
– smaller-than-normal urinary bladder capacity
– failure to awaken in response to a full urinary bladder
– above-normal production of urine at night (nocturia).

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 Urinary tract infections (UTIs)
• The most common bacterial infections and the second
most common illness (after colds) among women.
• About 10–15% of women develop UTIs several times a
month. Men get UTIs, too, but much less frequently.
• The female’s shorter urethra allows bacteria to enter the
urinary bladder more easily. In addition, the urethral and
anal openings are closer in females.
• Most first-time UTIs are caused by Escherichia coli (E.
coli) bacteria that have migrated to the urethra from the
anal area.

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 Urinary tract infections…
• E. coli bacteria are necessary for proper digestion and
are welcome in the intestinal tract, but they cause much
pain and suffering if they infect the urinary system.
• Personal hygiene is the first line of prevention. Care must
be taken to avoid transporting bacteria from the anal
area to the urethra.
• Girls should be taught to wipe from front to back and to
wash hands thoroughly after using the toilet. When
bathing, women and girls should wash from front to back
as well.

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Thank You!!!