Urinary System

Topics & Objectives

1. Kidney• Anatomy• Function

2. Glomerular filtration

3. Tubular reabsorption & secretion

4. Urine excretion & plasma clearance

Kidney Functions:

Ultimately regulate ECF volume (receive ~ 20% of cardiac output!)

1. Maintain H2O balance in the body

2. Maintain osmolarity

3. Regulation of ECF ions• Na+, Cl-, K+, H+, etc.

4. Maintain plasma volume & acid-base balance

5. Excretion of end products and foreign compounds

6. Producing EPO & renin

Figure 14.1Page 513

Renalvein

Inferiorvena cava

Urinarybladder

Urethra

Ureter

Aorta

Kidney

Renalartery

Ureter

Renalpelvis

Renalpyramid

Renalcortex

Renalmedulla

Nephrons

• ~ 1 million within kidney Functional unit for urine

formation

• Arrangement comprises renal cortex & renal medulla

• Each nephron composed of:1. Vascular component

2. Tubular component

CortexMedulla

Figure 14.3Page 514

CortexMedulla

Proximal tubule

Juxtaglomerularapparatus

Efferentarteriole

Afferentarteriole

Bowman’scapsule

Glomerulus

Distaltubule Collecting

duct

To renalpelvis

Loop of Henle

Peritubularcapillaries

Vascular Component: Glomerulus

• Location for H2O and solute filtration from blood

Arterioles• Afferent: to glomerular

capillaries• Efferent: drains

capillariesNo O2 extraction!

Peritubular capillaries• Supply renal tissue

Efferentarteriole

Afferentarteriole

Glomerulus

Peritubularcapillaries

Tubular Component: Bowman’s capsule

• Collects fluid from glomerulus

Fluid travels to:1. Proximal tubule2. Loop of Henle3. Passes through

juxtaglomerular apparatus Vascular/tubular component

4. Distal tubule

Proximal tubule

Juxtaglomerularapparatus

Bowman’scapsule

Distaltubule

Loop of Henle

Cortical nephron

Juxtamedullary nephron

Urine Formation

1. Glomerular filtration (protein-free)• ~ 20% of the plasma (1st step of urine formation)• ~ 50 gallons each day (PV ~ 65x/day)

2. Tubular reabsorption• Of the 50 gallons filtered, about 98% reabsorbed

3. Tubular secretion• ~ 80% of the plasma into the peritubular

capillaries

GF

Figure 14.6Page 516

80% of the plasmathat enters theglomerulus is not filteredand leaves throughthe efferent arteriole.20% of the

plasma thatenters theglomerulusis filtered.

Urine excretion(eliminatedfrom the body)

To venous system(conservedfor the body)

Peritubularcapillary

Kidneytubule(entire length,uncoiled)

Bowman’scapsule

Glomerulus

Afferentarteriole

Efferentarteriole

TR

TS

Glomerularcapillaries

Efferentarteriole

Peritubularcapillaries

Venousblood

UrineTubule (from proximal tubule to collecting duct)

Bowman’scapsule

Filtratepathway

Bloodpathway

Glomerularfiltration

Tubularreabsorption

Tubularsecretion

Figure 14.7Page 517

Glomerular Filtration

Figure 14.8 (1)Page 518

Glomerulus

Bowman’scapsule

Proximal convoluted tubule

Afferent arteriole Efferent arteriole

Glomerular capillary

Basementmembrane

Glomerular Filtration

Figure 14.8 (3)

Page 518

Endothelialcell

Lumen of glomerularcapillary

Lumen ofBowman’s capsule

Basementmembrane

pores

podocytes

Glomerular Filtration (cont.):

Occurs through pressure gradients…

1. Capillary blood pressure (~55mmHg) Favors filtration

2. Plasma osmotic pressure (~30mmHg) Caused by distribution of plasma proteins across

glomerular membrane Cannot cross into Bowman’s capsule

3. Bowman’s capsule hydrostatic pressure (~15mmHG) Pressure by the fluid

All three pressures determine filtration rate!

1) Changes in BP

2) Osmotic pressure

3) Hydrostatic pressure

Look at Table 14.1!

GFR Regulation1. Autoregulation

• Prevents spontaneous changes in GFR Vasoconstriction & vasodilation

a. Myogenic mechanism – response to stretchb. Tubuloglomerular feedback mechanism

2. Extrinsic sympathetic control• Long-term regulation of arterial BP

Sympathetic nervous system (no parasympathetic activity)

• Baroreceptor reflex

GFR autoregulation

1. Alterations in arteriolar afferent & efferent blood pressures

Afferent arteriole

Glomerulus

Efferent arteriole

Glomerularcapillaryblood pressure

Net filtrationpressure

Arterial blood pressure(increases blood flow into the glomerulus)

GFRFigure 14.10Page 520

Vasoconstriction(decreases blood flowinto the glomerulus)

Afferent arteriole

Glomerulus

Efferent arteriole

Net filtrationpressure

Glomerularcapillaryblood pressure

GFR

GFR autoregulation (cont.)

Afferent arteriole

Glomerulus

Efferent arteriole

Net filtrationpressure

Glomerularcapillaryblood pressure

GFR

Vasodilation(increases blood flowinto the glomerulus)

GFR autoregulation

1. Smooth muscle cells within afferent arterioleGranular cells – secretory

capabilities

2. Tubular cells (macula densa)Detect changes in the rate

of fluid passing through tubuleBring about

vasoconstriction or vasodilation

Efferentarteriole

Distaltubule

Bowman’scapsule

Afferentarteriole

GFR Autoregulation – Tubuloglomerular feedback

Efferentarteriole

Smoothmusclecell

Maculadensa

Distaltubule

Afferentarteriole

Granular cells

Podocyte

Glomerularcapillaries

Lumen ofBowman’scapsule

Endothelialcell

Arterial blood pressure

Driving pressure into glomerulus

Glomerular capillary pressure

GFR

Rate of fluid flow through tubules

Stimulation of macula densa cells to release vasoactive chemicals

Chemicals released that induce afferent arteriolar vasoconstriction

Blood flow into glomerulus

Glomerular capillary pressure to normal

GFR to normal

Extrinsic Control – Baroreceptors

Response to decreased BP• Sympathetically induced vasoconstriction• Afferent arterioles (sympathetically innervated)

Response to increased BP• Sympathetic stimulation decreases

Short-termadjustment for

Arterial blood pressure

Long-termadjustment for

Arterialblood pressure

Detection by aortic arch and carotid sinus baroreceptors

Cardiac output

Total peripheral resistance

Sympathetic activity

Generalized arteriolar vasoconstriction

Afferent arteriolar vasoconstriction

Glomerular capillary blood pressure

GFR

Urine volume

Conservation of fluid and salt

Arterial blood pressure

Tubular Reabsorption

GF

Figure 14.6Page 516

Peritubularcapillary

Bowman’scapsule

Glomerulus

Afferentarteriole

Efferentarteriole

TR

Tubular reabsorption: Ultimately attempting to maintain body’s

internal environment• Proper composition & volume

Filtered substance reabsorbed

Filtered substance excreted

Water 99 1

Sodium 99.5 0.5

Glucose 100 0

Urea (waste product) 50 50

Phenol (waste product) 0 100

Table 14.2

Tubularlumen

Tubularepithelial cell

Peritubularcapillary

Plasma

Tightjunction

4) Interstitialfluid

Material must pass through the cells (5 steps)

Figure 14.17Page 526

1) Luminalmembrane

5) Capillary wall

3) Basolateralmembrane

2) Cytosol

Transepithelial transport

Passive & Active Reabsorption

1. Passive: all steps follow electrochemical or osmotic gradients

2. Active: any one of the steps requiring energy• Sodium (80% of kidney’s total energy

requirement) ~ 67% in proximal tubule ~ 25% in loop of Henle ~ 8% in distal and collecting tubules

• Glucose• Phosphate

Constant percentage of Na+ reabsorption

Lumen Tubular cell Interstitial fluidPeritubularcapillary

Figure 14.18Page 527

Na+ pumped out against concentration gradient• Creates higher concentration in interstitial fluid &

allows for passive diffusion back into lumen

Diffusion

Diffusion

Na+

channelActive transport

BasolateralNa+– K+ ATPasecarrier

Distal tubule (~ 8% of total reabsorption) is hormonally regulated

• Related to total Na+ load in bodyChanges in ECF affect

osmotic pressuresex: Increased Na+ in ECF

causes increased H2O in ECF

• Ultimately regulates blood pressureRenin-angiotensin-

aldosterone system ↑Atrial natriuretic peptide ↓

Distaltubule

Granular cells release renin• In response to fall of NaCl/ ECF volume/ BP• Recognized by intrarenal baroreceptors

Sympathetic response to secrete more renin

• Ultimately trying to increase plasma volume

Within juxtaglomerular apparatus…

Figure 14.19Page 529

Liver Kidney LungsAdrenalcortex

Kidney

H2Oconserved

Na+ (and CI–)osmotically holdmore H2O in ECF

Na+ (and CI–)conserved

Vasopressin Thirst Arteriolarvasoconstriction

H2O reabsorption

by kidney tubules Fluid intake

NaCl / ECF volume /

Arterial blood pressure

Na+ reabsorption by kidney tubules ( CI– reabsorptionfollows passively)

Renin

Angiotensin-convertingenzyme

Angiotensinogen Angiotensin I Angiotensin II Aldosterone

Helps correct Helps correct

Cardiacatria

Atrial natriuretic peptide

Na+ reabsorptionby kidney tubules

Salt-conservingrenin-angiotensin-aldosterone system

Smooth muscleof afferent arterioles

Sympatheticnervous system

Afferentarteriolarvasodilation

Na+ excretion in urine

H2O excretion in urine

Na+ and H2O filtered

GFR

Cardiacoutput

Totalperipheralresistance

Arterial bloodpressure

NaCl / ECF volume /Arterial blood pressure

Figure 14.20Page 530

Inhibits aldosterone & renin secretion

Glucose and amino acid reabsorption• Na+ dependent secondary active transport

Co-transporters that do not require energy

• Maximal reabsorption rate depends on substance

No energyrequired

Cotransport carrier

No energyrequired Glucose

carrierBasolateralborder

Energyrequired

Na+–K+ pump

Blood vessel

Luminal border

Phosphate & Calcium reabsorption• Dependent upon total body content• Regulated by kidneys

Hormonally (parathyroid hormone)

Na+ reabsorption responsible for passive reabsorption of Cl-, H2O, and urea

Lumen Proximal tubular cell Peritubular capillaryInterstitial fluid

H2O (passive) reabsorption

• 80% in proximal tubules & loops of Henle

Figure 14.22Page 533

Osmosis

Osmosis

Hydrostaticpressure

Waterchannel

Glomerulus

Bowman’scapsule

Beginning ofproximaltubule

End ofproximaltubule

= Urea molecules

Peritubularcapillary

Urea (passive) reabsorption• Waste product of

protein• Becomes

increasingly concentrated

Na+ (active)

H2O (osmosis)

Na+ (active)

H2O (osmosis)

Passive diffusionof urea down itsconcentration gradient

44 mloffiltrate

125 mloffiltrate

Figure 14.23

Page 534

Tubular Secretion

Figure 14.6Page 516

Afferentarteriole

Efferentarteriole

Glomerulus

Bowman’scapsule

Kidneytubule(entire length,uncoiled)

Peritubularcapillary

GF

TS

Tubular secretion:

Hydrogen ions (H+)• Acid-base regulation throughout the body

Potassium (K+)• Early reabsorption into tubules not regulated• Secretion in distal tubules regulated

Na+-K+ pumpAldosterone

Organic anions & cations• Foreign compounds, chemical messengers

Renin

Angiotensin I

Angiotensin IIPlasma K+

Aldosterone

Tubular K+ secretion

Urinary K+ excretion

Tubular Na+ reabsorption

Urinary Na+ excretion

Na+/ ECF volume/arterial pressure

Figure 14.25Page 536

Aldosterone - dual regulation

1) Na+ & K+

Plasma Clearance

Fig. 14.26a Page 539

Glomerulus

Tubule

Peritubularcapillary

Inurine

Substance:

1) Filtered

2) NOT reabsorbed

3) NOT secreted

All filtered plasma is

cleared of substance

Substance:

1) Filtered

2) NOT secreted

3) Completely reabsorbed

None of filtered plasma is

cleared of substance

Substance:

1) Filtered

2) NOT secreted

3) Partially reabsorbed

Portion of filtered plasma is

cleared of substance

Substance:

1) Filtered

2) Secreted

3) NOT reabsorbed

ALL of filtered plasma is

cleared of substance

Regulation of plasma H2O

Fluids & solutes• Normal balance in body fluids called isotonic

300 mosm/liter

• HypotonicToo much H2O compared to solute (osmolality < 300)

• HypertonicToo little H2O compared to solute (osmolality > 300)

Osmotic gradient maintained in interstitial fluid of medulla• Dependent upon hydration levels

Descending limbof loop of Henleof juxtamedullarynephron

Medullaryinterstitial fluid

Fromproximaltubule

Todistaltubule

Medullaryinterstitial fluid

Ascending limbof loop of Henleof juxtamedullarynephron

Initial scene

Fig. 14.28a (2)Page 542

Step 1

Fromproximaltubule

Todistaltubule

Step 2

Step 3

Fromproximaltubule

Todistaltubule

Step 4

Step 5

Step 6 and on

Fromproximaltubule

Todistaltubule

Tubularlumenfiltrate Distal tubular cell

Peritubularcapillaryplasma

Waterchannel

Figure 14.29

Page 544

Further regulation Vasopressin

• Anti-diuretic hormone from hypothalamus

Increases permeability ofluminal membrane to H2Oby inserting newwater channels