the urinary system muse 2440 lecture #9 3/16/11. overview of kidney functions regulation of blood...

The Urinary System

Muse 2440lecture #93/16/11

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

Organs of the urinary system in a female i

Position and coverings of the kidneys

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

Internal anatomy of the kidneys

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

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

The structure of nephrons and associated blood vessels i

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

Histology of a renal corpuscle

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




Tubular reabsorptionfrom fluid into blood


Afferentarteriole


Efferentarteriole

Glomerularcapsule

1

2

Renal corpuscle Renal tubule and collecting duct




Tubular secretionfrom blood into fluid

Tubular reabsorptionfrom fluid into blood


Afferentarteriole


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

The filtration membrane

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



Basal lamina

Lumen of glomerulus


TEM 78,000x


Filtration slit

Pedicel


Basal lamina of glomerulus:prevents filtration of larger proteins


1

2



Basal lamina

Lumen of glomerulus


TEM 78,000x


Filtration slit

Pedicel


Basal lamina of glomerulus:prevents filtration of larger proteins

Slit membrane between pedicels:prevents filtration of medium-sizedproteins


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

The pressures that drive glomerular 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


CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg


Capsularspace


Efferent arteriole

Afferent arteriole

1 2



BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg

CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg


Capsularspace


Efferent arteriole

Afferent arteriole

1 2

3


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

Tuboglomerular feedback

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 routes: paracellular reabsorption and transcellular reabsorption i

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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Reabsorption and secretion in the proximal convoluted tubule i

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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Na+–K+-2Cl- symporter in the thick ascending limb of the loop of Henle

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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

Mechanism of urine concentration in long-loop juxtamedullary nephrons

(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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Summary of filtration, reabsorption, and secretion in the nephron and collecting duct

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Summary: Renal Function

Figure 26–16a A Summary of Renal Function.

Summary: Renal Function

Figure 26–16b A Summary of Renal Function.

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

Ureters, urinary bladder, and urethra in a female

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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Comparison between female and male urethras

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

the urinary system muse 2440 lecture #9 3/16/11. overview of kidney functions regulation of blood...

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