RENAL

PHYSIOLOGY
YOHANNES A.
DEBRE TABOR University
College of Health SCIENCES
Department of Biomedical
Sciences
Unit of Physiology
 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 • Have long loops of Henle
Henle that deep the medulla,
have extensive thin
• Supplied with segments
peritubular
capillaries • Supplied with vasa recta
• Involved in the • Involved in the production
formation of diluted of concentrated urine
urine.

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 Types of Nephrons …

Corticla nephrons

Juxtamedullary nephron

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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.Regulates ABP by release 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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 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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 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].

• 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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 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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 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. Renal blood flow: ↑RBF → ↑GFR
6. 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
 Tubular reabsorption & secretions
 Proximal convoluted tubule (PCT)
-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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Tubular reabsorption & secretions…
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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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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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 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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50
 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
• 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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 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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 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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 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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 Individual assignment
1. Briefly explain about myogenic regulation of
the heart.
2. Briefly explain chloride shift during
carbondioxide transport.
3. Briefly explain the function of the 12 pairs of
cranial nerves and their origin.
4. Briefly explain about barorecptor regulation
of blood pressure.
5. Explain about basal ganglia & their function.
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 THANK YOU !

• GOD BLESS YOU &

• GOD BLESS ETHIOPIA
–SPECIALLY
THE RENAL
PATIENT !!!

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