L8/9 Regulation of Body Fluid Osmolality and Volume Flashcards

1
Q

Normal plasma osmolality is ____________________, variation in either direction of _____________________ => operation of the body’s osmolality regulating mechanism

A

Normal plasma osmolality is 280-290mOsm/kg H2O, variation in either direction of ~3mOsm/kg H2O => operation of the body’s osmolality regulating mechanism

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2
Q

What regulates the Osmolality of Body Fluids?

A

Osmolality of plasma detected by osmoreceptors in supraoptic and paraventricular areas of the anterior hypothalamus=> regulate the release of ADH by posterior pituitary into the bloodstream

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3
Q

ADH is synthesized in the _____________________

Precursor is transported from the hypothalamus to the ________________within nerve fibers and is cleaved to a nonapeptide (9 aa) as it moves down the axons

In nerve terminals, ADH stored as insoluble complexes in _________________

A

ADH is synthesized in the hypothalamus (supraoptic nucleus)

Precursor is transported from the hypothalamus to the posterior pituitary within nerve fibers and is cleaved to a nonapeptide (9 aa) as it moves down the axons

In nerve terminals, ADH stored as insoluble complexes in secretory granules

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4
Q

When plasma is hyperosmolar ADH released from posterior pituitary binds to ______ receptors on _____________ cells of the collecting duct resulting in increased water reabsorption and excretion of concentrated urine:

○ Binding of _______ by ADH => shuttling of water channels (________) into and out of the apical membrane (____________ are persistently present on basolateral)

○ Further aided by the hyperosmolar gradient in the medullary interstitium (established by thick ascending limb and ADH)

A

When plasma is hyperosmolar ADH released from posterior pituitary binds to V2 receptors on principal cells of the collecting duct resulting in increased water reabsorption and excretion of concentrated urine:

○ Binding of V2 by ADH => shuttling of water channels (AQP2) into and out of the apical membrane (AQP3/4 are persistently present on basolateral)

○ Further aided by hyperosmolar gradient in the medullary interstitium (established by thick ascending limb and ADH)

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5
Q

How is the volume & pressure of the vascular system assessed?

A

Baroreceptors: Neuronal endings sensitive to stretch or distortion produced by arterial blood pressure changes, receptors located in both the low-pressure (left atrium and large pulmonary vessels) and the high-pressure (aortic arch and carotid sinus) sides of the circulatory system

Intrarenal baroreceptors: Pressure sensitive juxtaglomerular cells of afferent arterioles, which respond to decreased renal arterial pressure by secreting more renin

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6
Q

Under conditions due predominantly to water gain or loss, the sensory receptors that initiate the reflexes controlling ADH secretion are _________________

A

Under conditions due predominantly to water gain or loss, the sensory receptors that initiate the reflexes controlling ADH secretion are osmoreceptors

Osmoreceptors only require ~ 1% change while a 5% to 10% decrease in blood volume or pressure is required before ADH secretion is stimulated by baroreceptors

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7
Q

Baroreceptor control of ADH secretion?

A

Baroreceptors decrease their rate of firing in response to decrease in blood volume (5%-10%) leading to increased release of ADH (inverse relationship)
=> Elevated ADH increases the permeability of the collecting ducts
=> Water retained to help stabilize the extracellular volume

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8
Q

Priority of Kidneys facing circulatory collapse?

A

Haemorrhage increases ADH release via volume receptor (baroreceptors) response, so that water is retained (osmoregulation subordinated to volume regulation)

When faced with circulatory collapse, kidneys will continue to conserve water, even though by doing so they reduce body fluid osmolality (Reduces Set Point for ADH Secretion)

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9
Q

Differenced between Osmoreceptor and Baroreceptor ADH regulation?

A
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10
Q

Pituitary gland unable to secrete ADH

A

Central Diabetes Insipidus

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11
Q

Collecting ducts unable to respond to ADH due to V2 receptor mutation

A

Nephrogenic Diabetes Insipidus

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12
Q

Plasma ADH levels elevated above expected for body fluid osmolality, blood volume & pressure i.e.usually due to small tumors (i.e.lung oat cell carcinoma) producing ADH

A

Syndrome of Inappropriate ADH Secretion (SIADH)

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13
Q

Malfunctions of the ADH System?

A

Central Diabetes Insipidus: Pituitary gland unable to secrete ADH

Nephrogenic Diabetes Insipidus: Collecting ducts unable to respond to ADH due to V2 receptor mutation

Syndrome of Inappropriate ADH Secretion (SIADH): plasma ADH levels elevated above expected usually due to small tumors (i.e.lung oat cell carcinoma) producing ADH

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14
Q

ADH versus Thirst Thresholds?

A

ADH set point is 285 mOsm, thirst threshold is 295 mOsm so thirst is stimulated at fluid osmolality at which secretion of ADH is already maximal

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15
Q

__________________ denotes the volume of pure (solute-free) water that must be removed from, or added to, the flow of urine (in ml/min) to make it iso-osmotic with plasma.

How is it calculated?

Positive= __________ urine
Negative = ________ urine
Zero = ____________ urine

A

Free water clearance (CH2O) denotes the volume of pure (solute-free) water that must be removed from, or added to, the flow of urine (in ml/min) to make it iso-osmotic with plasma.

Free Water Clearance (CH2O) = Urine Flow Rate - (Urine Flow Rate (Urine Osmolality/ Plasma Osmolality)

Positive CH2O= hypotonic urine
Negative CH2O = hypertonic urine
Zero CH2O = Urine iso-osmotic w/ plasma

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16
Q

What determines the rate of activity of hypothalamic cells regulating ADH secretion from the Posterior Pituitary?

A

The rate of activity of hypothalamic cells is determined by the total synaptic input of Ossmorecepotrs + Baroreceptors however Baroreceptor influence predominates when changes in plasma volume are large

17
Q

How is Na+ Ballance Regulated?

A
  • Renal Sympathetic Nerves - Increases Reabsorption
  • RAAS - Increases Reabsorption
  • Natriuretic Peptides (ANP)- Increases Excretion
18
Q

Regulation of Blood Pressure in response to changes in arterial pressure?

Fast (Seconds): __________________

Intermediate (Minutes to Hours): ____________________

Slow (Hours to days): ________________________

A

Fast (Seconds): **Baroreceptor Reflex **

Intermediate (Minutes to Hours): Renal Actions (Peripheral Resistance)

Slow (Hours to days): Prolonged Renal Actions (Excretion of Salt/Water)

19
Q

What are the results of RAAS Activation?

A
  1. increase in blood pressure
  2. decrease in salt and water excretion by the kidneys
20
Q

Redundant Mechanisms Regulating Renin Release in response to Hemorrhage?

A

Afferent Arteriolar Baroreceptor Response: The JGA of Kidneys contain pressure-sensitive cells called granular cells (intrarenal baroreceptors) where Renin is synthesized and stored. Wall tension (and its rate of change i.e. the pulse pressure) at the granular cells regulates the release of renin (decreased renal perfusion pressure leads to increased RENIN RELEASE)

Sympathetic Nerves on Afferent Arteriols of JGA: Blood Volume contraction is detected by Arterial/Cardiopulmonary Baroreceptors which send afferent neural information to the brainstem vasomotor center => increases renal sympathetic nerve activity and adrenal secretion of epinephrine and norepinephrine => RENIN RELEASE

Alterations in the delivery of NaCl to the Macula Densa: Decreased renal perfusion results in a lower GFR and decreased filtered load of NaCl => Reduced uptake of NaCl across MD cells via NKCC2 channel=> decreased [ATP] and [Adenosine (ADO)] which OPOSE Renin release => DECREASE in [Ca2+] in granular cells => Increased RENIN RELEASE

21
Q

RAAS Pathway and its effects?

Renin released by _______________ (intrarenal baroreceptors) of the JGA in response to __________,__________, or ________=> Renin cleaves Angiotensinogen (Liver) to ANGI => ACE cleaves ANGI to ANG II

ANGII goes on to:

  • ___________________________
  • ___________________________
A

Renin released by Granular Cells (intrarenal baroreceptors) of the JGA in response to Low BP/Sympathetic Innervation/Decreased NaCl=> Renin cleaves Angiotensinogen (Liver) to ANGI => ACE cleaves ANGI to ANG II

ANGII goes on to:

  • Bind AT1 receptors => arterial/venous vasoconstriction => diastolic/systolic increases
  • Stimulates the adrenal cortex to produce aldosterone (Binds principal cells of cortical collecting tubule enhancing Na+ reabsorption and K secretion)
22
Q

Aldosterone enhances Na+ __________ and K ___________

Aldosterone freely crosses cell membranes and binds mineral corticoid receptors within the ____________ Cells of cortical collecting tubule=> > nucleus acts as a transcription factor that promotes gene expression and synthesis of:

  • _______________________________ in Basal Membrane
  • _______________________________ in Apical Membrane
  • _______________________________
A

Aldosterone enhances Na+ reabsorption and K+ secretion

Aldosterone freely crosses cell membranes and binds mineral corticoid receptors within the Principal Cells of cortical collecting tubule=> > nucleus acts as a transcription factor that promotes gene expression and synthesis of:

  • Na+-K+-ATPase pumps & K+ channels in Basal Membrane
  • ENaC channels (Na+) & K+ channels in Apical Membrane
  • SGK1 which further increases expression of ENaC in the Apical Membrane and activates K+ channels
23
Q

Role of Sympathetic Nerve Activity in response to severe hemorrhage??

  • Blood Volume contraction is detected by __________________ which send afferents to brainstem vasomotor center => Increased renal sympathetic nerve activity and adrenal secretion of epinephrine/norepinephrine
  • Neural signals originating in the vasomotor center reach _______________________________________ via renal sympathetic nerve fibers => renin release
  • _______________ also express _______________ receptors and stimulation of these receptors by epinephrine/ norepinephrine => renin release
A
  • Blood Volume contraction is detected by Arterial/Cardiopulmonary Baroreceptors which send afferents to brainstem vasomotor center => Increased renal sympathetic nerve activity and adrenal secretion of epinephrine/norepinephrine
  • Neural signals originating in the vasomotor center reach Granular Cells (intrarenal baroreceptors) via renal sympathetic nerve fibers => renin release
  • Granular cells also express β1 adrenergic receptors and stimulation of these receptors by epinephrine/ norepinephrine => renin release
24
Q

Fine-tuning of Na+ excretion achieved by controlling plasma concentration of __________

Absence =>___________ excreted

MAXIMAL plasma concentration => ______________excreted

A

Fine-tuning of Na+ excretion achieved by controlling plasma concentration of Aldosterone

Absence => ONLY ~3% of the filtered Na+ load excreted

MAXIMAL plasma concentration => NO Na+ excreted

25
Q

__________________ is the component of the ECF which is perfusing the tissues

A

Effective Circulating Volume (ECV) is the component of the ECF which is perfusing the tissues

26
Q

Factors that determine how much aldosterone is released?

A
  • RAAS =>ANGII binding Adrenal Cortex => INCREASED aldosterone
  • INCREASED plasma [K+] (small)=> INCREASED aldosterone (Aldosterone stimulates the production of SGK1 which further increases expression of ENaC in the Apical Membrane and activates K+ channels => increased K+ secretion)
  • DECREASED plasma [Na+] => INCREASED aldosterone (upregulates ENAC to increase Na+ Reabsorprtion)
27
Q

All Functions of ANGII? (7)

A
  1. Stimulates Aldosterone release from Adrenal Cortex => Aldosterone enhances Na+ reabsorption and K+ secretion in the principal cells of the cortical collecting tubules
  2. Binding of AT1 receptors by ANGII => arterial/venous vasoconstriction
  3. Stimulates PCT NaCl absorption (Na+/H+ Exchange (NHE3))
  4. Low ANG2 constricts renal EFFERENT arterioles (increases/maintaining) GFR
  5. High ANG2 constricts glomerular mesangial cells => reduces GFR
  6. Hypothalamus => increased thirst
  7. Increases secretion of ADH in the posterior pituitary
  • Retains water in the body (V2 receptors)
  • Potent vasoconstrictor (V1 receptors)
28
Q

The action of aldosterone is blocked by the diuretic drug ________________

A

The action of aldosterone is blocked by the diuretic drug Spironolactone

29
Q

Role of Natriuretic Peptides? (5)

A

The actions of NPs (ANP, BNP) antagonize the RAAS system (Increase Na+ excretion by increasing GFR and reducing Na+ reabsorption):

  1. Vasodilation of afferent and vasoconstriction of efferent arterioles of glomerulus => Increased GFR
  2. Inhibition of renin secretion by granular cells
  3. Inhibition of aldosterone secretion
  4. Inhibition of NaCl reabsorption by principal cells of the collecting duct (also caused by reduced levels of aldosterone)
  5. Inhibition of ADH secretion by the posterior pituitary and ADH action on the collecting duct
30
Q

What triggers the release of Natriuretic peptides? From where?

A

Cardiac stretch receptors monitor central volume and release natriuretic peptides when distended:

  • Atrial myocytes –Atrial Natriuretic Peptide (ANP)
  • Ventricular myocytes –Brain Natriuretic Peptide (BNP)
31
Q

Low ANGII preferentially constricts renal _______ arterioles thus increasing (maintaining) GFR

A

Low ANG2 preferentially constricts renal EFFERENT arterioles thus increasing (maintaining) GFR

32
Q

What determines long-term regulation of Blood Pressure?

A

Regulation of Na+ content is the ultimate determinant of blood pressure, via control of ECF volume which is dependent on the actions of Aldosterone

33
Q

Mechanisms that Stimulate Na+ Reabsorption?

A

RAAS
ADH
Sympathetic Nervous System