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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