university of jordan 1 1 1 renal system –l1 faisal i. mohammed, md, phd

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University of Jordan 1 University of Jordan 1 Renal system –L1 Faisal I. Mohammed, MD, PhD

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Page 1: University of Jordan 1 1 1 Renal system –L1 Faisal I. Mohammed, MD, PhD

University of Jordan 11University of Jordan 1

Renal system –L1

Faisal I. Mohammed, MD, PhD

Page 2: University of Jordan 1 1 1 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

University of Jordan 2

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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

University of Jordan

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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

University of Jordan

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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

University of Jordan

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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

University of Jordan

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Reabsorption and secretion in the proximal convoluted tubule

University of Jordan

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Reabsorption and secretion in the proximal convoluted tubule

University of Jordan

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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

University of Jordan

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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

University of Jordan

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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

University of Jordan

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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

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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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