chapter 17

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Chapter 17

Physiology of the Kidneys

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Chapter 17 Outline

Overview of Kidney Structure Nephron Glomerular Filtration Function of Nephron Segments Renal Clearance Hormonal Effects Na+, K+, H+, & HC03

- Relationships Clinical Aspects

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Kidney Function

Is to regulate plasma & interstitial fluid by formation of urine

In process of urine formation, kidneys regulate:Volume of blood plasma, which contributes to

BPWaste products in bloodConcentration of electrolytes

Including Na+, K+, HC03-, & others

Plasma pH

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Overview of Kidney Structure

17-4


Structure of Urinary System

Paired kidneys are on either side of vertebral column below diaphragmAbout size of

fist Urine flows from

kidneys into ureters which empty into bladder

Fig 17.1

17-5


Structure of Kidney

Cortex contains many capillaries & outer parts of nephrons

Medulla consists of renal pyramids separated by renal columns Pyramid contains minor calyces which unite to form a

major calyx

Fig 17.217-6


Structure of Kidney continued

Major calyces join to form renal pelvis which collects urine Conducts urine

to ureters which empty into bladder

Fig 17.3

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Micturition Reflex (Urination)

Actions of internal & external urethral sphincters are regulated by reflex center located in sacral part of cord

Filling of bladder activates stretch receptors that send impulses to micturition reflex center This activates Parasymp neurons causing contraction

of detrusor muscle that relaxes internal urethral sphincter creating sense of urgency

There is voluntary control over external urethral sphincter

When urination is consciously initiated, descending motor tracts to micturition center inhibit somatic motor fibers of external urethral sphincter & urine is expelled

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Nephron

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Nephron

Is functional unit of kidney responsible for forming urine >1 million nephrons/kidney

Is a long tube & has associated blood vessels

Fig 17.2

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Renal Blood Vessels

Blood enters kidney through renal arteryWhich divides into interlobar arteries

That divide into arcuate arteries that give rise to interlobular arteries

Fig 17.4

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Renal Blood Vessels

Interlobular arteries give rise to afferent arterioles which supply glomeruli

Glomeruli are mass of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule

Efferent arteriole drains glomerulus & delivers that blood to peritubular capillaries (vasa recta)

Blood from peritubular capillaries enters veins

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Fig 17.5

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Nephron Tubules

Tubular part of nephron begins with glomerular capsule which transitions into proximal convoluted tubule (PCT), then to descending & ascending limbs of Loop of Henle (LH), & distal convoluted tubule (DCT)

Tubule ends where it empties into collecting duct (CD)

Fig 17.2

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Glomerular (Bowman's) Capsule

Surrounds glomerulus Together they

form renal corpuscle

Is where glomerular filtration occurs Filtrate passes

into PCT

Glomerularcapsule

PCT

Fig 17.617-15


Proximal Convoluted Tubule

Walls consist of single layer of cuboidal cells with millions of microvilliWhich increase surface area for reabsorption Nephron Function animation

17-16


Type of Nephrons

Cortical nephrons originate in outer 2/3 of cortex

Juxtamedullary nephrons originate in inner 1/3 cortex Have long LHs Important in

producing concentrated urine

Fig 17.617-17

Glomerular Filtration

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Glomerular Filtration

Glomerular capillaries & Bowman's capsule form a filter for blood Glomerular Caps are fenestrated--have large

pores between its endothelial cells100-400 times more permeable than other

CapsSmall enough to keep RBCs, platelets, &

WBCs from passingPores are lined with negative charges to

keep blood proteins from filtering

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To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule

Glomerular Filtration continued

Fig 17.817-20


Fig 17.7

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Fig 17.9

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Glomerular Ultrafiltrate

Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure

Fig 17.10

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Glomerular Filtration Rate (GFR)

Is volume of filtrate produced by both kidneys/minAverages 115 ml/min in women; 125 ml/min

in menTotals about 180L/day (45 gallons)

So most filtered water must be reabsorbed or death would ensue from water lost through urination

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Regulation of GFR

Is controlled by extrinsic & intrinsic (autoregulation) mechanisms

Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli & thus GFR

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Sympathetic Effects

Sympathetic activity constricts afferent arteriole Helps maintain

BP & shunts blood to heart & muscles

Fig 17.11

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Renal Autoregulation

Allows kidney to maintain a constant GFR over wide range of BPs

Achieved via effects of locally produced chemicals on afferent arterioles

When average BP drops to 70 mm Hg afferent arteriole dilates

When average BP increases, afferent arterioles constrict

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Renal Autoregulation Is also maintained by negative feedback between afferent

arteriole & volume of filtrate (tubuloglomerular feedback) Increased flow of filtrate sensed by macula densa (part

of juxtaglomerular apparatus) in thick ascending LH Signals afferent arterioles to constrict

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Function of Nephron Segments

17-30


Reabsorption of Salt & H20

In PCT returns most molecules & H20 from filtrate back to peritubular capillariesAbout 180 L/day of ultrafiltrate produced; only

1–2 L of urine excreted/24 hoursUrine volume varies according to needs of

bodyMinimum of 400 ml/day urine necessary to

excrete metabolic wastes (obligatory water loss)

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Reabsorption of Salt & H20 continued

Return of filtered molecules is called reabsorption

Water is never transported Other molecules

are transported & water follows by osmosis

Fig 17.13

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PCT Filtrate in PCT is

isosmotic to blood (300 mOsm/L)

Thus reabsorption of H20 by osmosis cannot occur without active transport (AT) Is achieved by AT of

Na+ out of filtrate Loss of +

charges causes Cl- to passively follow Na+

Water follows salt by osmosis

Fig 17.1417-33


Insert fig. 17.14

Fig 17.15

17-34


Significance of PCT Reabsorption

≈65% Na+, Cl-, & H20 is reabsorbed in PCT & returned to bloodstream

An additional 20% is reabsorbed in descending loop of Henle

Thus 85% of filtered H20 & salt are reabsorbed early in tubuleThis is constant & independent of hydration

levelsEnergy cost is 6% of calories consumed at

restThe remaining 15% is reabsorbed variably,

depending on level of hydration 17-35


Concentration Gradient in Kidney

In order for H20 to be reabsorbed, interstitial fluid must be hypertonic

Osmolality of medulla interstitial fluid (1200-1400 m O sm) is 4X that of cortex & plasma (300 m O sm) This concentration gradient results largely

from loop of Henle which allows interaction between descending & ascending limbs

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Descending Limb LH

Is permeable to H20 Is impermeable to, &

does not AT, salt Because deep

regions of medulla are 1400 m O sm, H20 diffuses out of filtrate until it equilibrates with interstitial fluid This H20 is

reabsorbed by capillaries Fig 17.17

17-37


Ascending Limb LH

Has a thin segment in depths of medulla & thick part toward cortex

Impermeable to H20; permeable to salt; thick part ATs salt out of filtrate AT of salt causes

filtrate to become dilute (100 m O sm) by end of LH

Fig 17.1717-38


Vasa Recta

Is important component of countercurrent multiplier

Permeable to salt, H20 (via aquaporins), & urea

Recirculates salt, trapping some in medulla interstitial fluid

Reabsorbs H20 coming out of descending limb

Descending section has urea transporters

Ascending section has fenestrated capillaries

Fig 17.18

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17-44


Collecting Duct (CD)

Plays important role in water conservation Is impermeable to salt in medulla Permeability to H20 depends on levels of ADH

17-45


ADH

Is secreted by post pituitary in response to dehydration

Stimulates insertion of aquaporins (water channels) into plasma membrane of CD

When ADH is high, H20 is drawn out of CD by high osmolality of interstitial fluid & reabsorbed by

vasa recta

Fig 17.21

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Renal Clearance

17-48


Renal Clearance Refers to ability of kidney to remove substances from

blood & excrete them in urine Occurs by filtration & by secretion Secretion is opposite of reabsorption--substances from

vasa recta are transported into tubule & excreted Reabsorption decreases renal clearance; secretion

increases clearance

Fig 17.22

17-49


Secretion of Drugs

Many drugs, toxins, & metabolites are secreted by organic anion transporters of the PCT Involved in determining half-life of many

therapeutic drugs

17-50


Measurement of Renal Blood Flow

Not all blood delivered to glomerulus is filtered into glomerular capsule20% is filtered; rest passes into efferent

arteriole & back into circulationSubstances that aren't filtered can still be

cleared by active transport (secretion) into tubules

17-55


Glucose & Amino Acid Reabsorption

Filtered glucose & amino acids are normally 100% reabsorbed from filtrateOccurs in PCT by carrier-mediated cotransport

with Na+Transporter displays saturation if ligand

concentration in filtrate is too high Level needed to saturate carriers &

achieve maximum transport rate is transport maximum (Tm)

Glucose & amino acid transporters don't saturate under normal conditions

17-58


Glycosuria

Is presence of glucose in urine Occurs when glucose > 180-200mg/100ml

plasma (= renal plasma threshold)Glucose is normally absent because plasma

levels stay below this valueHyperglycemia has to exceed renal plasma

thresholdDiabetes mellitus occurs when hyperglycemia

results in glycosuria

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Hormonal Effects

17-60


Electrolyte Balance

Kidneys regulate levels of Na+, K+, H+, HC03-, Cl-,

& PO4-3 by matching excretion to ingestion

Control of plasma Na+ is important in regulation of blood volume & pressure

Control of plasma of K+ important in proper function of cardiac & skeletal muscles

17-61


Role of Aldosterone in Na+/K+ Balance

90% filtered Na+ & K+ reabsorbed before DCTRemaining is variably reabsorbed in DCT &

cortical CD according to bodily needsRegulated by aldosterone (controls K+

secretion & Na+ reabsorption) In the absence of aldosterone, 80% of

remaining Na+ is reabsorbed in DCT & cortical CD

When aldosterone is high all remaining Na+ is reabsorbed

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Renin-Angiotensin-Aldosterone System

Is activated by release of renin from granular cells within afferent arteriole Renin converts angiotensinogen to

angiotensin IWhich is converted to Angio II by

angiotensin-converting enzyme (ACE) in lungs

Angio II stimulates release of aldosterone

17-65


Regulation of Renin Secretion

Inadequate intake of NaCl always causes decreased blood volumeBecause lower osmolality inhibits ADH,

causing less H2O reabsorptionLow blood volume & renal blood flow

stimulate renin releaseVia direct effects of BP on granular cells &

by Symp activity initiated by arterial baroreceptor reflex (see Fig 14.26)

17-66


Macula Densa Is region of

ascending limb in contact with afferent arteriole

Cells respond to levels of Na+ in filtrate Inhibit renin

secretion when Na+ levels are high

Causing less aldosterone secretion, more Na+ excretion

Fig 17.26

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17-69


Atrial Natriuretic Peptide (ANP)

Is produced by atria due to stretching of walls Acts opposite to aldosterone Stimulates salt & H20 excretion Acts as an endogenous diuretic

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Renal Acid-Base Regulation

Kidneys help regulate blood pH by excreting H+ &/or reabsorbing HC03

-

Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ antiporter)

Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HC03

- & excrete H+

17-73


Urinary Buffers

Nephron cannot produce urine with pH < 4.5 Excretes more H+ by buffering H+s with HPO4

-2 or NH3 before excretion

Phosphate enters tubule during filtration Ammonia produced in tubule by deaminating

amino acids Buffering reactions

HPO4-2 + H+ H2PO4

-

NH3 + H+ NH4+ (ammonium ion)

17-76

Clinical Aspects

17-77


Diuretics

Are used to lower blood volume because of hypertension, congestive heart failure, or edema

Increase volume of urine by increasing proportion of glomerular filtrate that is excreted

Loop diuretics are most powerful; inhibit AT salt in thick ascending limb of LH

Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT

Carbonic anhydrase inhibitors prevent H20 reabsorption in PCT when HC0s

- is reabsorbed Osmotic diuretics increase osmotic pressure of filtrate

17-78


Kidney Diseases

In acute renal failure, ability of kidneys to excrete wastes & regulate blood volume, pH, & electrolytes is impairedRise in blood creatinine & decrease in renal

plasma clearance of creatinineCan result from atherosclerosis, inflammation

of tubules, kidney ischemia, or overuse of NSAIDs

17-80


Kidney Diseases continued

Glomerulonephritis is inflammation of glomeruliAutoimmune attack against glomerular

capillary basement membranesCauses leakage of protein into urine

resulting in decreased colloid osmotic pressure & resulting edema

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In renal insufficiency, nephrons have been destroyed as a result of a disease Clinical manifestations include salt & H20 retention &

uremia (high plasma urea levels) Uremia is accompanied by high plasma H+ & K+

which can cause uremic coma Treatment includes hemodialysis

Patient's blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane

Urea & other wastes are removed

Kidney Diseases continued

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chapter 17

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