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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 (hormone: Renin) 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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Anatomy and histology of the kidneys External anatomy
Renal hilium – indent where ureter emerges along with blood vessels, lymphatic vessels and nerves
3 layers of tissue Renal capsule – deep layer – continuous with outer
coat of ureter, barrier against trauma, maintains kidney shape
Adipose capsule – mass of fatty tissue that protects kidney from trauma and holds it in place
Renal fascia – superficial layer – thin layer of connective tissue that anchors kidney to surrounding structures and abdominal wall
Internal anatomy
Renal cortex – superficial Outer cortical zone Inner juxtamedullary zone Renal columns – portions of cortex that extend between
renal pyramids Renal medulla – inner region
Several cone shaped renal pyramids – base faces cortex and renal papilla points toward hilium
Renal lobe – renal pyramid, overlying cortex area, and ½ of each adjacent renal column
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Anatomy of the kidneys
Parenchyma (functional portion) of kidney Renal cortex and renal pyramids of medulla
Nephron – microscopic functional units of kidney Urine formed by nephron drains into
Papillary ducts Minor and major calyces Renal pelvis Ureter Urinary bladder
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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Figure 25.4a
Cortical radiate vein
Cortical radiate artery
Arcuate vein
Arcuate artery
Interlobar vein
Interlobar artery
Segmental arteries
Renal artery
Renal vein
Renal pelvis
Ureter
Renal medulla
Renal cortex
(a) Frontal section illustrating major blood vessels
Figure 25.4b
Aorta
Renal artery
Segmental artery
Interlobar artery
Arcuate artery
Cortical radiate artery
Afferent arteriole
Glomerulus (capillaries)
Nephron-associated blood vessels
Inferior vena cava
Renal vein
Interlobar vein
Arcuate vein
Cortical radiatevein
Peritubularcapillaries
and vasa recta
Efferent arteriole
(b) Path of blood flow through renal blood vessels
The nephron – functional units of kidney
2 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
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
Figure 25.5
Fenestratedendotheliumof the glomerulus
Podocyte
Basementmembrane
Glomerular capsule: visceral layer
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
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
Solutes in the fluid that drains into the renal pelvis remain in the fluid and are excreted
Excretion of any solute = glomerular filtration + secretion - reabsorption
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Structures and functions of a nephronsimplified schematicRenal 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
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
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
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
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
Glomerular filtration
Glomerular filtration rate GFR – 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
3 Mechanisms regulating GFR
1. 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
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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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 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
Reabsorption and secretion in proximal convoluted tubule (PCT)
Largest amount of solute and water reabsorption 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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Figure 25.5
Microvilli Mitochondria
Highly infolded plasma membrane
Proximal convoluted tubule cells
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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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
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 Proximal Convoluted Tubule Aldosterone - when blood volume and blood pressure
decrease Stimulates principal cells in collecting duct to reabsorb more
Na+ and Cl- and secrete more K+ Parathyroid hormone
Stimulates cells in Distal Convolute Tubule to reabsorb more Ca2+
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Regulation of facultative water reabsorption by ADH
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
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 (concentrates) 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
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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Formation of concentrated urine
Urine can be up to 4 times more concentrated than blood plasma
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
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 organisms that adapt to deserts have long loops of Henle
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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
(b) Recycling of salts and urea in the vasa recta(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferentarteriole
Efferentarteriole
Glomerulus
Distal convoluted tubule
Proximalconvolutedtubule
Symporters in thickascending limb causebuildup of Na+ and Cl–
Interstitial fluidin renal medulla
300
1200
1000
800
Osmoticgradient
600
400
H2OH2O
H2O
200
1200
980
600780
400580
200380
300
100
Loop of Henle1200 Concentrated urine
300
300
320
400
600
800
1000
1200
800
H2O
Urea
Papillaryduct
Collectingduct
300
500
700
900
1100
1200
400
800
1000
600
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symportersInterstitialfluid inrenal cortex
320
Juxtamedullary nephronand its blood supply together
Vasarecta
Loop ofHenle
H2O
H2O
H2O
H2O
H2O
H2O
H2O
1
H2O
H2O
Na+CI–
Na+CI–
H2O
Na+CI–
H2O
Na+CI–
(b) Recycling of salts and urea in the vasa recta(a) Reabsorption of Na+CI– and water in a long-loop juxtamedullary nephron
Glomerular (Bowman’s) capsule
Afferentarteriole
Efferentarteriole
Glomerulus
Distal convoluted tubule
Proximalconvolutedtubule
Symporters in thickascending limb causebuildup of Na+ and Cl–
Interstitial fluidin renal medulla
300
1200
1000
800
Osmoticgradient
600
400
H2OH2O
H2O
200
1200
980
600780
400580
200380
300
100
Loop of Henle1200 Concentrated urine
300
300
320
400
600
800
1000
1200
800
H2O
Urea
Papillaryduct
Collectingduct
Countercurrent flowthrough loop of Henleestablishes an osmoticgradient
300
500
700
900
1100
1200
400
800
1000
600
Na+CI–
Blood flow
Flow of tubular fluid
Presense of Na+-K+-2CI–
symportersInterstitialfluid inrenal cortex
320
Juxtamedullary nephronand its blood supply together
Vasarecta
Loop ofHenle
H2O
H2O
H2O
H2O
H2O
H2O
H2O
1
2
H2O
H2O
Na+CI–
Na+CI–
H2O
Na+CI–
H2O
Na+CI–
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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
look for pH, protein, urea, blood, ketone.
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
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
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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Urine Transport, Storage, and Elimination The Micturition Reflex and Urination
Begins when stretch receptors stimulate parasympathetic preganglionic motor neurons
Volume >500 mL triggers micturition reflex
Age-Related Changes in Urinary System Decline in number of functional nephrons Reduction in GFR Reduced sensitivity to ADH Problems with micturition reflex
Sphincter muscles lose tone leading to incontinence Control of micturition can be lost due to a stroke, Alzheimer
disease, and other CNS problems In males, urinary retention may develop if enlarged prostate
gland compresses the urethra and restricts urine flow