kidney regulation

Role of Kidney in Regulation of Arterial

Blood Pressure

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Presentation Agenda

Kidney Functions .E.C.V. control .NaturesisRAS system

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The kidneys - what are they for ?

Elimination of waste substancesSalvage of essential compoundsRegulation of ions: H+ (pH), Na+, K+, Ca2+

Regulation of plasma volume / blood pressureRegulation of plasma osmolalityProduction of hormones … 7

Regulation of body fluid osmolality & volume: Excretion of water and NaCl is regulated interacting with cardiovascular, endocrine, & central nervous systems

Regulation of electrolyte balance: Daily intake of inorganic ions (Na+, K+, Cl-, HCO3

-, H+, Ca2+, Mg+ & PO43-) should be

matched by daily excretion through kidneys.

Regulation of acid-base balance: Kidneys work in concert with lungs to regulate the pH in a narrow limits of buffers within body fluids. 8

Excretion of metabolic products & foreign substances :

urea from amino acid metabolism uric acid from nucleic acids creatinine from muscles end products of hemoglobin metabolites hormone metabolites

foreign substances ( e.g., drugs, pesticides, & other chemicals ingested in the food )

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Production and secretion of hormones: Renin ( activates the Renin- Angiotensin - Aldosterone system, thus regulating blood pressure & Na , K balance ) Prostaglandins/ kinins ( bradykinin = vasoactive , leading to modulation of renal blood flow & along with AngiotensinII affect the systemic blood flow ) 1,25-dihydroxyvitamin D3

( stimulates Ca2+ resorption &bone deposit ) Erythropoietin ( stimulates red blood cell formation by bone marrow ).10

CONTROL OF EXTRACELLULAR FLUID VOLUME

Effective circulating volume

Volume sensors

Kidney

Adjustment to NaCl excretion

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The 'effective circulating volume' (ECV) is that part of

the ECF that perfuses the tissues and is related to a

concept of the ‘fullness’ of the circulation.

Normally ECF and ECV are equivalent. However, under

pathological conditions, e.g. heart failure, the ECV may

be low in spite of the fact that ECF is normal.

Importantly the kidneys respond to changes of ECV:

when it is reduced Na excretion is reduced which also

retains water; when it is too high Na excretion is raised

(a natriuresis is induced) and water is correspondingly

lost.12

SENSORS OF EFFECTIVE CIRCULATING VOLUME

Most importantly ECV sensors exist in the high-pressure

(systemic arterial) and low pressure (systemic venous,

pulmonary) sides of the circulation.

High pressure ECV sensors:

Arterial baroreceptors (carotid sinus and aortic arch)

Juxtaglomerular apparatus of the kidney and the afferent arteriole

Low pressure ECV sensors:

Cardiac atria

Pulmonary vasculature 13

Arterial pressure is a signal for regulation of NaCl excretion. arterial pressure NaCl reabsorbed in the proximal tubule more NaCl to the MD TGF autoregulation RBF, GFR.

In addition, there is an accompanying increase in urine Na+ , volume output: pressure natriuresis/diuresis. Pressure natriuresis can normalize BP by decreasing the effective circulating volume – this response connects BP and ECFV.

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2. Decrease PT NaCl reabsorption

3. I ncrease [NaCl] at macula

densa generates TGF signal

Natriuresis

Diuresis “Pressure Natriuresis”

1. I ncrease BP & renal

perfusion pressure

I ncrease NaCl

delivery to

distal nephron

4. I ncrease aff erent arteriole resistance

5. Autoregulate RBF, GFR

40% increase volume flow f rom PT

?

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1. Summarize the chain of events known as “pressure natriuresis” - the effect of arterial blood pressure on renal excretion of NaCl.

2. Diagram the six feedback relationships connecting ECFV, BP and AngII/SNS.

3. Summarize how lesions in the regulation of renal sodium chloride transport and lesions in Na+ transporters themselves can lead to hypertension or hypotension.

4. Summarize the homeostatic mechanisms governing "escape" from mineralocorticoid excess (real or apparent excess): transport along the nephron, endocrine adjustments.

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AII fluid retentionvia aldosterone Na reabsorption

BP

AIISNSECFV

+

+

+

-

-

-

BP ECFVvia

pressure natriuresis

AII/SNS vasoconstriction

BP

PV=nRT

BP AII/SNSvia

baroreceptorsmacula densa

ECFV ANP renin AII aldosterone

Feedback relationship among blood pressure (BP), Angiotensin II and sympathetic nervous system (AII/SNS), and extracellular fluid volume (ECFV, a function of Na+ reabsorption)

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RENAL SYMPATHETIC NERVES

Decreased effective

circulating volume

Increased sympathetic

activity

baroreceptorreflex

Constriction of afferent and

efferent arterioles

Stimulation of renin secretion

Reduced GFR and filtered load of Na

Decreased Na excretion

Decreased Na excretion

NaCl reabsorption increased by

nephron

Sympathetic fibres innervate the afferent and efferent arterioles as well as cells of the nephron. The fibres respond as part of the efferent arm of the baroreceptor reflex.

An example

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RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEMThe renin-angiotensin-aldosterone system is the key in regulating ECV by controlling NaCl, and water, reabsorption by the nephron.

podocyte

Bowman’s space

juxtaglomerular cells

capillaries

mesangial cells

afferent

arteriole

macula densa

efferent

arteriole

Cells in the afferent/efferent arterioles of the glomerulus are the site of synthesis, storage and release of renin

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RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM1. Perfusion pressure

Decrease of perfusion pressure , as occurs if ECV is reduced, stimulates renin secretion

2. Sympathetic nerve activitySympathetic nerves activated, as occurs if ECV is reduced, increases renin secretion3. NaCl delivery to the macula densaWhen NaCl delivery to the distal tubule and macula densa is reduced , as would occur if ECV is reduced, increases renin secretion.In all three mechanisms renin secretion is reduced when the opposite conditions prevail.

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Renin is a proteolytic enzyme, its substrate is circulating

angiotensiogen. The result is a decapeptide, angiotensin I This is converted to an octapeptide angiotensin II in

the lung by an angiotensin converting enzyme (ACE)

Angiotensin II has the following actions Stimulates aldosterone release from the adrenal cortex Is a systemic (include renal arteriolar) vasoconstrictor Stimulates ADH secretion Enhances proximal tubule NaCl reabsorption and

inhibits renin release

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Liver

Lung

angiotensinogen

angiotensin I

Kidney

renin

Angiotensin II

aldosterone

Brain ADH

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ACTIONS OF ALDOSTERONE

Na+

ATPNa+

H2O

aldo

RAR

Nucl

mito

Aldosterone binds to a baso-

lateral receptor. The receptor complex

stimulates transcription of

apical Na+ channels and ATP

synthesis

Aldosterone conserves Na+

An increase of circulating levels

increases NaCl reabsorption via

principal cells in the distal tubule/

collecting duct

Na+ uptake from the lumen is enhanced and Cl- and H2O follow.

The process is relatively slow. 28

BP BV

Na+ depletion

NE release from nerve

ending

RENIN RELEASE

BP BV

Na+ retention+ -

Vasoconstriction

Aldosteronesecretion

Angiotensin release

++ +

++

+

Stimulants for ADH 1) ECF volume 2) osmolality of plasma

+

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Mean Arterial Pressure

MAP = CO X

CO = HR X SV

SNS Blood volume Heart contractility

Venous tone

PVR

myogenic tonevascular responsivenessnervous control

vasoactive metabolitesendothelial factorscirculating hormones

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Renalfunction

Bloodvolume

Venoustone

Venousreturn

Heartrate

Nervouscontrol

Muscularresponsiveness

Myocardialcontractility

Strokevolume

Cardiacoutput

CNSfactors

Reninrelease

Angiontensin II formation

Intrinsic vascularresponsiveness

Peripheralresistance

Nervouscontrol

Renalfunction

Mean arterialpressure

Factors that Govern the Mean Arterial Pressure

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HEMORRHAGE:

--- decreases arterial pressure

--- leading to activation of kidney sympathetic nerves via

baroreceptor reflex --- NOR elicits intense vasoconstriction of both afferent & efferent arterioles to cause lowering of RBF & GFR 33

--- A rise in sympathetic activity increases EPI & angiotensin II release , leading to further vasoconstriction (& thus RBF decrease) --- Resultant increase in vascular resistance in kidneys & elsewhere elevates total peripheral resistance => increase in blood pressure (BP = cardiac output . total peripheral resistance) => offsets the fall (due to hemorrhage) in mean arterial pressure

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kidney regulation

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