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Renal > Phys, Lectures 1-5 > Flashcards

Phys, Lectures 1-5 Flashcards

1
Q

TBW of a healthy person as a percent of their mass

A

60%

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2
Q

ICF volume of a healthy person as a percent of their mass

A

40%

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3
Q

ECF volume of a healthy person as a percent of their mass

A

20%

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4
Q

In a healthy person, what percent of total mass is plasma? What percent of total mass is interstitial fluid?

A

Plasma and IF make up ECF volume. ECF is 20% of total body mass.

Of that, roughly 3/4 is IF and 1/4 is plasma.

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5
Q

What solute is the most important determinant of ICF tonicity and volume?

A

K+

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6
Q

What solute is the most important determinant of ECF tonicity and volume?

A

Na+

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7
Q

What is the approximate osmolarity in ECF? ICF?

A

300 mOsm, both
Due to the higher [protein] in plasma and the associated negative charge, ions do not distribute evenly, though osmolarity does (Gibbs-Donnan effect)

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8
Q

Name indicators for TBW, ECF, and plasma

A

Water: Radio-labeled water or antipyrine
ECF: Radio-labeled Na+, inulin, or mannitol
Plasma: Radio-labeled albumin or Evans Blue

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9
Q

Formula for total blood volume, given plasma and Hct

A

TBV = plasma vol / (1-Hct)

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10
Q

What adjustments should be made when estimating TBW in a patient with obesity?

A

Multiple the mass of adiposity * 0.1 and add that to (70kg * 60%). We do this because adipocytes only hold 10% fluid.

ICF will be calculated as 67% of that total (not 40%) and ECF = 33% (not 20%).

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11
Q

What adjustments should be made if calculating TBW for a female patient and we are instructed to adjust for gender?

A

TBW should be calculated as 55% of body mass.

ICF will be calculated as 67% of that total (not 40%) and ECF = 33% (not 20%).

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12
Q

What adjustments should be made when calculating TBW for a newborn patient?

A

TBW should be calculated as 70% of total body mass.

ICF will be calculated as 67% of that total (not 40%) and ECF = 33% (not 20%).

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13
Q

What adjustments should be made when calculating TBW for a geriatric patient?

A

TBW should be calculated as 50% of total body mass.

ICF will be calculated as 67% of that total (not 40%) and ECF = 33% (not 20%).

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14
Q

If a patient is administered 60 uCi of radio-labeled albumin and after 2 hours, that patient has a concentration of 0.02 uCi/ml in their plasma (and we assume he has lost none of the indicator to urine), what can we assume?

A

Radio-labeled albumin is used to measure plasma volume levels.

The indicator dilution equation is:
Compartment volume = (amount injected - amount excreted) / concentration measured in plasma.

Since we assume he lost no radio-labeled albumin to urine, our equation is:

Plasma Volume = 60 / 0.02

The patient’s plasma volume is 3,000 mL

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15
Q

When ECF osmolarity increases, fluid will shift which direction?

A

From ICF –> ECF

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16
Q

When ECF osmolarity decreases, fluid will shift in which direction?

A

ECF –> ICF

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17
Q

The net effect of ADH on body fluids is …?

A

Hypotonic volume increase. ADH helsp regulates body water reabsorption.

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18
Q

The net effect of RAAS on body fluids is …?

A

Isotonic volume increase. RAAS helps regulate Na+ reabsorption.

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19
Q

The primary trigger for ADH release is …?

A

Increased plasma osmolarity

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20
Q

The primary trigger for RAAS activation is …?

A

Loss of plasma volume

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21
Q

How does excretion of a substance relate to the concentration that is filtered across the glomerulus?

A

Excretion in urine = (amount filtered) + (amount secreted) - (amount reabsorbed)

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22
Q

How do the pressures of the glomerulus and the peritubular capillaries compare, and why is this important?

A

The glomerulus has a high hydrostatic (pushing) pressure, while the peritubular capillaries have high oncotic (pulling) pressure. This system promotes reabsorption of solutes.

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23
Q

Describe the process by which nephrons intrinsically regulate their GFR.

A

Tubuloglomerular Feedback:

Levels of NaCl are “sensed” at the distal tubule by Macula Densa cells.

If flow through the tubule is very low, [NaCl] will also be low. Macula densa cells passively allow release from JGA cells. The RAAS system is activated and constriction of the EA occurs, increasing GFR and increasing tubule flow.

If flow through the tubule is very high, [NaCl] will also be high, and the osmotic change will cause a depolarization in these cells. This actively inhibits renin release, inhibiting the RAAS system. The depolarization also allows for the conversion of extracellular ATP –> adenosine, and adenosine constricts the AA, thus reducing GFR and tubule flow.

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24
Q

What kind of cells compose the JGA?

A

Macula densa cells in the distal tubule

JG cells/granular cells of the afferent arteriole

Extracellular mesangial cells but we don’t understand those very well.

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25
Why is PAH an ideal marker of RPF?
Because it is 100% cleared by the kidneys: everything that enters the renal artery is removed from the blood before reaching the renal vein. The clearance of PAH is equal to RPF.
26
How is clearance of inulin significant?
The clearance of inulin can be used to find GFR because it is not reabsorbed or secreted. Everything that enters the blood is either filtered and excreted, or remains in plasma. That means that if we can find what percent was filtered and excreted, we can tell how much is being filtered through the glomerulus.
27
How do endothelial cells contribute to the glomerular filtration barrier?
Fenestrations allow permeability to products smaller than 70 nm. RBCs, WBCs, albumin, and platelets are unable to pass.
28
How does the basement membrane of the glomerular barrier contribute to filtration?
Negative charge: it repels proteins (and molecules bound to proteins), preventing the filter from getting "clogged"
29
How do podocytes contribute to the glomerular filtration barrier?
Slit pores allow permability to products smaller than 40 nm
30
How does charge factor into a molecule's sieving coefficient?
Positive > neutral > negative
31
What pressures support filtration?
P(GC) | π(BS)
32
What pressures oppose filtration?
P(BS) | π(GC)
33
``` What are the normal values for: P(GC) P(BS) π(GC) π(BS) ```
P(GC) = 50 mmHg P(BS) = 10 mmHg π(GC) = 25 mmHg π(BS) = 0 mmHg
34
What is the equation for net filtration pressure? What is the normal value?
NFP = (PGC - PVS) - (πGC - πBS) We're subtracting the hydrostatic force that opposes filtration from the hydrostatic force that supports filtration From that we are subtracting the pulling force back into the glomerulus (less any pulling force into Bowman's space, but that should be 0). If the product is positive, we have filtration. If it is not, we have problems. 15 mmHg is the normal NFP value.
35
Atrophy of podocytes occurs in what disease process, and what occurs?
Minimal change disease is the loss of of filtration due to loss of podocyte feet, and can be primary or secondary. This allows for loss of protein in the urine.
36
In diabetes, how is the glomerular filtration barrier affected?
The BM thickens, making it harder for filtrate to pass.
37
What are the effects of NE/Epi to RBF and GFR?
Constriction of the AA causes decreased RBF and increased GFR
38
What are the effects of AngII and ADH on the efferent arteriole?
AngII and ADH cause constriction of the EA, decreasing RBF
39
What is the effect of adenosine on the AA?
Adenosine causes constriction of the AA, decreasing RBF.
40
Describe why there is a leveling-off effect of the GFR when the EA is constricted.
EA constriction causes decreases RPF and increased PGC. Because the PGC increases, GFR increases. The decreasing RPF means that there is less blood going through the vessels, so after a while the pressure levels off. The stabilizing PGC = leveling off of the GFR.
41
What is the equation for clearance of a substance?
Cl = [U]*UV / P
42
What is the equation for renal fraction?
RBF / CO Usually 20%
43
What is the equation for filtration fraction?
FF = GFR / RPF
44
If clearance of a substance is < GFR, what does this mean? | >GFR?
Cl < GFR means that there has been net reabsorption Cl > GFR means there has been net secretion (If the clearance of a substance = GFR, there has been no net secretion or absorption -- inulin, for example)
45
What is the equation to find filtered load?
FL = P[substance] * GFR
46
What is the equation to find GFR, and what is a normal value?
GFR = Kf * (PGC – PBS) - (πGC - πBS) A healthy GFR ~125
47
Describe Fanconi's syndrome
Generalized deficiency in reabsorption in the proximal tubule.
48
Describe Bartter syndrome
Deficiency of Na+ reabsorption in the ascending limb of the Loop of Henle due to defective NKCC transporters. Hypotension, hypocalcemia, ↑RAAS. Alkalosis can also occur.
49
Describe Gitelman syndrome
Mutation of NCCs in distal convoluted tubule leading to deficient Na+ reabsorption. Can cause some hypotension, ↑RAAS, but less severe than Bartter syndrome.
50
Describe Liddle syndrome
INCREASED activity of ENaCs in the cortical collecting duct, resulting in ↑Na+ reabsorption, ↓RAAS, and hypertension. Treated with amiloride.
51
What are the important transporters in the proximal tubule?
Apical side: N/H+ exchangers SGLT/Pi/AA/Na+ transporters (discussed later) Na+/HCO3- co-transporters (basolateral side) Na+/K+ pumps
52
What important paracellular transport occurs in the proximal tubule?
This segment is permeable to water. As Na+ is pumped into the interstitium, water follows paracellularly
53
What is the action of carbonic anhydrase inhibitors?
Carbonic anhydrase inhibitors reduce Na+ reabsorption and primarily act on the proximal tubule. Carbonic anhydrase is needed to allow the movement of bicarb from the lumen into the cell in the form of CO2, where it can then dissociate and help Na+ leave the basolateral side of the cell via Na+/HCO3- co-transporters. Inhibiting carbonic anhydrase inhibits this process (inhibits action of Na+/HCO3- transporters). Decreasing reabsorption of Na+ in the PT causes increased flow downstream, which causes loss of K+ in the collecting duct.
54
What are the important transporters in the ascending limb?
In addition to NHE's and Na+/K+ pumps seen in the PT, the AL has NKCCs, which bring in one Na+, one K+, and two Cl-.
55
What important paracellular transport occurs in the AL?
NKCCs bring one Na+, one K+, and two Cl- into the cell. K+ leaks back to the lumen via an apical K+ leak channel. This creates a + charge in the lumen, "pushing" Na+, Ca2+, and Mg2+ into the interstitium paracellularly. Because this segment is non-water-soluble, water does not travel paracellularly.
56
What is the action of furosemide?
Furosemide, a loop diuretic, inhibits NKCCs in the AL of the LOH. This decreases Na+ reabsorption. Decreasing reabsorption of Na+ in the AL causes increased flow downstream, which causes loss of K+ in the collecting duct.
57
What are the important transporters in the distal tubule?
In addition to Na+/K+ pumps seen in proximal segments, NCC transporters bring in one Na+ and two Cl-.
58
What is the action of thiazide diuretics?
Thiazide diuretics decrease Na+ reabsorption via inhibition of NCCs in the distal tubule. Decreasing reabsorption of Na+ in the distal tubule causes increased flow downstream, which causes loss of K+ in the collecting duct.
59
What are the important transporters found in the principal cells of the cortical collecting duct?
ENaCs are time-gated or endocytosed ~20-30 minutes. When active, they bring Na+ into the cell. ROMKs are also present, and secrete K+ into the tubular lumen. Na+/K+ pumps are present in all segments.
60
What is the action of Amiloride?
Amiloride inhibits ENaCs, ROMKs, and Na+/K+ pumps in the principal cells. These are K+ sparing! They do not increase distal flow significantly and they inhibit K+ secretion while decreasing Na+ reabsorption.
61
What are the actions of RAAS on the various transporters of the nephron?
RAAS is activated by the SNS, decreased flow (decreased [NaCl]) past the cells of the macula densa, or low pressure in the afferent arteriole. Renin converts angiotensinogen to angI, and ACE cleaves angI into angII. AngII increases reabsorption of Na+ in the proximal tubule by increasing activity of NHEs, Na+/HCO3- transporters, and Na+/K+ pumps. It also has activity outside of the nephron. AngII also stimulates release of ADH and aldosterone, allowing "enhancing" effect in the AL and CD. RAAS activation results in an ISOtonic volume increase.
62
What are the actions of ADH on the various transporters of the nephron?
ADH works in the AL, CCD, and MCD: AL: increases NKCC activity in the AL, CCD: increased ENaC expression and increased Na+/K+ activity MCD: increased Na+/H2O reabsorption via increased UTA1 and AQP2 expression. These combined effects are not as significant as AngII's proximal effects. ADH causes a HYPOtonic volume increase.
63
What are the actions of aldosterone on the various transporters of the nephron?
Aldosterone works in the CCD, increasing ENaC expression, AQP2 insertion, and H+ secretion from intercalated cells. These combined effects are not as significant as AngII's proximal effects.
64
What stimuli trigger ADH action in the nephron?
*Increased plasma osmolarity AngII (via RAAS, which is in turn stimulated by SNS, low AA pressure, or decreased flow at macula densa) Decreased pressure sensed by baroreceptors in the atria
65
What stimuli trigger aldosterone action in the nephron?
AngII (via RAAS, which is in turn stimulated by SNS, low AA pressure, or decreased flow at macula densa)
66
What are the stimuli for ANP/BNP secretion?
- Cardiac distention (caused by volume increase at atria) (cardiac distention may be secondary to SNS stimulation) - AngII reaching the cardiac tissue (this is the "brake pedal" for the RAAS system)
67
What are the actions of ANP/BNP?
ANP/BNP works to reduce ECFV bina decreasing Na+ reabsorption and increasing water excretion. It inhibits RAAS, causing an isotonic fluid decrease, and increases vasodilation, decreasing BP.

Renal (3 decks)

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