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CPR Week 7 > 3.7.5. Control and Comp of Fluids I II and III > Flashcards

3.7.5. Control and Comp of Fluids I II and III Flashcards

1
Q

Plasma osmolarity (Posm) - sensed by ___________.

A

Plasma osmolarity (Posm) - sensed by hypothalamic osmoreceptors

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2
Q

Formula for plasma osmolarity

A

Posm = ECFosm - ICFosm

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3
Q

ECV is proportional to what?

A

ECV is proportional to CO, TPR, blood volume, and central venous pressure - all of these factors contribute to the ECV, so you can’t accurately measure just one…

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4
Q

this is the overall “fullness of the vascular system”

A

Effective circulating volume (ECV)

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5
Q

Systems that regulate the ECV

A

intrarenal sensors include the Juxtaglomerular Apparatus and systemic Hemodynamic Effects

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6
Q

Difference in the body between sensing plasma osmolarity and ECV and how it responds to each?

A

Plasma osmolarity - this is a very responsive and sensitive system (it’ll react more readily to smaller changes and with a more delicate change)

ECV - this is a less sensitive, but much more of a potent system (it’ll take a larger physiological deviation to stimulate this response, but it makes larger changes)

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7
Q

When our body senses a relative water loss, it will respond by excreting less water and taking in more.

How is this done biochemically?

A

Loss of H2O from the ECF leads to an increase in plasma osmolarity and a decrease in ECV.

Antidiuretic hormone (ADH) and thirst mechanism increases

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8
Q

Tubules that do not demonstrate water reabsorption

A

The Ascending Loop of Henle and Distal Convoluted Tubule do NOT demonstrate water reabsorption

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9
Q

Which tube is modifiable, thus allwing for ADH to act?

A

Collecting duct

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10
Q

Where along the pathway is water secreted?

A

NEVER

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11
Q

This is where most water reabsorption occurs

A

Proximal tubule

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12
Q

What is ADH and how is it made?

A

it is a nonapeptide neurohormone that induces vasoconstriction in the kidney and blood vessels

it is synthesized by the cell bodies in the supraoptic nucleus (SON, a part of the hypothalamus), stored in vesicles in the axons of those neurons, and released at the synapse in the posterior pituitary

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13
Q

What are neurohormones

A

(recall that neurohormones are chemicals made by a neuron that are released into the bloodstream and induce some hormonal effect downstream)

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14
Q

Relationship between Posm and ADH. Get specific.

A

As Posm increases, ADH increases proportionally with it

~10x increase in ADH seen for every 3% change in Posm

Huge results for a very slight change

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15
Q

What does ADH actually do?

A

it stimulates principal cells (aka “intercalated cells”) to take up more water

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16
Q

What happens when ADH binds to V2?

A

results in increased PKA levels and phosphorylation of aquaporin (AQP-2) receptors that are associated with vesicular membranes.

The vesicles are then trafficked to the apical surface of the principal cells, where they fuse with the membrane and integrate the new AQP receptors.

A net influx of water through the apical membrane occurs, and the water leaves the cell into the blood through the basolateral surface, which has its own aquaporin (AQP-4).

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17
Q

What happens when ADH binds to V1?

A

ADH can also bind to the V1 receptor on vascular smooth muscle, which induces vasoconstriction

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18
Q

As long as ADH is bound to the V2 receptor, H2O can do what?

A

As long as ADH is bound to the V2 receptor, H2O can follow a pathway down its osmotic gradient from the lumen of the collecting duct, through the AQP-2 into principal/dark cell, and into the blood

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19
Q

If ADH isn’t bound, water won’t go in. Why?

A

if ADH isn’t bound, AQP-2s are downregulated, so even though the osmotic gradient remains, the tools aren’t there to let water through.

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20
Q

On a stable, low-Na diet, _____% of the filtered sodium is ultimately excreted

A

On a stable, low-Na diet, ~1% of the filtered sodium is ultimately excreted

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21
Q

Where is most of the sodium reabsorbed?

A

Proximal tubule = 67%

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22
Q

How much sodium is absorbed in eac area along the nephron?

A 
Glomerulus = Sodium is freely filtered
Proximal tubule = 67%
Loop of Henle = 25%
DT = 3%
CD = 4%
Urine = 1% excreted out
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23
Q

3 Na pumps of the PCT

A
  1. Sodium-Coupled Transporter

1 sodium and 1 other molecule are transported into the cell
the other molecule flows down its concentration gradient, and Na just tags along for the ride

  1. Sodium-Hydrogen Exchanger (NHE-3)

1 sodium goes into the cell as 1 proton is secreted into the filtrate

maintains electroneutrality within the cell

  1. Sodium-Potassium-ATPase

this maintains the Na gradient on the basolateral side, thus allowing cotransport to occur on the apical side

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24
Q

Pumps of the Thick Ascending loop

A
  1. Sodium-Potassium-Chloride Cotransporter (NKCC) - also called “Bumetanide-sensitive cotransporter”
  2. Potassium Channel (ROMK)
  3. Sodium-Potassium-ATPase
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25
Q

Discuss the Sodium-Potassium-Chloride Cotransporter (NKCC) - also called “Bumetanide-sensitive cotransporter”

A

if ion channels were cars, this guy would be a bus

1 Na+, 1 K+, and 2 Cl- ions are shuttled into the cell from the lumen of the ascending limb

electroneutrality is maintained

this channel is important because it creates a K-recycling mechanism that the ROMK channel can use

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26
Q

Discuss ROMK

A

Potassium Channel (ROMK)

a specific type of K-channel that sends K into the lumen of the ascending limb

this channel is important because it creates a K-recycling mechanism that the NKCC transporter can use

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27
Q

Na Pumps for the DCT

A

Sodium-Chloride Cotransporter (NCC), also called the “Thiazide-sensitive cotransporter” (TSC)

Sodium-Potassium-ATPase

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28
Q

Discuss the NCC pump

A

Brings 1 Na and 1 Cl into the cell from the lumen of the DCT

electroneutrality is maintained

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29
Q

Pumps of the Collecting Duct

A

Epithelial Sodium Channel (ENaC), also called the Amiloride-sensitive sodium channel

Sodium-Potassium-ATPase

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30
Q

Discuss the ENaC pump including what else we call it

A

Epithelial Sodium Channel (ENaC), also called the Amiloride-sensitive sodium channel

this is simply a channel that allows Na to flow in freely, w/o cotransport

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31
Q

Name the four major signaling systems that control sodium reabsorption and excretion

A

1) Direct Hemodynamic Effects (on different systems)
2) RAAS
3) Sympathetic Nervous System
4) Natriuretic Hormones

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32
Q

What does autoregulation have to do with direct hemodynamic effects?

A

on GFR: recall that “autoregulation” means that GFR stays relatively constant over a wide range of perfusion pressures

33
Q

Discuss pressure natriuresis

A

on Urine Output: as perfusion pressure increases, urine volume increases: this is called pressure natriuresis

This occurs because of changes in tubule reabsorption

34
Q

Which law do we need to consider to understand hemodynamic effects on tubular ressorption? Discuss it.

A

To understand hemodynamic effects on tubular reabsorption, recall Starling’s Law (rearranged for easier memorization):

net fluid movement = K * (Pc - Pi) - (πc - πi)

35
Q

under ____ conditions, Na and H2O mostly return to the ____ ____, with the potential for backleak existing if:

A

under NORMAL conditions, Na and H2O mostly return to the peritubular capillary, with the potential for backleak existing if pressure in the interstitial space gets too high

36
Q

the initial increase in ECV causes what?

A

the initial increase in ECV causes renal perfusion pressure to increase as well. Both renal blood flow (RBF) and glomerular filtration rate (GFR) increase, but the latter increases less.

This leads to a FF decrease (FF = GFR/RBF)

37
Q

After our FF decrease (FF = GFR/RBF), what happens physiologically?

A

physiologically speaking, this is important because in the peritubular capillaries, we INCREASE the capillary hydrostatic pressure (Pc) and DECREASE the capillary oncotic pressure (πc)

in addition, we see diminished return of Na and H2O to the peritubular capillaries

38
Q

ALONE, the kidney can compensate for large amonts of Na by:

A

ALONE, the kidney can compensate for large amonts of Na by increasing its perfusion pressure drastically

39
Q

How can the kidney respond to Na increases with regards to neurohormones?

A

ALONE, the kidney can compensate for large amonts of Na by increasing its perfusion pressure drastically

COMBINED WITH NEUROHORMONES, there’s an “infinite gain”. So, you can increase Na intake and excretion infinitely, w/o increasing perfusion pressure hardly at all

40
Q

Juxtaglomerular cells in the afferent arteriole are close to the ___ ____.

A

Juxtaglomerular cells in the afferent arteriole are close to the macula densa cells

41
Q

When ECV is low, ___ ___ senses ___ ___ and cause the _____ cells to release ____.

A

When ECV is low, macula densa senses low Na and cause the juxtaglomerular cells to release renin

42
Q

in the principal cells, _____ stimulates transcription and upregulation of _____ channels on the apical surface (____ response), and later on upregulates ______ on the basolateral surface (____ response).

the net result of this is increased Na _____, and thus decreased Na ____ overall

A

in the principal cells, aldosterone stimulates transcription and upregulation of ENaC channels on the apical surface (early response), and later on upregulates Na-K-ATPase on the basolateral surface (late response).

the net result of this is increased Na reabsorption, and thus decreased Na removal overall

43
Q

Function of Renin

A

Catalyzes the cleavage of angiotensinogen into Angiotensin I

44
Q

Effect of BP on sympathetic activity

A

As BP (and consequently the ECV) increases, sympathetic activity will DECREASE

45
Q

ANP is released in response what?

A

ANP is released in response to an increase in stretch of atrial mechanoreceptors (ANP = atrial natriuretic peptide)

46
Q

ANP counteracts basically all of what ____ does. When it’s released, ___________________ is seen

A

ANP counteracts basically all of what RAAS does. When it’s released, increased sodium excretion (and water) is seen

47
Q

“natiuresis” = ?

A

“natiuresis” = sodium in urine (makes sense, given the name)

48
Q

Medical interventions that tend to reduce sodium and water in the body will do what?

A

Medical interventions that tend to reduce sodium and water in the body will lower blood volume and BP

49
Q

What do ACE inhibitors do?

A

prevents secretion of aldosterone

limits sodium channel expression

50
Q

Thiazide diuretics

A

inhibit the Sodium-Chloride (Thiazide-sensitive) cotransporter

51
Q

ACE inhibitors and Thiazide diuretics both do these things:

A

reduced Na reabsorption
therefore, increased excretion

increased H2O excretion

reduced ECV

reduced BP

52
Q

Changes in ECV/blood volume reflect changes in these two things:

A

Changes in ECV/blood volume reflect changes in Na and H2O retention

53
Q

Decreased blood volume leads to:

A

A decrease in ECV, which leads to an increase in RAAS and sympathetic tone, which lead to an increase in Sodium and H2O reabsorption

54
Q

Heart failure causes this in sodium and H2O reabsorption

A

A decrease in ECV, which leads to an increase in RAAS and sympathetic tone, which lead to an increase in Sodium and H2O reabsorption

55
Q

Effective circulating volume is influenced more/less by decreased cardiac function and more/less by Na+ and H2O intake and excretion.

A

Effective circulating volume is influenced more by decreased cardiac function and less by Na+ and H2O intake and excretion.

56
Q

Most of the body’s potassium is stored ____ ____.

A

Most of the body’s potassium is stored inside cells

57
Q

Describe the acute extra renal response to potassium homeostasis

A

Increased Pk results in increased insulin secretion, increased epinephrine release, increased aldosterone

The first two effects occur in minutes, the third in hours (because more Na pumps must be inserted)

Response = increase in K+ uptake from blood into cells (mostly in skeletal muscle)

58
Q

Compare potassium and sodium reabsorption through the nephron

A

K has similar numbers as Na.

Sodium:
Glomerulus = Sodium is freely filtered
Proximal tubule = 67%
Loop of Henle = 25%
DT = 3%
CD = 4%
Urine = 1% excreted out

Potassium:
Glomerulus = K is freely filtered
Proximal tubule = 65%
Loop of Henle = 25%
DT +CD = ? (Little absorption, little secretion, it depends!)
(K secretion is under hormonal control and determines in large part how much K is excreted)
Urine = 1-80% excreted out

59
Q

For K, Secretion is through the ___ ___ principal cells as ___ ____ works and K+ builds up within the cell

A

Secretion is through the collecting duct principal cells as Na/K ATPase pump works and K+ builds up within the cell

60
Q

Name the five signal systems that regulate potassium secretion in the nephron

A

Serum K+ Concentration

Aldosterone

Tubular Flow Rate

ADH - not a major factor

Acid-Base status

61
Q

K+ secretion _____ with increasing Pk, but ____ modulates the secretory capacity

A

K+ secretion still increases with increasing Pk, but aldosterone modulates the secretory capacity

62
Q

Aldosterone increases what, and why?

A

Aldosterone increases the expression of both secretory K+ channel and Na/K ATPase to increase secretory capacity

63
Q

Discuss Tubular Flow Rate

A

increased flow rate increases the K+ secretion AND excretion

Slow flow allows for the electrochemical gradient across the collecting tubules to reach equilibrium, and inhibits flow into urine

64
Q

Discuss ADH on K channels

A

ADH increase the # of apical K channel principal cells, which increases the secretory capacity

Usually balanced by changes in the flow rate

65
Q

Acid/Base effects on K and WHY?

A

Acidosis inhibits Na/K pump and secretory K channel while Alkalosis stimulates.

This is due to the transfer of H+ during ATPase normal function

66
Q

Effect of Loop Diuretics

A
  1. Decrease Na reabsorption, leading to an increased Distal flow rate
  2. Decrease effective circulating volume to increase aldosterone
  3. Decrease Loop K+ reabsorption to increase Distal K+ delivery.

All of these lead to a enormous K+ excretion

67
Q

In the Proximal Tubule:

As Na and H2O are reabsorbed, Ca’s concentration ____ in the urine, driving the movement of Ca from the ___ to the ____

A

As Na and H2O are reabsorbed, Ca’s concentration increases in the urine, driving the movement of Ca from the urine to the blood

68
Q

Where is calcium secreted in the nephron?

A

NOWHERE

69
Q

Where is Ca reabsorbed in the nephron?

A 
Glomerulus = Only about 60% of plasma Ca is filtered. 40% is bound to protein
Proximal Tubule = 60% reabsorbed
Loop of Henle = 30%
DT/CD = 9%
Urine = 1% excreted
70
Q

Low plasma [Ca] causes more ___ to be released.

What does this thing do?

A

Low plasma [Ca] causes more PTH to be released

Pulls Ca and PO4 out of the bones

Increases Ca uptake from the intestines

Decreases Ca excretion & increases phosphate excretion

71
Q

in the Loop of Henle and distal nephron, Ca is actively transported in a transcellular fashion. The transporters responsible for this specific action are:

A

Ca-Na antiporters on the basolateral membrane

Ca-ATPases on the basolateral membrane

72
Q

As with glucose, a Tmax exists for PO4 transporters

What happens when we exceed it? Where are the levels normally?

A

When this Tmax is exceeded, whatever PO4 is left behind will be excreted in the urine

The normal phosphate levels are right around the Tmax… if plasma levels increase, then these receptors will reach their maximum transport ability more quickly (compared to glucose transporters)

73
Q

PTH reduces _____ so that more PO4 will be excreted

A

PTH reduces the Tmax so that more PO4 will be excreted

74
Q

in the proximal tubule, reabsorption of phosphate is perfomed by

A

Na-PO4 cotransporters on the apical side

PO4-X- antiporters on the basolateral side (where X- is any particular anionic compound)

75
Q

Where is the nephron is K reabsorbed?

A

Glomerulus = Phosphate freely filtered
Proximal tubule = 80%
Distal Tubule = 10%
Urine = excrete last 10%

76
Q

Like Ca, most of ____ is bound to proteins in the blood, so only a small amount is filtered to begin with…

A

Like Ca, most of Mg (60%) is bound to proteins in the blood, so only a small amount is filtered to begin with…

77
Q

UNLIKE OTHER IONS, only ____ of Mg is reabsorbed in the proximal tubule

A

UNLIKE OTHER IONS, only 25% of Mg is reabsorbed in the proximal tubule

the loop of Henle does about 70% of Mg reabsorption

78
Q

Where is Mg mostly reabsorbed?

A

the loop of Henle does about 70% of Mg reabsorption

the distal tubule and collecting duct reabsorbs about 5%

urine contains ~1% Mg that was initially filtered

79
Q

triggers that increase Mg excretion include

A

increased plasma [Mg]
increased extracellular volume
increased extracellular [Ca]

CPR Week 7 (12 decks)

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