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Renal > Lecture 6: Tubular Fxn 1 > Flashcards

Lecture 6: Tubular Fxn 1 Flashcards

1
Q

Define fractional reabsorption (FR)

A

The fraction of the filtered solute that has been reabsorbed

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2
Q

What is the equation for determining fractional reabsorption?

A

FR = 1 - FE

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3
Q

Where does virtually all regulation of potassium excretion occur?

A

Connecting tubule (CNT)

Collecting duct (CD)

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4
Q

List four routes for water output from the body, identifying the output that is most closely regulated

A

Insensible loss (skin, lungs)

Sweat

In feces

Urine **

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5
Q

List a typical normal plasma osmolality (Posm) and the typical range for urine osmolality (Uosm)

A

Posm = 290 mOsm/kg H2O

Uosm = 50 - 1200 mOsm/kg H2O

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6
Q

Estimate the fluid intake needed to excrete an osmotic load of 600 mOsm/day if Uosm is equal to the normal:

A) max Uosm
B) Posm
C) min Uosm

A

A) 0.5 L

B) 2.0 L

C) 12 L

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7
Q

What are the values for minimum Uosm and maximum Uosm?

A

Minimum
50 mOsm/kg H2O

Maximum
1200 mOsm/kg H2O

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8
Q

What is the value of Posm?

A

300 mOsm/kg H2O

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9
Q

How much does the proximal tubule reabsorb of Na + anions and water?

A

2/3

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10
Q

List four general steps involved in isoosmotic reabsorption form the PT into the peritubular capillaries and list the driving forces for each step

A

Step 1: Na/K ATPase pumps sodium out to interstitium
Driving force: ATP

Step 2: at lumen side, uptake of Na + anions occurs
Driving force: electrochemical Na gradient

Step 3: transcellular reabsorption of water through water channels
Driving force: osmotic gradient

Step 4: bulk flow of water and solute from interstitium to peritubular capillaries
Driving force: convection/ Starling forces

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11
Q

What about the peritubular capillaries makes it easy to accept so much flow of solutes and fluid?

A

They are fenestrated

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12
Q

For transcellular transport, describe the energy sources for

Primary active transport
Secondary active transport

In moving solutes against their electrochemical gradients

A

Primary active:
ATP

Secondary active:
One solute moves down its concentration gradient in order to power the movement of another solute up its gradient

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13
Q

What kind of transport occurs in uniporters?

A

Facilitated diffusion

Movement due to single solute’s electrochemical gradient

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14
Q

Differentiate between transcellular and paracellular transport

A

Transcellular = through cell

Paracellular = between cells (via tight junctions)

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15
Q

Describe the driving force and pathway for paracellular solute reabsorption

List important examples of solutes reabsorbed this way in the PT

A

Diffusion across “leaky” tight junctions into the lateral interstitial space

Driving force = electrochemical gradient, PASSIVE TRANSPORT

Examples:
Na, Cl, Ca, Mg, K, urea

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16
Q

Why is paracellular transport important?

A

Helps kidneys lower energy costs

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17
Q

How would an increase in filtration fraction affect peritubular capillary oncotic pressure (Pi(PTC)) and how would that change fluid reabsorption in proximal tubule?

A

Both would increase

Increasing GFR increases peritubular capillary oncotic pressure

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18
Q

Define glomerulotubular balance (GTB)

A

Near linear relationship between filtration (GFR) and reabsorption in proximal tubule as a means of stabilizing excretion to make sure we don’t lose a lot of fluid to urine

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19
Q

Briefly describe mechanisms for GTB that involve changes in starling forces to PT and luminal mechanism

A

Starling force changes:
Parallel changes in filtration fraction and peritubular capillary oncotic pressure

Luminal mechanism:
Luminal flow rate - shear strain on PT brush border recruits apical co-transporters

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20
Q

List the FR in the PT for water, sodium, chloride, bicarbonate, nutrients (glucose and amino acids), and bone minerals (calcium, phosphate)

A

Water, sodium chloride = 2/3

Bicarbonate = 80-90%

Glucose, amino acids = 100

Calcium = 50-60%

Phosphate = 80%

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21
Q

Describe the most important examples of “asymmetrical” solute transport in the PT

Explain why such asymmetrical solute transport is energetically more efficient for the kidney

A

S1 = early PT
Low Cl reabsorption (little permeability)

S2/S3 = late PT
High [Cl] and reabsorption

Energetically more favorable to have asymmetry because it establishes a concentration gradient to act as driving force for Cl transport to go down its gradient

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22
Q

Describe reabsorption of sodium in the PT

A

Transcellular = active 1/2
Basolateral Na/K ATPase
Driving force: gradient at apical side to power Na uptake into cell
Things that establish Na apical gradient: 1) symporters with glucose, amino acids, phosphate
2) NH3 pumps out H to bring in Na

Paracellular = passive 1/2
Na reabsorption secondary to Cl paracellular reabsorption (which generates lumen positive potential)

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23
Q

Describe asymmetry in reabsorption of bicarbonate in PT

A

Transcellular reabsorption because of preference for early PT reabsorption

Important players:
NH3: to recycle H and bring in Na

H ATPase: helps recycle H

Carbonic anhydride: makes bicarbonate

NBC1: pumps out Na and bicarbonate into blood

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24
Q

Describe reabsorption of chloride into PT

A

Most occurs in late PT

Transcellular:
Cl anion exchange: powered by organic anions that move down their gradients from inside cell to lumen
NHE3 brings Na in and sends H out so that it can combine with anion and bring them in for recycling as an acid

Paracellular:
Tight junctions permeable to Cl in later PT and establish electrochemical gradient

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25
Q

Describe reabsorption of glucose in PT

A

100% reabsorbed transcellularly

SGLT2 = early PT

SGLT1 = late PT

Glucose pushed into blood via GLUT2 basolateral uniporter

26
Q

Describe reabsorption of amino acids in PT

A

Majority transcellular

Na-coupled symporters will bring in sodium and amino acid

27
Q

What is the role of amino acid reabsorption in high protein diet?

A

High protein diet induces hyper filtration through tubuloglomerular feedback:

More AA’s in tubular fluid means more Na will be brought in with symptorter - leaves less sodium to reach macula densa

Macula densa responds with sending signals to increase GFR

28
Q

Describe phosphate reabsorption in PT

A

Transcellular:

Na-coupled symporter = NPT

29
Q

How is phosphate reabsorption regulated?

A

Hormones PTH and FGF will induce endocytosis of NPTs (Na-coupled symporters) so as to reduce reabsorption of phosphate

30
Q

Identify and describe the mechanism for a class of anti-diabetic drugs that acts in the PT

A

“Gliflozins” inhibit SGLT-2 to block reabsorption of glucose in early PT

Effect is that downstream SGLT in late PT will increase reabsorption of filtered glucose

31
Q

Define transport maximum (Tm) and identify an important solute that has a Tm in the PT

A

Tm = maximum tubules can reabsorb before the remainder gets excreted

Glucose has Tm = 375 mg/min in PT

32
Q

Describe the relative water permeability of the PT, thick ascending limb, DCT, connecting tubule (CNT) and collecting duct (CD)

Name the channel responsible for water permeability of the PT

A

PT = always permeable
High constitutive water permeability via AQP-1 in apical AND basolateral membrane

Thick AL, DCT = low/no permeability

CNT/CD = regulated water permeability

33
Q

TF/P ratios for chloride initially rise as fluid moves along the PT. THis is because:

A

Bicarbonate is the anion preferentially reabsorbed in S1

Near isoosmotic reabsorption leads ot rising TF/P for chloride

34
Q

For organic cation secretion:

A) describe the basolateral and apical transporters involved

B) list important examples of endogenous molecules and drugs that are substrates

A

A) cross basolateral via organic cation transporter (OCT); cross into lumen via cation antiporter

B) endogenous = creatinine, dopamine, epinephrine, histamine
Drugs = cimetidine, cisplatin

35
Q

For organic anion secretion:

A) describe the basolateral and apical transporters involved

B) list important examples of endogenous molecules and drugs that are substrates

A

A) cross basolateral end via organic anion transporter (OAT) and into lumen via ATP pump (MDR or MRP) or anion exchanger

B) endogenous = creatinine, bile salts, fatty acids, oxalate, irate
Drugs = PAH, penicillin, furosemide

36
Q

Describe secretion characteristics of organic anions in PT

A

Secretion not affected by protein binding

Limited by transport maximum

Inhibited by probenecid (inhibits OATs)

37
Q

Briefly describe urate transport in the PT

A

Secretion and reabsorption occur in PT

Majority of urate is net reabsorbed

38
Q

Describe hypouricemia

It can be a result of mutations to which transporters?

A

Uric acid lost to urine and blood levels decrease

GLUT9 and URAT1

39
Q

What disease is associated with high P(urate)?

A

Hyperuricemia/gout

Can’t be secreted to urine and so levels accumulate in the blood

40
Q

Name drug that can decrease P(urate) and explain its mechanism

A

Thiazides = competes for secretion

Probenecid = inhibits reabsorption

41
Q

For loop of Henle describe transporters or other pathways for reabsorption of

Na, K, Cl, Ca, and Mg

In the thick AL, identifying the driving force for each

Predict effect of inhibiting NKCC2 or ROMK on reabsorption of each

A

NKCC2 = symporter for Na, Cl, and K

ROMK = transporter for K into lumen

CLC-KB = basolateral chloride channel

Paracellular cation transport for Na, Ca, Mg, and K (driving force = lumen positive trans-epithelial potential)

Inhibition of NKCC2 or ROMK would decrease reabsorption of solutes

42
Q

What happens where there is high calcium levels in the blood?

A

High calcium levels would be sensed by CaSR, which will inhibit trans-epithelial potential and paracellular transport

This allows calcium to build in the urine until the level in the blood can get readjusted or regulated

43
Q

What is Bartter’s syndrome?

A

Genetic loss of function mutation that involves impaired salt reabsorption because NKCC2, ROMK, or CLC-KB transporters are affected

And all 3 transporters work together in sync

44
Q

If you could sample tubular fluid at the end of the cortical thick AL and measure its osmolality, what would you find?

A

The fluid would have a lower osmolality than the plasma

45
Q

Explain why the thick AL is a diluting segment, appreciating that tubular fluid at the macula densa has a lower osmolality than plasma - regardless of the final osmolality of the urine

A

Thick AL is where salt comes out, but there’s no permeability for water, so water stays in and dilutes the little salt remaining

46
Q

Why is it important to study changes in the hydraulic and oncotic pressure differences in the renal circulation?

A

Differences in glomerular capillaries can be used to calculate NFP = important GFR determinant

Differences in peritubular capillaries can be used to calculate net reabsorption pressure = important determinant of reabsorption of water and solutes in PT

47
Q

What form of the Starling equation is used to describe filtration in glomerular capillaries?

A

GFR =
Kf [ (P(GC) - P(BS)) - Pi(GC)]

Where GC = glomerular capillary
BS = Bowman’s space

48
Q

Why is there no sigma or Pi(BS) term in the starling equation for GFR?

A

Glomerular capillary endothelial cells do NOT have a large pore system - this means significant filtration of plasma proteins does not occur

Normal filtration barrier there is therefore “perfectly reflective) (sigma = 1)

So the filtrate would not contain a significant concentration of plasma proteins, therefore oncotic pressure in Bowman’s space = 0 (no need for Pi(BS))

49
Q

What form of starling equation is used to describe reabsorption in peritubular capillaries?

A

Jv = Kf
[ P(PTC) - P(ISF) ] -
Sigma* [ Pi(PTC) - Pi(ISF) ]

PTC = peritubular capillary
ISF = interstitial fluid
50
Q

What does a negative value of Jv for the peritubular capillary form of starling equation indicate?

A

Net reabsorption

51
Q

What does the area between the hydraulic pressure curve and oncotic pressure curve in the GLOMERULAR capillaries represent?

In the peritubular capillaries?

A

Glomerular capillaries =
Net filtration pressure (NFP)

Peritubular capillaries =
NFP also, BUT since oncotic pressure is greater than hydraulic, the NFP turns negative and is therefore best described as a net reabsorption pressure

52
Q

How can GFR be increased according to the Starling equation?

A

Increase:
Kf

P(GC) - hydraulic pressure

Decrease P (BS)

And/or
Decrease Pi(GC) - oncotic pressure
53
Q

What is the best way to produce an isolated increase in GFR without change in RPF?

A

Increase P(GC)

Hydraulic pressure of glomerular capillaries

54
Q

What is the best way to increase P(GC)?

A

Dilate afferent arteriole (decrease resistance)

Constrict efferent arteriole (increase Resistance)

OR for isolate increase in GFR (to keep RPF constant RVR can’t change):

Decrease in resistances of afferent and efferent arterioles

55
Q

What is glomerulotubular balance (GTB)?

A

Increase in fluid reabsorption from PT into the peritubular capillaries following an increase in GFR

AKA load dependence

56
Q

How can GFR be decreased according to the Starling equation?

Indicate the best way to produce an isolated decrease in GFR (no change in RPF)

A

Decrease Kf

Decrease P(GC) ***

Increase P(BS)

And/or increase Pi(GC)

57
Q

How can P(GC) be decreased?

A

Constrict afferent article (increase resistance)

Dilate efferent arteriole (decrease resistance)

To produce isolated decrease in GFR (and keep RPF constant, RVR can’t change)
Equal increases in resistances of afferent and efferent arterioles

58
Q

What is the term used to describe decrease in fluid reabsorption from the PT into the peritubular capillaries following a decrease in GFR?

A

also called GTB

Glomerulotubular balance

59
Q

What are the main transporters responsible for sodium reabsorption in the

Thick AL
DCT
CNT/CD

A

Thick AL:
Na-K-2Cl cotransporter (NKCC2)

DCT:
NaCl cotransproter (NCC)

CNT/CD:
Epithelial Na channel (ENaC)

60
Q

What is the equation for fractional excretion of solute?

A

FE =

U(x) * Vdot / P(x) * GFR

61
Q

What is the equation for fraction reabsorbed of a solute?

A

FR = 1 - FE

Renal (17 decks)

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