Week 1: Sodium and volume homeostasis Flashcards
Analyze the relationship between Na intake, plasma [Na], and plasma volume. describe how extracellular volume is sensed in the body.
- sodium is primary determinant of ECF and plasma blood volume since it is main cation in ECF
- If NaCl in body increases, plasma volume increases with no change in osmolality
- varying salt in diet affects plasma volume, high Na+ diet expands plasma volume but doesn’t change interstitial fluid volume or body weight
- ISF compartment can store Na non osmotically on negatively charged matrix molecules in skin and/or move into muscle in exchange for K+
- plasma volume sensed by stretch receptors
Describe sensors in renin angiotensin system. Summarize the major pathways that carry information to modulate renin release.
SENSORs
1. renal afferent arteriolar baroreceptors “myogenic”
-senses stretch
2. macula densa NKCC senses low [NaCl] “Macula densa transport”
3. extrarenal baroreceptors to CNS? increases SNS input to JGA “neurogenic”
These sensors induce renin release from JG cells
Localize renal granular cells that produce renin. What controls release of renin?
Juxtaglomerular apparatus: region consisting of macula densa, extraglomerular mesangium, and juxtaglomerular cells
- JG cells: specialized afferent arteriolar SMCs that make and store renin
- Renin is stored in granules in JG cells, released in response to increase in cAMP (from MD or SNS input) or decrease in cell [Ca2+] set off by less volume/stress
Compare and contrast the effects of AngII on vascular, endocrine, and renal targets.
- CV: systemic vasoconstriction of arterioles
- Endocrine
- increase ADH release, aldosterone, thirst - Renal
- regulation of GFR: constricts efferent arterioles and glomerular mesangial cells to help maintain GFR in face of decreased RBF
- increase Na+ transporter #s: NHE3, NKCC, NCC, and collecting duct (ENaC)
- aldosterone also amplifies previous by increasing NaCl reabsorption and K+,H+ secretion in distal tubule (NCC) and collection duct (ENaC)
Describe local RAS.
-activation can amplify Na+ reabsorption locally, without further systemic vasoconstriction
0may be good therapeutic target in HTN
Identify the location of aldosterone synthesis, and the factors that stimulate aldosterone synthesis and release.
- made in zona glomerulosa of adrenal gland
- synthesis stimulated by: increase AngII, increase plasma [K+], ACTH, low Na+ diet (indirectly)
- synthesis inhibited by: ANP
What is the mechanism of action of aldosterone. Explain the importance of both mineralocorticoid receptors and 11 B-OH steroid dehydrogenase for aldosterone action.
- mineralocorticoid receptors (MR_ are activated by steroid binding–>moves to nucleus, binds to DNA regulatory regions (MRE)–>alters transcription rates
- stimulates synthesis of serine/threonin kinase (Sgk), which acts on Na channels, causing less degradation of Na channels
- MR is also activated by glucocorticoids. Need 11 B-OH-SD to metabolize glucocorticodes to a form that doesn’t bind MR, otherwise will have MR saturation and increased aldosterone
ID the regions of the nephron where aldosterone acts. Explain the renal actions of aldosterone on Na, K, and H transport and excretion.
- distal tubule: activates NaCl co transporters
- CCD: increases apical and basolateral Na transporter activity–>increasing K+ and H+ secretion
- Na reabsorption drives secretion of K+ and H+ into lumen of collecting duct
- Sgk increase apical ENaC by decreased degradation and increased activation, increases pump activity also
- slower action: increases # of channels, Na/K ATPases, NCC by transcription
Summarize the renal responses to decreased ECF volume and the signals that trigger the responses.
- decreased ECF volume leads to:
- thirst, increased SNS, increased ADH, decreased ANP, increased Renin and therefore AngII
- AngII: increased NaCl reabsorption in PT, and in DT and CDD (also via aldosterone)–>decreased NaCl excretion
- AngII also increases thirst
- SNS activity also increases renin production
Describe where ANP is made, the stimulus that provides its secretion, and list the targets and actions of ANP.
-ANP made in atria and stored in atrial granules
-released in response to atrial stretch which increases cellular Ca2+ and stimulates fusion of vesicles and release of contents to blood
-it activates guanylate cyclase-> increased cGMP, which inhibits IMCD NaCl reabsorption via amiloride sensitive channels
TARGETS
1. CV: vasodilation
2. Endocrine: decreased renin, aldosterone, ADH
3. renal: increased GFR by decreased afferent arteriole resistance, and decreased Na reabsorption in IMCD
Summarize the renal responses to increased ECF volume and decrease the signals that trigger the response.
- decreased SNS, ADH, renin and AngII
- increased ANP
- leads to decreased NaCl reabsorption in PT, DT, CDD
- increased NaCl excretion
Why can’t ANP correct edema in CHF?
- ANP released due to increased atrial stretch from increased ECF volume
- not enough Na gets to IMCD for ANP to have diuretic effect
- anti-natriuretic hormones induced work to increase Na reabsorption along nephron before the IMCD
Signals that stimulate renin release
- Myogenic: decrease bp means less cell Ca, activates renin
- increase BP, stress and increase cell Ca inhibits Renin (via inhibition of AC5/6) - Decrease NaCl transport by MD
- due to decrease ECF vol. or decreased GFR
- signals to afferent arteriole via prostaglandins, increase cAMP–>release renin - Neurogenic
- decrease extrarenal baroreceptor stretch–>CNS–>increase sympathetic tone to afferent arteriole–>stimulates cAMP–>renin release - Metabolic: high glucose levels and renin release?
- Hormones: AngII via AT1R raises cell Ca2+ and inhibits renin release. ANP via cGMP inhibits renin release
