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    Anatomy and Physiology, Seventh Edition

    Rod R. SeeleyIdaho State University

    Trent D. Stephens

    Idaho State University

    Philip Tate

    Phoenix College

    Copyright The McGraw-Hill Companies, Inc. Permission required forreproduction ordisplay.

    *See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.

    Chapter 26Chapter 26

    Lecture OutlineLecture Outline**

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    Kidney Functions

    Filters blood plasma returns useful substances to blood

    eliminates waste

    Regulates osmolarity of body fluids, blood volume, BP

    acid base balance

    Secretes renin and erythropoietin

    Detoxifies free radicals and drugs

    Gluconeogenesis

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    Nitrogenous Wastes

    Urea

    proteinspamino acids pNH2 removedpforms ammonia, liver converts to urea

    Uric acid nucleic acid catabolism

    Creatinine

    creatine phosphate catabolism

    Renal failure

    azotemia: oBUN, nitrogenous wastes inblood

    uremia: toxic effects as wastesaccumulate

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    Excretion

    Separation of wastes from body fluidsand eliminating them; by four systems

    respiratory: CO2 integumentary: water, salts, lactic acid,

    urea

    digestive: water, salts, CO2, lipids, bile

    pigments, cholesterol

    urinary: many metabolic wastes, toxins,drugs, hormones, salts, H+ and water

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    The Nephron

    Functional and histologicalunit of the kidney

    Parts of the nephron:Bowmans capsule,proximal tubule, loop ofHenle (nephronic loop),distal tubule

    Urine continues from thenephron to collectingducts, papillary ducts,minor calyses, major

    calyses, and the renalpelvis

    Collecting ducts, parts of theloops ofHenle, and papillaryducts are in the renalmedulla

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    Types ofNephrons

    Juxtamedullary nephrons.Renal corpuscle near thecortical medullary border.Loops ofHenle extend deep

    into the medulla. Cortical nephrons. Renal

    corpuscle nearer to theperiphery of the cortex.Loops ofHenle do notextend deep into themedulla.

    Renal corpuscle. Bowmanscapsule plus a capillary bedcalled the glomerulus.

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    Renal Corpuscle Bowmans capsule:

    outer parietal (simplesquamous epithelium)

    and visceral (cellscalled podocytes)layers.

    Glomerulus: network ofcapillaries. Blood entersthrough afferentarteriole, exits throughefferent arteriole.

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    Nephron Functions: Overview

    Figure 19-2:Filtration, reabsorption, secretion, and excretion

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    Filtration

    Movement of fluid, derived from blood flowing through the

    glomerulus, across filtration membrane Filtrate: water, small molecules, ions that can pass through

    membrane

    Pressure difference forces filtrate across filtration membrane

    Renal fraction: part oftotal cardiac outputthat passes

    through the kidneys. Varies from 12-30%; averages 21% Renal blood flow rate: 1176 mL/min = 21% x 5600 ml

    Renal plasma flow rate: renal blood flow rate X fraction ofblood that is plasma: 650 mL/min = 1176 x 55%

    Filtration fraction: part of plasma that is filtered into lumenof Bowmans capsules; average 19%

    Glomerular filtration rate (GFR): amount of filtrate producedeach minute. 125 ml/min = 180 L/day; 650 ml x 19% =125ml/min

    Average urine production/day: 1-2 L. Most of filtrate must be

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    Filtration Filtration membrane: filtration barrier. It prevents blood cells and

    proteins from entering lumen of Bowmans capsule, but is many timesmore permeable than a typical capillary

    Fenestrated endothelium, basement membrane and pores formedby podocytes

    Filtration pressure: pressure gradient responsible for filtration; forcesfluid from glomerular capillary across membrane into lumen ofBowmans capsules

    Forces that affect movement of fluid into or out of the lumen ofBowmans capsule

    Glomerular capillary pressure (GCP): blood pressure insidecapillary tends to move fluid out of capillary into Bowmans capsule

    Capsule pressure (CP): pressure of filtrate already in the lumen

    B

    lood colloid osmotic pressure (B

    COP): osmotic pressurecaused by proteins in blood. Favors fluid movement into thecapillary from the lumen. BCOP greater at end of glomerularcapillary than at beginning because of fluid leaving capillary andentering lumen

    Filtration pressure (10 mm Hg) = GCP (50 mm Hg) CP (10 mmHg) BCOP (30 mm Hg)

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    Filtration Pressure

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    Filtration High glomerular capillary pressure results from

    Low resistance to blood flow in afferent arterioles

    Low resistance to blood flow in glomerular capillaries

    High resistance to blood flow in efferent arterioles: smalldiameter vessels

    Filtrate is forced across filtration membrane Changes in afferent and efferent arteriole diameter

    alter filtration pressure Dilation of afferent arterioles/constriction efferent

    arterioles increases glomerular capillary pressure,increasing filtration pressure and thus glomerularfiltration

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    Regulation of Glomerular

    Filtration If the GFR is too high:

    Urine output rises p Dehydration, electro-

    lyte depletion If the GFR is too low:

    Everything is reabsorbed, including wastes thatare normally disposed of

    GFR is controlled by adjusting glomerularblood pressure through: Autoregulation

    Sympathetic control

    Hormonal mechanisms: Renin and Angiotensin

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    Autoregulation and Sympathetic

    Stimulation Autoregulation

    Renal autoregulation maintains a nearly constant glomerular filtration

    rate over a wide range of systemic blood pressure

    GFR constant as systemic BP changes between 90 and 180 mm

    Hg

    Involves changes in degree of constriction in afferent arterioles As systemic BP increases, afferent arterioles constrict and prevent

    increase in renal blood flow

    Increased rate of blood flow of filtrate past cells of macula densa:

    signal sent to juxtaglomerular apparatus, afferent arteriole constricts

    Sympathetic stimulation: norepinephrine Constricts small arteries and afferent arterioles

    Decreases renal blood flow and thus filtrate formation

    During shock or intense exercise: intense sympathetic stimulation, rate

    of filtrate formation drops to a few mm

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    Renal Autoregulation of GFR o BP p constrict afferent

    arteriole, dilate efferent

    q BP p dilate afferentarteriole, constrictefferent

    Stable for BP range of80

    to 170 mmHg (systolic) Cannot compensate for

    extreme BP

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    Renal Autoregulation of GFR Myogenic mechanism

    o BP p stretches afferent arteriole p

    afferent arteriole constricts p restoresGFR

    Tubuloglomerular feedback

    Macula densa on DCT monitors tubular

    fluid and signals juxtaglomerular cells(smooth muscle, surrounds afferent arteriole) toconstrict afferent arteriole to q GFR

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    Negative Feedback Control of GFR

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    Sympathetic Control of GFR Strenuous exercise or acute conditions

    (circulatory shock) stimulate afferent

    arterioles to constrict

    q GFR and urine production, redirecting

    blood flow to heart, brain and skeletal

    muscles

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    Renin-Angiotensin Aldosterone

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    Effects of Angiotensin II

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    Tubular Reabsorption:

    Overview Tubular reabsorption: occurs as filtrate flows

    through the lumens of proximal tubule, loop ofHenle, distal tubule, and collecting ducts

    Results because of Diffusion

    Facilitated diffusion

    Active transport

    Cotransport

    Osmosis

    Substances transported to interstitial fluid andreabsorbed into peritubular capillaries; 99% offiltrate volume. These substances return to generalcirculation through venous system

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    Tubular Reabsorption and

    Secretion

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    Peritubular Capillaries Blood has unusually high COP here,

    and BHP is only 8 mm Hg (or lower when

    constricted by angiotensin II); this favorsreabsorption

    Water absorbed by osmosis and carries

    other solutes with it (solvent drag)

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    Proximal Convoluted Tubules

    (PCT) Reabsorbs 65% of GF to peritubular capillaries

    Great length, prominent microvilli and abundant mitochondria for

    active transport

    Reabsorbs greater variety of chemicals than other parts ofnephron

    transcellular route - through epithelial cells of PCT

    paracellular route - between epithelial cells of PCT

    Transport maximum: when transport proteins of cell membrane are

    saturated; blood glucose > 220 mg/dL some remains in urine(glycosuria); glucose Tm = 320 mg/min

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    Mechanisms of Reabsorption in the Proximal Convoluted Tubule

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    Tubular

    Maximum

    Maximum rate at which asubstance can be activelyabsorbed

    Each substance has its owntubular maximum

    Normally, glucoseconcentration in the plasma(and thus filtrate) is lower thanthe tubular maximum and all

    of it is reabsorbed; none of itis found in the urine

    In diabetes mellitus tubularload exceeds tubularmaximum and glucoseappears in urine. Urine

    volume increases becauseglucose in filtrate increasesosmolality of filtrate reducingthe effectiveness of waterreabsorption (osmoticdiuresis).

    Accounts for dehydration of

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    Reabsorption in Loop ofHenle

    Loop of Henle descends intomedulla; interstitial fluid is highin solutes.

    Water reabsorption is NOTcoupled to solute reabsorption!

    Descending thin segment ishighly permeable to water.

    Water moves out of nephron,reducing the volume of filtrateby another 15% and increasingits osmolarity (moreconcentrated).

    Ascending thin segment is notpermeable to water, but is

    permeable to solutes. Solutesdiffuse out of the tubule and intothe more dilute interstitial fluidas the ascending limb projectstoward the cortex.

    At the end of the loop ofHenle,inside of nephron is 100 mOsm

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    Reabsorption in Distal Tubule and

    Collecting Duct

    Active transport ofNa+ out of tubule cells into interstitialfluid with cotransport of Cl-

    Na+ moves from filtrate into tubule cells due to

    concentration gradient

    Collecting ducts extend from cortex (interstitial fluid 300mOsm/kg) through medulla (interstitial fluid very high)

    Water moves by osmosis from distal tubule and collecting

    duct into more concentrated interstitial fluid

    Permeability of wall of distal tubule and collecting ductshave variable permeability to water

    Urine can vary in concentration from low volume of high

    concentration to high volume of low concentration

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    Tubular Secretion of PCT

    and Nephron Loop

    Waste removal urea, uric acid, bile salts, ammonia, catecholamines, many

    drugs

    Acid-base balance secretion of hydrogen and bicarbonate ions regulates pH of

    body fluids

    Primary function of nephron loop

    water conservation generates salinity gradient, allows CD to conc. urine

    also involved in electrolyte reabsorption

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    DCT

    and Collecting Duct Principal cells receptors for hormones;

    involved in salt/water balance

    Intercalated cells involved in

    acid/base balance

    Function

    fluid reabsorption here is variable,

    regulated by hormonal action

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    DCT

    and Collecting Duct Aldosterone effects

    q BP p renin release p angiotensin II

    formation

    angiotensin II stimulates adrenal cortex

    adrenal cortex secretes aldosterone

    promotes Na+

    reabsorption p promotes waterreabsorption p q urine volume p maintains

    BP

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    DCT

    and Collecting Duct Effect of ADH

    dehydration stimulates hypothalamus

    hypothalamus stimulates posterior pituitary

    posterior pituitary releases ADH

    ADHo water reabsorption

    q urine volume

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    DCT and Collecting Duct

    Atrial natriuretic peptide (ANP) atria secrete ANP in response to o BP

    has four actions:

    1. dilates afferent arteriole, constricts efferent

    arteriole - o GFR

    2. inhibits renin/angiotensin/aldosterone pathway

    3. inhibits secretion and action of ADH

    4. inhibits NaCl reabsorption

    Promotes Na+ and water excretion, o urine

    volume, q blood volume and BP

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    DCT

    and Collecting Duct Effect of PTH

    o calcium reabsorption in DCT - o blood Ca2+

    o

    phosphate excretion in PCT

    ,q

    new boneformation

    stimulates kidney production of calcitriol

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    Collecting Duct Concentrates

    Urine

    Osmolarity 4x as concentra-

    ted deep in medulla

    Medullary portion of CD ismore permeable to water than

    to NaCl

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    Control of Water Loss Producing hypotonic urine

    NaCl reabsorbed by cortical CD

    water remains in urine

    Producing hypertonic urine

    dehydration p oADHp o aquaporinchannels, o CDs water permeability

    more water is reabsorbed

    urine is more concentrated

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    Medullary Concentration Gradient

    In order to concentrate urine (and prevent a

    large volume of water from being lost), thekidney must maintain a high concentration ofsolutes in the medulla

    Interstitial fluid concentration (mOsm/kg) is

    300 in the cortical region and graduallyincreases to 1200 at the tip of the pyramids inthe medulla

    Maintenance of this gradient depends upon

    Functions of loops ofHenle Vasa recta flowing countercurrent to filtrate in

    loops ofHenle

    Distribution and recycling of urea

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    Osmotic Gradient in the Renal

    Medulla

    Figu

    re25

    .13

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    Countercurrent Exchange

    System Formed by vasa recta

    provide blood supply to medulla

    do not remove NaCl from medulla

    Descending capillaries water diffuses out of blood

    NaCl diffuses into blood

    Ascending capillaries water diffuses into blood

    NaCl diffuses out of blood

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    Countercurrent Multiplier

    Recaptures NaCl and returns it to renal medulla Descending limb

    reabsorbs water but not salt

    concentrates tubular fluid

    Ascending limb reabsorbs Na+, K+, and Cl-

    maintains high osmolarity of renal medulla

    impermeable to water

    tubular fluid becomes hypotonic

    Recycling of urea: collecting duct-medulla urea accounts for40% of high osmolarity of medulla

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    Countercurrent Multiplier

    ofNephron Loop Diagram

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    Figure 20-10: Countercurrent exchange in the medulla of the kidney

    Loops ofHenle and vasa rectafunction together to maintain a highconcentration of solutes in theinterstitial fluids of the medulla andto carry away the water and solutesthat enter the medulla from theloops ofHenle and collecting ducts

    Water moves out of descendinglimb and enters vasa recta

    Solutes diffuse out of ascending

    thin segment and enter vasa recta,but water does not

    Solutes transported out of thicksegment of ascending enter thevasa recta

    Excess water and solutes carried

    away from medulla without reducinghigh concentration of solutes

    Concentration of filtrate reduced to100 mOsm/kg by the time it reachesdistal tubule

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    Maintenance of Osmolarity

    in Renal Medulla

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    Summary ofTubular

    Reabsorption and Secretion

    F i f C d

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    Formation of Concentrated

    Urine Antidiuretic hormone (ADH) inhibits diuresis In the presence of ADH, 99% of the water in filtrate is

    reabsorbed

    ADH-dependent water reabsorption is called facultative

    water reabsorption ADH is the signal to produce concentrated urine

    Stimulates the insertion ofaquaporins into apical membranes of

    DCT and collecting ducts

    The kidneys ability to respond depends upon the high

    medullary osmotic gradient

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    Formation of Dilute Urine

    Filtrate is diluted in the ascending loop ofHenle.

    Water permeability of collecting ducts is extremely low Dilute urine is created by allowing this filtrate to continue into the renal pelvis

    (water diuresis)

    Ocurrs as long as antidiuretic hormone (ADH) is not being secreted

    Collecting ducts remain impermeable to water; no further water reabsorption

    occurs

    Sodium and selected ions can be removed by active and passive mechanisms

    Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)

    Diabetes insipidus-condition in which no ADH is secreted or kidney fails to

    respond to ADH; 20-25 L of urine excreted per day

    Osmotic diuresis- increased urine flow due to increase solute excretion; occurs in

    diabetes mellitus or inadequate Na+ reabsorption

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    Composition and Properties of Urine

    Appearance

    almost colorless to deep amber; yellow color due to urochrome, from

    breakdown of hemoglobin (RBCs)

    Odor - as it stands bacteria degrade urea to ammonia

    Specific gravity

    density of urine ranges from 1.001 -1.028

    Osmolarity - (blood - 300 mOsm/L) ranges from50 mOsm/L to 1,200 mOsm/L in dehydrated person

    pH - range: 4.5 - 8.2, usually 6.0 Chemical composition: 95% water, 5% solutes

    urea, NaCl, KCl, creatinine, uric acid

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    Urine Volume

    Normal volume - 1 to 2 L/day

    Polyuria > 2L/day

    Oliguria < 500 mL/day

    Anuria - 0 to 100 mL/day

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    Diabetes

    Chronic polyuria of metabolic origin

    With hyperglycemia and glycosuria

    diabetes mellitus I and II, insulinhyposecretion/insensitivity

    gestational diabetes, 1 to 3% of pregnancies

    ADH hyposecretion diabetes insipidus; CD q water

    reabsorption

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    Diuretics

    Effects

    o urine output

    q blood volume Uses

    hypertension and congestive heart failure

    Mechanisms of action o GFR q tubular reabsorption

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    Voiding Urine - Micturition

    200 ml urine in bladder, stretch receptors sendsignal to sacral spinal cord

    Signals ascend to inhibitory synapses on sympathetic neurons

    micturition center(integrates info from amygdala, cortex) Signals descend to

    further inhibit sympathetic neurons

    stimulate parasympathetic neurons

    Result urinary bladder contraction

    relaxation of internal urethral sphincter

    External urethral sphincter - corticospinal tracts to

    sacral spinal cord inhibit somatic neurons - relaxes

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    Neural Control of Micturition