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ObjectivesObjectives

� To discuss factors that control GFR.

� To address how B.P. can affect GFR & introduce topic of renal suppression.

� To outline the different control mechanisms that influence filtration rates.

� To introduce the renin-angiotensinmechanism to regulate GFR.

Factors affecting GFRFactors affecting GFR

o Total surface area

o Filtration membrane permeability

o NFP changes

Kidney diseases (increase NFP)

Hemorrhage (decrease NFP)

o Blood Pressure changes (direct correlation)

o Dehydration – inhibits filtrate formation.

Blood Pressure FactorsBlood Pressure Factors

Hypotension – If extreme then glomerular filtration will stop:

If GBHP = CHP no filtration

Termed renal suppression.

Hypertension – not as significant because the body has stretch receptors that constrictsafferent arterioles. Maintains GFR

Control of GFRControl of GFR

Intrinsic Controls – Adjusting resistance to blood flow.

Maintains a nearly constant GFR when MAP is in

the range of 80–180 mm Hg

A. Myogenic mechanism – stretching muscles of afferent arterioles

B. Tubuloglomerular feedback mechanism –

Controls vasodilation or vasoconstriction of the afferent arterioles, located in walls of distal tubules – respond to osmotic signals; senses changes in the juxtaglomerular apparatus

Control of GFRControl of GFR

Extrinsic Controls – Maintains systemic BPA. Sympathetic nervous system controls – Release of

norepinephrine constrict afferent arterioles and thus decrease filtration formation.

B. Renin-angiotensin mechanism -Juxtaglomerular cells (JG) cells that sense blood

pressure changes in the afferent arteriole release renin.* See Fig 25.12

* Renin ultimately raises BP (See pg 16-18 in SG)

Figure 25.12

Stretch of smoothmuscle in walls of afferent arterioles

Blood pressure inafferent arterioles; GFR

Vasodilation ofafferent arterioles

GFR

Myogenic mechanismof autoregulation

Release of vasoactivechemical inhibited

Intrinsic mechanisms directly regulate GFR despite

moderate changes in blood pressure (between 80 and 180 mm Hg mean arterial pressure).

Extrinsic mechanisms indirectly regulate GFR

by maintaining systemic blood pressure, whichdrives filtration in the kidneys.

Tubuloglomerularmechanism ofautoregulation

Hormonal (renin-angiotensin)mechanism

Neural controls

SYSTEMIC BLOOD PRESSURE

GFR

Macula densa cellsof JG apparatus of kidney

Filtrate flow andNaCl in ascendinglimb of Henle’s loop

Targets

Granular cells ofjuxtaglomerularapparatus of kidney

Angiotensinogen Angiotensin II

Adrenal cortex Systemic arterioles

(+) Renin

Release

Catalyzes cascaderesulting in conversion

(+)

(+)

(+)

Kidney tubules

Aldosterone

Releases

Targets

Vasoconstriction;peripheral resistance

Blood volume

Na+ reabsorption;water follows

Systemic

blood pressure

(+)

(+)

(–)

Increase

Decrease

Stimulates

Inhibits

Baroreceptors inblood vessels ofsystemic circulation

Sympatheticnervous system

(+)

(–)

Vasodilation ofafferent arterioles

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Effects of Angiotensin IIEffects of Angiotensin II

1. Constricts arteriolar smooth muscle, causing MAP to rise

2. Stimulates the reabsorption of Na+

◦ Acts directly on the renal tubules

◦ Triggers adrenal cortex to release aldosterone

3. Stimulates the hypothalamus to release ADH and activates the thirst center

Effects of Angiotensin IIEffects of Angiotensin II

4. Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid re-absorption

5. Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration

Glomerulus

Glomerular capsule

Afferent arteriole

Efferent arteriole

Red blood cell

Podocyte cell body (visceral layer)

Foot processesof podocytesParietal layer

of glomerularcapsule

Proximaltubule cell

Lumens of glomerularcapillaries

Endothelial cellof glomerularcapillary

Efferent arteriole

• Macula densa cellsof the ascending limbof loop of Henle

• Granular cells

• Extraglomerularmesangial cells

Afferent arteriole

Capsularspace

Renal corpuscleJuxtaglomerular

apparatus

Mesangial cellsbetween capillaries

Juxtaglomerularapparatus