Sodium balance

From Iusmphysiology

• started here on 03/28/11.

Contents 1 Sodium Balance 1.1 Objectives 1.2 Kidneys are important to Na balance 1.3 Na reabsorption along the nephron 1.4 Factors that effect Na reabsorption 1.4.1 Glomerular filtration rate 1.4.2 Mineralocorticoids (aldosterone) 1.4.3 Intrarenal physical forces (Starling forces) 1.4.4 Natriuretic hormones 1.4.5 Renal sympathetic nerves 1.4.6 Changes in intrarenal distribution of blood flow 1.4.7 Estrogens 1.4.8 Osmotic diuretics 1.4.9 Poorly reabsorbable anions 1.4.10 Diuretic drugs

Sodium Balance

Objectives

• Compare the amounts of sodium which are filtered, reabsorbed, and excreted in a day.
• Indicate the percentages of filtered sodium that are reabsorbed in the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct.
• Explain how the following factors affect sodium excretion:
  • glomerular filtration rate,
  • mineralocorticoids (aldosterone),
  • intrarenal physical forces,
  • natriuretic hormones (atrial brain, and kidney natriuretic peptides; guanylin and uroguanylin; others),
  • renal sympathetic nerves,
  • changes in intrarenal distribution of blood flow, estrogens, osmotic diuretics, poorly reabsorbed anions, and diuretic drugs.
  • Explain why the volume of the extracellular fluid is dependent on its sodium content.
  • Discuss the input and output of sodium from the body.
  • Describe the renal response to a change in dietary sodium intake.
  • Explain how changes in effective arterial blood volume lead to changes in renal sodium excretion.
    • Explain why renal salt and water retention is a key element in the development of generalized edema.

Kidneys are important to Na balance

• The kidneys filter lots of plasma yet retain nearly all of the Na; 99.6%.
• The kidneys even keep most of the K filtered, though K is sometimes lost at the collecting duct as a mechanism for retaining Na.

Na reabsorption along the nephron

• 70% of the filtered Na is reabsorbed in the proximal convoluted tubule.
• 90% of the filtered Na is reabsorbed by the end of the Loop of Henle.
• The most important Na regulation point is the collecting duct, though it does not reabsorb a huge percentage.
• There are four locations where diuretics take action: PT, LH, DT, and CD.
  • Note that location of action determines effectiveness.

Factors that effect Na reabsorption

• There are a sooo many things that affect Na reabsorption:
  • Glomerular filtration rate
  • Mineralocorticoids (aldosterone)
  • Intrarenal physical forces (Starling forces)
  • Natriuretic hormones
  • Renal sympathetic nerves
  • Changes in intrarenal distribution of blood flow
  • Estrogens
  • Osmotic diuretics
  • Poorly reabsorbable anions
  • Diuretic drugs

Glomerular filtration rate

• Recall that as GFR falls, so will the Na excretion because the filtrate will spend more time in the tubule so there will be more time for the epithelial cells to reabsorb the Na.
  • And conversely, as GFR increases, Na excretion increases.
  • Be careful because Na excretion and Na reabsorption are affected exactly opposite as GFR changes.
• We know that the proximal tubule reabsorbs 2/3 of the Na in the filtrate regardless of GFR.

What is GT balance?

Mineralocorticoids (aldosterone)

• Recall that aldosterone (from the glomerulosa of the adrenal gland) causes principal cells of the collecting duct to put ENaC on their apical membrane and Na / K ATPase on the basolateral membrane thus increasing water reabsorption.
  • Recall that ENaC is a passive channel and it is the movement of Na by Na/K ATPase that drives increased Na reabsorption.

• Secretion of aldosterone is primarily controlled by the renin-angiotensin pathway.
• We know that a baseline level of aldosterone is always secreted because pts with adrenalectomy only reabsorb 98% of their filtered Na instead of 99.6%.
• Addison's Disease is a disease of adrenal insufficiency; that is Addison's disease results from too little aldosterone production.
  • If there is too little aldosterone, then too little AQ2 is put on the collecting duct cells and too little water is reabsorbed.
  • So we expect Addison's disease to lead to: nausea, vomiting, low blood pressure that falls further when standing, causing dizziness or fainting (hypovolemia), a craving for salty foods due to salt loss

Why does nausea and vomiting result from Na wasting?

• Aldosterone escape:
  • Aldosterone escape is a phenomenon in which the kidney--under high doses of mineralocorticoids like aldosterone--stops responding to the mineralocorticoid as expected (that is, the kidney stops retaining water even in the presence of mineralocorticoid signaling).
  • Note that DOCA is a potent mineralocorticoid.

• Aldosterone breakthrough:
  • Aldosterone breakthrough is a phenomenon in which the adrenals--under high doses of ACE-inhibitors--re-establishes normal aldosterone levels.
  • That is, ACE-inhibitors are given (let say, to reduce blood volume in an hypertensive pt) so renin levels are high, angiotensin II levels are low and aldosterone levels are initially low (which is achieving our purpose of less water reabsoprtion and less extracellular volume) and then aldosterone levels return to pre-treatment levels.

Intrarenal physical forces (Starling forces)

• Recall that Starling forces include hydrostatics and colloid osmotic pressures and determine flow in and out of capillaries.
• These forces affect reabsorption at the PCT, also.

• Saline treatment:
  • Adding saline will increase the extracellular volume and therefore increase the capillary hydrostatic pressure (more volume in the same system means more pressure) and decrease the blood osmotic pressure drawing water into the blood (same amount of protein in the extracellular compartment but more water and Na).
    • Note that this means less force drawing Na and water into the blood.
  • Note that treating with DOCA is an endogenous way to add saline because DOCA will cause increased Na reabsorption (via ENaC and Na / K ATPase) and water will follow.

• In response to Saline / DOCA treatment:
  • Capillary hydrostatic pressure has increased and blood osmotic pressure has decreased so there is less force moving Na and water into the blood.
  • So the renal response to saline / DOCA is a decrease in reabsorption of Na, widening of tight junctions and subsequent back-leak of Na into filtrate and thus increased Na excretion.

Natriuretic hormones

• Atrial natriuretic peptide is released by endocrine cells of the cardiac atria in response to stretch receptors.
  • That is, when extracellular fluid levels are high and atria are "overfilled" during the cardiac cycle, atrial natriuretic peptide is released.
• ANP (atrial natriuretic peptide) acts on collecting duct and afferent arteriole.

• ANP on the collecting duct:
  • ANP acts on the collecting duct to decrease ENaC on the apical membrane and decrease Na / K ATPase on the basolateral membrane. That is ANP has the exact opposite effect of aldosterone.
  • Recall that less ENaC and less Na / K ATPase will cause less reabsorption of Na and therefore less water reabsorption and less water in the extracellular compartment (to fix the atrial over-filling problem).

• ANP on the afferent arteriole:
  • ANP dilates the afferent arteriole which increases GFR.
  • Recall that increased GFR means increased filtrate flow rate and decreased Na reabsorption (and therefore less water reabsorption and less volume in the extracellular compartment).

Renal sympathetic nerves

• Sympathetic innervation is used to decrease renal blood flow and GFR in traumatic situations.
• Recall that decreased GFR will mean slower filtrate movement, more Na reabsorption, and increased water retention which is good when your leg has been chopped off.

Why does reduced RBF (renal blood flow) cause increased Na retention?

Changes in intrarenal distribution of blood flow

Get explanation from audio.

Estrogens

• We know that Na and water are retained at higher levels when estrogen levels are elevated (via ovarian cycle or exogenous delivery).
• We suspect that estrogen may have a direct effect on tubular reabsorption.

Osmotic diuretics

• Recall "osmotic diuresis" means "peeing because of osmotic pull of water into urine".
• Osmotic diuresis can be induced by exogenously delivering a large amount of a small molecule (like mannitol) that is excreted via the urine.
  • The presence of the mannitol in the filtrate increases the osmotic force of the filtrate and inhibits Na reabsorption.
• Osmotic diuresis is possible because the distal nephron has limited capacity to move Na against an osmotic gradient.

Poorly reabsorbable anions

• As a positively charged ion, Na+ may remain in the filtrate (that is, not be reabsorbed) when there are many negatively charged ions that command a the presence of a balancing positively-charged ion.
• Examples of negatively charged ions that inhibit Na reabsorption include sulfate, phosphate, and ketones.

Diuretic drugs

• Note that all diuretics work by blocking Na reabsorption, but each works at a different location on the nephron.