Regulation of Sodium and Water Balance Flashcards
Main substances exerting osmotic pressure in compartments:
• cells: ?
• interstitial fluid: ?
plasma: ?
K+
Na+
protein (usually albumin)
What two electrolytes are particularly abundant in the ECF?
Na+
Cl-
What electrolytes are particularly abundant in the ICF?
K+
Pi
What determines the distribution of body water?
Osmotic pressure
Water & Na balance are regulated independently by specific pathways designed to prevent large changes in plasma osmolality. What happens as a result of…
increased total body Na+ content –>
H2O osmosis from cells, renal H2O retention –> increased extracellular fluid volume.
Thus, increased Na+ in the body expands extracellular fluid volume and effective circulating volume.
How is plasma Na+ balance (and therefore osmolarity) regulated?
primarily by changes in water balance
•Total Body Na+ content = ?
•Total Body Na+ content = dietary Na+ intake - urinary Na+ excretion
•Dietary Na+ intake is not regulated in humans. How do we control body Na+ content?
the kidneys control body Na+ content by adjusting urinary excretion
What activates retention and excretion of Na+?
Increased ECF volume activates mechanisms that increase Na+ excretion.
Decreased ECF volume causes Na+ to be stored.
Where is the bulk of Na+ reabsorption done in the kidney?
Proximal Tubule, loop of henle
Where is the fine tuning of the Na+ reabsorption handled?
At the distal nephron
What are the major functions of the early proximal tubule?
Isosmotic reabsorption of solute and water
What are the early proximal tubule cellular mechanisms?
Na +-glucose, Na+-amino acid, Na +-phosphate cotransport
Na +-H +exchange
What hormones act at the early proximal tubule?
PTH inhibits Na +-phosphate cotransport
Angiotensin II stimulates Na +-H +exchange
What are the diuretics associated with the early proximal tubule?
Osmotic diuretics
Carbonic anhydrase inhibitors
What are the major functions of the late proximal tubule?
Isosmotic reabsorption of solute and water
What are the cellular mechanisms of the late proximal tubule?
NaCl reabsorption driven by Cl −gradient
What hormones act at the late proximal tubule? diuretics?
none.
Osmotic diuretics
What are the major functions of the thick ascending limb of the loop of henle?
Reabsorption of NaCl without water; Dilution of tubular fluid ;Single effect of countercurrent multiplication; Reabsorption of Ca 2+ and Mg 2+ driven by lumen-positive potential
What are the cellular mechanisms of the thick ascending loop of henle?
Na +-K +-2Cl− cotransport
What hormones act at the thick ascending limb of the loop of henle?
ADH stimulates Na +-K +-2Cl−cotransport
What diuretics act at the thick ascending limb of the loop of henle?
Loop diuretics
What is the major function of the early distal tubule?
Reabsorption of NaCl without water
Dilution of tubular fluid
What are the cellular mechanisms of the early distal tubule?
Na +-Cl −cotransport
What hormones act at the early distal tubule?
PTH stimulates Ca 2+reabsorption
What diuretics act at the early distal tubule?
Thiazide diuretics
What is the function of the Late Distal Tubule and Collecting Ducts (principal cells)
Reabsorption of NaCl
Variable water reabsorption
What are the cellular mechanisms of the late distal tubule and collecting ducts (principle cells)
Na +channels (ENaC)
K + channels
AQP2 water channels
What hormones act on the Late Distal Tubule and Collecting Ducts (principal cells)?
Aldosterone stimulates Na +reabsorption and K+ secretion
ANP inhibits Na+ reabsorption in collecting duct
What diuretics act on the Late Distal Tubule and Collecting Ducts (principal cells)
K +-sparing diuretics
What is the function of the Late Distal Tubule and Collecting Ducts (α-intercalated cells)?
Reabsorption of K +
Secretion of H +
What are the cellular mechanisms associated with the Late Distal Tubule and Collecting Ducts (α-intercalated cells)
H +-K +ATPase
H + ATPase
What hormones act at the Late Distal Tubule and Collecting Ducts (α-intercalated cells)?
Aldosterone simulates H+ secretion
What diuretic actions happen at the Late Distal Tubule and Collecting Ducts (α-intercalated cells)?
K +-sparing diuretics
In the early proximal convoluted tubule what is the one countertransport and what does it drive?
•Na+-H+ is the one countertransport and drives HCO3- resorption
In the early proximal convoluted tubule, how are glucose, AA’s, and HCO3- transported?
secondary active transport
By the end of the early PCT nearly all of what five compounds has been reabsorbed?
•At the end of the early proximal convoluted tubule all glucose, 85% of filtered HCO3-, and most phosphate, lactate, and citrate is reabsorbed
The diffusion of Cl- in the late proximal convoluted tubule generates what?
a lumen-positive potential difference
What is the major regulatory mechanism of the proximal tubule?
glomerotubular balance
What does glomerotubular balance do? How does it accomplish this?
By enacting changes to the filtration fraction and Starling forces (πc) this maintains a constant fractional reabsorption and keeps the balance between filtration and reabsorption
What hormone regulates the Na+ reabsorption in the principle cells of the late distal tubule and collecting duct?
Aldosterone
Water reabsorption in the late distal tubule and collecting duct is variable. How is it controlled?
ADH/AVP
Where is aldosterone secreted?
Zona glomerulosa of the adrenal cortex
How does aldosterone act on principle cells?
It diffuses into the cell and induces the synthesis of mRNA for proteins involved with Na+ transport.
What do K+ sparing diuretics do in principle cells?
interfere with Na+ reabsorption
What factors promote Na+ reabsorption?
(3)
–Activation of renal sympathetic nerves
–Activation of renin/angiotensin system
–Secretion of aldosterone
•Factors that promote Na+ excretion:
(3)
–Release of atrial, brain natriuretic peptides (ANP, BNP)
–Release of urodilatin
–Intrarenal prostaglandins
What factors promote renin secretion?
(3)
Sympathetic stimulation
Tubuloglomerular feedback
Intrarenal baroreceptor (wall of afferent arteriole)
What causes renal sympathetic stimulation? How does this lead to renin secretion?
•due to fall in perfusion pressure through the cardiopulmonary baroreceptors: directly stimulates renin secretion via β1 receptor activation in the JG apparatus
How do internal receptors stimulate renin secretion?
•Intrarenal baroreceptor (wall of afferent arteriole): afferent arteriolar vasoconstriction –> decreased pressure at granular cells –> increased renin secretion
What leads to TGF ramping up renin secretion?
decreased NaCl delivery to macula densa –> increased renin secretion
What effect do loop diuretics have on renin secretion?
since effective circulating volume drops due to the diuretics, renin secretion is increased
What six things does Ang II stimulate?
- •Systemic arteriolar constriction
- •Renal arteriolar constriction: efferent > afferent.
- •Na+ reabsorption: PCT (via ↑ Na-H exchanger activity) > TAL, CCD (can result in a contraction alkalosis
- •Thirst
- •ADH secretion from posterior pituitary
- •Aldosterone secretion from adrenal cortex
What are the renal effects of Ang II
Outline the Response of renin/angiotensin mechanism to decreased ECF volume
What three things does aldosterone do in the late distal convoluted tubule and collecting duct (principle cells)?
- Stimulates sodium reabsorption
- Stimulates potassium secretion
- Stimulates H+ secretion (↑ H +-ATPase activity in intercalated cells of CCD)
•What would happen to K & H excretion in a patient with hyperaldosteronism?
excretion of both would increase
What are 6 actions of ANP?
- •ANP increases GFR: Afferent arteriolar dilation, efferent arteriolar constriction
- •ANP inhibits Na+ reabsorption in medullary collecting duct
- •ANP suppresses renin secretion
- •ANP suppresses aldosterone secretion
- •ANP is a systemic vasodilator
- •ANP suppresses AVP secretion, actions
Outline the ANP response to increased ECF volume
Where, and due to what, is urodilatin secreted?
•Secreted by DCT, collecting duct in response to increased arterial pressure and ECF volume
What does Urodilatin do? What does it specifically not do?
- Urodilatin suppresses Na+ and water reabsorption by medullary collecting duct
- Unlike ANP and BNP, urodilatin has no effect on systemic circulation
What effect do intrarenal prostaglandins (PGE2) have on Na+ in the kidney? How do they effect this?
They increase Na+ excretion
By…
•Increase GFR by dilating renal arterioles
•Suppress Na+ reabsorption in thick ascending limb, cortical collecting duct-
What are the (3) actions of ADH?
- increases permeability of late distal tubule and collecting duct to water (via the insertion of aquaporins)
- Increases the activity of na+-K+-2Cl- cotransporter
- Increases urea permeability in the inner medullary collecting ducts
Where is AVP synthesized?
Hypothalamus
What are the two major stimuli for ADH release?
Hyperosmolality
Volume depletion
Which are more important - hypothalamic osmoreceptors or hepatic osmoreceptors?
hypothalamic
What are the sensors of plasma osmolarity? How do they effect change?
What is affected?
hypothalamic receptors
ADH and thirst
Urine osmolarity and water intake are affected
What sensors regulate volume?
Macula densa
afferent arterioles
atria
carotid sinus
What do the volume regulating sensors sense?
Adequate tissue perfusion
How do the volume regulating sensors enact change? What does this lead to?
RAAS; ANP; NE ADH
Urinary sodium; Thirst
What are the 6 neurohumoral factors controlling Na+ reabsorption?
- •sympathetic activity,
- angiotensin II,
- aldosterone,
- ANP,
- BNP,
- urodilatin
What factors control AVP secretion?
Osmolality
Blood pressure
