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Renal system –L1
Faisal I. Mohammed, MD, PhD
University of Jordan 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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Overview of kidney functions Regulation of blood ionic composition Regulation of blood pH Regulation of blood volume Regulation of blood pressure Maintenance of blood osmolarity Production of hormones (calcitrol and erythropoitin) Regulation of blood glucose level Excretion of wastes from metabolic reactions and foreign
substances (drugs or toxins)
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Organs of the urinary system
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Internal anatomy of the kidneys
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Blood and nerve supply of the kidneys Blood supply
Although kidneys constitute less than 0.5% of total body mass, they receive 20-25% of resting cardiac output
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 Reunite to form efferent arteriole (unique) 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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Blood supply of the kidneys
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The nephron – functional units of kidney2 parts
Renal corpuscle – filters blood plasma Glomerulus – capillary network Glomerular (Bowman’s) capsule – double-
walled cup surrounding glomerulus Renal tubule – filtered fluid passes into
Proximal convoluted tubule Descending and ascending loop of Henle
(nephron loop) Distal convoluted tubule
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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 25-20% 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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Cortical Nephron
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Juxtamedullary Nephron
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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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Renal corpuscle
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Renal tubule and collecting duct
Proximal convoluted tubule cells have microvilli with brush border – increases surface area
Juxtaglomerular appraratus 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
Intercalated cells – role in blood pH homeostasis
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Overview of renal physiology1. Glomerular filtration
Water and most solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubule
2. Tubular reabsorption As filtered fluid moves along tubule and through collecting duct,
about 99% of water and many useful solutes reabsorbed – returned to blood
3. 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
4. Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted
5. Excretion of any solute = glomerular filtration + secretion - reabsorption
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Structures and functions of a nephron
Renal corpuscle Renal tubule and collecting duct
Peritubular capillaries
Urine(containsexcretedsubstances)
Blood(containsreabsorbedsubstances)
Fluid inrenal tubule
Afferentarteriole
Filtration from bloodplasma into nephron
Efferentarteriole
Glomerularcapsule
1
Renal corpuscle Renal tubule and collecting duct
Peritubular capillaries
Urine(containsexcretedsubstances)
Blood(containsreabsorbedsubstances)
Tubular reabsorptionfrom fluid into blood
Fluid inrenal tubule
Afferentarteriole
Filtration from bloodplasma into nephron
Efferentarteriole
Glomerularcapsule
1
2
Renal corpuscle Renal tubule and collecting duct
Peritubular capillaries
Urine(containsexcretedsubstances)
Blood(containsreabsorbedsubstances)
Tubular secretionfrom blood into fluid
Tubular reabsorptionfrom fluid into blood
Fluid inrenal tubule
Afferentarteriole
Filtration from bloodplasma into nephron
Efferentarteriole
Glomerularcapsule
1
2 3
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Glomerular Filtration
GFR = 125 ml/min = 180 liters/day
• Plasma volume is filtered 60 times per day
• Glomerular filtrate composition is about thesame 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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Glomerular filtration
Glomerular filtrate – fluid that enters capsular space Daily volume 150-180 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 Prevents filtration of most plasma proteins, blood cells and
platelets 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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Filtration slitPedicel of podocyte
Fenestration (pore) ofglomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM 78,000x
(a) Details of filtration membrane
Filtration slit
Pedicel
Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through
Podocyte of viscerallayer of glomerular(Bowman’s) capsule
1
Filtration slitPedicel of podocyte
Fenestration (pore) ofglomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM 78,000x
(a) Details of filtration membrane
Filtration slit
Pedicel
Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through
Basal lamina of glomerulus:prevents filtration of larger proteins
Podocyte of viscerallayer of glomerular(Bowman’s) capsule
1
2
Filtration slitPedicel of podocyte
Fenestration (pore) ofglomerular endothelial cell
Basal lamina
Lumen of glomerulus
(b) Filtration membrane
TEM 78,000x
(a) Details of filtration membrane
Filtration slit
Pedicel
Fenestration (pore) of glomerularendothelial cell: prevents filtration ofblood cells but allows all componentsof blood plasma to pass through
Basal lamina of glomerulus:prevents filtration of larger proteins
Slit membrane between pedicels:prevents filtration of medium-sizedproteins
Podocyte of viscerallayer of glomerular(Bowman’s) capsule
1
2
3
The filtration membrane
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Glomerular Filtration
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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
Capsular hydrostatic pressure is the hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and represents “back pressure”
Blood colloid osmotic pressure due to presence of proteins in blood plasma and also opposes filtration
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NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg
GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg
Capsularspace
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 HYDROSTATICPRESSURE (CHP) = 15 mmHg
GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg
Capsularspace
Glomerular(Bowman's)capsule
Efferent arteriole
Afferent arteriole
1 2
Proximal convoluted tubule
NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg
BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg
CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg
GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg
Capsularspace
Glomerular(Bowman's)capsule
Efferent arteriole
Afferent arteriole
1 2
3
Proximal convoluted tubule
The pressures that drive glomerular filtration
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Glomerular filtration
Glomerular filtration rate – amount of filtrate formed in all the renal corpuscles of both kidneys each minute Homeostasis requires kidneys maintain a relatively constant
GFR Too high – substances pass too quickly and are not
reabsorbed Too low – nearly all reabsorbed and some waste
products not adequately excreted GFR directly related to pressures that determine net
filtration pressure
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Clearance
• Renal clearance of a substance is the volume of plasma completely cleared of a substance per min by the kidneys.
• “Clearance” describes the rate at which substances are removed (cleared) from the plasma.
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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
Where : Cs = clearance of substance SPs = plasma conc. of substance SUs = urine conc. of substance SV = urine flow rate
Cs = Us x V = urine excretion rate s Ps Plasma conc. s
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For a substance that is freely filtered, but not reabsorbed or secreted (inulin, 125 I-iothalamate, creatinine), renal clearance is equal to GFR
Use of Clearance to Measure GFR
amount filtered = amount excreted
GFR x Pin = Uin x V
GFR =
Pin
Uin x V
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Calculate the GFR from the following data:
Pinulin = 1.0 mg / 100mlUinulin = 125 mg/100 mlUrine flow rate = 1.0 ml/min
GFR =125 x 1.0
1.0= 125 ml/min
GFR = Cinulin =Pin
Uin x V
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Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow
Use of Clearance to Estimate Renal Plasma Flow
Cx = renal plasma flow
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Paraminohippuric acid (PAH) is freely filtered and secretedand is almost completely cleared from the renal plasma
Use of PAH Clearance to Estimate Renal Plasma Flow
1. amount enter kidney =RPF x PPAH
3. ERPF x Ppah = UPAH x V
ERPF = UPAH x V
PPAH
ERPF = Clearance PAH
2. amount entered = amount excreted~
~ 10 % PAHremains
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Calculation of Tubular Reabsorption
Reabsorption = Filtration -Excretion
Filt s = GFR x Ps
Excret s = Us x V
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Calculation of Tubular Secretion
Secretion = Excretion - Filtration
Filt s = GFR x Ps
Excret s = Us x V
VPAH = 0.1
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Theoretically, if a substance is completely cleared from the plasma, its clearance rate would equal renal plasma flow
Use of Clearance to Estimate Renal Plasma Flow
Cx = renal plasma flow
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Clearances of Different Substances
Clearance of inulin (Cin) = GFR
if Cx < Cin : indicates reabsorption of x
Clearance of PAH (Cpah) ~ effective renal plasma flow
Substance Clearance (ml/min inulin 125 PAH 600 glucose 0 sodium 0.9 urea 70
Clearance creatinine (Ccreat) ~ 140 (used to estimate GFR)
if Cx > Cin : indicates secretion of x
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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 blood pressure and resulting blood flow
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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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Renal ArteryPressure (mmHg)
100
Renal Blood Flow
Glomerular Filtration Rate
Renal Autoregulation
80
Time (min)0 1 2 3 4 5
120
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3 Mechanisms regulating GFR
1. Renal autoregulation
a. Kidneys themselves maintain constant renal blood flow and GFR using
1. Myogenic mechanism – occurs when stretching triggers contraction of smooth muscle cells in afferent arterioles – reduces GFR
2. Tubuloglomerular mechanism – macula densa provides feedback to glomerulus, inhibits release of NO causing afferent arterioles to constrict and decreasing GFR
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Myogenic Mechanism
Arterial Pressure
Blood Flow and GFR
VascularResistance
Intracell. Ca++
Cell Ca++
EntryStretch ofBlood Vessel
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Structure of the juxtaglomerular apparatus:macula densa
Structure of the juxtaglomerular apparatus:macula densa
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Macula Densa Feedback
GFR
Distal NaCl Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance(macula densa feedback)
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Macula Densa Feedback
Proximal NaCl Reabsorption
Distal NaCl Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance
GFR
(macula densa feedback)
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Regulation of GFR by Ang II
GFR Renin
AngII
Macula Densa NaCl
Efferent Arteriolar
Resistance
BloodPressure
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50 100 150 2000
Renal Blood Flow ( ml/min)
1600
1200
800
0
400
120
80
0
40
Glomerular Filtration Rate (ml/min)
Arterial Pressure (mmHg)
Ang II Blockade Impairs GFR Autoregulation
NormalAng II Blockade
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Macula densa feedback
mechanism for regulating GFR
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Tuboglomerular feedback
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Mechanisms regulating GFR2. 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
3. Hormonal regulation Angiotensin II reduces GFR – potent vasoconstrictor of both
afferent and efferent arterioles Atrial natriuretic peptide increases GFR – stretching of atria
causes release, increases capillary surface area for filtration
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Summary of neurohumoral control of GFR and renal blood flow
Effect on GFR Effect on RBF
Sympathetic activityCatecholaminesAngiotensin IIEDRF (NO)EndothelinProstaglandins
increase decrease no change
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Thank YouThank You
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Renal system –L3
Faisal I. Mohammed, MD, PhD
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Tubular reabsorption and tubular secretion Reabsorption – return of most of the filtered water
and many solutes to the bloodstream About 99% of filtered water reabsorbed Proximal convoluted tubule cells make largest
contribution around 67% Both active and passive processes
Secretion – transfer of material from blood into tubular fluid Helps control blood pH Helps eliminate substances from the body
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Reabsorption routes and transport mechanisms Reabsorption routes
Paracellular reabsorption Between adjacent tubule cells Tight junction do not completely seal off interstitial fluid from tubule fluid Passive
Transcellular reabsorption – through an individual cell Transport mechanisms
Reabsorption of Na+ especially important Primary active transport
Sodium-potassium pumps in basolateral membrane only Secondary active transport
Symporters, antiporters Transport maximum (Tm)
Upper limit to how fast it can work Obligatory vs. facultative water reabsorption
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Reabsorption routes: paracellular reabsorption and transcellular reabsorption
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Reabsorption and secretion in proximal convoluted tubule (PCT)
Largest amount of solute and water reabsorption two thirds Secretes variable amounts of H+, NH4
+ and urea Most solute reabsorption involves Na+
Symporters for glucose, amino acids, lactic acid, water-soluble vitamins, phosphate and sulfate
Na+ / H+ antiporter causes Na+ to be reabsorbed and H+ to be secreted
Solute reabsorption promotes osmosis – creates osmotic gradient Aquaporin-1 in cells lining PCT and descending limb of loop of
Henle As water leaves tubular fluid, solute concentration increases
Urea and ammonia in blood are filtered at glomerulus and secreted by proximal convoluted tubule cells
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Glucose Transport Maximum
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Transport Maximum
Some substances have a maximum rate of tubular transport due to saturation of carriers, limited ATP, etc
• Transport Maximum: Once the transport maximum isreached for all nephrons, further increases in tubularload are not reabsorbed and are excreted.
• Threshold is the tubular load at which transport maximum isexceeded in some nephrons. This is not exactly the same as the transport maximum of the whole kidney becausesome nephrons have lower transport max’s than others.
• Examples: glucose, amino acids, phosphate, sulphate
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Reabsorption and secretion in the proximal convoluted tubule
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Reabsorption and secretion in the proximal convoluted tubule
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Reabsorption and secretion in the proximal convoluted tubule
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Changes in concentration in proximal tubule Changes in concentration in proximal tubule
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Reabsorption in the loop of Henle Chemical composition of tubular fluid quite different from
filtrate Glucose, amino acids and other nutrients reabsorbed
Osmolarity still close to that of blood Reabsorption of water and solutes balanced
For the first time reabsorption of water is NOT automatically coupled to reabsorption of solutes Independent regulation of both volume and osmolarity of
body fluids Na+-K+-2Cl- symporters function in Na+ and Cl- reabsorption –
promotes reabsorption of cations Little or no water is reabsorbed in ascending limb – osmolarity
decreases
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Na+–K+-2Cl- symporter in the thick ascending limb of the loop of Henle
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Early Distal Tubule
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Early Distal Tubule
Functionally similar to thick ascending loop Not permeable to water (called diluting segment)
Active reabsorption of Na+, Cl-, K+, Mg++
Contains macula densa (tubuloglomerular balance)Major site where parathyroid hormone stimulates
reabsorption of Ca+ depending on body’s needs
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Reabsorption and secretion in the late distale convoluted tubule and collecting duct
Reabsorption on the early distal convoluted tubule Na+-Cl- symporters reabsorb Na+ and Cl-
Major site where parathyroid hormone stimulates reabsorption of Ca+ depending on body’s needs
Reabsorption and secretion in the late distal convoluted tubule and collecting duct 90-95% of filtered solutes and fluid have been returned by now Principal cells reabsorb Na+ and secrete K+
Intercalated cells reabsorb K+ and HCO3- and secrete H+
Amount of water reabsorption and solute reabsorption and secretion depends on body’s needs
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Reabsorption and secretion in the late distale convoluted tubule and collecting duct
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Late Distal and Cortical Collecting Tubules Principal Cells – Secrete K+
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Tubular LumenTubular Cells
Na +
ATP
Cl -
K+
H+ATP
Late Distal and Cortical Collecting Tubules Intercalated Cells –Secrete H+
H2O (depends on
ADH)
H +
ATPK+ ATP
ATP
K+
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Changes in concentrations of substances in the
renal tubules
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Hormonal regulation of tubular reabsorption and secretion
Angiotensin II - when blood volume and blood pressure decrease Decreases GFR, enhances reabsorption of Na+, Cl- and
water in PCT Aldosterone - when blood volume and blood pressure
decrease Stimulates principal cells in late distal and collecting
duct to reabsorb more Na+ and Cl- and secrete more K+ Parathyroid hormone
Stimulates cells in DCT to reabsorb more Ca2+
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Antidiuretic hormone (ADH or vasopressin) Increases water permeability of
cells by inserting aquaporin-2 in last part of DCT and collecting duct
Atrial natriuretic peptide (ANP) Large increase in blood volume
promotes release of ANP Decreases blood volume and
pressure by inhibiting reabsorption of Na+ and water in PCT and collecting duct, suppress secretion of ADH and aldosterone
Regulation of facultative water reabsorption by ADH
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Production of dilute and concentrated urine Even though your fluid intake can be highly variable,
total fluid volume in your body remains stable Depends in large part on the kidneys to regulate the
rate of water loss in urine ADH controls whether dilute or concentrated urine is
formed Absent or low ADH = dilute urine Higher levels = more concentrated urine through
increased water reabsorption
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Formation of dilute urine
Glomerular filtrate has same osmolarity as blood 300 mOsm/liter
Fluid leaving PCT is isotonic to plasma When dilute urine is being formed, the osmolarity
of fluid increases as it goes down the descending loop of Henle, decreases as it goes up the ascending limb, and decreases still more as it flows through the rest of the nephron and collecting duct
THANK YOU
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Renal system –L4
Faisal I. Mohammed, MD, PhD
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Control of Extracellular Osmolarity(NaCl Concentration)
• ADH• Thirst ] ADH -Thirst Osmoreceptor System
Mechanism:increased extracellular osmolarity (NaCl)stimulates ADH release, which increases H2O reabsorption, and stimulates thirst(intake of water)
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Formation of dilute urine
Osmolarity of interstitial fluid of renal medulla becomes greater, more water is reabsorbed from tubular fluid so fluid become more concentrated
Water cannot leave in thick portion of ascending limb but solutes leave making fluid more dilute than blood plasma
Additional solutes but not much water leaves in DCT
Low ADH makes late DCT and collecting duct have low water permeability
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• Continue electrolyte reabsorption• Decrease water reabsorption
Mechanism: Decreased ADH release and reduced water permeability in distal and collecting tubules
Formation of a dilute urine
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Formation of concentrated urine
Urine can be up to 4 times more concentrated than blood plasma i.e maxinmal osmolarity is 1200 mOsm/liter
Ability of ADH depends on presence of osmotic gradient in interstitial fluid of renal medulla
3 major solutes contribute – Na+, Cl-, and urea 2 main factors build and maintain gradient
Differences in solute and water permeability in different sections of loop of Henle and collecting ducts
Countercurrent flow of fluid though descending and ascending loop of Henle and blood through ascending and descending limbs of vasa recta
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Formation of a Concentrated Urine whenantidiuretic hormone (ADH) are high.
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Countercurrent multiplication Process by which a progressively increasing osmotic
gradient is formed as a result of countercurrent flow Long loops of Henle of juxtamedullary nephrons function as
countercurrent multiplier Symporters in thick ascending limb of loop of Henle cause
buildup of Na+ and Cl- in renal medulla, cells impermeable to water
Countercurrent flow establishes gradient as reabsorbed Na+ and Cl- become increasingly concentrated
Cells in collecting duct reabsorb more water and urea Urea recycling causes a buildup of urea in the renal medulla Long loop of Henle establishes gradient by countercurrent
multiplication
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Countercurrent exchange
Process by which solutes and water are passively exchanged between blood of the vasa recta and interstitial fluid of the renal medulla as a result of countercurrent flow
Vasa recta is a countercurrent exchanger Osmolarity of blood leaving vasa recta is only slightly
higher than blood entering Provides oxygen and nutrients to medulla without
washing out or diminishing gradient Vasa recta maintains gradient by countercurrent
exchange
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Recirculation of urea absorbed from medullary collecting duct into interstitial fluid.
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Urea Recirculation
• Urea is passively reabsorbed in proximal tubule (~ 50% of filtered load is reabsorbed)• In the presence of ADH, water is reabsorbed in
distal and collecting tubules, concentratingurea in these parts of the nephron
• The inner medullary collecting tubule is highlypermeable to urea, which diffuses into the medullary interstitium
• ADH increases urea permeability of medullarycollecting tubule by activating urea transporters (UT-1)
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Mechanism of urine concentration in long-loop juxtamedullary nephrons
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Summary of Tubule Characteristics
Permeability H2O NaCl Urea
Active NaCl Transport
Proximal ++ +++ + +Thin Desc. 0 +++ + +Thin Ascen. 0 0 + +Thick Ascen. +++ 0 0 0Distal + +ADH 0 0Cortical Coll. + +ADH 0 0Inner Medullary + +ADH 0 +++
Coll.
TubuleSegment
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Changes in osmolarity of the tubular fluid
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Summary of filtration, reabsorption, and secretion in the nephron and collecting duct
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Evaluation of kidney function
Urinalysis Analysis of the volume and physical, chemical and
microscopic properties of urine Water accounts for 95% of total urine volume Typical solutes are filtered and secreted substances
that are not reabsorbed If disease alters metabolism or kidney function,
traces if substances normally not present or normal constituents in abnormal amounts may appear
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Evaluation of kidney function
Blood tests Blood urea nitrogen (BUN) – measures blood nitrogen that is part
of the urea resulting from catabolism and deamination of amino acids
Plasma creatinine results from catabolism of creatine phosphate in skeletal muscle – measure of renal function
Renal plasma clearance More useful in diagnosis of kidney problems than above Volume of blood cleared of a substance per unit time High renal plasma clearance indicates efficient excretion of a
substance into urine PAH administered to measure renal plasma flow
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Glucose 180 180(gm/day)
Renal Handling of Water and SolutesFiltration Reabsorption Excretion
Water 180 179 (liters/day)
Sodium 25,560 25,410 (mmol/day)
Creatinine 1.8 1.8(gm/day)
1
0
150
0
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Renal Regulation of Acid-Base Balance
• Kidneys eliminate non-volatileacids (H2SO4, H3PO4) (~ 80 mmol/day)
• Filtration of HCO3- (~ 4320 mmol/day)
• Secretion of H+ (~ 4400 mmol/day)• Reabsorption of HCO3
- (~ 4319 mmol/day)• Production of new HCO3
- (~ 80 mmol/day)• Excretion of HCO3
- (1 mmol/day)
Kidneys conserve HCO3- and excrete acidic
or basic urine depending on body needs
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Reabsorption of bicarbonate (and H+ secretion) in different segments of renal tubule. Reabsorption of bicarbonate (and H+ secretion) in different segments of renal tubule.
Key point:For each HCO3
-
reabsorbed, theremust be a H+
secreted
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Mechanisms for HCO3- reabsorption and Na+ -
H+ exchange in proximal tubule and thick loop of Henle
Mechanisms for HCO3- reabsorption and Na+ -
H+ exchange in proximal tubule and thick loop of Henle
Minimal pH~ 6.7
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HCO3- reabsorption and H+ secretion in intercalated cells of late distal and collecting tubules
MinimalpH ~4.5
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• Acidosis:- increased H+ secretion- increased HCO3
- reabsorption- production of new HCO3
-
• Alkalosis:- decreased H+ secretion- decreased HCO3
- reabsorption- loss of HCO3
- in urine
Renal Compensations forAcid-Base Disorders
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Interstitial Fluid
Tubular Cells
Tubular Lumen
H+HCO3- + H+
H2CO3
CO2 + H2OCO2
CarbonicAnhydrase
Cl- Cl- Cl-
ATP + Buffers-
In acidosis all HCO3- is titrated and
excess H+ in tubule is buffered
newHCO3
-
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Buffering of secreted H+ by filtered phosphate (NaHPO4
-) and generation of “new” HCO3-
Buffering of secreted H+ by filtered phosphate (NaHPO4
-) and generation of “new” HCO3-
“New” HCO3-
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Production and secretion of NH4+ and HCO3
- by proximal, thick loop of Henle, and distal tubules
Production and secretion of NH4+ and HCO3
- by proximal, thick loop of Henle, and distal tubules
“New” HCO3-
H++NH3
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Buffering of hydrogen ion secretion by ammonia (NH3) in the collecting tubules.
Buffering of hydrogen ion secretion by ammonia (NH3) in the collecting tubules.
“New” HCO3-
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Urine transportation, storage, and elimination Ureters
Each of 2 ureters transports urine from renal pelvis of one kidney to the bladder
Peristaltic waves, hydrostatic pressure and gravity move urine
No anatomical valve at the opening of the ureter into bladder – when bladder fills it compresses the opening and prevents backflow
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Urinary bladder and urethra Urinary bladder
Hollow, distensible muscular organ Capacity averages 700-800mL Micturition – discharge of urine from bladder
Combination of voluntary and involuntary muscle contractions
When volume increases stretch receptors send signals to micturition center in spinal cord triggering spinal reflex – micturition reflex
In early childhood we learn to initiate and stop it voluntarily Urethra
Small tube leading from internal urethral orifice in floor of bladder to exterior of the body
In males discharges semen as well as urine
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Urinary bladder and its innervation
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Normal Cystometrogram
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Once urine enters the renal pelvis, it flows through the ureters and enters the bladder, where urine is stored.
Micturition is the process of emptying the urinary bladder.
Two processes are involved:
(1) The bladder fills progressively until the tension in its wall reses above a threshold level, and then
(2) A nervous reflex called the micturition reflex occurs that empties the bladder.
The micturition reflex is an automatic spinal cord reflex; however, it can be inhibited or facilitated by centers in the brainstem and cerebral cortex.
Micturition
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