1. Renal System
By:
Dr.Rabia
Altaf

2. Intended Learning Outcomes
 Introduction to Renal System.
 Multiple Functions of the Kidneys
 Physiologic Anatomy of the Kidneys
 Renal Blood Supply
 Nephron

3. Location of the Kidneys
 Dimensions
 Reddish-brown, bean shaped
 12cm long, 6cm wide, 3cm thick
 High on posterior abdominal wall
 at the level of T12 to L3- superior lumbar region
 Retroperitoneal & against the dorsal body wall
 The right kidney is slightly lower than the left ,convex
laterally
 Attached to ureters, renal blood vessels, and nerves
at renal hilus (medial indention)
 Atop each kidney is an adrenal gland

4. Coverings of the Kidneys
 Adipose capsule
 Surrounds the kidney
 Provides protection to the kidney
 Helps keep the kidney in its correct location against
muscles of posterior trunk wall
 Ptosis-kidneys drop to a lower position due to rapid
fat loss, creating problems with the ureters.
 Ptosis can lead to hydronephrosis, a condition
where urine backs up the ureters and exerts
pressure on the kidney tissue.
 Renal capsule
 Surrounds each kidney

5.  The organs of the urinary
system include
• the paired kidneys,
• paired ureters,
• urinary bladder
• urethra
Renal System

6. Multiple Functions of the Kidneys in Homeostasis
 Excretion of Metabolic Waste Products, Foreign Chemicals, Drugs, and Hormone
Metabolites.
 Conserving valuable nutrients, by preventing their loss in urine
 Regulation of Water and Electrolyte Balances.
 Regulation of ArterialPressure.
 Regulation of Acid-Base Balance.
 Regulation of Erythrocyte Production.
 Regulation of 1,25–Dihydroxyvitamin D3 Production.
 Glucose Synthesis.
Renal System

7. General Organization of the Kidneys and Urinary Tract
Physiologic Anatomy of the Kidneys

8. General Organization of the Kidneys and Urinary Tract
Physiologic Anatomy of the Kidneys

9. Physiologic Anatomy of the Kidneys
 Three regions of kidneys
 Renal cortex – outer region, forms an
outer shell
 Renal columns – extensions of cortex-
material inward
 Renal medulla – inside the cortex,
contains medullary (renal) pyramids
 Medullary pyramids – triangular
regions of tissue in the medulla,
appear striated
 Renal pelvis – inner collecting tube,
divides into major and minor calyces
 Calyces – cup-shaped structures
enclosing the tips of the pyramids
that collect and funnel urine towards
the renal pelvis

10. Physiologic Anatomy of the Kidneys
 The walls of the calyces,
pelvis, and ureter contain
contractile elements that
propel the urine toward the
bladder, where urine is
stored until it is emptied
by micturition

11. Renal Blood Supply

12. The NEPHRON Is the Functional Unit of the Kidney
 In the kidneys, the functional units—the smallest
structures that can carry out all the functions of a
system— are the nephrons
 Each nephron consists of a
 Renal corpuscle
o glomerular (Bowman’s) capsule
o the glomerulus (glomerular capillaries)
 a renal tubule
o The renal tubule has three crucial functions:
1) reabsorbing all the useful organic nutrients in the
filtrate;
2) reabsorbing more than 90 percent of the water in the
filtrate;
3) secreting into the tubule lumen any wastes that did
not pass into the filtrate at the glomerulus.

13. The NEPHRON Is the Functional Unit of the Kidney
 the total glomerulus is encased in Bowman’s
capsule.
 Fluid filtered from the glomerular capillaries
flows into Bowman’s capsule and
 then into the proximal tubule, which lies in the
cortex of the kidney.
 From the proximal tubule, fluid flows into the
loop of Henle, which dips into the renal medulla.
 Each loop consists of a descending and an
ascending limb.
 The walls of the descending limb and the lower
end of the ascending limb are very thin and
therefore are called the thin segment of the loop
of Henle.

14. The NEPHRON Is the Functional Unit of the Kidney
 After the ascending limb of the loop has
returned partway back to the cortex, its
wall becomes much thicker, and it is
referred to as the thick segment of the
ascending limb.
 At the end of the thick ascending limb is a
short segment, which is actually a plaque
in its wall, known as the macula densa.
 Beyond the macula densa, fluid enters the
distal tubule, which, like the proximal
tubule, lies in the renal cortex.
 Collecting duct.

15. The NEPHRON Is the Functional Unit of the Kidney
 Blood arrives at the renal corpuscle by way of an
afferent arteriole.
 Blood leaves the glomerulus in an efferent
arteriole.
 It flows into a network of capillaries called the
peritubular capillaries, which surround the renal
tubule.
 These capillaries in turn drain into small venules
that return the blood to the venous system

20. URINE FORMATION
Different segments of the nephron form urine by filtration, reabsorption, and
secretion
 Basic Processes of Urine Formation
 Filtration.
 Reabsorption of substances from
the renal tubules into the blood
 Secretion of substances from the
blood into the renal tubules.
Urinary excretion rate = Filtration rate - Reabsorption rate + Secretionrate

21. URINE FORMATION
 The substance shown in panel A is filtered
by the glomerular capillaries but is neither
reabsorbed nor secreted.e.g. Certain waste
products in the body, such as creatinine
 In panel B, typical for many of the
electrolytes of the body.
 In panel C, This pattern occurs for some of
the nutritional substances in the blood, such
as amino acids and glucose, allowing them
to be conserved in the body fluids.
 The substance in panel D, This pattern often
occurs for organic acids and bases,
permitting them to be rapidly cleared from
the blood and excreted in large amounts in
the urine.

22. Excretion Rate of different
Substances
Panel A
• Substance is freely filtered by the
glomerular capillaries but is neither
reabsorbed nor secreted.
• Excretion rate = Filtration rate
• Eg: Creatinine
Panel B
• Substance is freely filtered but is also
partly reabsorbed from the tubules
• Excretion rate < Filtration rate
• Eg: Most of the electrolytes

23. Excretion Rate of different
Substances
Panel C
• Substance is freely filtered & is fully
reabsorbed thus is not excreted
• Excretion rate = 0
• Eg: AA andGlucose
Panel D
• Substance is freely filtered & is not
reabsorbed, but additional quantities
of this substance are secreted from
the peritubular capillary
• Excretion rate = Filtration rate +
Secretion rate
• Eg : Organic acids and Bases blood

24. Glomerular Filtration
• It is the “First Step” in Urine Formation.
• Blood is filtered through Filtration Barrier.
• Endothelium
• Basement Membrane
• Filtration slit

25. URINE FORMATION
Glomerular Filtration—The First Step in Urine Formation
Composition of the Glomerular Filtrate
Glomerular filtrate is essentially:
Devoid of cellular elements like RBC/WBC/PLTand
Protein-free
The concentrations of most salts and organic molecules,
are similar to the concentrations in the plasma.
Exceptions include
Calcium and fatty acids
Because of the fact that, they are partially bound to the
plasma proteins.
Almost one half of the plasma calcium and most of
the plasma fatty acids are bound to proteins, and these
bound portions are not filtered through the glomerular
capillaries.

26. URINE FORMATION
GFR Is About 20 Per Cent of the Renal Plasma
Flow
 the GFR is determined by
1) the balance of Hydrostatic and colloid
osmotic forces acting across the capillary
membrane and
2) the capillary filtration coefficient (Kf), the
product of the permeability and filtering
surface area of the capillaries.
 The filtration fraction is calculated as follows:
Filtration fraction = GFR/Renal plasma flow

27. Glomerular Filtration
Filterability
• It is the “Degree of easiness for a substance to cross the
glomerulus”
• It is inversely propotional to Molecular weight (MW).
• Negative charged molecules cross less easily than positive
charged molecule for same MW, due to the fact that
basement membrane and podocytes are also negatively
charged.

28. URINE FORMATION
Glomerular Capillary Membrane
Filterability of Solutes Is Inversely Related to
Their Size.
 The glomerular capillary membrane is thicker
than most other capillaries, but it is also much
more porous and therefore filters fluid at a
high rate.
 Despite the high filtration rate, the glomerular
filtration barrier is selective in determining
which molecules will filter, based on their size
and electrical charge.

29. URINE FORMATION
Determinants of the GFR
The GFR is determined by
1) the sum of the hydrostatic and colloid osmotic forces across the
glomerular membrane, which gives the net filtration pressure,
2) the glomerular capillary filtration coefficient, Kf.
Expressed mathematically,
GFR = Kf × Net filtration pressure

30. URINE FORMATION
Determinants of the GFR
 Net filtration pressure
 These forces include
1) Glomerular hydrostatic pressure, PG,
which promotes filtration;
2) the hydrostatic pressure in
Bowman’s capsule (PB) outside the
capillaries, which opposes filtration;
3) the colloid osmotic pressure of the
glomerular capillary plasma proteins
(π G), which opposes filtration; and
4) the colloid osmotic pressure of the
proteins in Bowman’s capsule (π B),
which promotes filtration.
The GFR can therefore be expressed as
GFR = Kf × (PG – PB – πG + πB)
PG – PB – πG +πB

31. URINE FORMATION
Determinants of the GFR
GFR = Kf × (PG – PB – πG +πB)
 Increased Glomerular Capillary
Filtration Coefficient Increases GFR
Kf = GFR/Net filtrationpressure
 Increased Bowman’s Capsule
Hydrostatic Pressure Decreases GFR
 Increased Glomerular Capillary
Colloid Osmotic Pressure Decreases
GFR
 Increased Glomerular Capillary
Hydrostatic Pressure Increases GFR
PG – PB – PG +PB

32. Glomerular hydrostatic pressure
• It is determined by three variables:
(1) Arterial pressure
∞ GFR
(2) Afferent arteriolar resistance
1/∞ GFR
(3) Efferent arteriolar resistance
∞ GFR in the beginning; later on 1/∞ GFR
The initial increase causes blood to stay in glomerulus for
longer time thus GFR increases , but as soon as resistance
increases more than 3 folds in efferent arteriole the RPF
decreases, So GFR also declines

33. Filtration Fraction ( FF = GFR / RPF )
• It is the ratio of the GFR to the RPF.
• Increasing the filtration fraction also concentrates the plasma
proteins and raises the glomerular colloid osmotic pressure.
Glomerular colloid osmotic pressure

34. URINE FORMATION
Determinants of the GFR

35. Renal Blood Flow:
 In an average 70-kilogram man, the combined blood flow through both kidneys is
about 1100 ml/min, or about 22 per cent of the cardiac output.
 As with other tissues, blood flow supplies the kidneys with nutrients and removes
waste products.
Renal Blood Flow and Oxygen Consumption:
 On a per gram weight basis, the kidneys normally consume oxygen at twice the rate
of the brain but have almost seven times the blood flow of the brain.
 A large fraction of the oxygen consumed by the kidneys is related to the high
rate of active sodium reabsorption by the renal tubules.
 If renal blood flow and GFR are reduced and less sodium is filtered, less sodium
is reabsorbed and less oxygen is consumed.
 Therefore, renal oxygen consumption varies in proportion to renal tubular sodium
reabsorption, which in turn is closely related to GFR and the rate of sodium
filtered.

36. Determinants of Renal Blood Flow:
Renal blood flow is determined by the pressure gradient across the renal
vasculature
Pressure gradient =
 The total vascular resistance through the kidneys is determined by the sum of the
resistances in the individual vasculature segments, including the arteries,
arterioles, capillaries, and veins
 An increase in the resistance of any of the vascular segments of the kidneys tends to
reduce the renal blood flow,
 whereas a decrease in vascular resistance increases renal
blood flow

37. Physiologic Control of Glomerular Filtration and Renal Blood Flow:
 The determinants of GFR that are most variable and subject to physiologic control
include
• the glomerular hydrostatic pressure and
• the glomerular capillary colloid osmotic pressure.
These variables, in turn, are influenced by the:
• Sympathetic nervous system,
• Hormones and autacoids and
• Other feedback controls that are intrinsic to the kidneys.
 Sympathetic Nervous System Activation DecreasesGFR
• Essentially all the blood vessels of the kidneys, including the afferent and the efferent arterioles, are richly
innervated by sympathetic nerve fibers.
• Strong activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal
blood flow and GFR

38. Control of GFR:
1. NE and Epinephrine:
Released from adrenal medulla.
They constrict afferent and efferent arterioles, causing reductions in RBF & thus GFR is reduced.
2. Endothelin:
Released by damaged vascular endothelial cells
It is a powerful vasoconstrictor.
Causes renal vasoconstriction & thus decreases GFR.
3. eNO:
Released by the endothelium
Decreases Renal Vascular Resistance and Increases GFR.
4. PGs and Bradykinin:
It causes vasodilation & GFR is increased.
These vasodilators are not of major importance in regulating GFR in normal conditions, but Under stressful
conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti-inflammatory drugs
(NSAID’s), such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR
5. Angiotensin:
It preferentially constricts efferent arterioles. It should be kept in mind that increased angiotensin II formation
usually occurs in circumstances associated with volume depletion, which tend to decrease GFR. In these
circumstances, angiotensin II, by constricting efferent arterioles, helps prevent decreases in glomerular hydrostatic
pressure and GFR. Thus it is better to say “Angiotensin II prevents ↓in GFR due to volume depletion”.

40. Autoregulation of GFR and Renal Blood Flow:
 Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant,
despite marked changes in arterial blood pressure. This relative constancy of GFR and renal blood flow is
referred to as autoregulation.
 Importance of GFR Autoregulation in Preventing Extreme Changes in Renal
Excretion:
 The autoregulatory mechanisms of the kidney are not 100 per cent perfect, but they do
prevent potentially large changes in GFR and renal excretion of water and solutes that
would otherwise occur with changes in blood pressure.
 Change in arterial pressure exerts much less of an effect on urine volume for two
reasons:
(1) renal autoregulation prevents large changes in GFR that would otherwise occur, and
(2) there are additional adaptive mechanisms in the renal tubules that allow them to
increase their reabsorption rate when GFR rises, a phenomenon referred to as
glomerulotubular balance

41. Role of Tubuloglomerular Feedback in Autoregulation of GFR:
 To perform the function of autoregulation, the kidneys have a feedback
mechanism that links changes in sodium chloride concentration at the macula
densa with the control of renal arteriolar resistance.
 The tubuloglomerular feedback mechanism has two components that act
together to control GFR:
(1) an afferent arteriolar feedback mechanism and
(2) an efferent arteriolar feedback mechanism.
These feedback mechanisms depend on special anatomical arrangements of the
juxtaglomerular complex

42. Tubuloglomerular Feedback
Juxtaglomerular
apparatus
(1) Macula densa
(2) Juxtaglomerular (JG) cells
(3) Extraglomerular mesangium

43. Tubuloglomerular Feedback
• Not completely understood.
• Experiment suggests that decreased GFR slows the
flow rate in the loop of Henle, causing increased
reabsorption of sodium and chloride ions in the
ascending loop of Henle, thereby reducing the
concentration of sodium chloride at the macula densa
cells.

44. Tubuloglomerular Feedback
• This decrease in sodium chloride concentration initiates a signal from the
macula
densa that has two effects :
1. It decreases resistance to blood flow in the afferent arterioles
• Which raises glomerular hydrostatic pressure and helps return GFR toward
normal
2. It increases renin release from the juxtaglomerular cells
• Renin increases the formation of angiotensin I from angiotensinogen, which is
converted to angiotensin II.
• Finally, the angiotensin II constricts the efferent arterioles, thereby
increasing glomerular hydrostatic pressure and returning GFR toward
normal.

45. Autoregulation of GFR and Renal Blood Flow
Role of Tubuloglomerular Feedback in Autoregulation of GFR
 Decreased Macula Densa Sodium Chloride
Causes Dilation of Afferent Arterioles and
Increased Renin Release.

46. Tubuloglomerul
ar
Feedback

47. • Myogenic Autoregulation of Renal Blood Flow andGFR
• Another mechanism that contributes to maintenance
of a relatively constant renal blood flow and GFR.
• Ability of individual blood vessels to resist stretching
during increased arterial pressure, a phenomenon
referred to as the myogenic mechanism.
• Muscles of small arterioles respond to increased
wall tension or wall stretch by contraction of the
vascular smooth muscle.

48. Myogenic Autoregulation of Renal Blood Flow andGFR (cont.)
• Stretch of the vascular wall allows increased
movement of calcium ions from the extracellular fluid
into the cells, causing them to contract.
• This contraction prevents over distention of the vessel
and at the same time, by raising vascular resistance,
helps prevent excessive increases in renal blood flow
and GFR when arterial pressure increases.

49. Why increased protein intake causes increased
GFR?
• GFR and renal blood flow increase 20 to 30 per cent within
1 or 2 hours after a person eats a high-protein meal.
Possible explanation is :
• Increased release of AA in blood, which are reabsorbed in the
PCT.
• AA and sodium are reabsorbed together by the proximal
tubules, increased amino acid reabsorption also stimulates
sodium reabsorption in PCT.
• This decreases sodium delivery to the macula densa, which
elicits a
tubuloglomerular.
• Decreased afferent arteriolar resistance then raises renal

50. Why polyuria in Diabetes?
• Large increases in blood glucose levels in
uncontrolled diabetes mellitus.
• Because glucose is also reabsorbed along with
sodium in PCT, increased glucose delivery to the
tubules causes them to reabsorb excess sodium
along with glucose.
• This, in turn, decreases delivery of sodium
chloride to the macula densa, activating a
tubuloglomerular feedback.

51. REFERENCES
59
BOOKS:
 Textbook of Medical Physiology by Guyton & Hall 11th Edition, Chapter26