Na + Homeostasis. Sodium reabsorption by the nephron 1% 3% 6% 65% 25% Percentages give the proportion from filtered load reabsorbed Normally, only 1%

Na+ Homeostasis

Sodium reabsorption by the nephron

1%

3%

6%65%

25%

Percentages give the proportionfrom filtered load reabsorbed

Normally, only 1% or less is excreted

But this 1% is a significant quantity

Na+ Balance

Na+ balance will be maintained if the following is true

Intake = Excretion

OR

If Na+ content is high, increase excretionIf Na+ content is low, increase reabsorption

Na+ Content of the Body

Na+ content of the body can not be detected

What can be measured are: Concentration of in ECF, strongly correlated to ECF osmolality

as it is the main solute in ECF ECF volume, which correlated with blood volume and

arterial blood pressure

Na+ Content of the Body

Would changes in Na+ content of the body primarily result in changes in:

? Osmolality of ECF

? Volume of ECF

Mechanisms of Na+ Homeostasis

These mechanisms are responsive mostly to Change in ECF volume and its consequences which are Change in blood volume Change in blood pressure

Response of Na+ regulatory mechanisms to change is osmolality is minimalNa+ Homeostatic are directed towards regulateing blood volume and arterial blood pressure

Total Vs Effective Blood Volume

Effective blood volume – volume of blood available for perfusion, the blood volume contained in the arterial system

Total blood volume – volume of blood in the whole circulatory system

Na+ homeostatic mechanisms are linked to the effective blood volume

Total Vs Effective Blood Volume

Can the effective blood volume change when the total blood volume remains the same?

Yes, due to changes in venous capacityExample: “septic shock” blood vessels are dilated, effective blood volume

decreased but total blood volume is normal

Glomerular Mechanisms

Raised Blood Volume Raised Blood Pressure

Increased Renal Blood Flow

Increased Glom CapillaryHydrostatic Pressure

Increased GFR

Trend Towards Increased Na+ and H2O excretion

Increased Glom CapillaryOncotic Pressure,

Glomerular Mechanisms

Raised Blood Volume Raised Blood Pressure

Increased Renal Blood Flow

Increased Glomerular CapillaryHydrostatic Pressure

Increased GFR

Trend Towards Increased Na+ and H2O excretion

Baroreceptor mechanism

Glomerular arteriolar dilatation (mostly afferent)

Decreased Glomerular CapillaryOncotic Pressure

Glomerular Mechanisms

Raised Blood Volume

Atrial Distention

Atrial Natriuretic Peptide

Increased GFR – dilatation of afferent arteriole

Proximal Tubular Mechanisms

1. Increased delivery of Na+ to the proximal tubule

Proximal tubular reabsorption of Na+ is on a percentage basis Total reabsorbed in increased but the total unabsorbed by

the proximal tubule is also increased

More Na leaves the proximal tubule and enters the loop of Henle

Proximal Tubular Mechanisms

2. Status of the peritubular capillaries

Higher hydrostatic pressure in peritubular capillaries Lower oncotic pressure in the peritubular capillariesReabsorption is inhibited

Minor decrease in the percentage of Na+ absorbed in the proximal tubuleBut constitutes a significant decrease in quantity if Na+ reabsorbed

Proximal Tubular Mechanisms

3. Increased interstitial pressure

Higher arterial pressure results in higher medullary interstitial pressure

Reabsorption is inhibited – mediated by a reduction of Na+K+ATPase activity

Proximal Tubular Mechanisms

4. Flow rate (minor effect only)

Higher GFR will increase flow rate in the tubule Less Na+ reabsorption takes place

Loop of Henle

No significant Na+ regulatory mechanism in Loop of Henle

JGA & Distal Tubule

Major contributor to Na+ homeostasis1. JUXTAGLOMERULAR APPARATUS Sensor function

renal arteriolar pressure distal tubular flow

Secretion of renin

2. DISTAL TUBULE Modulation of Na+ reabsorption

Juxtaglomerular Apparatus

Sensory function1. Granular cells of afferent arteriole – sensitive to pressure

within the arteriole High pressure – renin secretion is inhibited

2. Macula Densa – sensitive to fluid flow rateNaCl flow rate

High flow rate – renin secretion is reduced

Renin Secretion

Renin secretion is by afferent arteriolar granular cells

STIMULI1. Granular cells themselves2. Macula densa3. Renal sympathetic nerves (through beta 1 receptors)

Renin Secretion

High blood volume High blood pressure

Distension of afferent arteriole

Raised GFR & reduced proximal

tubular reabsorption

High distal tubular flow rate

Inhibition of sympathetic nerves

Inhibition of renin secretion

Renin Secretion

Renin secretion is

Inhibited by high effective blood volume and high blood pressure

Increased when effective blood volume and blood pressure are low

Renin Angiotensin Aldosterone System

Angiotensinogen

Angiotensin I

Angiotensin II

Arteriolar constriction

Aldosterone secretion

Renin

Increase distal tubularNa+ reabsorption

Decrease GFR

Renin activates mechanisms that increase Na+ and water retention

ADH secretion

Angiotensin converting

enzyme

Overview of Na+ Homeostasis

Changes in effective blood volume and blood pressure

Arteriolar changes, hydrostatic & oncotic pressure changes, endocrine responses

Responses by glomerulus, proximal tubule and distal tubule

Modulation of Na+ excretion

Compensation of changes in effective blood volume and blood pressure