RENAL PHYSIOLOGY

URINARY SYSTEM
• Excretion is the process by which unwanted substances and metabolic wastes are eliminated from

body.

• A large amount of waste materials and carbon dioxide are produced in tissues during metabolic

process.

• In addition, residue of undigested food, heavy metals, drugs, toxic substances and pathogenic

organisms like bacteria are also present in the body.

• All these substances must be removed to keep the body in healthy condition
 Various systems/organs in the body are involved in performing excretory function

1. Digestive system excretes food residues in the form of feces.

2. Lungs remove carbon dioxide and water vapor.
3. Skin excretes water, salts and some wastes. It also removes heat from body.
4. Liver excretes many substances like bile pigments, heavy metals, drugs, toxins, bacteria, etc.
through bile.

Although various organs are involved in removal of wastes from body, their excretory capacity is
limited, but renal system has maximum excretory capacity.
Functions of Kidneys
1. Role in Homeostasis
i. Excretion of Waste Products
Kidneys excrete the unwanted waste products, which are formed during metabolic activities:
a. Urea (end product of amino acid metabolism)
b. Uric acid (end product of nucleic acid metabolism)
c. Creatinine (end product of metabolism in muscles)
d. Bilirubin (end product of hemoglobin degradation)
e. Harmful foreign chemical substances such as toxins, drugs, heavy metals pesticides, etc.

ii. Maintenance of Water Balance

Kidneys maintain water balance in body by conserving water when it is decreased and excreting
water when it is excess in the body.

iii. Maintenance of Electrolyte Balance

• Maintenance of electrolyte balance, especially sodium in relation to water balance.
• Kidneys retain sodium if osmolarity of body water decreases and eliminate sodium when
osmolarity increases.
iv. Maintenance of Acid–Base Balance

• The pH of blood and body fluids should be maintained within narrow range for healthy living. It is
achieved by function of kidneys.

• Body is under constant threat to develop acidosis, because of production of lot of acids during
metabolic activities.

• However, it is prevented by kidneys, lungs and blood buffers, which eliminate these acids.

• Among these organs, kidneys play major role in preventing acidosis.

• In fact, kidneys are the only organs, which are capable of eliminating certain metabolic acids like
sulfuric and phosphoric acids.
2. Hemopoietic function

• Kidneys stimulate the production of erythrocytes by secreting erythropoietin.

• Erythropoietin is the important stimulating factor for erythropoiesis.

• Kidney also secretes another factor called thrombopoietin, which stimulates the production of
thrombocytes.

3. Regulation of blood pressure

• Kidneys play an important role in long-term regulation of arterial blood pressure by two ways:
i. By regulating volume of extracellular fluid
ii. Through renin-angiotensin mechanism.
4. Endocrine function
Kidneys secrete many hormonal substances.
i. Erythropoietin
ii. Thrombopoietin
iii. Renin
iv. 1,25-dihydroxycholecalciferol (calcitriol)
v. Prostaglandins

5. Regulation of blood calcium level

Kidneys play a role in the regulation of blood calcium level by activating 1,25-
dihydroxycholecalciferol into vitamin D.
Vitamin D is necessary for absorption of calcium from intestine.
 Physiologic Anatomy of the Kidneys

Location:
• The two kidneys lie on the posterior wall of
abdomen, outside the peritoneal cavity.

Weight and size:

• Each kidney of adult human weighs about 150 g
and is about the size of a clenched fist and bean
shaped.
 Structure of Kidney

• The kidney is surrounded by a tough, fibrous

capsule.

• The medial side of each kidney contains an

indented region called hilum through which
pass the renal artery and vein, lymphatics,
nerve supply, and ureter.

Parts of kidney:
• Cortex
• Medulla
• Renal pyramids
• Papilla
• Minor calyxes
• Major calyxes
• Renal pelvis
 Structure of Functional Unit

➢ The Nephron Is Functional Unit of the Kidney

✓ Each kidney in the human contains about 1 million nephrons, each capable of forming urine.

✓ The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease or normal
aging, there is a gradual decrease in nephron number.

✓ After age 40, the number of functioning nephrons usually decreases about 10% every 10 years.

Types of Nephrons

Cortical ----- Renal corpuscle in outer portion of cortex and short loops of Henle extend only into
outer region of medulla

Juxtamedullary ----- Renal corpuscle deep in cortex and long loops of Henle extend deep into
medulla
Copyright 2009, John Wiley & Sons, Inc.
Renal Blood Supply
✓ Blood flow to the two kidneys is normally about 20-26% of cardiac output, or 1100 ml/min-
1300 ml/min.
✓ The renal artery enters the kidney through hilum and then branches progressively.
✓ The renal circulation is unique in that it has two capillary beds, the glomerular and
peritubular capillaries.
✓ High hydrostatic pressure in the glomerular capillaries (about 60 mm Hg) causes rapid fluid
filtration, whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13
mm Hg) permits rapid fluid reabsorption.
•
Vascular Structures Supplying Juxtamedullary Nephrons
• Cortical nephrons ---- the entire tubular system is surrounded by an extensive network of
peritubular capillaries.

• Juxtamedullary nephrons ---- The tubular portion of juxtamedullary nephrons is supplied by

some specialized capillaries called vasa recta. These capillaries are straight blood vessels hence
the name vasa recta.

• Vasa recta arise directly from efferent arteriole of juxtamedullary nephrons and run parallel to the
renal tubule into medulla and ascend up towards cortex and empty into cortical veins
 Juxtaglomerular Apparatus

• It is a specialized organ situated near the glomerulus of each nephron (juxta = near).

• It is formed by three different structures:

1. Macula densa
2. Extraglomerular mesangial cells
3. Juxtaglomerular cells

Functions of juxtaglomerular apparatus

• Secretion of hormones (Renin and Prostaglandin).
• Regulation of glomerular blood flow and glomerular
filtration rate.
Renin Angiotensin System
 Actions of Angiotensin II

On blood vessels:
i. Angiotensin II, a potent constrictor of arterioles increases arterial blood pressure by directly acting
on blood vessels and causing vasoconstriction.
ii. It increases blood pressure indirectly by increasing the release of noradrenaline, general
vasoconstrictor from postganglionic sympathetic fibers.

On kidney:
Angiotensin II regulates glomerular filtration rate by
• Constricting the efferent arteriole, which causes decrease in filtration after an initial increase
• Contracting the glomerular mesangial cells, leading to decrease in surface area of
glomerular capillaries and filtration
• Increasing sodium reabsorption from renal tubules.

On adrenal cortex:
• It stimulates secretion of aldosterone from adrenal cortex.
• Aldosterone acts on renal tubules and increases retention of sodium, which is also responsible for
elevation of blood pressure.
On brain:

i. Angiotensin II inhibits the baroreceptor reflex and thereby indirectly increases the blood pressure.
Baroreceptor reflex is responsible for decreasing the blood pressure

ii. It increases water intake by stimulating the thirst center

iii. It increases the secretion of Corticotropin-releasing hormone (CRH) from hypothalamus. CRH in
turn increases secretion of adrenocorticotropic hormone (ACTH) from pituitary

iv. It increases secretion of antidiuretic hormone (ADH) from hypothalamus.

Urine Formation By Kidneys
• Urine formation is a blood cleansing function.
• Kidneys excrete unwanted substances along with water from the blood as urine.
• Normal urinary output is 1 to 1.5 L/day.

Processes of Urine Formation

The urine formation includes three processes:

• When blood passes through glomerular capillaries, plasma is filtered into Bowman capsule. This
process is called glomerular filtration.

• Filtrate from Bowman capsule passes through tubular portion of nephron. Many wanted substances
like glucose, amino acids, water and electrolytes are reabsorbed from the tubules. This process is
called tubular reabsorption.

• Some unwanted substances are secreted into the tubule from peritubular blood vessels. This
process is called tubular secretion or excretion.
Step I: Glomerular Filtration
• It is the process by which blood is filtered while passing through the glomerular capillaries by
filtration membrane.
• It is the first process of urine formation.
Filtration Membrane
Filtration membrane is formed by three layers:
1. Glomerular capillary membrane
• Glomerular capillary membrane is formed by single layer of endothelial cells, which are attached to
basement membrane.
• The capillary membrane has many pores called fenestrae or filtration pores with a diameter of 0.1 µ.
2. Basement membrane
• Basement membrane of glomerular capillaries and basement membrane of visceral layer of
Bowman capsule fuse together.
• The fused basement membrane separates the endothelium of glomerular capillary and epithelium of
visceral layer of Bowman capsule.
3. Visceral layer of Bowman capsule
• This layer is formed by a single layer of flattened epithelial cells resting on a basement membrane.
• Each cell is connected with the basement membrane by cytoplasmic extensions called pedicles or
feet.
• Epithelial cells with pedicles are called podocytes.
• Pedicles interdigitate leaving small cleft like spaces in between. The cleft like space is called slit
pore or filtration slit. Filtration takes place through these slit pores.
• A thin membrane, the slit membrane, extends across each filtration slit; it permits the passage of
molecules having a diameter smaller than 0.006–0.007 um, including water, glucose, vitamins,
amino acids, very small plasma proteins, ammonia, urea, and ions.
Process of Glomerular Filtration

• When blood passes through glomerular capillaries, plasma is filtered into Bowman capsule.

• All the substances of plasma are filtered except plasma proteins.

• The filtered fluid is called glomerular filtrate.

Ultrafiltration

• Glomerular filtration is called ultrafiltration because even minute particles are filtered except
plasma proteins due to their large molecular size.

• The protein molecules are larger than slit pores present in the endothelium of capillaries.
Principle of Filtration
• The use of pressure to force fluids and solutes through a membrane is the same in glomerular
capillaries as in capillaries elsewhere in body.
• However, the volume of fluid filtered by renal corpuscle is much larger than in other
capillaries of body for three reasons:
1. Glomerular capillaries present a large surface area for filtration
• The mesangial cells regulate how much of this surface area is available for filtration.
• When mesangial cells are relaxed, surface area is maximal, and glomerular filtration is very high.
• Contraction of mesangial cells reduces the available surface area, and glomerular filtration
decreases.
2. The filtration membrane is thin and porous
• Glomerular capillaries also are about 50 times leakier than capillaries in most other tissues, mainly
because of their large fenestrations.
3. Glomerular capillary blood pressure is high
• Because efferent arteriole is smaller in diameter than afferent arteriole, resistance to the outflow of
blood from glomerulus is high.
• As a result, blood pressure in glomerular capillaries is considerably higher than in capillaries
elsewhere in body.
Glomerular Filtration Rate (GFR)

Total quantity of filtrate formed in all nephrons of both kidneys in a given unit of time.
Normal GFR is 125 mL/minute or about 180 L/day.

Filtration Fraction
• Filtration fraction is the fraction (portion) of renal plasma, which becomes filtrate.
• About 20% of plasma flowing through kidney is filtered through glomerular capillaries.
Filtration Fraction = Glomerular Filtration Rate x 100
Renal Plasma Flow
= 125 mL/min × 100
650 mL/min
= 19.2%

Normal filtration fraction varies from 15 - 20%.

Determinants of GFR
GFR = Kf x Net filtration pressure
Kf = Glomerular capillary filtration coefficient

• Kf is the measure of membranes permeability to water.

• The normal filtration coefficient is 12.5 ml/min/mmHg of filtration pressure

• The net filtration pressure represents the sum of hydrostatic and colloid osmotic forces that either
favor or oppose the filtration across glomerular capillaries.

• Glomerular filtration depends on three main pressures. One pressure promotes filtration and two
pressures oppose filtration
The Pressures That Drive Glomerular Filtration
 Factors Regulating GFR
1. Renal Blood Flow
• GFR is directly proportional to renal blood flow.
• Normal blood flow to both the kidneys is 1300 mL/min.

2. Glomerular Capillary Pressure

• GFR is directly proportional to glomerular capillary pressure.
• When glomerular capillary pressure increases, the GFR also increases.

3. Colloidal Osmotic Pressure

• GFR is inversely proportional to colloidal osmotic pressure, which is exerted by plasma proteins in
the glomerular capillary blood.
• When colloidal osmotic pressure increases as in the case of dehydration or increased plasma
protein level, GFR decreases.
• When colloidal osmotic pressure is low as in hypoproteinemia, GFR increases.
4. Hydrostatic Pressure in Bowman Capsule
• GFR is inversely proportional to this.
• When hydrostatic pressure increases in Bowman capsule, it decreases GFR.
• Hydrostatic pressure in Bowman capsule increases in conditions like obstruction of urethra and
edema of kidney beneath renal capsule.

5. Constriction of Afferent Arteriole

Constriction of afferent arteriole reduces the blood flow to glomerular capillaries, which in turn
reduces GFR.

6. Constriction of Efferent Arteriole

• If efferent arteriole is constricted, initially the GFR increases because of stagnation of blood in the
capillaries.
• Later when all the substances are filtered from this blood, further filtration does not occur.
• It is because, efferent arteriolar constriction prevents outflow of blood from glomerulus and no
fresh blood enters the glomerulus for filtration.
7. Systemic Arterial Pressure
• Renal blood flow and GFR are not affected as long as mean arterial blood pressure is in between
60 and 180 mm Hg due to autoregulatory mechanism.
• Variation in pressure above 180 mm Hg or below 60 mm Hg affects renal blood flow and GFR
accordingly, because autoregulatory mechanism fails beyond this range.

8. Sympathetic Stimulation
• Afferent and efferent arterioles are supplied by sympathetic nerves.
• The mild or moderate stimulation of sympathetic nerves does not cause any significant change
either in renal blood flow or GFR.
• Strong sympathetic stimulation causes severe constriction of blood vessels by releasing the
neurotransmitter substance, noradrenaline. The effect is more severe on the efferent arterioles than
on the afferent arterioles.
• So, initially there is increase in filtration but later it decreases.
9. Surface Area of Capillary Membrane
• GFR is directly proportional to the surface area of capillary membrane.
• If the glomerular capillary membrane is affected as in the cases of some renal diseases, the surface
area for filtration decreases. So there is reduction in GFR.

10. Permeability of Capillary Membrane

• GFR is directly proportional to the permeability of glomerular capillary membrane.
• In many abnormal conditions like hypoxia, lack of blood supply, presence of toxic agents, etc. the
permeability of capillary membrane increases.
• In such conditions, even plasma proteins are filtered and excreted in urine.

11. Contraction of Glomerular Mesangial Cells

• Glomerular mesangial cells are situated in between the glomerular capillaries.
• Contraction of these cells decreases surface area of capillaries resulting in reduction in GFR.
12. Hormonal and Other Factors
Many hormones and other secretory factors alter GFR by affecting blood flow through glomerulus.

Factors increasing GFR by vasodilatation

i. Atrial natriuretic peptide
ii. Brain natriuretic peptide
iii. cAMP
iv. Dopamine
v. Endothelial derived nitric oxide
vi. Prostaglandin (PGE2)

Factors decreasing GFR by vasoconstriction

i. Angiotensin II
ii. Endothelins
iii. Noradrenaline
iv. Platelet activating factor
v. Platelet derived growth factor
vi. Prostaglandin (PGF2)
Renal Autoregulation
• Renal autoregulation is important to maintain glomerular filtration rate (GFR).

• Blood flow to kidneys remain normal even when the mean arterial blood pressure vary widely
between 60 and 180 mm Hg. This helps to maintain normal GFR.

Mechanisms involved in renal autoregulation

Two mechanisms are involved in renal autoregulation:
1. Myogenic response
2. Tubuloglomerular feedback.
1. Myogenic Response

• Whenever blood flow to kidneys increases, it stretches the elastic wall of afferent arteriole.

• Stretching of the vessel wall increases flow of calcium ions from extracellular fluid into the cells, which
leads to the contraction of smooth muscles in afferent arteriole, which causes constriction of afferent
arteriole.

• So, the blood flow is decreased.

2. Tubuloglomerular Feedback

• It is the mechanism that regulates GFR through renal tubule and macula densa.

• When glomerular filtrate passes through terminal portion of thick ascending segment, macula densa acts
like a sensor.

• Macula densa detects the concentration of NaCl in tubular fluid via Na+K+2Cl– cotransporter (NKCC2)
and accordingly alters glomerular blood flow and GFR.
 When the concentration of sodium chloride decreases in filtrate

• When concentration of sodium chloride decreases in filtrate, GFR decreases.

• Macula densa secretes prostaglandin (PGE2), bradykinin and renin.

• PGE2 and bradykinin cause dilatation of afferent arteriole, while renin induces the formation of
angiotensin II, which causes constriction of efferent arteriole.

• The dilatation of afferent arteriole and constriction of efferent arteriole leads to increase in glomerular
blood flow and GFR.

When the concentration of sodium chloride increases in filtrate

• When concentration of sodium chloride increases in filtrate, GFR increases.

• Macula densa releases adenosine from ATP, which acts on afferent arteriole via adenosine A1 receptors
and causes constriction of afferent arteriole.

• So the blood flow through glomerulus decreases leading to decrease in GFR.

• Factors increasing the sensitivity of tubuloglomerular feedback
i. Adenosine
ii. Thromboxane
iii. Prostaglandin E2
iv. Hydroxyeicosatetranoic acid.

• Factors decreasing the sensitivity of tubuloglomerular feedback

i. Atrial natriuretic peptide
ii. Prostaglandin I2
iii. Cyclic AMP (cAMP)
iv. Nitrous oxide.