Sodium Handling Flashcards
What does “1 equivalent of Na” actually mean?
• Has to do with molarity, 1 equivalent of Na = 1 mole of sodium
Of the ECF fluid compartment, which is 1/3 of the TBW, how much is in the plasma and how much is in the interstitium of the body’s tissues?
- 3/4 in interstitial fluid compartment
* 1/4 in plasma fluid compartment
Why are electrolyte abnormalities primarily water problems?
- Water is freely permeable across most cell membranes but ions are not
- If osmotic gradients are established between compartments then water will move
What are rules that govern osmotic fluid movement?
• Water-permeable membrane must separate two compartments with different concentration of impermeable solutes
• Water moves into higher solute concentration (toward higher osmolality) • Freely permeable solutes (urea) do not affect water movement • Magnitude of gradient (osmotic) determines magnitude of water movement • Water will move until either osmotic gradient is gone or hydrostatic pressure causes equilibrium Is there an osmotic gradient between the capillary and the interstitium? • Mostly NO, because of the fenestrated epithelium that allows for rough equilibration of solutes between these two compartments • The exception is albumin, dextran, and other large proteins (hence infusions of these maintained in the plasma)
What is really being discussed when we are talking about ECF sodium?
- We are talking about disorders of ECF volume when we are talking about sodium
- Same with hyper and hyponatremia, it is a water problem, not a sodium problem
- Maintenance of ECF volume determines the MAP and left ventricular filling volume
What is the purpose of the integrated homeostatic response?
- Maintain ECF volume
- Made up of two key components: afferent limb (EABV sensor) and efferent limb (regulates the rate of sodium excretion by the kidney)
What are the components of the integrated homeostatic response?
- Maintain ECF volume
- Made up of two key components: afferent limb (EABV sensor) and efferent limb (regulates the rate of sodium excretion by the kidney)
What does the flowchart of the homeostatic response say about volume expansion?
- Starts normal extracellular volume
- Volume expansion
- Activation of volume sensors
- Renal effector mechanism
- Natriuresis
What does the flowchart of the homeostatic response say about volume contraction?
- Volume contraction and decrease in effective aterterial blood volume can be the same thing
- Starts normal extracellular volume
- Activation of volume sensors
- Renal effector mechanism
- Anti-natriuresis
What happens in volume expansion?
- On the venous side, atrial stretch receptors signal hypothalamic and medullary centers in brain to decrease renal sympathetic activity
- Net result is loss of sodium and water in the kidney and reduction in the initial ECF volume expansion
- The opposite is the case with volume reduction
What volume sensors are in the afferent limb?
• Low pressure baroreceptors ○ Cardiac atria receptors ○ Left ventricular receptors ○ Pulmonary vascular bed receptors • High pressure baroreceptors ○ Carotid sinus body (bifurcation) ○ Aortic body (in aortic arch) • Intrarenal sensors ○ JGA = juxtaglomerular apparatus ○ Releases renin • Hepatic and central nervous system sensors
What decreases renin secretion?
- Increased arterial blood pressure
- Increased sodium delivery
- Angiotensin II
- ANP
What increases renin secretion?
• Decreased arterial pressure • Decreased sodium delivery • Beta adrenergic action • PGEI, PGE2 • Nitric oxide ○ All the things that dilate the afferent arteriole
What is tubuloglomerular feedback?
- Increased distal delivery of sodium chloride to macula densa (in the JGA) increases afferent arteriolar tone and returns RBF and GFR towards normal values
- Increased sodium chloride just after the glomerulus likely means that filtration is increased, which is most likely due to pressure (hydrostatic pressure is main filtration driving force)
What is the Glomerulo-tubular balance?
- Works with tubuloglomerular feedback and the renal autoregulation pathway to maintain GFR
- Fundamental property of the kidney whereby changes in GFR automatically induce a proportional change in the rate of proximal tubular sodium reabsorption
- Fractional excretion of sodium is maintained constant in the setting of increases or decreses in GFR
Which hormones are active in ECF volume contraction and what do they do?
• Angiotensin II, aldosterone, catecholamines, vasopressin
• Vasoconstriction, increase MAP, increase GFR
Which hormones are active in seetings of ECF volume overload?
• Prostaglandins, bradykinin, atrial natriuretic peptide, dopamine
• These induce natriuresis
When is the sympathetic nervous system active in the kidney and what does it do?
- Sympathetic system innervates the afferent and efferent arterioles of the glomerulus
- Stimulated in volume contraction and is needed for sodium conservation
- Results in anti-natriuretic effect
- Also increases renin release from JGA which in turn releases anti-natriuretic hormones A2 and aldosterone
What are the four main areas for sodium handling in the kidney?
- Proximal tubule
- Thick ascending limb of the loop of henle
- Distal convoluted tubule
- Principal cell of cortical collecting duct
Is there a gradient for sodium to follow in the proximal tubule?
- Yes. Filtrate sodium concentration is the plasma concentration, which is 140mEq/L and the inside of the tubular epithelium is 15-35 mEq/L
- Gradient is maintained by the action of the ubiquitous sodium pump Na/K ATPase at the basolateral side
- The entry of sodium into the cell is coupled to chloride, phosphate, glucose, amino acids and lactate sodium-dependent co-transport
- Sodium can also be increased through Na/H+ antiporter (sodium in and hydrogen out)
What is affected by loop diuretics?
- The Na/K/2Cl channel is inhibited
- Dilution of the urine in the TALH is thus inhibited
- Result is concentrated urine and water and salt excretion
What are the active transporters in the TALH?
- (Lumenal) Na/K/2Cl cotransporter, Na/H+ antiporter
* (basolateral) Na/K ATPase, K/Cl cotransporter, Na/HCO3 cotransporter
What ions should you assume as passively moving through the TALH?
- Potassium leaks to the apical side
- Chloride leaks to basolateral side
- Calcium, magnesium, ammonia all leak from lumenal to basolateral side
How much of the filtered sodium is reabsorbed in the loop of henle?
- 30% in the thick ascending limb of the loop of Henle (TALH)
- Impermeable to water but very salt permeable
- DILUTION is going on in TALH so that osmolality of tubular fluid is about 150mOsm/Kg water at the end of it (1/2 of plasma)
- Resorption here through lumenal membrane through Na/K/2Cl co-transporter (active)
What are the cotransporters that use Sodium influx as their energy source?
- (lumenal side) Glucose, amino acids, phosphate, lactate, chloride
- (basolateral side) Na/K ATPase (sodium out potassium in), bicarbonate transporter (get bicarb out and sodium out to drive bicarb formation)
What process will drive the generation and reabsorption of bicarbonate?
• Na/H+ antiporter. H+ out, sodium in
How does the distal convoluted tubule participate in urine dilution?
• Sodium reabsorbed across lumenal membrane by three mechanisms
• Sodium channels (also drives chloride into cell)
• NaCl reabsorption by Na/Cl cotransporter
• Sodium transport through parallel Na/H+ antiport and Cl/base exchange with recycling of H+ and base
○ Both Na and Cl need their antiporters with H+ and base, respectively, to keep the cycle going
What channels/transporters are inhibited by diuretics in the distal convoluted tuble?
- Thiazides inhibit the Na/Cl cotransporter
- Amiloride inhibits the passive Na leak channel in the apical membrane
- These will both inhibit NaCl reabsorption, concentrating the urine and leading to salt and water excretion
