Sodium Handling Flashcards Preview

Nephrology > Sodium Handling > Flashcards

Flashcards in Sodium Handling Deck (68):
1

What does "1 equivalent of Na" actually mean?

• Has to do with molarity, 1 equivalent of Na = 1 mole of sodium

2

Of the ECF fluid compartment, which is 1/3 of the TBW, how much is in the plasma and how much is in the interstitium of the body's tissues?

• 3/4 in interstitial fluid compartment
• 1/4 in plasma fluid compartment

3

Why are electrolyte abnormalities primarily water problems?

• Water is freely permeable across most cell membranes but ions are not
• If osmotic gradients are established between compartments then water will move

4

What are rules that govern osmotic fluid movement?


• Water-permeable membrane must separate two compartments with different concentration of impermeable solutes

• Water moves into higher solute concentration (toward higher osmolality)
• Freely permeable solutes (urea) do not affect water movement
• Magnitude of gradient (osmotic) determines magnitude of water movement
• Water will move until either osmotic gradient is gone or hydrostatic pressure causes equilibrium
Is there an osmotic gradient between the capillary and the interstitium?
• Mostly NO, because of the fenestrated epithelium that allows for rough equilibration of solutes between these two compartments
• The exception is albumin, dextran, and other large proteins (hence infusions of these maintained in the plasma)

5

What is really being discussed when we are talking about ECF sodium?

• We are talking about disorders of ECF volume when we are talking about sodium
• Same with hyper and hyponatremia, it is a water problem, not a sodium problem
• Maintenance of ECF volume determines the MAP and left ventricular filling volume

6

What is the purpose of the integrated homeostatic response?

• Maintain ECF volume
• Made up of two key components: afferent limb (EABV sensor) and efferent limb (regulates the rate of sodium excretion by the kidney)

7

What are the components of the integrated homeostatic response?

• Maintain ECF volume
• Made up of two key components: afferent limb (EABV sensor) and efferent limb (regulates the rate of sodium excretion by the kidney)

8

What does the flowchart of the homeostatic response say about volume expansion?

• Starts normal extracellular volume
• Volume expansion
• Activation of volume sensors
• Renal effector mechanism
• Natriuresis

9

What does the flowchart of the homeostatic response say about volume contraction?

• Volume contraction and decrease in effective aterterial blood volume can be the same thing
• Starts normal extracellular volume
• Activation of volume sensors
• Renal effector mechanism
• Anti-natriuresis

10

What happens in volume expansion?

• On the venous side, atrial stretch receptors signal hypothalamic and medullary centers in brain to decrease renal sympathetic activity
• Net result is loss of sodium and water in the kidney and reduction in the initial ECF volume expansion
• The opposite is the case with volume reduction

11

What volume sensors are in the afferent limb?



• Low pressure baroreceptors
○ Cardiac atria receptors
○ Left ventricular receptors
○ Pulmonary vascular bed receptors
• High pressure baroreceptors
○ Carotid sinus body (bifurcation)
○ Aortic body (in aortic arch)
• Intrarenal sensors
○ JGA = juxtaglomerular apparatus
○ Releases renin
• Hepatic and central nervous system sensors

12

What decreases renin secretion?

• Increased arterial blood pressure
• Increased sodium delivery
• Angiotensin II
• ANP

13

What increases renin secretion?

• Decreased arterial pressure
• Decreased sodium delivery
• Beta adrenergic action
• PGEI, PGE2
• Nitric oxide
○ All the things that dilate the afferent arteriole

14

What is tubuloglomerular feedback?

• Increased distal delivery of sodium chloride to macula densa (in the JGA) increases afferent arteriolar tone and returns RBF and GFR towards normal values
• Increased sodium chloride just after the glomerulus likely means that filtration is increased, which is most likely due to pressure (hydrostatic pressure is main filtration driving force)

15

What is the Glomerulo-tubular balance?

• Works with tubuloglomerular feedback and the renal autoregulation pathway to maintain GFR
• Fundamental property of the kidney whereby changes in GFR automatically induce a proportional change in the rate of proximal tubular sodium reabsorption
• Fractional excretion of sodium is maintained constant in the setting of increases or decreses in GFR

16

Which hormones are active in ECF volume contraction and what do they do?

• Angiotensin II, aldosterone, catecholamines, vasopressin
• Vasoconstriction, increase MAP, increase GFR
Which hormones are active in seetings of ECF volume overload?
• Prostaglandins, bradykinin, atrial natriuretic peptide, dopamine
• These induce natriuresis

17

When is the sympathetic nervous system active in the kidney and what does it do?

• Sympathetic system innervates the afferent and efferent arterioles of the glomerulus
• Stimulated in volume contraction and is needed for sodium conservation
• Results in anti-natriuretic effect
• Also increases renin release from JGA which in turn releases anti-natriuretic hormones A2 and aldosterone

18

What are the four main areas for sodium handling in the kidney?

• Proximal tubule
• Thick ascending limb of the loop of henle
• Distal convoluted tubule
• Principal cell of cortical collecting duct

19

Is there a gradient for sodium to follow in the proximal tubule?





• Yes. Filtrate sodium concentration is the plasma concentration, which is 140mEq/L and the inside of the tubular epithelium is 15-35 mEq/L
• Gradient is maintained by the action of the ubiquitous sodium pump Na/K ATPase at the basolateral side
• The entry of sodium into the cell is coupled to chloride, phosphate, glucose, amino acids and lactate sodium-dependent co-transport
• Sodium can also be increased through Na/H+ antiporter (sodium in and hydrogen out)

20

What is affected by loop diuretics?

• The Na/K/2Cl channel is inhibited
• Dilution of the urine in the TALH is thus inhibited
• Result is concentrated urine and water and salt excretion

21

What are the active transporters in the TALH?

• (Lumenal) Na/K/2Cl cotransporter, Na/H+ antiporter
• (basolateral) Na/K ATPase, K/Cl cotransporter, Na/HCO3 cotransporter

22

What ions should you assume as passively moving through the TALH?

• Potassium leaks to the apical side
• Chloride leaks to basolateral side
• Calcium, magnesium, ammonia all leak from lumenal to basolateral side

23

How much of the filtered sodium is reabsorbed in the loop of henle?

• 30% in the thick ascending limb of the loop of Henle (TALH)
• Impermeable to water but very salt permeable
• DILUTION is going on in TALH so that osmolality of tubular fluid is about 150mOsm/Kg water at the end of it (1/2 of plasma)
• Resorption here through lumenal membrane through Na/K/2Cl co-transporter (active)

24

What are the cotransporters that use Sodium influx as their energy source?

• (lumenal side) Glucose, amino acids, phosphate, lactate, chloride
• (basolateral side) Na/K ATPase (sodium out potassium in), bicarbonate transporter (get bicarb out and sodium out to drive bicarb formation)

25

What process will drive the generation and reabsorption of bicarbonate?

• Na/H+ antiporter. H+ out, sodium in

26

How does the distal convoluted tubule participate in urine dilution?


• Sodium reabsorbed across lumenal membrane by three mechanisms
• Sodium channels (also drives chloride into cell)
• NaCl reabsorption by Na/Cl cotransporter
• Sodium transport through parallel Na/H+ antiport and Cl/base exchange with recycling of H+ and base
○ Both Na and Cl need their antiporters with H+ and base, respectively, to keep the cycle going

27

What channels/transporters are inhibited by diuretics in the distal convoluted tuble?

• Thiazides inhibit the Na/Cl cotransporter
• Amiloride inhibits the passive Na leak channel in the apical membrane
• These will both inhibit NaCl reabsorption, concentrating the urine and leading to salt and water excretion

28

What are the two types of cells in the cortical collecting duct?

• Principal cells and intercalated cells
• Intercalated = type a and B, involved in hydrogen ion secretion (A) and bicarbonate secretion (B)
• Principal = Na/K exchange through leak channels, Cl/Bicarb antiporter, basolateral side drives sodium influx through Na/K ATPase

29

What drug inhibits channels/transporters in the cortical collecting duct?

• Amiloride inhibits the apical sodium leak channel in principal cells in the cortical collecting duct

30

As long as the starling forces across the capillary membranes are not altered, what is true about the ECF interstitium and intravascular?







• ECF volume loss is shared equally by the two ECF compartments (intravascular and interstitial) as long as the capillaries are normal

31

What happens in Bartter's and Gitelman's syndromes?

• Unusual mechanisms of renal sodium loss involving failure of the effector mechanism
• Bartter's = early in life, mutation in Na/K/2Cl cotransporter in TALH
○ Results in hypokalemia, hypomagnesemia, metabolic alkalosis, high plasma renin and aldosterone, increased calcium excretion, normal blood pressure
• Gitelman's = older people, mutatinon in NaCl cotransporter in distal tubule
○ Hypokalemia, hypomagnesemia, metabolic alkalosis, reduced urinary excretion of calcium

32

What are some examples of intrinsic renal disease leading to renal losses of sodium and water?

• Non-oliguric acute renal failure
• Diuretic phase of acute renal failure
• Post-obstructive diuresis
• Salt wasting nephropathy
• Medullary cystic disease
• Tubulo-interstitial disease

33

What are some examples of "failure of effector mechanism" leading to renal water loss?

• Solute diuresis, glucosuria
• Diuretic agents
• Adrenal insufficiency
• Selective aldosterone deficiency
• Mutations in sodium transporters (Bartter's and Gitelman's syndromes)

34

What can result in volume contraction?

• Renal loss or extra-renal loss. That is your first question.
• Renal = salt+water, or water alone, secondary to either a loss of effector mechanism or an intrinsic kidney disease that changes output mechanism
• Extra-renal = GI tract, skin losses, hemorrhage, third spacing (loss into peritoneal cavity or some other potential space)

35

As long as the starling forces across the capillary membranes are not altered, what is true about the ECF interstitium and intravascular?

• ECF volume loss is shared equally by the two ECF compartments (intravascular and interstitial) as long as the capillaries are normal

36

What are some examples of intrinsic renal disease leading to renal losses of sodium and water?

• Non-oliguric acute renal failure
• Diuretic phase of acute renal failure
• Post-obstructive diuresis
• Salt wasting nephropathy
• Medullary cystic disease
• Tubulo-interstitial disease

37

What are some examples of "failure of effector mechanism" leading to renal water loss?

• Solute diuresis, glucosuria
• Diuretic agents
• Adrenal insufficiency
• Selective aldosterone deficiency
• Mutations in sodium transporters (Bartter's and Gitelman's syndromes)

38

What can result in volume contraction?

• Renal loss or extra-renal loss. That is your first question.
• Renal = salt+water, or water alone, secondary to either a loss of effector mechanism or an intrinsic kidney disease that changes output mechanism
• Extra-renal = GI tract, skin losses, hemorrhage, third spacing (loss into peritoneal cavity or some other potential space)

39

What is associated with upper GI tract losses?

• Loss of gastric fluid (acidic) causing a metabolic alkalosis
• Lower GI is associated with loss of bicarb-rich pancreatic fluid and thus metabolic acidosis

40

What kind of fluid loss happens through the skin?

• From sweating, burns and fever
• Sweating and fever loss is hypotonic where burns is isotonic loss

41

ECF volume contraction will trigger what cardiovascular response?

• Increase sympathetic tone
○ Increased HR, inotropic function, systemic vascular resistance
• Increased vasocontrictor hormone release (A2, AVP, endothelin)

42

ECF volume contraction will trigger what renal response?

• Try to replenish lost fluids and conserve and reabsob salt and water
• Decreased GFR thus smaller filtered load of sodium
• Activation of renal sympathetic tone
○ Vasoconstriction of afferent arteriole and increased tubular reabsorption of sodium
• Decreased hydrostatic pressure and incrased oncotic pressure in peritubular capillaries
• Stimulation of RAAS
• Increased secretion of ADH=vasopressin=AVP from posterior pituitary
• Inhibited secretion of atrial natriuretic peptide from atrial myocytes

43

What will you find on history and physical that points to ECF volume contraction?

• Mild contraction = only thirst, postural dizziness, weakness
• Severe = lightheadedness/dizziness, palpitations, decreased urine output
• Gonna die = confusion/obtunded, lack of urine output, profound weakness
• Look for weight changes, orthostatic hypotension (more than 15mmHg) or tachycardia (over 20bpm)
• Interstitial fluid loss can be seen by decreased elasticity and turgor of skin (tough in elderly)
• Dry mucus membranes are suggestive
• Flat neck veins, cold/clammy extremeties, cyanosis

44

What will you see in the serum that can make you think "volume contraction"?

• Increased BUN/Creatinine ratio in the plasma
○ Normal is 10-15:1, but in avid Na reabsorption you get more than 20:1 through urea following Na passively
• Metabolic alkalosis indicating upper GI loss
• Metabolic acidosis indicating lower GI loss
• Increased hematocrit and serum albumin because of hemoconcentration (loss of water)

45

What will you see in urine that makes you think "volume contraction"?




• Urinary sodium
○ Usually pretty low in contraction with normal kidneys.
○ In volume contraction with high urine sodium think ATN
• Fractional excretion of sodium
○ Reflects amount of filtered sodium that is excreted
○ Less than 1% in prerenal azotemia
○ More than 2% in oliguric acute renal failure
○ FENa = (Urine-Na*Plasma-Cr)/Plasma-Na*Urine-Cr) *100%
• Urine Specific gravity and osmolality
○ Indicate dilute or concentrated
○ High specific gravity and osmolality in volume contraction because of resorption of sodium and water
○ Low specific gravity and osmolality in situations where serum osmolality is low due to volume expansion

46

What does the urine to plasma creatinine ratio suggest/reflect?

• 40:1 or more in pre-renal azotemia
• 20:1 or less in ATN

47

What happens if the kidney can't concentrate?

• Isothenuria means consistent SG of 1.010. reflects severe renal injury

48

What is considered dilute and concentrated urine?

• Dilute = hyposthenuric = specific gravity 1.003 or lower and 50mOsm/kg or less
• Concentrated = 1.035 specific gravity or more and in the 1200 mOsm/kg range

49

What percentage of sodium can be reabsorbed in a healthy proximal convoluted tubule?

65-70% (chloride and water will follow passively in the proximal convoluted tubule), channels involved are Na/H+ antiporter and apparently just sodium channels that allow sodium to flow into the cell because of Na/K ATPase action at the basolateral membrane

50

What percentage of sodium can be reabsorbed in a healthy thick ascending loop of henle? (TALH)

about 25% (NaCl together into interstitium), the Na/K/2Cl cotransporter is being inhibited through direct chloride reabsorption inhibition. side effect is calcium and magnesium are not reabsorbed well either

51

What percentage of sodium can be reabsorbed in a healthy distal convoluted tubule?

about 5% (NaCl together into interstitium)

52

What percentage of sodium can be reabsorbed in the collecting duct?

about 1-2% (not very much), Na/K ANTIPORT

53

what do thiazide diuretics do?

Act at the distal convoluted tubule. Inhibit reabsorption of Na and Cl through the Na/Cl cotransporter.
* they increase the excretion of Na, Cl, K and water. In the long term there will be increased excretion of Magnesium but decreased excretion of Calcium.
* they can also increase urea reabsorption (into interstitium) and increase plasma uric acid levels (gout)

54

where do potassium sparing diuretics work?

Distal portion of distal convoluted tubule and in the collecting ducts.
* prevent excretion of potassium, and thereby decrease reabsorption of sodium
* these are used in combo with other ones to keep potassium from going too far down
* Amiloride and Triamterene

55

Spironolactone acts on what cell and where in the kidney?

Spironolactone is an aldosterone inhibitor. It acts on the intercalated cells in the COLLECTING DUCTS of the kidney.
* normally aldosterone binding to aldosterone receptors will induce these intercalated cells to make more Na/K antiporter on the basolateral surface of the cells. this increases reabsorption of sodium and also increases secretion and excretion of potassium (in the urine)

56

How is volume corrected in acute hemorrhage?



• Give blood to correct hypovolemic shock
• Plasma explanders like albumin and dextran solutions are alternative choices. These preferentially expand the intravascular volume

57

How can potassium loss from the serum be treated?

• Adding potassium chloride to the IV saline solution

58

When you give normal saline, how much of that volume ends up where?

• It stays in the ECF, but remember that the ECF is really two different compartments: the interstitial fluid and the intravascular fluid
• It gets separated 80% to the interstitium and 20% stays in the intravascular compartment

59

How does ECF volume expansion occur?


• Volume expansion occurs when renal and extrarenal fluid losses do not match water and salt intake
• Disturbed starling forces
○ Reduced EABV and edema formation
○ CHF causing increase in capillary hydrostatic pressure
○ Nephrotic syndrome where protein loss leads to decreased oncotic pressure in capillaries
○ Cirrhosis - both low albumin and portal hypertension so there is both an increase in hydrostatic pressure and a decrease in oncotic pressure
• Primary hormone excess
○ Overproduction of mineralocorticoids or vasopressin
○ Primary hyperaldosteronism
○ Cushing's syndrome
○ Syndrome of inappropriate secretion of anti-diuretic hormone
• Primary renal sodium retention
○ Acute glomerulonephritis

60

What do mineralocorticodies do in the kidney?

• Promote sodium reabsorption

61

Edema results from an increase in hydrostatic pressure or a decrease in oncotic pressure in the capillaries. What maintains edema?

• The afferent limb volume sensors perceive a reduced effective arterial circulating volume
• Stimulates the efferent limb effector elements to retain sodium and water to maintain ECF volume via the integrated homeostatic response
• All told, formation and persistance of edema comes from:
○ Alteration in starling forces, arterial underfilling thus less EABV, excessive renal sodium and water retention

62

What is the flow chart of reduced cardiac output that results in sodium and water retention in the kidneys?

• Reduced cardiac output
• Activation of ventricular and arterial receptors
• The receptor activation will increase non-osmotic ADH secretion, increase sympathetic nervous system tone and cause RAAS activation
• ADH causes renal water retention and, along with SNS tone, increases peripheral and renal arterial vascular resistance
• RAAS activation will increase sodium retention through aldosterone and increasing the amount of sodium resorbed in the collecting ducts
• All the sodium and water retention will maintain the arterial circulatory integrity (increase blood volume)

63

What problems characterize cirrhosis that lead to underfilling of arterial circulation?

• Intrahepatic hypertension
• Portal hypertension
• Splanchnic vasodilation
• Hypoalbuminemia
○ The overall net effect is increased capillary hydrostatic pressure and decreased capillary oncotic pressure and loss of fluids into interstitium

64

Compare the maximal excretion of either salt or water compared to filtered loads

• Maximal excretion is a super small portion of the filtered loads
• This MUST be because filtered loads are large (a good deal of the cardiac output to the kidneys which is a ton) and you have to get all that stuff back to keep from losing important solutes

65

How much of the filtered water and sodium can regulatory mechanisms in the kidney affect?

• Only 8% of filtered load of water and 2% of filtered load of sodium

66

In terms of sodium handling, what is the primary energetic event?

• Sodium actively extruded from the interior of the tubular epithelium by basolateral Na/K ATPase ion pump
• Thus there is a gradient for sodium to enter the cell through the apical membrane
• Many co-transporters use the sodium gradient to reabsorb important materials (glucose, amino acids, etc)

67

What is the most common mechanism for chloride movement?

• Paracellular, or through the tight junctions.
• Just think of it as leaking from lumen to interstitium

68

How does glucose get into the tubular epithelium and how does it leave?

• Because the sodium gradient is so high, it gets favorably co-transported with sodium into the tubular epithelium through the apical membrane and the Na/glucose co-transporter
• The sodium gradient is high enough to power glucose concentration in the cell
• High glucose concentration in the tubular epithelia allow for passive flow to the interstitium through "leak" channels