SM 189a/190a - Functional Renal Anatomy and Glomerular Filtration, Regulation Flashcards

1
Q

Which of the following would tend to decrease GFR?

  1. An increase in hydrostatic pressure in the glomerular capillary
  2. A decrease in oncotic pressure in the glomerular capillary
  3. A decrease in total glomerular capillary surface area
A

c. A decrease in total glomerular capillary surface area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

If solute delivery to the juxtaglomerular apparatus is too high, which cells respond?

What is the response?

A
  • Macula densa senses increase in solute (Na+) delivery
  • Macula densa releases adenosine
  • Adenosine causes extraglomerular mesangial cells to contract and cause vasocaonstriction of the afferent arteriole
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the equation for clearance (kidney)?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which of the following is NOT a component of the glomerular permeability barrier?

a. Visceral epithelial cells (a.k.a. podocytes)
b. Glomerular basement membrane
c. Parietal epithelial cells (a.k.a. Bowman’s capsule)
d. Negatively charged glycosaminoglycans
e. Glomerular capillary endothelial cells

A

c. Parietal epithelial cells (a.k.a. Bowman’s capsule)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What fraction of cardiac output goes through the kidney?

A

20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

If solute delivery to the juxtaglomerular apparatus is too low, which cells respond?

What is the response?

A
  • Macula densa senses decrease in solute (Cl-) delivery and/or flow
  • Signals to the granular cells in the wall of the afferent arteriole
  • Granular cells release renin
  • Renin secretion -> Increased Angiotensin II production
  • Angiotensin II ->
    • Increased Na/H exchange
    • Constriction of the efferent arteriole
    • Aldosterone secretion -> Na+ reabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the requirements for the use of creatinine clearance for GFR?

A
  • Renal function must be in steady-state
  • No vigorous activity or muscle breakdown
  • No protein loading
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the function of the macula densa?

A

The macula densa…

  • Senses changes in solute concentration and tubular flow
  • Communicates to granular cells in wall of afferent arteriole if solute (Cl-) delivery and flow are low
    • -> Granular cells release renin
  • Communicates to extraglomerular mesangial cells of solute (Na+) delivery and flow are high
    • -> Mesangial cells contract, causing constriction of the afferent arteriole (tubuloglomerular feedback)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which macromolecules will filter through the glomerular permeability barrier more easily:
Positively charged, negatively charged, or neutral?

Why?

A

Positively charged

The glomerular basement membrane contains anionic glycosaminoglycans that repell negatively charged molecules

[smaller molecules filter more easily than large]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do the Starling forces change from the affertent to efferent arterioles of the glomerulus?

A
  • PGC remains constant, may drop slightly
  • PBS remains constant
  • πGC increases
    • Fluid is leaving, protein concentration in the glomerular capillary increases
  • πBS remains zero

Filtration stops when πGC increases to oppose PGC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are mesangial cells?

A

Supporting cells of the glomerulus that help to maintain capillary structure

They can contract (contain actin and myosin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Where in the kidney does filtration occur?

A

Glomerulus

(Located in the cortex)

Filtration = fluid going from capillaries to Bowman’s space; this is the ultrafiltrate that will eventually become urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Does albumin filter into the urine?

Why or why not?

A

Albumin does not filter into the urine

It is large and negatively charged - it cannot get through the glomerular permeability barrier

(Fenestrated endothelium, GBM, Foot processes of podocytes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What mechanisms affect LpS?

A

Mesangial cell contraction can decrease capillary surface area

Decreased surface area (S) = decreaed GFR

Lp remains constant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which of the following statements about creatinine is FALSE?

  1. Creatinine is freely filtered by the glomerulus
  2. Creatinine is neither reabsorbed nor secreted by the tubules
  3. Creatinine is a clinically useful marker of GFR
  4. Cimetidine may increase the plasma creatinine concentration
A

b. Creatinine is neither reabsorbed nor secreted by the tubules

(I think this is right, but let me know if not!)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where in the kidney does filtration take place?

A

Glomerulus

Filtration = movement from glomerular capillaries -> Bowman’s capsule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is angiotensin II?

What are the effects?

A

Angiotensin II is a potent vasoconstrictor

  • Kidney
    • Vasoconstriction of the efferent arteriole
    • -> Raises PGC and increases GFR in response to low Cl- delivery to the macula densa or beta-1 adrenergic stimulation
  • Systemic
    • Rise in blood pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the basis for the structural difference between the thin and thick ascending loop of Henle?

What does this tell us about their functions?

A

The thick ascending limb is thick because the walls are full of mitochondria

The mitochondria in the thick ascending limb generate ATP that fuels active transport of NaCl into the medulla to increase osmolality in the medullay, which drives the countercurrent multiplier

19
Q

Describe the sequence of events that happens if renal blood flow increases

A
  • PGC (Hydrostatic pressure in the glomerular capillary) increases
  • GFR increases
  • Macula densa senses increased NaCl in the ultrafiltrate
  • Macula densa releases ATP into extracellular space
  • ATP is converted to adenosine
  • Adenosine activates mesangial cells to contract, causing vasoconstriction of the afferent arteriole
  • PGC decreases
  • GFR returns to normal
  • Macula densa senses return to normal, stops releasing ATP into the extracellular space
20
Q

Which of the following statements is most consistent with tubuloglomerular feedback?

  1. increased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
  2. decreased NaCl delivery to the thick ascending limb causes increased proximal fluid reabsorption.
  3. increased NaCl delivery to the thick ascending limb causes no change in proximal fluid reabsorption.
  4. increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate
  5. increased NaCl delivery to the thick ascending limb causes increased glomerular filtration rate
A

D. increased NaCl delivery to the thick ascending limb causes decreased glomerular filtration rate

21
Q

What is the equation for glomerular filtration rate (GFR)?

A
  • Δπ = π inside of the glomerular capillary
    • Oncotic pressure inside of Bowman’s space is zero
  • Hydrostatic pressure in the glomular is the driver of glomerular filtration
22
Q

What are the major differences between cortical and juxtamedullary nephrons

A
  • Location
    • Cortical: mid-outer cortex
    • Juxtamedullary: boundary of cortex and outer medulla
  • Loop of Henle
    • Cortical: short
    • Juxtamedullary: long
  • Function
    • Cortical: recieve 95% of filtrate
    • Juxtamedullary: establish high osmolarity in the inner medulla -> countercurrent multiplier
  • Abundance
    • Cortical: more abunant
    • Juxtamedullary: less abundant
23
Q

Why doesn’t renal artery pressure have a large effect on GFR?

A

The afferent arteriole that leads into the glomerulus “protects” the glomerular capillary bed from changes in renal artery pressure

The affernet arteriole is under control of the intrinsic myogenic reflex, vasoconstrictors, and vasodilators

24
Q

What is the role of renin secretion in autoregulation of GFR?

A

Renin secretion -> Angiotensin II production (via RAAs)

Active when renal arterial pressure is low

Responsible for raising glomerular capillary pressure to maintian GFR

25
Q

What signals to the macula densa inhibit the release of renin?

A
  • High Cl- delivery
  • Angiotensin II (negative feedback)
  • ANP
  • Vasopressin
26
Q

If a patient is doing a 24h collection to measure creatinine clearance, what will yo use if the patient did not collect all of their urine?

A

Creatinine in the urine will be lower than expected

(Calculate the expected level using age, lean body mass, and plasma creatinine)

27
Q

How would efferent arteriole dilation affect GFR?

Why?

A

Dilation of the efferent arteriole would decrease GFR

Dilation -> decreased pressure in the glomerulus -> PGC (hydrostatic pressure in the glomerular capillaries) ->
decreased GFR

28
Q

Where in the RAA system do beta blockers act?

What do they do?

A

Beta-1 adrenergic stimulation causes renin release

Beta blockers prevent renin release, thus inhibiting the RAA system that produes Angiotensin II

29
Q

Which cells make up the juxtaglomerular apparatus?

What do they do?

A
  • Macula densa
    • Senses Na+ delivery and flow through the renal tubule
    • Signals to respond to changes
      • If Na+ delivery is high, signals mesangial cells to contract the afferent arteriole
      • If Na+ delivery is low, signals granular cells to release renin
  • Extraglomerular mesangial cells
    • Contract to constrict the afferent arteriole if Na+ delivery to the macula densa is too high
  • Granular cells
    • Release renin if Na+ delivery to the macula densa is too low
30
Q

Angiotensin II constricts the [afferent/efferent] arteriole, resulting in [increased/decreased] GFR

A

Angiotensin II constricts the efferent** arteriole, resulting in **increased GFR

31
Q

What trigger promotes signals from the macula densa that result in renin release?

A
  • Low Cl- delivery
  • Beta-1 adrenergic stimuli
  • Catecholamines
  • PTH
  • Glucagon
32
Q

What types of cells are found in the glomerulus?

A
  • Endothelial cells
  • Visceral epithelial cells (podocytes)
    • Create slit diaphragms
  • Parietal epithelial cells
    • Make up the outer lining of Bowman’s Capsule
  • Mesangial cells
33
Q

How does creatinine clearance change as we age?

A

Creatine clearance decreases as we age

However, muscle mass also decreases as we age, so creatine production is lower as well

34
Q

Where in the kidney are the glomeruli located?

A

The cortex

Cortical nephrons are in the mid-outer cortex

Juxtamedullary nephrons are right above the boundary between the cortex and the outer medullay

35
Q

What is normal for GFR?

A

Male: ~125 mL/min, = 180 L/day

Female: ~95 mL/min = 137 L/day

36
Q

What is reabsorption?

Where in the kidney does reabsorption take place?

A

Reabsorption is movement from tubular fluid -> peritubular capillaries

Reabsorption takes place throughout the kidney tubule, from the proximal convoluted tubule through the connecting duct

37
Q

Describe the structure of the of the glomerular basement membrane

A
  • Anionic glycosaminoglycans
  • Type IV collagen
  • Laminin
  • Fibronectin

The GBM is negatively charged

(negatively charged plasma proteins (ex: albumin) cannot easily filter out of the glomerular capillaries)

38
Q

What is Renin?

What does it do?

A

A proteolytic enzyme that cleaves Angiotensinogen to
Angiotensin I

The rate-limiting enzyme of the RAAs pathway

39
Q

What is the difference between filtration and secretion in the kidney tubule?

A

Filtration: from glomerular capillaries -> Bowman’s capsule

Secretion: any substances moving from peritubular capillaries/interstitial space -> kidney tubule distal to Bowman’s casule

40
Q

Describe the RAA system

A

Renin is the rate-limiting step

41
Q

Why is oncotic pressure in Bowman’s space zero under normal conditions?

A

Oncotic pressure is exerted by large plasma proteins that are stuck on one side of a membrane.

Plasma proteins cannot get out of the glomerular capillary into Bowman’s space – they are, by definition, undfilterable.

Therefore, the oncotic pressure inside of Bowman’s capsule is zero

42
Q

What are the 3 main mechanisms of autoregulation of GFR?

A
  • Myogenic reflex
    • First line of defense
    • Protects the kidney from fluctuations in systemic blood pressure
  • Tubuloglomerular feedback
    • Active when renal arterial pressure is high
    • Responsible for preventing increases in glomerular capillary pressure
  • Renin secretion (-> Angiotensin II)
    • Active when renal arterial pressure is low
    • Responsible for raising glomerular capillary pressure to maintian GFR
43
Q

What is the major driver of glomerular filtration?

A

Hydrostatic pressure in the glomerular capillary

(Usually much higher than hydrostatic pressure in Bowman’s space)

44
Q

What is the role of tubuloglomerular feedback in autoregulation of GFR?

A

Active when renal arterial pressure is high

Responsible for preventing increases in glomerular capillary pressure

(Macula densa releases adenosine, causing mesangial cells to contract, which constricts the afferent arteriole)