1. Faisal I. Mohammed, MD, PhD Yanal Shafagoj, MD, PhD
Renal system –L1-2
Faisal I. Mohammed, MD, PhD
Yanal Shafagoj, MD, PhD
University of Jordan
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2. Objectives List the functions of the renal system
Give an anatomical overview of the urinary system
Describe the renal system functional unit –Nephron- and its types
Outline the process of urine formation and define GFR
Introduce the principle of clearance
Describe GFR regulation
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3. Overview of kidney functions
Regulation of blood ionic composition (e.g., Na+, K+, Ca++)
Regulation of blood pH (acid-base status)
Regulation of blood volume (Volume expansion and edema)
Regulation of blood pressure (hypertension)
Maintenance of blood osmolarity
Production of hormones (calcitrol and erythropoitin)
Regulation of blood glucose level (Starvation)
Excretion of wastes from metabolic reactions and foreign substances (drugs or toxins: urea Creatinine Uric acid)
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4. Organs of the urinary system
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5. Internal anatomy of the kidneys
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6. Blood and nerve supply of the kidneys
Blood supply
Although kidneys constitute less than 0.5% of total body mass (≈ 300 gm), they receive 20-25% of resting cardiac output (1250 ml/min)
Left and right renal artery enters kidney
Branches into segmental, interlobar, arcuate, interlobular arteries
Each nephron receives one afferent arteriole
Divides into glomerulus – capillary ball (glomerular capillaries)
Reunite to form efferent arteriole (unique…not venule)
Divide to form peritubular capillaries or some have vasa recta
Peritubular venule, interlobar vein and renal vein exits kidney
Renal nerves are part of the sympathetic autonomic nervous system
Most are vasomotor nerves regulating blood flow
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7. Blood supply of the kidneys
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8. The nephron – functional units of kidney
2 parts
Ultrafiltration Device: Renal corpuscle – filters blood plasma
Glomerulus – capillary network
Glomerular (Bowman’s) capsule – double-walled cup surrounding glomerulus
Epithelium of the renal tubule which modifies the ultrafiltrate:
Proximal convoluted tubule
Descending and ascending loop of Henle (nephron loop)
Distal convoluted tubule
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9. Nephrons
Renal corpuscle and both convoluted tubules in cortex, loop of Henle extend into medulla
Distal convoluted tubule of several nephrons empty into single collecting duct
Cortical nephrons – 80-85% of nephrons
Renal corpuscle in outer portion of cortex and short loops of Henle extend only into outer region of medulla
Juxtamedullary nephrons – other 15-20%
Renal corpuscle deep in cortex and long loops of Henle extend deep into medulla
Receive blood from peritubular capillaries and vasa recta
Ascending limb has thick and thin regions
Enable kidney to secrete very dilute or very concentrated urine
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10. Cortical Nephron
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11. Juxtamedullary Nephron
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12. Histology of nephron and collecting duct
Glomerular capsule
Visceral layer has podocytes that wrap projections around single layer of endothelial cells of glomerular capillaries and form inner wall of capsule
Parietal layer forms outer wall of capsule
Fluid filtered from glomerular capillaries enters capsular (Bowman’s) space
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13. Renal corpuscle
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14. Renal tubule and collecting duct
Proximal convoluted tubule cells have microvilli with brush border – increases surface area for absorption
Juxtaglomerular apparatus helps regulate blood pressure in kidney
Macula Densa – cells in final part of ascending loop of Henle
Juxtaglomerular cells – cells of afferent and efferent arterioles contain modified smooth muscle fibers
Last part of distal convoluted tubule and collecting duct
Principal cells – receptors for antidiuretic hormone (ADH) and aldosterone…secrete K+
Intercalated cells – role in blood pH homeostasis
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15. Overview of renal physiology
Glomerular filtration
Water and most solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubule
Tubular reabsorption
As filtered fluid moves along tubule and through collecting duct, more than 99% of water and many useful solutes reabsorbed – returned to blood
Tubular secretion
As filtered fluid moves along tubule and through collecting duct, other material secreted into fluid such as wastes, drugs, and excess ions – removes substances from blood
Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted as urine
Excretion of any solute = glomerular filtration + secretion - reabsorption
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16. Structures and functions of a nephron
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Tubular secretion
from blood into fluid
Tubular reabsorption
from fluid into blood
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1 2 3
Renal corpuscle
Renal tubule and collecting duct
Peritubular capillaries
Urine
(contains
excreted
substances)
Blood
reabsorbed
Tubular reabsorption
from fluid into blood
Fluid in
renal tubule
Afferent
arteriole
Filtration from blood
plasma into nephron
Efferent
Glomerular
capsule 1 2
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17. Glomerular Filtration
GFR = 125 ml/min = 180 liters/day
Plasma volume is filtered 60 times per day
Glomerular filtrate composition is about the
same as plasma, except for large proteins
Filtration fraction (GFR / Renal Plasma Flow)
= 0.2 (i.e. 20% of plasma is filtered)
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18. Glomerular filtration
Glomerular filtrate – fluid that enters capsular space
Daily volume ≈180 liters – more than 99% returned to blood plasma via tubular reabsorption
Filtration membrane – endothelial cells of glomerular capillaries and podocytes encircling capillaries
Permits filtration of water and small solutes. MW less than 70 K
Prevents filtration of most plasma proteins, blood cells and platelets…especially if they are negatively charged
3 barriers to cross – glomerular endothelial cells fenestrations, basal lamina between endothelium and podocytes and pedicels of podocytes create filtration slits
Volume of fluid filtered is large because of large surface area, thin and porous membrane, and high glomerular capillary blood pressure
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19. The filtration membrane
Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Basal lamina of glomerulus:
prevents filtration of larger proteins
Slit membrane between pedicels:
prevents filtration of medium-sized
proteins
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1 2 3
Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1
Filtration slit
Pedicel of podocyte
Fenestration (pore) of
glomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM
78,000x
(a) Details of filtration membrane
Pedicel
Fenestration (pore) of glomerular
endothelial cell: prevents filtration of
blood cells but allows all components
of blood plasma to pass through
Basal lamina of glomerulus:
prevents filtration of larger proteins
Podocyte of visceral
layer of glomerular
(Bowman’s) capsule 1 2
The filtration membrane
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20. Glomerular Filtration
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Figure 26.10a, b

21. Net filtration pressure
Net filtration pressure (NFP) is the total pressure that promotes filtration
NFP = GBHP – CHP – BCOP
Glomerular blood hydrostatic pressure is the blood pressure of the glomerular capillaries forcing water and solutes through filtration slits=60 mmHg
Capsular hydrostatic pressure is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and represents “back pressure”=18 mmHg
Blood colloid osmotic pressure due to presence of proteins in blood plasma and also opposes filtration=32 mmHg
NFP = =10 mmHg
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22. The pressures that drive glomerular filtration
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 60 mmHg 18 mmHg 32 mmHg
= 10 mmHg
BLOOD COLLOID
OSMOTIC PRESSURE
(BCOP) = 32 mmHg
CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 18 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 60 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1 2 3
Proximal convoluted tubule
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1
Proximal convoluted tubule
NET FILTRATION PRESSURE (NFP)
=GBHP – CHP – BCOP
= 55 mmHg 15 mmHg 30 mmHg
= 10 mmHg
CAPSULAR HYDROSTATIC
PRESSURE (CHP) = 15 mmHg
GLOMERULAR BLOOD
HYDROSTATIC PRESSURE
(GBHP) = 55 mmHg
Capsular
space
Glomerular
(Bowman's)
capsule
Efferent
arteriole
Afferent arteriole 1 2
Proximal convoluted tubule
The pressures that drive glomerular filtration
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23. Glomerular filtration
Glomerular filtration rate – amount of filtrate formed in all the renal corpuscles of both kidneys each minute=125 ml/min
Homeostasis requires kidneys maintain a relatively constant GFR
Too high – substances pass too quickly and are not reabsorbed …loosing valuable substances such as a.a
Too low – nearly all reabsorbed and some waste products not adequately excreted such as urea and creatinine
GFR directly related to pressures that determine net filtration pressure
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24. Clearance “Clearance” describes the rate at which substances
are removed (cleared) from the plasma.
The unit is ml/min
Renal clearance of a substance is the volume of
plasma completely cleared of a substance
per min by the kidneys.
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25. Clearance Technique
Renal clearance (Cs) of a substance is the volume of
plasma completely cleared of a substance per min.
Cs x Ps = Us x V
Cs = Us x V = urine excretion rate
Ps Plasma conc.
Where : Cs = clearance of substance S
Ps = plasma conc. of substance S
Us = urine conc. of substance S
V = urine flow rate
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26. Use of Clearance to Measure GFR
For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, creatinine), renal clearance is equal to GFR
amount filtered = amount excreted
GFR x Pin
= Uin x V
GFR =
Pin
Uin x V
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27. Calculate the GFR from the following data:
Pinulin = 1.0 mg / 100ml
Uinulin = 125 mg/100 ml
Urine flow rate = 1.0 ml/min
GFR = Cinulin =
Pin
Uin x V
GFR =
125 x 1.0
1.0
= 125 ml/min
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28. Cx = renal plasma flow Use of Clearance to Estimate Renal Plasma Flow
Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow
Cx = renal plasma flow
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29. Use of PAH Clearance to Estimate Renal Plasma Flow
Paraminohippuric acid (PAH) is freely filtered and secreted
and is almost completely cleared from the renal plasma
1. amount enter kidney =
RPF x PPAH
2. amount entered = amount excreted ~
3. ERPF x Ppah = UPAH x V
~ 10 % PAH
remains
ERPF =
UPAH x V
PPAH
ERPF = Clearance PAH
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30. Reabsorption = Filtration -Excretion
Calculation of Tubular Reabsorption
Reabsorption = Filtration -Excretion
Filt s = GFR x Ps
Excret s = Us x V
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31. Calculation of Tubular Secretion
Secretion = Excretion - Filtration
Filt s = GFR x Ps
VPAH = 0.1
Excret s = Us x V
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32. Cx = renal plasma flow Use of Clearance to Estimate Renal Plasma Flow
Theoretically, if a substance is completely cleared from
the plasma, its clearance rate would equal renal plasma flow
Cx = renal plasma flow
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33. Clearances of Different Substances
Substance Clearance (ml/min
inulin
PAH
glucose
sodium
urea
Clearance of inulin (Cin) = GFR
if Cx < Cin : indicates reabsorption of x
if Cx > Cin : indicates secretion of x
Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)
Clearance of PAH (Cpah) ~ effective renal plasma flow
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34. GFR regulation : Adjusting blood flow
GFR is regulated using three mechanisms
1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation
All three mechanism adjust renal arterial blood pressure and the resulting arterial blood flow
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35. Local Control of GFR and renal blood flow
1. Autoregulation of GFR and Renal Blood Flow
Myogenic Mechanism
Macula Densa Feedback
(tubuloglomerular feedback)
Angiotensin II ( contributes to GFR but
not RBF autoregulation)
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36. Renal Autoregulation 120 100 Renal Artery Pressure (mmHg) 80
Glomerular
Filtration Rate
Renal Blood
Flow 1 2 3 4 5
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Time (min)

37. 3 Mechanisms regulating GFR
Renal autoregulation
Kidneys themselves maintain constant renal blood flow and GFR using
Myogenic mechanism – occurs when stretching triggers contraction of smooth muscle cells in afferent arterioles – reduces GFR
Tubuloglomerular mechanism – macula densa provides feedback to glomerulus, inhibits release of NO causing afferent arterioles to constrict and decreasing GFR
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38. Myogenic Mechanism Arterial Pressure Stretch of Blood Vessel Cell Ca++
Entry
Intracell. Ca++
Vascular
Resistance
Blood Flow
and
GFR
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39. Structure of the juxtaglomerular apparatus: macula densa
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40. Macula Densa Feedback GFR Distal NaCl Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
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41. Macula Densa Feedback Proximal NaCl Reabsorption Distal NaCl Delivery
Macula Densa NaCl Reabsorption
(macula densa feedback)
Afferent Arteriolar Resistance
GFR
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42. Regulation of GFR by Ang II
Macula
Renin
GFR
Densa NaCl
Blood
Pressure
AngII
Efferent Arteriolar
Resistance
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43. Ang II Blockade Impairs GFR Autoregulation.
Ang II Blockade Impairs GFR Autoregulation
1600
1200
Renal
Blood Flow
( ml/min)
800
Normal
400
Ang II Blockade
120
Glomerular
Filtration
Rate (ml/min) 80 40 50
100
150
200
Arterial Pressure (mmHg)
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44. Macula densa feedback mechanism for regulating GFR
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45. Tuboglomerular feedback
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46. Mechanisms regulating GFR
Neural regulation
Kidney blood vessels supplied by sympathetic ANS fibers that release norepinephrine causing vasoconstriction
Moderate stimulation – both afferent and efferent arterioles constrict to same degree and GFR decreases
Greater stimulation constricts afferent arterioles more and GFR drops
Hormonal regulation
Angiotensin II increases GFR – potent vasoconstrictor for efferent arterioles
Atrial natriuretic peptide increases GFR – stretching of atria causes release, increases capillary surface area for filtration
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47. Summary of neurohumoral control of GFR and renal blood flow
Effect on GFR Effect on RBF
Sympathetic activity
Catecholamines
Angiotensin II
EDRF (NO)
Endothelin
Prostaglandins
increase
decrease
no change
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48. Thank You
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