ICL 1.2: Renal Physiology I Flashcards

1
Q

what is the glomerulus and juxtaglomerular apparatus?

A

glomerulus is the blood coming in through the afferent arteriole and leaving through the efferent arteriole and getting filtered in the glomerulus

everything except proteins and RBCs get filtered at the glomerulus

under normal conditions, there should be no protein in the urine or else it means there’s a problem!

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2
Q

what is the main barrier to the filtration of molecules through the glomerulus?

A

the size and charge of the basement membrane that actually contributes to the barrier for the filtration of proteins or any other molecule

as the size increases the filtration decreases

the charge also matters: 60% is filtered when it’s positive, 20% when it’s positive and 0% when it’s negatively charged so molecules of the same size will have increased filtration if they’re positively charged! –> if the size is small the charge doesn’t really matter though

water, sodium, glucose and insulin are 100% filterable but myoglobin and albumin are not!

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3
Q

what are glomerular diseases?

A

intrinsic glomerular cells (Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells ) and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease

some examples include:
1. nephrotic syndrome

  1. nephritic syndrome
  2. glomerulonephritis
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4
Q

what is minimal change nephropathy?

A

a condition in certain kidney diseases in which the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology –> negative charges of the basement membrane usually repel negatively charged proteins so without it you’ll start to see albumin in the urine!

probably related to an immunological response with abnormal T-cell secretion of cytokines that reduce anions in the glomerular capillary or podocyte proteins

some lower molecular weight proteins, especially albumin, appear in the urine (proteinuriaoralbuminuria)
most common in young children but also seen in adults with autoimmune disorders

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5
Q

what is renal blood flow?

A

RBF is the combined blood flow through the kidneys

the kidney receives 20% of the cardiac output = about 1 L

the renal cortex receives most of it while the blood flow in the renal medulla (vasa recta) is only 1-2% of the RBF

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6
Q

what are the 2 equations for RBF?

A

RBF = RPF/(1-hematocrit)

RBF = (renal artery pressure - renal vein pressure)/total renal vascular resistance

RBF = renal blood flow

RPF = renal plasma flow; the flow of plasma

hematocrit = proportion by volume of RBF that consists of RBC

renal artery pressure = systemic arterial pressure

renal vein pressure = 3-4 mmHg

total renal resistance = afferent + efferent arteriole resistances

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7
Q

what is the equation for total renal resistance?

A

total renal resistance = afferent + efferent arteriole resistances

increasing ANY of the two reduces renal blood flow

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8
Q

what is GFR?

A

GFR = glomerular filtration rate

it’s how much blood is being filtered by all the individual nephrons combined per minute! it’s an index of kidney function

GFR is equal to the sum of the filtration rates of all functioning nephrons

normal = 60-120

kidney disease = 15-60

kidney failure = 0-15

glomerular ultrafiltration is the first step in line formation! the ultra filtrate has solute concentrations similar to blood plasma, except for proteins and formed elements

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9
Q

what is the filtration fraction?

A

FF = GFR/renal plasma flow

filtration fraction is the fraction of the renal plasma that is filtered

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10
Q

if renal plasma flow is 500 mL/min and hematocrit is 50%, what is the blood flow to the kidneys?

A

RBF = RPF/(1-hematocrit)

RBF = 500/(1-.50)
RBF = 500/0.5
RBF = 1000 mL = 1 L/minute
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11
Q

calculate the filtration fraction if GFR = 120 mL/min and RPF = 500 mL/min

A

FF = GFR/renal plasma flow

FF = 120/500
FF = 0.24

the amount of blood that’s filtered out of the total amount

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12
Q

calculate the filtration fraction if GFR = 0.15 L/min and RPF = 600 mL/min

A

FF = GFR/renal plasma flow

FF = 150/600
FF = 0.25

convert the L into mL!

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13
Q

determine filtration fraction if renal blood flow = 1.25 L/min, Hct = 40% and GFR = 125 mL/minute

A

FF = GFR/renal plasma flow

RBF = RPF/(1-hematocrit)
RPF = RBF*(1-Hct)
RPF = 1250(1-0.4)
RPF = 750
FF = GFR/RPF
FF = 125/750
FF = 0.16
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14
Q

if the GFR is reduced by 1/2 due to a glomerular disease with no change in renal blood flow, the filtration fraction would be ____of the normal

A

FF = GFR/RPF

since RBF didn’t change then RPF didn’t change either but GFR is reduced by 1/2

so the filtration fraction would be 1/2 the normal!

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15
Q

what is the normal GFR, RBF, RPF and FF in an adult?

A

GFR = 125 mL/min

RBF = 1 L/min

RPF = 600 mL/min

FF = 0.2

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16
Q

what are the physical forces that effect GFR?

A

net filtration pressure is positive in the glomerular capillaries!

πB is basically zero because Bowman’s capsule oncotic pressure is zero because no protein gets filtered so there’s no protein in that space to contribute to the oncotic space! but there IS hydrostatic pressure because 20% of water gets filtered here

GFR = Kf x ( PG + πB – PB – πG)

GFR = Kf x ( PG – PB – πG)

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17
Q

what is the glomerular capillary filtration coefficient?

A

GFR = Kf x ( PG + πB – PB – πG)

Kf is the glomerular capillary filtration coefficient and it depends on the thickness of the capillaries! changes in Kf are not a primary mechanism for the normal day-today regulation of GFR

Kf= hydraulic conductivity X surface area of the glomerular capillaries

chronic uncontrolled HTN and DM decreases Kf by increasing the thickness of the glomerular capillary membrane and reducing hydraulic conductivity

so if Kf increases, GFR increases and if Kf decreases, GFR decreases

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18
Q

how does Bowman’s capsule pressure regulate GFR? what’s the equation for GFR based on Starling forces?

A

normally, changes in Bowman’s capsule pressure do not regulate GFR

but obstruction of the urinary tract increases PB and reduces GFR

GFR = Kf x ( PG + πB – PB – πG)

conditions that could cause this include precipitation of calcium or of uric acid may lead to “stones” that lodge in the urinary tract raising PB –> this eventually leads tohydronephrosis(distention & dilation of renal pelvis & calyces)

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19
Q

if the RBF is reduced by 1/2 with no change in GFR, the filtration fraction would be _____of the normal

A

FF = GFR/RPF

if RBF is reduced then RPF is reduced but GFR isn’t changed so FF is doubled!

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20
Q

if the RBF is reduced by half with no change in GFR, the unfiltered blood in the glomerulus will be ____and the proteins in the blood will be ____ compared to the normal

A

less and concentrated

if RBF is reduced it means that less blood is coming through the kidney but you’re still filtering the same amount of blood so there is less unfiltered blood! this means the amount of unfiltered proteins will be less because FF has increased

FF increases which means you filter more = less unfiltered blood in the glomerulus –> less unfiltered blood in the glomerulus means higher relative concentration of protein

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21
Q

if the GFR is reduced by half due to glomerular disease with no change in renal blood flow or filtration properties, the Bowman’s capsule oncotic pressure would:

A. double

B. 1/2

C. unchanged

A

C. unchanged

when the FF is increased the blood becomes more concentrated with protein –> if that’s the case then the Bowman’s capsule oncotic pressure will NOT change because protein never goes to the Bowman’s capsule!

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22
Q

if the RBF is reduced by 1/2 with no change in GFR or filtration properties, the glomerular capillary oncotic pressure would be:

A. increased

B. decreased

C. unchanged

A

RBF is reduced but GFR is unchanged, unfiltered blood is less and proteins will be more concentrated

so 500 mL of blood is coming, 125 is being filtered so 375 mL is unfiltered and it’s more concentrated with protein

so oncotic pressure in the glomerular capillary will be increased

this is because there is more protein in whatever solution is left behind so the capillary oncotic pressure is increased! part of the blood that’s coming is getting filtered but for some reason the part getting filtered doesn’t change yet less blood is coming so then the blood leaving the glomerulus in the efferent arteriole is more concentrated because the fluid volume is less which increases the oncotic pressure

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23
Q

what are the two factors that influence the glomerular capillary colloid osmotic pressure?

A
  1. arterial plasma colloid osmotic pressure (high πc = high πG)
  2. filtration fraction (high FF concentrates the plasma proteins and raises πG)

high FF means more fluid is filtered but that doesn’t mean GFR is increased too

24
Q

how does a high FF effect GFR?

A

FF = GFR/RPF

high FF raises πG which decreases GFR

even though GFR doesn’t change when renal blood flow changes due to any resistance in the kidney, this decreases RBF but if there’s no change in GFR then the FF will increase which will eventually lead to a decrease in GFR

even with a constant glomerular hydrostatic pressure, increased blood flow into the glomerulus tends to increase GFR while decreased blood flow into the glomerulus tends to decrease GFR

25
Q

what can cause decrease in RBF?

A

ANY obstruction in the kidney including afferent or efferent arterioles

26
Q

what factors determine glomerular capillary hydrostatic pressure?

A

increased PG increases GFR

PG is determined by:
1. arterial pressure (increased AP raises PG and thereby GFR)

  1. afferent arteriolar resistance (RA)

increased RA means there is less blood getting to the glomerulus so PG will be decreased and subsequently GFR – if you dilate the afferent arteriole this will allow for more blood flow causing increased PG and increased GFR

  1. efferent arteriolar resistance (RE)

increased RE during efferent arteriole constriction means PG is increased and GFR increases too – if you dilate the efferent arteriole then you’re decreased PG which decreases GFR

RBF is decreased in both 2 and 3 so an increase in RA or RE will decrease RBF!

27
Q

calculate the GFR if the glomerular capillary filtration coefficient Kf = 10 mL.min/mmHg, Bowman’s capsule hydrostatic pressure = 20 mmHg, glomerular capillary oncotic pressure = 35 mmHg and glomerular capillary hydrostatic pressure = 70 mmHg

A

GFR = Kf x ( PG + πB – PB – πG)

GFR = 10(70+0-35-20)
GFR = 10(15)
GFR = 150
28
Q

the net glomerular filtration pressure in a patient is 18 mmHg. if PGC = 60 mmHg and πGC = 30 mmHg, what is PBC?

A

GFR = Kf x (PG + πB – PB – πG)

18 = (60+0-PB-30)
18 = 30-PB
-12 = -PB

PB = 12

29
Q

how does afferent arteriolar constriction effect GFR?

A

constriction of afferent arterioles reduces GFR

30
Q

how does efferent arteriolar constriction effect GFR?

A

efferent arteriolar constriction has a biphasic effect on GFR

at moderate levels of constriction there is a slight increase in GFR

with severe constriction there is a decrease in GFR

initially there’s an increase in hydrostatic pressure due to increased efferent resistance which increases PG and consequently increases GFR –> however, over time the increased GFR increases FF which means glomerular oncotic pressure increases because protein is getting concentrated in the glomerulus – this opposes filtration! so that’s why initially there’s increased GFR but then it ultimately leads to a decrease in GFR

side note: RBF decreases in both!!!

31
Q

what changes would you expect to find after administering a vasodilator drug that causes a 50% decrease in afferent arteriolar resistance and no change in arterial pressure?

A. decreased RBF, GFR and peritubular capillary hydrostatic pressure

B. decreased RBF and GFR but increased peritubular capillary hydrostatic pressure

C. increased RBF, GFR and peritubular capillary hydrostatic pressure

D. increased RBF and GFR but no change in peritubular capillary hydrostatic pressure

E. increased RBF and GFR but decreased peritubular capillary hydrostatic pressure

A

C. increased RBF, GFR and peritubular capillary hydrostatic pressure

decrease in afferent arteriolar resistance increases RBF because there’s vasodilation!

no change in arterial pressure but with vasodilation means more blood is coming to the glomerular capillary which means hydrostatic pressure in the glomerulus increases and therefore GFR is increased too; all the pressure is increased in both the glomerular and peritubular capillaries!

increased PG
increased GFR
increased RBF

32
Q

how does strong SNS activation effect GFR?

A

it decreases GFR

the blood vessels of the kidneys are richly innervated by sympathetic nerve fibers and STRONG activation of the renal sympathetic nerves constrict renal arterioles and decrease RBF and GFR

severe, acute distur­bances lasting for a few hours = brain ischemia, severe hemorrhage)

moderate or mild sympathetic stimulation has little influence on RBF and GFR because sym­pathetic tone does not have much influence on RBF in a healthy resting person

33
Q

how does norepinephrine and epinephrine effect the renal circulation?

A

theyconstrict afferent and efferent arterioles reducing GFR and RBF

but only under extreme conditions!!

34
Q

how does endothelin effect the renal circulation?

A

increased endothelin, which happens in vases of vascular injury, causes renal vasoconstriction and decreased GFR

35
Q

how does endothelial-derived NO effect the renal circulation?

A

basal levels maintain vasodilation of the kidneys!

drugs that inhibit NO formation, impaired NO production increases renal vascular resistance, decreases GFR and increases blood pressure

36
Q

how do prostaglandins effet renal circulation?

A

prostaglandins opposes vasoconstriction of afferent arterioles & prevent excessive reductions in GFR and renal blood flow under normal conditions

under stressful conditions (volume depletion or after surgery) NSAIDs like aspirin that inhibit prostaglandin synthesis may cause significant reductions in GFR

37
Q

how does angiotensin II effect the GFR and RBF?

A

angiotensin II constricts both the efferent and afferent arterioles which means RBF would decrease in both cases

however, GFR would decrease with afferent constriction and increase with efferent constriction

so since FF = GFR/RPF and RPF is decreased due to the decreased RBF but GFR isn’t changing, then theoretically FF should increase but this isn’t happening in reality…instead there’s preferential constriction of efferent arterioles because NO and prostaglandins oppose afferent arteriole constriction! so that means efferent constriction will decrease RBF and increase GFR and this is the overall effect of angiotensin II

this happens because when angiotensin is released it’s due to decreased in arterial pressure or volume depletion which is causing a decrease in GFR due to low glomerular hydrostatic pressure! this is detected by the macula densa which will then release renin and cause production of angiotensin which selectively constricts the efferent arterioles thereby increasing the GFR which balances out the initial decrease in GFR!

angiotensin selectively constricts efferent arterioles and helps to minimize decrease in GFR due to decrease in arterial pressure

38
Q

what is the long term adjustment of arterial blood pressure by the kidney?

A

vasoconstriction of afferent arterioles

39
Q

how does the autoregulation of the kidney work?

A

20% of your blood goes to the kidneys and gets filtered but GFR remains constant irrespective of changes in arterial blood pressure –> even if you have an increase in BP which increases hydrostatic glomerular capillary pressure that means way more blood is filtered and you’d be peeing a TON more urine! but this doesn’t happen because of autoregulation and small changes in BP don’t lead to changes in urination

autoregulation is independent of nervous and endocrine system!!

two components:

  1. myogenic response: responds to changes in arterial pressure
  2. tubuloglomerular feedback: TGF responds to changes in tubular [NaCl]
40
Q

what is tubuloglomerular autoregulation of the kidney?

A

feedback is coming from the tubule to the glomerulus

filtration is happening in the glomerulus so if the tubule is giving feedback to the glomerulus, GFR will be changed!

RAAS is activated when there’s a decrease in NaCl which increases renin and angiotensin secretion which increases efferent arteriolar resistance which increases GFR! this offsets the initial decrease in GFR from the decreased arterial pressure/decreased glomerular hydrostatic pressure

when there’s an increase in arterial pressure the glomerular hydrostatic pressured GFR increase so RAAS will be deactivated

the other part of of the tubuloglomerular feedback outside RAAS activation is when the macula densa senses increased NaCl from increased arterial pressure, it can increase afferent arteriole resistance to decrease GFR! it does this via ATP and adenosine (if BP is low, there won’t be ATP and adenosine around)

so RAAS is more active when there’s a decrease in pressure while afferent arteriolar vasodilation is increased with high BP

41
Q

what is myogenic autoregulation of the kidney?

A

as soon as there’s an increase in BP, the renal afferent arteriole gets stretched which signals the smooth muscle to constrict which increases the resistance

this offsets the increase in pressure and RBF and the GFR is kept constant

42
Q

how does high protein intake effect RBF and GFR?

A

high protein intake increase RBF and GFR due to changes in tubuloglomerular feedback

protein ingestion causes increased amino acid levels which are then reabsorbed in the proximal tubule which increases NaCl reabsorption in the proximal tubule because you need NaCl for the cotransport of AA

then the macula densa senses low NaCl! we have plenty of sodium but we just reabsorbed a bunch of it so your kidney is trying to reabsorb more sodium and it does this by decreasing afferent arteriolar resistance to increase GFR!

43
Q

why is there hyper-filtration in DM?

A

hyperfiltration in diabetes partly due to changes in tubuloglomerular feedback –> in DM there’s more glucose which also requires NaCl for its cotransport so there’s more NaCl being resorbed which makes the kidney think there’s low NaCl levels since the [NaCl] urine at the macula densa is decreased –> this means the kidney will react by increasing afferent arteriole diameter to increase glomerular capillary hydrostatic pressure to ultimately increase GFR

GFR increases progressively as diabetes develops!

increased GFR is due to afferent arteriolar dilation and increased PG

the arteriolar dilation is partly mediated by TGF

increased PG may contribute to development of diabetic nephropathy

44
Q

what does the amount of urine represent?

A

urine + all the substances in the urine represent the sum of three basic renal processes = glomerular filtration, tubular reabsorption, and tubular secretion

urinary excretion = glomerular filtration - tubular reabsorption + tubular secretion

filtration = nondiscriminant filtration of a protein-free plasma from the glomerulus into Bowman’s capsule

reabsorption = selective movement of filtered substances from the tubular lumen into the peritubular capillaries

secretion = selective movement of non filtered substances from the peritubular capillaries into the tubular lumen

45
Q

what is clearance?

A

the volume of plasma per unit time from which all of a specific substance is removed (cleared) by the kidneys

if the plasma passing through the kidneys contains 1 mg of a substance in each ml and if 1 mg of this substance is also excreted into the urine each min, then 1 ml/min of the plasma is “cleared” of the substance

clearanceis the volume of plasma that would be necessary to supply the amount of substance excreted in the urine per unit of time

46
Q

what is the equation for clearance?

A

Cs = (Us x V)/Ps

Cs = clearance rate of substance S

Ps = plasma concentration of S

Us = urine concentration S

V = urine flow rate

(Us x V) = excretion

47
Q

what does renal clearance for any solute depend on?

A
  1. glomerular filtration: for freely filtered solutes, changes in GFR directly affect the clearance

so if there’s more GFR, more will be cleared

  1. increased tubular reabsorption reduces clearance for a solute
  2. increased tubular secretion increases clearance for a solute
48
Q

how is clearance used to measure GFR?

A

you can use clearance to measure GFR! this is only if a substance is freely filtered without any reabsorption or secretion

ex. inulin

whatever is filtered will be secreted in the urine so that means the amount of plasma from which that substance is cleared in 1 minute is the volume of plasma filtered in 1 minute –> the amount of inulin filtered is the volume of plasma filtered in 1 minute which is the GFR!

GFR = (Us x V)/Ps

49
Q

what substance can be used to estimate GFR?

A

creatinine clearance and plasma creatinine concentration can be used to estimate GFR

creatinine is a by-product of muscle metabolism and it is cleared almost entirely by glomerular filtration

creatinineclearance(CCr) provides a reasonable estimate of GFR

widely used clinically since itdoes not require intravenous infusion

approximation ofchangesin GFR can be obtained by measuring plasma creatinine concentration (PCr) (which is inversely proportional to GFR)

as renal disease progresses and GFR declines, serum creatinine increases! this is because decreased GFR means there’s less filtration of creatinine and less urinary creatinine excretion! so creatinine excretion < creatinine production which means there will be an increase in serum creatinine

in renal disease, as GFR declines less creatinine is filtered and serum creatinine gradually increases!

50
Q

how can you estimate RPF?

A

if a substance iscompletelycleared from the plasma, then clearance = RPF

so if there’s 500 mL of blood in the kidney every minute then the substance will be cleared in 500 mL

para-aminohippurate (PAH) (90% cleared from the plasma) used for estimating RPF

the amount of PAH delivered to the kidneys (RPF × PPAH) = amount excreted in the urine (UPAH× V)

so there is filtration and secretion happening and almost all the PAH entraining the kidney leaves in the urine vs. with insulin there is only filtration, no secretion or reasorbtion so 20% is filtered and lost through the urine

RPF = (U(PAH) x V)/P(PAH)

51
Q

the maximum clearance rate possible for a substance that is totally cleared from the plasma is equal to which of the following?

A. GFR

B. RPF

C. filtered load of that substance

D. urinary excretion rate of the substance

E. filtration fraction

A

B. RPF

it’s totally cleared from the plasma, not just from the filtered load

only 20% of the plasma is filtered while 80% goes through the efferent arteriole and would also need to be secreted

52
Q

what is GFR vs RPF?

A

RBF = the rate at which blood is entering and leaving the entire kidney

GFR = the amount of the blood that gets filtered through all the nephrons which is about 20% of the CO

RPF = blood has RBC, WBC, proteins etc. but minus the RBCs is the plasma! it’s about 40% of the blood is plasma and only the plasma portion of the blood is what’s available to be filtered!!

so that’s why when a substance is just getting filtered then it’s equivalent to the GFR but if it’s being totally cleared from the blood it’s equal to the renal plasma flow!!

53
Q

a patient has creatinine clearance of 100 mL/min, a plasma K+ concentration of 4 mol/L, a urine flow rate of 2.0 mL/minute and a urine K+ concentration of 60 mmol/L. what is his approximate rate of potassium excretion?

A

you don’t need to know GFR or clearance for this! so the excretion rate of K+ is the concentration of the substance in the urine x flow rate of the urine

excretion = 60 mmol/L x 2 mL/min

= 0.12 mmol/min

54
Q

a patient collects 3.6 L of urine in a 24 hour period. his plasma and urine creatinine are 4 mg/dL and 24 mg/dL respectively. what is the GFR in this patient?

A

creatinine clearance is the GFR!!

Cs = Us x V/Ps

V = 3600/24x60 = 2.5 mL/min (flow rate)

Cs = (24x2.5)/4
Cs = 15
55
Q

what is the approximate RPF in a patient with a urine flow rate of 1 mL/min and plasma and urine PAH concentration of 0.05 mg/dL and 30 mg/dL respectively

A

clearance of PAH = RPF

Cs = Us x V/Ps
Cs = (30x1)/0.05
Cs = 600
56
Q

what is the renal blood flow if the Hct = 0.5 and RPF = 600 mL?

A

RBF = RPF/(1-hematocrit)

RBF = 600/(1-0.5)
RBF = 1200
57
Q

you are infused with an antibiotic so that plasma concentration is 0.05 mg/mL. the antibiotic is excreted at a concentration of 1.5 mg/mL and the urine flow rate is 1 mL/min. what is the clearance of the substance?

A
Cs = Us x V/Ps
Cs = (1.5 x 1)/0.05
Cs = 30 mL/min