ECF VOLUME

Maintaining a normal extracellular fluid volume (ECF) by the renal system

What is required for long-term control of blood pressure?

Total amount of sodium in the ECF

What determines ECF volume?

Increased sodium leads to increased water retention and thus ECF volume

How are sodium and water retention related in controlling ECF volume?

Problems with sodium balance

What do disorders in ECF volume (e.g., edema) reflect?

Changes in sodium concentration, causing osmotic water flows and neurological symptoms

How do disorders of water balance manifest?

Effective circulating volume (ECV) and absolute ECF volume

What distinction is emphasized in this session regarding fluid volumes?

Control of ECV

Through what mechanism does negative feedback control of overall ECF volume operate?

Blood volume in circulation and the pressure within specific circulatory parts

What is ECV related to?

The kidney

What organ is the main ECV sensor?

High rate of perfusion

Why is the kidney a good ECV sensor?

Juxtaglomerular apparatus (JGA)

What specific part of the kidney is the primary ECV sensor?

Changes in afferent arteriolar wall tension

What does the JGA sense to indicate renal perfusion?

Decreased renal perfusion (less stretch on the afferent arteriole)

What triggers increased renin release from the JGA?

Renin-angiotensin-aldosterone endocrine axis

What endocrine axis is activated by renin?

Redundant systems

How many systems does the body have for controlling important variables like ECV?

Arterial baroreceptors, low-pressure receptors in the pulmonary system and cardiac atria

Besides the JGA, what other receptors provide information about pressure and perfusion?

Alters renal sodium excretion

What does the kidney do when changes in ECV are detected?

Changes in water excretion, controlled by ADH

How are changes in ECF sodium content and circulating volume coupled?

ECV

What is the true controlled variable: ECV or absolute ECF volume?

Low cardiac output, even with increased total ECF volume

Why can patients with congestive heart failure have low effective circulating volume?

Maladaptive sodium and water retention and edema

What can low ECV in heart failure lead to?

Activation of the renin-angiotensin system, stimulation of the sympathetic nervous system, increase in ADH secretion, changes in Starling's forces

What are the four main ways a decrease in ECV is counteracted?

Reduced renal perfusion

What is the stimulus for renin secretion from the JGA?

Increased angiotensin II and aldosterone levels

What are the main hormonal consequences of renin release?

Directly increases renal sodium excretion, is a direct vasoconstrictor, stimulates ADH secretion, stimulates aldosterone secretion

What are the main effects of angiotensin II?

Increases renal sodium retention

What is the main effect of aldosterone on the kidney?

Baroreceptor reflex activates the sympathetic nervous system

What happens if a decrease in ECV reduces mean arterial blood pressure?

Vasoconstriction, increased heart rate, and myocardial contractility

How does the sympathetic nervous system support blood pressure and cardiac output?

Directly increase renin secretion

What effect do renal sympathetic nerves have on renin secretion?

Crosstalk

What type of interaction exists between the renin-angiotensin system and the sympathetic nervous system?

Reduces flow and stimulates renin release

How does vasoconstriction in the afferent arteriole affect renin secretion?

Direct activation of beta-1 receptors on renin-secreting cells

What type of adrenergic receptor activation occurs to stimulate renin release?

Loss of sodium chloride and water

Low ECV due to what type of loss affects Starling's forces in the nephron?

Become more concentrated

What happens to serum proteins when ECV is low due to fluid loss?

Decreases

What happens to hydrostatic pressure in capillaries throughout the body when ECV is low?

Increase the tendency of the nephron to reabsorb fluid back into the blood

How do changes in Starling's forces in peritubular capillaries affect fluid reabsorption when ECV is low?

Support and normalize mean arterial blood pressure

What is the overall goal of the four major actions that counteract low ECV?

Not simply the opposite of those seen with decreased circulatory volume

How do the responses to high effective circulating volume compare to those with decreased volume?

Low

In persons with normal effective circulating volume and osmolarity, what is the general activity level of the RAAS system, ADH, and sympathetic nervous tone?

Less important

Therefore, what happens to the scope for further suppression of these systems in high effective circulating volume states?

Designed to activate strongly when volume is low

What is the primary design function of the RAAS, ADH, and sympathetic nervous systems regarding volume status?

Remain significant

What happens to the significance of changes in Starling's forces in high volume states?

Increases

What happens to capillary hydrostatic pressures during volume loading?

Dilutes

What happens to oncotic pressure during volume loading?

More difficult for reabsorbed fluid from the nephron to enter the capillary circulation, thus promoting sodium and water excretion

How do changes in peritubular capillaries affect fluid reabsorption during high volume states?

Atrial natriuretic peptide (ANP)

High effective circulating volume is associated with the secretion of what peptide?

Promotes the loss of sodium and water in the urine (natriuresis)

What is the main effect of ANP?

Cardiac atria in response to greater atrial stretch caused by an increase in venous blood volume

Where is ANP secreted from and in response to what?

Systemic venous system (around two-thirds)

Where does most of the blood volume reside, leading to increased cardiac preload in high circulatory volume?

Low-pressure baroreceptors in the atria

What type of baroreceptors are stretched, leading to increased ANP secretion?

Small increases in glomerular filtration rate (GFR), directly inhibiting sodium reabsorption in the later part of the collecting duct, subtle roles in inhibiting sodium-retaining hormones like ADH and renin-angiotensin

What are the mechanisms of action of ANP?

Brain natriuretic peptide (BNP)

What is another clinically important natriuretic peptide?

The ventricles of the heart

Where is BNP produced?

Heart failure

In what clinical condition do BNP levels increase?

Decreasing excess volume load on the heart

What is the physiological action of BNP similar to ANP?

Pressure natriuresis

What is the phenomenon where increased arterial blood pressure causes increased renal sodium excretion called?

Intrinsic renal control over sodium excretion

What does the persistence of pressure natriuresis even in the absence of hormones and sympathetic nerves indicate?

An angiotensin II system isolated inside the kidney and local nitric oxide production

What mechanisms are thought to be involved in pressure natriuresis?

A steep relationship

What type of relationship exists between arterial blood pressure and sodium excretion in pressure natriuresis?

Acts independently and in concert with other mechanisms to support sodium balance and maintain normal blood pressure

How does pressure natriuresis contribute to sodium balance and blood pressure regulation?

Shifted to the right (higher pressure)

How is the pressure natriuresis curve affected in patients with hypertension?

Maintain blood pressure at pathologically high levels and exhibit aggressive regulation of sodium excretion within their new, higher "normal" blood pressure range

What are the characteristics of sodium regulation in hypertensive patients?

Salt-sensitive

What term describes hypertensive patients where increased sodium intake leads to a greater rise in blood pressure?

Increase their salt excretion rate

How can other individuals deal with high salt intake without a large rise in blood pressure?

Separate variables

How should extracellular fluid volume (ECF) and osmolarity be regarded?

Visualize the relationships between volume and osmolarity

What is the purpose of Darrow-Yannet diagrams?

X-Y plot of volume (X-axis) versus osmolarity of fluid (Y-axis)

What are the axes of a Darrow-Yannet diagram?

About 42 liters with a normal osmolarity of around 290 mOsm

What is the approximate total body water and normal osmolarity in a classic 70 kg man?

Two-thirds is intracellular fluid (ICF), and roughly one-third is ECF

What are the approximate proportions of intracellular fluid (ICF) and extracellular fluid (ECF) in total body water?

Visualize changes in osmolarity or volume of the ICF and ECF compartments

What can the basic Darrow-Yannet diagram be used to visualize?

ECF volume can contract with osmolarity staying the same, increasing, or decreasing

What are the possibilities for osmolarity changes when ECF volume contracts?

Isosmotic contraction

What type of volume contraction occurs with no change in overall osmolarity but a decrease in ECF volume?

Secretory diarrhea or hemorrhage

Give examples of isosmotic volume contraction.

No osmotic driving force for water exchange with ICF, so ICF volume is unchanged

What happens to ICF volume during isosmotic contraction?

Low ECV mechanisms are activated; salt or water ingestion/infusion is needed for restoration

What compensatory mechanisms are activated and what is required for restoration in isosmotic contraction?

Hyperosmotic volume contraction

What type of volume contraction involves a decrease in ECF volume and an increase in osmolarity?

Sweating (loss of dilute sodium chloride)

Give an example of hyperosmotic volume contraction.

Water shifts from the ICF to the ECF by osmosis

What fluid shift occurs during hyperosmotic volume contraction?

Both ECF and ICF have higher osmolarity and have lost water

What are the steady-state changes in ECF and ICF in hyperosmotic volume contraction?

Strong ADH response is activated due to both increased osmolarity and decreased volume

What hormonal response is activated in hyperosmotic volume contraction?

Hyposmotic volume contraction

What type of volume contraction involves a decrease in both ECF volume and osmolarity?

Adrenocortical insufficiency (Addison's disease)

Give an example of hyposmotic volume contraction.

Net water flux from the ECF to the ICF due to the more dilute ECF, leading to increased ICF volume at steady state

What fluid shift occurs during hyposmotic volume contraction?

Both ECF volume and overall body fluid osmolarities are reduced

What are the steady-state changes in ECF volume and overall body fluid osmolarity in hyposmotic volume contraction?

Normal effective circulating volume cannot be restored due to lack of aldosterone system

What is a challenge in restoring volume in hyposmotic volume contraction due to Addison's disease?

Aggressive ADH response driven by low ECF volume, causing water retention and further dilution despite low osmolarity

What paradoxical hormonal response can occur in hyposmotic volume contraction?

ECF volume can also expand with osmolarity being normal, increased, or decreased

What are the possibilities for osmolarity changes when ECF volume expands?

Isosmotic volume expansion

What type of volume expansion occurs with no change in osmolarity but an increase in ECF volume?

Isotonic saline infusion

Give an example of isosmotic volume expansion.

No fluid shift between ECF and ICF due to no change in osmolarity

What fluid shift occurs during isosmotic volume expansion?

ICF volume and body fluid osmolarity are unchanged, only ECF volume increases

What are the changes in ICF volume and osmolarity in isosmotic volume expansion?

Mechanisms to counter high ECV (e.g., increased ANP) will promote renal sodium excretion

What compensatory mechanisms are activated in isosmotic volume expansion?

Hyperosmotic volume expansion

What type of volume expansion involves an increase in both ECF volume and osmolarity?

Ingestion of salt without water

Give an example of hyperosmotic volume expansion.

Salt enters ECF and increases ECF osmolarity

What is the initial effect of salt ingestion without water?

Water shifts from the ICF to the ECF by osmosis

What fluid shift occurs during hyperosmotic volume expansion?

Increased ECF volume, decreased ICF volume, and increased osmolarity of all body fluids

What are the steady-state changes in fluid compartments and osmolarity in hyperosmotic volume expansion?

Increased ADH secretion occurs due to high osmolarity, initially causing further volume expansion via water retention

What hormonal response is activated in hyperosmotic volume expansion?

Mechanisms to counter high ECV will promote renal sodium excretion

What compensatory mechanisms are activated in hyperosmotic volume expansion?

Hyposmotic volume expansion

What type of volume expansion involves an increase in ECF volume and a decrease in osmolarity?