Lecture 12: Regulation Of Na Excretion Flashcards
List the components of sodium regulation
ECV
Sensors:
Arterial + renal BRs
cardiopulmonary receptors
Effectors:
Urinary excretion
Nerves/hormones = sympathetic division, RAAS, ADH, ANP, vasodilator PGs
What is total body sodium sensed by?
Surrogate =
ECV
Define effective circulating volume (ECV; arterial filling)
Explain how it differs from ECF
ECV = the part of the ECF that can activate mechanisms to bring changes in sodium excretion
It’s the part of the ECF that is in the arterial system and can be sensed by regulatory mechanisms involved in sodium homeostasis
Identify two diseases in which ECF and ECV are dissociated, explaining why total body sodium is increased in these diseases
HF
Nephrotic syndrome
Sensors detect decreased ECV (even though the ECF is actually increased) - sodium- retaining mechanisms get activated
Describe effects of volume depletion on ECF, ECV and CO
ECF = dec. ECV = dec.
CO = dec.
(Loss of vol. = dec. PL)
Describe effect of HF on ECF, ECV and CO
ECF = inc.
ECV = dec.
(Less vol/stretch sensed leading to water/salt retention that will inc. ECF)
CO = dec.
What are effects of nephrotic syndrome on ECF, ECV and CO
ECF = inc.
ECV = dec.
CO = no change or dec.
Define pressure natriuresis, briefly describing the proposed mechanisms for this effect
Phenomenon of BP’s direct effect on sodium excretion
Mediated mainly by dec. Na reabsorption
When there is inc. Na intake (and more total body sodium), ECV inc. = inc. BP = inc. renal perfusion pressure = dec. Na reabsorption and inc. GFR = inc. sodium excretion
Describe the effect of increased nerve traffic on kidney function/sodium excretion
Nerves and hormones speed up sodium balance and decrease impact of dietary salt on total body sodium
Dec. ECV = dec. stretch of arterial BRs = inc. symp. Tone to kidneys
+ inc. sodium reabsorption
+ inc. renin secretion
+ as a last resort: dec. GFR
Describe innervation of kidney
EXCLUSIVELY sympathetic
3 main innervated:
+ AA
+ granular cells
+ tubular epithelium
Receptor subtypes:
alpha1, alpha2, beta1
Describe effect of low levels of sympathetic stimulation
Alpha2 receptors on PT + beta on DCT get stimulated
Inc. NHE in PT
=
Inc. Na reabsorption in PT and inc. Na reabsorption in DCT via NCC
Describe effect of intermediate levels of sympathetic stimulation
Beta1 receptors on granular cells stimulated
Inc. renin secretion
=
Activation of RAAS
=
Inc. Na reabsorption AND renovascular effects
Describe effect of high levels of sympathetic stimulation
“Last resort of neural regulation”
Alpha1 on AA stimulated = Vasoconstriction = Dec. RBF and GFR
Describe indirect/direct relationships amongst effectors of sodium homeostasis
ECV + arterial BRs = direct
arterial BRs + symp. Tone = indirect
Symp. Tone + sodium excretion = indirect
Symp. Tone + RAAS = direct
RAAS + sodium excretion = indirect
What are hormonal regulators of Na balance and ECV?
Vasoconstrictors + anti-natriuretic hormones:
+ AngII
+ Aldosterone
+ Vasopressin (ADH)
Vasodilators + natriuretic hormones:
+ ANP/BNP
+ PGs
+ NO
Describe effects of AngII on systemic circulation, renovascular, and tubules
Systemic circulation:
Vasoconstriction = Inc. SVR = inc. BP
Renovascular:
More vasoconstriction on EA than AA = dec. RPF & inc. GC hydraulic pressure = inc. FF & ____ effect on GFR
PT: inc. Na reabsorption via NHE
DCT/CNT/CD:
Inc. aldo and direct stimulation of NCC and ENaC = inc. Na reabsorption
For volume depletion, what are pattern of RAAS components in the plasma?
Dec. stretch on arterial and intracranial BRs from depletion = Inc. renin secretion = Inc. AngII = inc. aldosterone
What are effects of PGs on kidney function?
Systemic circulation
Renovascular
Tubules
Counteract neurohormonal vasoconstriction
systemic circulation:
Local vasodilation = dec. SVR = dec. cardiac AF and BP
Renovascular:
Vasodilation @AA = inc. RPF + GFR
Thick AL and CD:
Dec. Na reabsorption (in humans?)
What increases PG synthesis?
Neurohormonal activation:
AngII
ADH
Sympathetic stimulation
What effect do PGs have on renin?
Inc. renin secretion
What effect can NSAIDs have when there is nerurohormonal activation?
Dec. renal perfusion and GFR
Little effect on renal fxn under normal conditions
Describe effect of ACEI on glomerular hemodynamics
ACEI = dec. synthesis of AngII = AA and EA vasodilation (EA»_space; AA = dec. GC hydraulic pressure) = dec. RVR = inc. RPF
What does vasopressin do?
Allows reabsorption of water in CNT/CD
What regulates ADH secretion?
P(osm) and ECV
Inc. P(osm) = inc. ADH
Dec. ECV = inc. ADH
What are non-osmotic stimuli ?
High levels of AngII
Severe vomiting, pain + major stress (post-op)
Significant decrease in ECF or ECV
Describe relationship between osmotic and non-osmotic stimuli
Osmotic stimulus more potent vs. non-osmotic
Strong non-osmotic can OVERRIDE osmotic
Describe effects of high levels and any levels of ADH
High levels = systemic circulation:
ADH = V1 vasoconstrictor = inc. SVR = inc. BP
any level = CNT/CD:
Binding to V2 receptor on principal cells = insertion of AQP2 channels on apical side = inc. water reabsorption = dec. water excretion
What do osmoregulation and volume regulation sense?
What do they affect?
Osmoregulation
Sense: plasma osmolality
Effects: water excretion (via ADH) + water intake (via thirst)
Volume regulation
Sense: ECV
Effects: sodium excretion
Describe effects of ANP/BNP on systemic circulation, renovascular effects, and tubules
Systemic circulation:
Vasodilation = dec. SVR = dec. cardiac AL
Renovascular:
Dilate AA + constrict EA = inc. GC hydraulic pressure, inc. RPF = inc. GFR = dec. renin secretion
CD (IMCD):
Oppose actions of aldosterone = dec. Na reabsorption
What are NO actions in the kidneY?
Vasodilation and inc. GFR
Inc. Na excretion
Describe circumstances in which it is dangerous to administer an NSAID
True volume depletion or low ECV
Examples: HF or cirrhosis
What is TGF?
Tubuloglomerular feedback
Negative feedback system in kidney
Macula densa senses salt delivered to alter GFR in the same nephron
Describe proposed mechanisms for TGF
Sense:
Macula densa cells sense NaCl via NKCC2 while cilia sense flow
Effects:
Paracrine mediators constrict/dilate AA to induce change in GFR
What are effects on GFR of inc. NaCl delivery to macula densa?
Release of paracrine mediators (inc. adenosine) =
AA constriction
=
Dec. GFR
What are effects of dec. NaCl delivery to macula densa?
Release of paracrine mediators (Dec. Adenosine, inc. PGE2) = AA dilation = Inc. GFR
Explain why TGF stabilizes the function of the nephron but does not stabilize TB sodium
TGF autoregulates GFR in single nephrons!!!
Will affect distal nephron that shares same macula densa
Describe glomerulotubular balance (GTB) and the proposed mechanism for it
Describes positive relationship between tubular fluid flow rate and reabsorption
Inc. in GFR + filtered load = inc. reabsorption of solutes (mainly PT) so that fraction of solute reabsorbed remains constant
What is GTB mediated by?
Physical factors
Flow-mediated changes by microvilli on apical surface of PT
