Week 1: Sodium and volume homeostasis Flashcards

1
Q

Analyze the relationship between Na intake, plasma [Na], and plasma volume. describe how extracellular volume is sensed in the body.

A
  • 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
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2
Q

Describe sensors in renin angiotensin system. Summarize the major pathways that carry information to modulate renin release.

A

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

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3
Q

Localize renal granular cells that produce renin. What controls release of renin?

A

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
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4
Q

Compare and contrast the effects of AngII on vascular, endocrine, and renal targets.

A
  1. CV: systemic vasoconstriction of arterioles
  2. Endocrine
    - increase ADH release, aldosterone, thirst
  3. 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)
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5
Q

Describe local RAS.

A

-activation can amplify Na+ reabsorption locally, without further systemic vasoconstriction
0may be good therapeutic target in HTN

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6
Q

Identify the location of aldosterone synthesis, and the factors that stimulate aldosterone synthesis and release.

A
  • made in zona glomerulosa of adrenal gland
  • synthesis stimulated by: increase AngII, increase plasma [K+], ACTH, low Na+ diet (indirectly)
  • synthesis inhibited by: ANP
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7
Q

What is the mechanism of action of aldosterone. Explain the importance of both mineralocorticoid receptors and 11 B-OH steroid dehydrogenase for aldosterone action.

A
  • 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
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8
Q

ID the regions of the nephron where aldosterone acts. Explain the renal actions of aldosterone on Na, K, and H transport and excretion.

A
  • 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
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9
Q

Summarize the renal responses to decreased ECF volume and the signals that trigger the responses.

A
  • 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
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10
Q

Describe where ANP is made, the stimulus that provides its secretion, and list the targets and actions of ANP.

A

-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

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11
Q

Summarize the renal responses to increased ECF volume and decrease the signals that trigger the response.

A
  • decreased SNS, ADH, renin and AngII
  • increased ANP
  • leads to decreased NaCl reabsorption in PT, DT, CDD
  • increased NaCl excretion
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12
Q

Why can’t ANP correct edema in CHF?

A
  • 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
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13
Q

Signals that stimulate renin release

A
  1. Myogenic: decrease bp means less cell Ca, activates renin
    - increase BP, stress and increase cell Ca inhibits Renin (via inhibition of AC5/6)
  2. Decrease NaCl transport by MD
    - due to decrease ECF vol. or decreased GFR
    - signals to afferent arteriole via prostaglandins, increase cAMP–>release renin
  3. Neurogenic
    - decrease extrarenal baroreceptor stretch–>CNS–>increase sympathetic tone to afferent arteriole–>stimulates cAMP–>renin release
  4. Metabolic: high glucose levels and renin release?
  5. Hormones: AngII via AT1R raises cell Ca2+ and inhibits renin release. ANP via cGMP inhibits renin release
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