70: Extracellular Fluid Volume

Question 1

SENSORS:

• Osmolarity: _______ Osmoreceptors
• Volume (receptors sense _____): Carotid ____, Aortic _____, Renal _____ Arteriole, Atria.

Answer 1

SENSORS:

• Osmolarity: Hypothalamic Osmoreceptors
• Volume (receptors sense stretch): Carotid Sinus, Aortic Arch, Renal Afferent Arteriole, Atria.

Question 2

EFFERENT (correcting) PATHWAYS:

_____: ADH/AVP, Thirst

_____: Renin-Angiotensin-Aldosterone, Sympathetic NS, ADH/AVP, Atrial Natriuretic Peptide (ANP).

ANP is released from the ____ that increases naturesis.

Natriuresis is the process of ____ of sodium in the urine via action of the kidney.

Answer 2

EFFERENT (correcting) PATHWAYS:

Osmolarity: ADH/AVP, Thirst

Volume: Renin-Angiotensin-Aldosterone, Sympathetic NS, ADH/AVP, Atrial Natriuretic Peptide (ANP).

ANP is released from the atria that increases naturesis.

Natriuresis is the process of excretion of sodium in the urine via action of the kidney.

Question 3

EFFECTORS:

______: Kidney, Brain (thirst)

_____:

1) _____ term: Heart (change in cardiac output), Blood Vessels (increase TPR)
2) ____ term: Kidney (not as fast of a response via increasing and decreasing the exrection of sodium and water).

Answer 3

EFFECTORS:

Osmolarity: Kidney, Brain (thirst)

Volume:

1) Short term: Heart (change in cardiac output), Blood Vessels (increase TPR)
2) Long term: Kidney (not as fast of a response via increasing and decreasing the exrection of sodium and water).

Question 4

REGULATED PARAMETERS:

_____: Renal Free Water Excretion, Water consumption

Volume:

1) _____ Term: Blood Pressure = R x CO
2) _____ Term: Renal Sodium Excretion

Answer 4

REGULATED PARAMETERS:

Osmolarity: Renal Free Water Excretion, Water consumption

Volume:

1) Short Term: Blood Pressure = R x CO
2) Long Term: Renal Sodium Excretion

Question 5

The total amount (Moles) of sodium in the ECF determines the ECF _____ (& body weight via water retention). More sodium in the ECF results in a ____ ECF volume (volume expansion) and less sodium in the ECF results in a smaller ECF volume (volume contraction).

An abrupt increase in Na consumption is absorbed into the circulation and causes an initial increase in plasma osmolarity, which induces an increase release of _____into the circulation. Increased circulating levels of ADH/AVP induce ____ and increased consumption of water as well as increased _____ of water in excess of solutes (free water) in the kidney.

This dilutes and ____ the plasma osmolarity toward a value of 280 mOsm/L and also increases the plasma volume. Recall, the total amount (Moles) of sodium in the ECF determines the ECF volume. More sodium in the ECF results in a larger ECF volume (volume expansion). The increase in plasma volume is more slowly ____ over time by a gradual decrease in renal Na reabsorption and an increase in Na excretion.

Answer 5

The total amount (Moles) of sodium in the ECF determines the ECF volume (& body weight via water retention). More sodium in the ECF results in a larger ECF volume (volume expansion) and less sodium in the ECF results in a smaller ECF volume (volume contraction).

An abrupt increase in Na consumption is absorbed into the circulation and causes an initial increase in plasma osmolarity, which induces an increase release of ADH/AVP into the circulation. Increased circulating levels of ADH/AVP induce thirst and increased consumption of water as well as increased absorption of water in excess of solutes (free water) in the kidney.

This dilutes and reduces the plasma osmolarity toward a value of 280 mOsm/L and also increases the plasma volume. Recall, the total amount (Moles) of sodium in the ECF determines the ECF volume. More sodium in the ECF results in a larger ECF volume (volume expansion). The increase in plasma volume is more slowly reduced over time by a gradual decrease in renal Na reabsorption and an increase in Na excretion.

Question 6

An abrupt decrease in Na consumption, where Na excretion exceeds Na consumption, will result in an initial decrease in plasma osmolarity, which _____ and decreases release of ADH/AVP into the circulation. Decreased circulating levels of ADH/AVP decreases thirst and the consumption of water as well as decreases absorption of water in excess of solutes (free water) in the kidney. This concentrates and increases the plasma osmolarity toward a value of ____ mOsm/L and also _____ the plasma volume. Recall, the total amount (Moles) of sodium in the ECF determines the ECF volume. Less sodium in the ECF results in a smaller ECF volume (volume _____). The decrease in plasma volume is more slowly increased over time by a gradual regulatory ____ in renal Na reabsorption and decreased Na excretion.

With age, the physiological burden of “off loading” excess Na consumed becomes increasingly more difficult and is a contributing factor to the increasingly greater prevalence of ______ in the aged population.

Answer 6

An abrupt decrease in Na consumption, where Na excretion exceeds Na consumption, will result in an initial decrease in plasma osmolarity, which inhibits and decreases release of ADH/AVP into the circulation. Decreased circulating levels of ADH/AVP decreases thirst and the consumption of water as well as decreases absorption of water in excess of solutes (free water) in the kidney. This concentrates and increases the plasma osmolarity toward a value of 280 mOsm/L and also decreases the plasma volume. Recall, the total amount (Moles) of sodium in the ECF determines the ECF volume. Less sodium in the ECF results in a smaller ECF volume (volume contraction). The decrease in plasma volume is more slowly increased over time by a gradual regulatory increase in renal Na reabsorption and decreased Na excretion.

With age, the physiological burden of “off loading” excess Na consumed becomes increasingly more difficult and is a contributing factor to the increasingly greater prevalence of hypertension in the aged population.

Question 7

In response to ECF volume expansion, the kidney _____ the urinary output of sodium and water by decreasing the magnitude of sodium and water reabsorption from the tubular fluid along the nephron, _____ a change in the GFR. In response to ECF volume contraction, the kidney _____ the urinary output of sodium and water from tubular fluid by increasing the magnitude of sodium and water reabsorption in the _____ (predominant) and _____ (subordinate) segments of the nephron. Severe ECF volume contraction (hemorhage) will also induce a _____ in GFR.

The relation of dietary intake of sodium to urinary output of sodium, or sodium balance, is so well-regulated in healthy patients that sodium output in the urine _____ dietary intake. In response to an increase or decrease in dietary sodium intake, the kidneys will respond by decreasing or increasing the magnitude of sodium reabsorption over a period of several days until a higher or lower level of urinary sodium output is achieved. The result is a sodium balance, but at a higher or lower and essentially _____ level of sodium input and output.

Answer 7

In response to ECF volume expansion, the kidney increases the urinary output of sodium and water by decreasing the magnitude of sodium and water reabsorption from the tubular fluid along the nephron, without a change in the GFR. In response to ECF volume contraction, the kidney decreases the urinary output of sodium and water from tubular fluid by increasing the magnitude of sodium and water reabsorption in the proximal (predominant) and distal (subordinate) segments of the nephron. Severe ECF volume contraction (hemorhage) will also induce a decrease in GFR.

The relation of dietary intake of sodium to urinary output of sodium, or sodium balance, is so well-regulated in healthy patients that sodium output in the urine closely matches dietary intake. In response to an increase or decrease in dietary sodium intake, the kidneys will respond by decreasing or increasing the magnitude of sodium reabsorption over a period of several days until a higher or lower level of urinary sodium output is achieved. The result is a sodium balance, but at a higher or lower and essentially equivalent level of sodium input and output.

Question 8

THE KIDNEYS INCREASE Na+ EXCRETION IN RESPONSE TO AN ______ IN ECF VOLUME.

Answer 8

THE KIDNEYS INCREASE Na+ EXCRETION IN RESPONSE TO AN INCREASE IN ECF VOLUME.

Question 9

An acute increase in Na(Cl) consumption will result in an acute increase in ECF volume as indicated by an _____ in weight. The positive Na balance effectively increases the amount of Na(Cl) in the ECF, resulting in an ____smotic expansion of the ECF volume. The kidneys respond by _____ Na excretion, measured as urine [Na] x urine flow. The increase in Na excretion results from a _______ in Na reabsorption in one or more segments of the nephron. The increase in sodium excretion occurs in a volume urine necessary to excrete the excess Na ___osmotically, effectively taking an excess of ___osmotic volume from the ECF and excreting it into the urine.

The converse also occurs in negative Na balance resulting from an acute decrease Na(Cl) consumption. In this instance, an acute decrease in ECF volume will be indicated by a ______ in weight. The negative Na balance effectively decreases the amount of Na(Cl) in the ECF, resulting in an ______ osmotic contraction of the ECF volume. The kidneys respond by ______ Na excretion, measured as urine [Na] x urine flow. The decrease in Na excretion results from an ______ in Na reabsorption in one or more segments of the nephron. The increase in sodium reabsorption and an associated proportionate ______ in tubular fluid reabsorption effectively limits a further reduction in plasma volume by returning an increased volume of ______ osmotic tubular fluid to the plasma.

Kidney brings ecf volume back to normal by decreasing water and sodium in ______ proportions.

Answer 9

An acute increase in Na(Cl) consumption will result in an acute increase in ECF volume as indicated by an increase in weight. The positive Na balance effectively increases the amount of Na(Cl) in the ECF, resulting in an isosmotic expansion of the ECF volume. The kidneys respond by increasing Na excretion, measured as urine [Na] x urine flow. The increase in Na excretion results from a decrease in Na reabsorption in one or more segments of the nephron. The increase in sodium excretion occurs in a volume urine necessary to excrete the excess Na isosmotically, effectively taking an excess of isosmotic volume from the ECF and excreting it into the urine.

The converse also occurs in negative Na balance resulting from an acute decrease Na(Cl) consumption. In this instance, an acute decrease in ECF volume will be indicated by a decrease in weight. The negative Na balance effectively decreases the amount of Na(Cl) in the ECF, resulting in an isosmotic contraction of the ECF volume. The kidneys respond by decreasing Na excretion, measured as urine [Na] x urine flow. The decrease in Na excretion results from an increase in Na reabsorption in one or more segments of the nephron. The increase in sodium reabsorption and an associated proportionate increase in tubular fluid reabsorption effectively limits a further reduction in plasma volume by returning an increased volume of isosmotic tubular fluid to the plasma.

Kidney brings ecf volume back to normal by decreasing water and sodium in equal proportions.

Question 10

Diuretic drugs decrease plasma volume by “forcing” the kidney to ______ excretion of sodium and water in the urine. This ______ hydrostatic pressure in the capillaries and increases oncotic pressure in the capillaries, which favors absorption of edematous fluid in the extravascular (interstitial) space back into the intravascular space.

Answer 10

Diuretic drugs decrease plasma volume by “forcing” the kidney to increase excretion of sodium and water in the urine. This decreases hydrostatic pressure in the capillaries and increases oncotic pressure in the capillaries, which favors absorption of edematous fluid in the extravascular (interstitial) space back into the intravascular space.

Question 11

Edema is an excess accumulation of fluid in the ______ space due to cardiac, renal, hepatic or endocrine dysfunction. Edema results from an imbalance of hydrostatic and oncotic pressures across the capillary wall, which induces a shift in fluid distribution from the intravascular to the ______ space resulting in isotonic retention of sodium and water as well as ______ effective circulating volume. A decreased circulating volume ______ renal perfusion pressure and activates the renin-angiotensin-aldosterone system, which further ______ sodium retention and edema.

Answer 11

Edema is an excess accumulation of fluid in the interstitial space due to cardiac, renal, hepatic or endocrine dysfunction. Edema results from an imbalance of hydrostatic and oncotic pressures across the capillary wall, which induces a shift in fluid distribution from the intravascular to the extravascular space resulting in isotonic retention of sodium and water as well as decreased effective circulating volume. A decreased circulating volume decreases renal perfusion pressure and activates the renin-angiotensin-aldosterone system, which further increases sodium retention and edema.

Question 12

Changes in the effective circulating volume, not the total ECF volume, induce regulation of sodium ______.

The effective circulating volume is a functional, not an anatomical, blood volume reflecting the extent of tissue/organ perfusion where blood pressure is sensed.

The effective circulating volume normally ______ the total ECF volume, both intra- and extravascular volumes.

The effective circulating volume may be ______ than total ECF volume in disease states such as congestive heart failure or other pathophysiologies causing edema.

Answer 12

Changes in the effective circulating volume, not the total ECF volume, induce regulation of sodium excretion.

The effective circulating volume is a functional, not an anatomical, blood volume reflecting the extent of tissue/organ perfusion where blood pressure is sensed.

The effective circulating volume normally parallels the total ECF volume, both intra- and extravascular volumes.

The effective circulating volume may be less than total ECF volume in disease states such as congestive heart failure or other pathophysiologies causing edema.

Question 13

ECF volume baroreceptors:

“CENTRAL” VASCULAR Baroreceptors

_____ Pressure (very important): Atria & Pulmonary vasculature

_____ Pressure (less important): Carotid Sinus, Aortic arch, & Juxtaglomerular Apparatus (renal afferent arteriole)

SENSORS IN THE CNS (less important)

SENSORS IN THE LIVER (less important)

Answer 13

ECF volume baroreceptors:

“CENTRAL” VASCULAR Baroreceptors

Low Pressure (very important): Atria & Pulmonary vasculature

High Pressure (less important): Carotid Sinus, Aortic arch, & Juxtaglomerular Apparatus (renal afferent arteriole)

SENSORS IN THE CNS (less important)

SENSORS IN THE LIVER (less important)

No “sensor” exists which directly senses change in vascular volume. Rather, because of the interdependent relationship of vascular volume to vascular pressure, where a decrease or increase in volume results in a decrease and increase in vascular pressure, intravascular pressure serves as a surrogate measure of intravascular volume as well as the ECF volume.

Question 14

Shock = extreme ____perfusion

Answer 14

Shock = extreme hypoperfusion

Question 15

Renin-angiotensin-aldosterone (RAA) hormonal system:

Angiotensinogen, the substrate of the enzyme ____, is synthesized by the liver and released into the systemic circulation.

Renin is synthesized and stored in granular cells of the ____ apparatus (JGA) of the kidney. Decreased effective circulating volume ____ renin release by the JGA. Renin is a protease that converts angiotensinogen to angiotensin___.

Angiotensin I is converted to Angiotensin II (ANG II) by ____. ACE is located on the luminal surface of vascular endothelium throughout the body, and is abundant in the vasculature of the ____ and also present in the vasculature of the ____.

The most important factor controlling ANG II levels in the plasma is ____ release from the granular cells of the JGA.

Sodium retention is promoted by the actions of Angiotensin ____ as well as Aldosterone.

A. angiotensin II promotes sodium retention by stimulating Na/H exchange in ____ tubule cells

B. angiotensin II ____ renal plasma flow, which promotes increased Na reabsorption

C. Aldosterone induces an increase in sodium reabsorption by the late ____ tubule and early ____ duct

Angiotensinogen (Renin) -> Ang ____ (ACE) -> ANG ____ -> Adrenal releases Aldoseterone -> Aldosterone ____ sodium reabsorption -> ____ sodium excretion -> ____ in BP due to H2O retention

Answer 15

Renin-angiotensin-aldosterone (RAA) hormonal system:

Angiotensinogen, the substrate of the enzyme renin, is synthesized by the liver and released into the systemic circulation.

Renin is synthesized and stored in granular cells of the juxtaglomerular apparatus (JGA) of the kidney. Decreased effective circulating volume increases renin release by the JGA. Renin is a protease that converts angiotensinogen to angiotensin I.

Angiotensin I is converted to Angiotensin II (ANG II) by angiotensin converting enzyme (ACE). ACE is located on the luminal surface of vascular endothelium throughout the body, and is abundant in the vasculature of the lungs and also present in the vasculature of the kidney.

The most important factor controlling ANG II levels in the plasma is renin release from the granular cells of the JGA.

Sodium retention is promoted by the actions of Angiotensin II as well as Aldosterone.

A. angiotensin II promotes sodium retention by stimulating Na/H exchange in proximal tubule cells

B. angiotensin II decreases renal plasma flow, which promotes increased Na reabsorption

C. Aldosterone induces an increase in sodium reabsorption by the late distal tubule and early collecting duct

Angiotensinogen (Renin) -> Ang 1 (ACE) -> ANG 2 -> Adrenal releases Aldoseterone -> Aldosterone increases sodium reabsorption -> decreased sodium excretion -> increase in BP due to H2O retention

Question 16

____ renal sympathetic nerve activity (SNS) induces renal vasoconstriction and increased Na reabsorption which reduces renal sodium excretion.

Answer 16

Increased renal sympathetic nerve activity (SNS) induces renal vasoconstriction and increased Na reabsorption which reduces renal sodium excretion.

Question 17

The posterior pituitary releases ADH/AVP which ____ water reabsorption.

Answer 17

The posterior pituitary releases ADH/AVP which promotes water reabsorption.

Question 18

Reduced ECF volume also ____ the release of atrial natriuretic peptide (ANP) which reduces sodium excretion.

ANP is a peptide hormone secreted by the cardiac ____ that in pharmacological doses promotes salt and water ____ and lowers blood pressure. ANP has exactly the opposite function of the ____.

Answer 18

Reduced ECF volume also decreases the release of atrial natriuretic peptide (ANP) which reduces sodium excretion.

ANP is a peptide hormone secreted by the cardiac atria that in pharmacological doses promotes salt and water excretion and lowers blood pressure. ANP has exactly the opposite function of the aldosterone.

Question 19

Three Renal Mechanisms Regulating Renin Release:

1. local renal baroreceptors in ____ arterioles respond to ____ pressure and increase secretion of renin by granular cells
2. ____ systemic arterial blood pressure stimulates baroreceptor reflex, which causes ____ sympathetic drive to JGA, increasing the secretion of renin
3. cells of ____ sense tubular fluid sodium concentration and, if ____, cause increased release of renin from granular/juxtaglomerular cells into the afferent arteriole blood supply

Answer 19

Three Renal Mechanisms Regulating Renin Release:

1. local renal baroreceptors in afferent arterioles respond to low pressure and increase secretion of renin by granular cells
2. decreased systemic arterial blood pressure stimulates baroreceptor reflex, which causes increased sympathetic drive to JGA, increasing the secretion of renin
3. cells of macula densa sense tubular fluid sodium concentration and, if low, cause increased release of renin from granular/juxtaglomerular cells into the afferent arteriole blood supply

Question 20

ANGIOTENSIN II Induces aldosterone release from the adrenal cortex

Acts on the hypothalamus to:

1) ____ thirst
2) Induces release of ____ from posterior pituitary

ANGIOTENSIN II Vaso ____ renal and other systemic vessels. In kidney, ____ the efferent more than the afferent arterioles, which increases GFR and the amount of sodium to the macula densa

ANGIOTENSIN II increases Starling forces favoring ____ of tubular fluid by peritubular capillaries

ANGIOTENSIN II Enhances Na/H exchange in the ____ tubule, which increases sodium reabsorption

ANGIOTENSIN II Induces ____ of renal tubule cells

Answer 20

dANGIOTENSIN II Induces aldosterone release from the adrenal cortex

Acts on the hypothalamus to:

1) increase thirst
2) Induces release of ADH/AVP from posterior pituitary

ANGIOTENSIN II Vasoconstricts renal and other systemic vessels. In kidney, constricts the efferent more than the afferent arterioles, which increases GFR and the amount of sodium to the macula densa

ANGIOTENSIN II increases Starling forces favoring reabsorption of tubular fluid by peritubular capillaries

ANGIOTENSIN II Enhances Na/H exchange in the proximal tubule, which increases sodium reabsorption

ANGIOTENSIN II Induces hypertrophy of renal tubule cells

Question 21

ALDOSTERONE is a mineralocorticoid secreted into circulation by the adrenal ____

ALDOSTERONE is the PRIMARY ____ term regulator of salt balance and extracellular fluid volume, and therefore, blood pressure

ALDOSTERONE acts on kidney tubules to increase the ____ of Na+ as well as water. Aldosterone increases sodium & then ADH ____ water so these 2 work together.

ALDOSTERONE acts on the ____ nephron to increase the secretion and excretion of K+

ALDOSTERONE Induces increased Na reabsorption by “principal cells” in the late ____ tubule and early ____ duct in the renal cortex.

Increased Na reabsorption results from an induced increase in Na transporter expression:

• ____ basolateral membrane Na+/K+-pumps
• ____ apical membrane Na+ channels
• ____ mitochondrial enzymes (ATP)

Solute reabsorption in cortical nephron segments is rapidly returned to the general circulation and does ____ participate in the counter current multiplication of the cortico-medullary solute concentration gradient.

Answer 21

ALDOSTERONE is a mineralocorticoid secreted into circulation by the adrenal cortex

ALDOSTERONE is the PRIMARY long term regulator of salt balance and extracellular fluid volume, and therefore, blood pressure

ALDOSTERONE acts on kidney tubules to increase the reabsorption of Na+ as well as water. Aldosterone increases sodium & then ADH increases water so these 2 work together.

ALDOSTERONE acts on the distal nephron to increase the secretion and excretion of K+

ALDOSTERONE Induces increased Na reabsorption by “principal cells” in the late distal tubule and early collecting duct in the renal cortex.

Increased Na reabsorption results from an induced increase in Na transporter expression:

	- increased basolateral membrane Na+/K+-pumps
 		- increased apical membrane Na+ channels
  		- increased mitochondrial enzymes (ATP)

Solute reabsorption in cortical nephron segments is rapidly returned to the general circulation and does not participate in the counter current multiplication of the cortico-medullary solute concentration gradient.

Question 22

ALDOSTERONE ACTS ON ____ CONVOLUTED TUBULE AND CORTICAL ____ TUBULE.

Answer 22

ALDOSTERONE ACTS ON DISTAL CONVOLUTED TUBULE AND CORTICAL COLLECTING TUBULE.

Question 23

Excretion = ____ - ____ + ____.

Sodium is never ____. There is too ____ sodium in the western diet. Our tubules can ____ potassium, but not sodium. Our MAIN way of decreasing sodium is to ____ reabsorption. We eat sodium a hell of a lot ____ than we can excrete it. Sodium increases your blood pressure like crazy in a quick amount of time and makes you ____. Angiotensin receptor blocker treats ____.

Importantly, the “renal handling” of Na does NOT include secretion of Na by any segment of the nephron and an increase in Na excretion only results from an ____ in the amount of Na filtered and/or a ____ in the amount of Na reabsorbed, mostly in the late distal tubule and cortical collecting tubule in response to a ____ in circulating levels of aldosterone. The absence of the ability of the nephron to secrete Na is problematic, given the availability of Na in the modern western diet, where the rate of Na consumption may vastly exceed the ability of the kidney to excrete excess Na, causing increased plasma volume and ____ blood pressure.

Answer 23

Excretion = filtration - reabsorption + secretion.

Sodium is never secreted. There is too much sodium in the western diet. Our tubules can secrete potassium, but not sodium. Our MAIN way of decreasing sodium is to decrease reabsorption. We eat sodium a hell of a lot faster than we can excrete it. Sodium increases your blood pressure like crazy in a quick amount of time and makes you hypertensive. Angiotensin receptor blocker treats hypertension.

Importantly, the “renal handling” of Na does NOT include secretion of Na by any segment of the nephron and an increase in Na excretion only results from an increase in the amount of Na filtered and/or a decrease in the amount of Na reabsorbed, mostly in the late distal tubule and cortical collecting tubule in response to a decrease in circulating levels of aldosterone. The absence of the ability of the nephron to secrete Na is problematic, given the availability of Na in the modern western diet, where the rate of Na consumption may vastly exceed the ability of the kidney to excrete excess Na, causing increased plasma volume and increased blood pressure.

Question 24

Na reabsorption in the late distal tubule and collecting duct is functionally coupled to K secretion such that an increase or decrease in transcellular Na ______ occurs simultaneously with an increase or decrease in transcellular K ______.

Transcellular Na reabsorption results from uptake across the luminal membrane mediated by Na ______ and efflux across the basolateral membrane mediated by ______ (into the blood). Transcellular K secretion results from uptake across the basolateral membrane mediated by ______ and efflux across the luminal membrane mediated by K ______.

The functional coupling of transcellular Na reabsorption to transcellular K secretion, in the same cell, arises from the ______, which mediates the obligate coupling of Na efflux to K influx across the basolateral membrane, thus, maintaining a low intracellular Na concentration and high intracellular K concentration. The functional coupling of Na reabsorption to K secretion in the late distal tubule and collecting duct is important because an increased delivery of Na to these terminal nephron segments will not only result in a compensatory ______ in Na reabsorption but also an ______ in K secretion, which increases K loss in the urine and possible ______ kalemia.

Answer 24

Na reabsorption in the late distal tubule and collecting duct is functionally coupled to K secretion such that an increase or decrease in transcellular Na reabsorption occurs simultaneously with an increase or decrease in transcellular K secretion.

Transcellular Na reabsorption results from uptake across the luminal membrane mediated by Na channels and efflux across the basolateral membrane mediated by Na/K ATPase (into the blood). Transcellular K secretion results from uptake across the basolateral membrane mediated by Na/K ATPase and efflux across the luminal membrane mediated by K channels.

The functional coupling of transcellular Na reabsorption to transcellular K secretion, in the same cell, arises from the Na/K ATPase, which mediates the obligate coupling of Na efflux to K influx across the basolateral membrane, thus, maintaining a low intracellular Na concentration and high intracellular K concentration. The functional coupling of Na reabsorption to K secretion in the late distal tubule and collecting duct is important because an increased delivery of Na to these terminal nephron segments will not only result in a compensatory increase in Na reabsorption but also an increase in K secretion, which increases K loss in the urine and possible hypokalemia.

Question 25

Sodium reabsorption in the late distal tubule and collecting duct is regulated by circulating levels of ______, a steroid hormone secreted from the adrenal cortex, which vary in response to differences in dietary sodium intake and sodium output in the urine. In positive sodium balance where sodium consumption exceeds sodium excretion, aldosterone levels are ______, which reduces Na reabsorption and increases Na excretion to an amount equal to Na consumed. This regulation restores Na balance, but does not immediately eliminate the Na added to the ECF during the period of regulation. The consequence of adding Na to the ECF is an ECF volume ______.

In negative sodium balance where sodium consumption is less than sodium excretion, aldosterone levels are ______, which increases Na reabsorption and decreases Na excretion to an amount equal to Na consumed. This regulation restores Na balance, but does not immediately restore the Na lost from the ECF during the period of regulation. The consequence of loosing Na from the ECF is an ECF volume ______.

Answer 25

Sodium reabsorption in the late distal tubule and collecting duct is regulated by circulating levels of aldosterone, a steroid hormone secreted from the adrenal cortex, which vary in response to differences in dietary sodium intake and sodium output in the urine. In positive sodium balance where sodium consumption exceeds sodium excretion, aldosterone levels are reduced, which reduces Na reabsorption and increases Na excretion to an amount equal to Na consumed. This regulation restores Na balance, but does not immediately eliminate the Na added to the ECF during the period of regulation. The consequence of adding Na to the ECF is an ECF volume expansion.

In negative sodium balance where sodium consumption is less than sodium excretion, aldosterone levels are increased, which increases Na reabsorption and decreases Na excretion to an amount equal to Na consumed. This regulation restores Na balance, but does not immediately restore the Na lost from the ECF during the period of regulation. The consequence of loosing Na from the ECF is an ECF volume contraction.

Question 26

Hormone-specific secretogogues typically refer to agents which ______ release of hormone into the circulation.

Secretogogues for aldosterone:

1) Angiotensin ______: induces release of ACTH by anterior pituitary
2) ______ Plasma [K+]
2) ______

Answer 26

Hormone-specific secretogogues typically refer to agents which increase release of hormone into the circulation.

Secretogogues for aldosterone:

1) Angiotensin II: Angiotensin II induces release of ACTH by anterior pituitary
2) Increased Plasma [K+]
2) Adrenocorticotropic Hormone (ACTH)

Question 27

More or less circulating aldosterone ______ or ______ renal Na reabsorption and renal K secretion resulting in ______ or ______ Na excretion as well as increased or decreased K excretion. Importantly, where an increase or decrease renal Na reabsorption occurs, a corresponding ______ or ______ in water reabsorption will also occur, either directly at the level of the proximal and distal nephron or indirectly, as a result of increasing or decreasing plasma osmolarity, which induces increased or decreased absorption of water in excess of solute (free water).

Thus, most importantly, water ______ Na, where an increase or decrease in renal Na reabsorption from the tubular fluid to the circulation occurs directly or indirectly with an ______ or ______ in water reabsorption from the tubular fluid to the circulation. This effectively increases or decreases plasma volume and blood pressure.

Answer 27

More or less circulating aldosterone increases or decrease renal Na reabsorption and renal K secretion resulting in decreased or increased Na excretion as well as increased or decreased K excretion. Importantly, where an increase or decrease renal Na reabsorption occurs, a corresponding increase or decrease in water reabsorption will also occur, either directly at the level of the proximal and distal nephron or indirectly, as a result of increasing or decreasing plasma osmolarity, which induces increased or decreased absorption of water in excess of solute (free water).

Thus, most importantly, water follows Na, where an increase or decrease in renal Na reabsorption from the tubular fluid to the circulation occurs directly or indirectly with an increase or decrease in water reabsorption from the tubular fluid to the circulation. This effectively increases or decreases plasma volume and blood pressure.

Question 28

Hyper_____ is an electrolyte disturbance that is defined by an elevated sodium level in the blood. _____ is generally not caused by an excess of sodium, but rather by a relative _____ of free water in the body. For this reason, hypernatremia is often synonymous with the less precise term, dehydration.

Answer 28

Hypernatremia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body. For this reason, hypernatremia is often synonymous with the less precise term, dehydration.

Question 29

Hypernatremia:

An _____ in plasma sodium concentration ([Na]) to a level above 145 mEq/L

Symptoms include lethargy, weakness, and irritability

Severe symptoms (seizures and coma) may occur occur at a [Na] above 158 mEq/L.

In general, caused by a loss of water in _____ of solutes (free water) from the plasma due to inadequate consumption of water in excess of solute and/or an inappropriate renal excretion of water in excess of solute. Hypernatremia is a disorder of water balance, not sodium.

Hypernatremia is problematic in patients who cannot ask for water (infants, those with impaired mental status) or when water consumption is limited.

Answer 29

Hypernatremia:

An increase in plasma sodium concentration ([Na]) to a level above 145 mEq/L

Symptoms include lethargy, weakness, and irritability

Severe symptoms (seizures and coma) may occur occur at a [Na] above 158 mEq/L.

In general, caused by a loss of water in excess of solutes (free water) from the plasma due to inadequate consumption of water in excess of solute and/or an inappropriate renal excretion of water in excess of solute. Hypernatremia is a disorder of water balance, not sodium.

Hypernatremia is problematic in patients who cannot ask for water (infants, those with impaired mental status) or when water consumption is limited.

Question 30

Hypovolemic Hypernatremia (_____ hydration) causes:

1) _____ water consumption
2) _____ sweating
3) _____ diarrhea
4) _____ renal excretion of water (polyuria):

A) diabetes mellitus – _____ suria (excede capacity of proximal tubule to reabsorb glucose & it remains in tubular fluid & raises its osmolatiry then water follows & you pee it out)

B) diabetes insipidus – central (inadequate release of _____ to respond to increased osmolarity) and/or nephrogenic (inability of collecting duct to _____ to normal; ADH levels)

Hypervolemic Hypernatremia causes:

1) Excessive hypertonic fluid _____ (seawater) or i.v. infusion of hypertonic saline
2) _____ aldosteronism

Answer 30

Hypovolemic Hypernatremia (dehydration) causes:

1) Inadequate water consumption
2) Extreme sweating
3) Severe diarrhea
4) Excessive renal excretion of water (polyuria):

A) diabetes mellitus – glucosuria (excede capacity of proximal tubule to reabsorb glucose & it remains in tubular fluid & raises its osmolatiry then water follows & you pee it out)

B) diabetes insipidus – central (inadequate release of ADH to respond to increased osmolarity) and/or nephrogenic (inability of collecting duct to respond to normal; ADH levels)

Hypervolemic Hypernatremia causes:

1) Excessive hypertonic fluid consumption (seawater) or i.v. infusion of hypertonic saline
2) Hyperaldosteronism

Question 31

Hyponatremia: A _____ in plasma sodium concentration ([Na]) to a level below the normal range of 135 – 145 mEq/L. Symptoms include nausea, vomiting, headache, lethargy, fatigue, loss of appetite, restlessness and irritability, muscle weakness, spasms or cramps. Severe symptoms (neurological deficits, brain swelling, seizures, coma) may occur at a plasma [Na] below 125 mEq/L

Hyponatremia is caused by a gain of water in _____ of solutes (free water) in the plasma (hypo-osmolarity) due to:

1) in extreme, excess consumption of water = _____ dypsea
2) an inappropriate increase in “free water” reabsorption by the kidney – SIADH = syndrome of inappropriate _____ release

Answer 31

Hyponatremia: A decrease in plasma sodium concentration ([Na]) to a level below the normal range of 135 – 145 mEq/L. Symptoms include nausea, vomiting, headache, lethargy, fatigue, loss of appetite, restlessness and irritability, muscle weakness, spasms or cramps. Severe symptoms (neurological deficits, brain swelling, seizures, coma) may occur at a plasma [Na] below 125 mEq/L

Hyponatremia is caused by a gain of water in excess of solutes (free water) in the plasma (hypo-osmolarity) due to:

1) in extreme, excess consumption of water = polydypsea
2) an inappropriate increase in “free water” reabsorption by the kidney – SIADH = syndrome of inappropriate ADH release

Question 32

Hypervolemic Hyponatremia:

1) an “inappropriate” reabsorption of water in _____ of solutes from the tubular fluid to the plasma effectively increases plasma volume and dilutes plasma [Na]
2) may occur in: congestive heart failure, kidney failure, liver failure, the Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH), polydipsia

Hypovolemic Hyponatremia:

1) may occur in a clinical setting where plasma volume _____ is extreme (hemorrhage, prolonged exercise in the heat, diuretic drug therapy) where consumption of water as well as increased “water in excess of solute” reabsorption by the kidney is insufficient to correct volume depletion but is sufficient to _____ plasma [Na]
2) Addison’s disease (adrenal insufficiency – _____ aldosteronism)
3) _____ vomiting or diarrhea

Answer 32

Hypervolemic Hyponatremia:

1) an “inappropriate” reabsorption of water in excess of solutes from the tubular fluid to the plasma effectively increases plasma volume and dilutes plasma [Na]
2) may occur in: congestive heart failure, kidney failure, liver failure, the Syndrome of Inappropriate Anti-Diuretic Hormone (SIADH), polydipsia

Hypovolemic Hyponatremia:

1) may occur in a clinical setting where plasma volume reduction is extreme (hemorrhage, prolonged exercise in the heat, diuretic drug therapy) where consumption of water as well as increased “water in excess of solute” reabsorption by the kidney is insufficient to correct volume depletion but is sufficient to decrease plasma [Na]
2) Addison’s disease (adrenal insufficiency – hypoaldosteronism)
3) severe vomiting or diarrhea