Renal Function Flashcards

1
Q

What constitutes the three layers of the glomerular filtration barrier?

A
  1. Capillary endothelium
  2. Glomerular basement membrane
  3. Podocyte epithelium
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2
Q

What size molecules are filtered through?

A
  • Molecules < 20 Å are freely filtered

- Molecules > 42 Å are not filtered

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3
Q

What are the layers of the GBM?

A
  1. lamina rara externa
  2. lamina densa
  3. lamina rara interna
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4
Q

What is the clinical importance of the GBM?

A

Lamina rara interna and lamina rara externa
•Composed of proteoglygans
•Predominantely heparin sulfate proteoglycans
•Proteoglycans provide electronegative charge to
GBM

Lamina densa
•Composed of:
•Type 4 Collagen and Laminin II
•Specific structural chains are affected clinically

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5
Q

What is the relationship between, size, charge, and filterability?

A

Smaller cationic and neutral dextrans will diffuse readily, the larger they are, the harder it becomes. Anions have difficulty crossing due to glycocalyx

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6
Q

What passes the filtration barrier?

A

Freely: water, small solutes (glucose, amino acids, electrolytes), concentrations equal on both sides of membrane

Not freely filtered: large molecules, eg proteins, formed elements (cells), miniscule amounts of protein get through

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7
Q

How do you calculate urinary excretion? Tubular reabsorption?

A

UE = amount filtered - amount reabsorbed + amount secreted

Tubular reabsorption = glomerular filtration - urinary excretion + amount secreted

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8
Q

How do you calculate urine excretion rate? Urine flow rate?

A

Urinary conc. of x = concentration/volume

V = urine volume/time

So, Urinary excretion rate of x = Ux * V

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9
Q

What is the equation for Renal clearance?

A

clearance of substance x = (conc. of x in urine * flow rate)/conc. of x in plasma

Cx = (Ux * V)/Px

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10
Q

What is GFR defined as?

A

Volume of plasma filtered into the combined nephrons of both kidneys per unit of time (mL/min)

  • protein free
  • cell free
  • otherwise similar to plasma, isosmotic
  • ~20% of RBF
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11
Q

What is Filtration Fraction?

A

FF = GFR/RBF

*As FF increases, the oncotic pressure of the efferent arteriole increases, facilitating reabsorption of tubular fluid

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12
Q

How do we calculate Filtered Load?

A

FL = GFR x Px

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13
Q

How can we use renal clearance to estimate GFR?

A

Filtered amount = excreted amount

so GFR = (Ux * V)/Px {normal = ~125 mL/min}

directly proportional to clearance if:
1. Substance must be freely filterable in the glomeruli.
2. Substance must be neither reabsorbed nor secreted
by the renal tubules.
3. Substance must not be synthesized, broken down, or
accumulated by the kidney.
4. Substance must be physiologically inert (not toxic and
without effect on renal function).

ex: inulin & creatinine

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14
Q

What is the effect of the SNS of the renal system?

A

Local renal sympathetic nerves are activated:

  1. Constricts renal arterioles (which decreases GFR)
  2. Increases tubular reabsorption of water and salt
  3. Activates RAAS (further increases tubular reabsorption)
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15
Q

List the SNS receptor subtypes and their effects.

A

alpha1 = causes powerful vasoconstriction, afferent > efferent; and Na-K ATPase to increase Na+ reabsorption

beta1 = causes renin release and RAAS

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16
Q

What are the forces causing filtration by the glomerular capillaries?

A

starling forces: Net filtration pressure of +10mm Hg

17
Q

What 3 physical factors contribute to GFR?

A
  1. Hydraulic conductivity (permeability/porosity of the fenestrated endothelium). (Lp)
  2. Surface area for filtration (Sf).
    -Hydraulic conductivity (Lp) x surface area (Sf) =
    ultrafiltration coefficient (Kf)
  3. Capillary ultrafiltration pressure (PUF)

GFR = Kf * Puf

18
Q

What can alter ultrafiltration pressure? (Puf)

A

Changing glomerular capillary Pressure (Pgc) which is determined by:

  • renal arterial BP
  • afferent resistance
  • efferent resistance

*Puf = Pgc - Pbc - onc(gc)

19
Q

What influences the ultrafiltration coefficient (Kf)?

A

Kf = hydraulic conductivity * surface area

-mesangial cells influence surface area

20
Q

How does regulation at the arterioles affect GFR?

A

Constriction or dilation affects the blood flow entering or leaving the glomerulus and thus it’s ability to filter. constriction at the afferent or dilation at the efferent decreases Puf and GFR; in a similar fashion, dilation at the afferent and constriction at the efferent increases Puf and GFR.

*think of the effect on blood flow through glomerulus, water hose analogy

21
Q

What are the glomerular vasoconstrictors?

A

sympathetics (catecholamines)
-activate alpha1, of which more are on afferent than
efferent
endothelin
ATP/adenosine
angiotensin II
- primarily constricts efferent, raises GFR, druing
diminished renal perfusion, ACE inhibitors counteract
this

22
Q

What are the glomerular vasodilators?

A
Prostaglandins
bradykinin
NO
Dopamine
ANP
ACE-inhibitors
23
Q

What is the concept of glomerulartubular balance?

A

=what happens at the glomerulus affects the tubule

Mechanisms:

  1. Changes in pressure in the efferent arteriole.
  2. Increased delivery of solutes to proximal tubule.
  3. Increased GFR rate and fluid flowing through the proximal tubule increases shear strain on the apical microvilli, which upregulates apical sodium transporter insertion, which promotes Na+reabsorption.

Increasing GFR leads to…
1.↑PTC (peritubular cap) oncotic pressure
2.More stuff dumped into PT
Both result ↑reabsorption rates in the tubules

24
Q

How does renal autoregulation maintain RBF and GFR?

A

Increasing pressure leads to increased resistance
•Local reflex between vascular smooth muscle cells •Physiological feedback via juxtaglomerular apparatus

reflex mech: during high bp, local myogenic reflex is stimulated and blood vessels resist stretch ->afferent constriction, efferent dilation (*protect glomerulus)

juxtaglomerular mech:
1. Macula densa cells (sense NaCl, maintain Na delivery to
tubule)
2. Juxtaglomerular (granular) cells
•Renin
3. Extraglomerular mesangial (lacis) cells

25
Q

If you increase NaCl delivery to the macula densa….

A

1.↑delivery of NaCl to macula densa
2.↑Na+reabsorbed via NKCC2
3.More ATP/adenosine is released
•ATP binds P2X1
•Ado binds A1
4.Calcium is released to vascular smooth muscle cells
surrounding afferent arteriole
5.Afferent arteriole constricts
6.Which ↓GFR & ↓renin release

*opposite with a decrease in NaCl

26
Q

What promotes renin Secretion?

A
  • ↓NaCl delivery to the macula densa stimulates renin secretion
  • Renal sympathetic stimulation also directly stimulate renin via β1 receptor activation in JG apparatus
27
Q

In the case of decreased renal perfusion pressure:

A
  • Macula densa signals to JG cells to secrete renin
    • Renin -> angiotensinII -> restore BP
    • Results in efferent arteriolar vasoconstriction
  • Macula densa also results in afferent arteriolar dilation.
    • Mediated by NO
28
Q

What stimulates renin release?

A
  1. Decreased blood pressure (JGA)
  2. Decreased NaCl delivery to the macula densa(NaCl sensor)
  3. Decreased renal perfusion pressure (renal baroreceptors)
29
Q

Angiotensin II actions:

A
  1. +aldosterone
  2. Vasoconstrict efferent arteriole
  3. Enhances TGF
  4. Stimulates thirst and ADH release
30
Q

Integrated response to decreased ECV, sympathetic response:

A
  1. Increases renal vascular resistance
  2. Increased Na+reabsorption
  3. Enhances renin release (indirectly)
31
Q

Integrated response to decreased ECV, big picture:

A
  1. The GFR decreases.
  2. Na+reabsorption by the proximal tubule and loop of Henle is increased.
  3. Na+reabsorption by the distal tubule and collecting duct is enhanced.
  4. Water reabsorption is enhanced

(correction takes hours -> days)

32
Q

What are the intrinsic and extrinsic mechanisms in renal hemodynamics, respectively?

A

Intrinsic: autoregulation, tubuloglomerular feedback

Extrinsic: SNS, hormones, composition of blood

33
Q

How do we calculate Fractional Excretion?

A

i.e. What percentage of whatever has been filtered actually gets excreted?

If FE = 1.0 then 100% of whatever was filtered gets excreted
If FE = 0.9 then 90% of whatever was filtered gets excreted (reabsorption occurred)
If FE = 1.1 then 110% of whatever was filtered gets excreted (secretion occurred)

so, FEx = amount of x excreted/amount of x filtered
= (Ux)(V)/(Px)(GFR)