Lecture 4: RBF + GFR Flashcards
Explain the anatomical or physiological reasons for the following unique hemodynamics and metabolic characteristics of the kidneys:
(A) blood flow per 100g tissue is highest of all organs
(B) O2 consumption/ 100 g tissue is highest of all organs except the heart
(C) (CaO2 - CvO2) different is lowest of all major organs
(A) Higher blood flow because the kidneys have lower vascular resistance
(B) Higher O2 consumption because with more RBF, there is more reabsorption that needs to be done
(C) lowest difference because of preglomerular shunting - so less O2 delivered to tissue itself
What percentage of CO is RBF?
20%
What does the flow through the afferent arterioles equal?
20% of CO
What does flow through the efferent arterioles equal to?
80% of the RPF
How do organs relate in terms of delta P and resistance ?
All organs perfumed by systemic circulation have about the same delta P
Organs have DIFFERENT flows because of differences in vascular resistance
Why is vascular resistance in the kidneys low?
Kidney has multiple resistances in parallel
All capillaries are open
What does low (CaO2 - CvO2) in the kidney mean?
Indicates that VdotO2/RBF ratio is low
Increased blood flow means more demand
Does not indicate that consumption is low!
Differentiate between effects of increased blood flow in kidneys and heart
Heart = inc. CBF protects against ischemia
Kidneys = inc. RBF means inc. risk of ischemia because of more work it has to do
List the approximate PO2 in the renal artery, renal cortex, renal medulla, and renal vein
Explain how preglomerular shunting and countercurrent O2 exchange affect PO2 in the renal cortex and medulla
Cortex = 45 mmHg
Medulla = 30 mmHg
Renal Vein = 70 mmHg
Less O2 delivered into tissue itself - why O2 so low in medulla
What contributes to low PO2 in the medulla?
Preglomerular shunting
Low blood flow to medulla
What does regulation of RBF involves changes in?
RVR
Changes in arterioles….but kidney has 2 arterioles!!! Afferent and Efferent arterioles
What is the distribution of vascular resistance in the kidneys?
50% in afferent arterioles
35% in efferent arterioles
15% in peritubular capillaries
Apply the Starling equation to GFR and compare this equation to the Starling equation for filtration in a typical capillary, specifying the normal pressure values in each equation
typical capillary:
Jv = Kf [(Pc - Pi) - sigma(Pi(p) - Pi(i)]
Glomerular capillary (GFR): GFR = Kf [ P(GC) -P(BS) - Pi(GC) ]
Equation for GFR doesn’t account for proteins filtering into bowmann’s space because the glomerular capillaries are reflective!
Hydraulic pressure in typical: 35 to 17 (arterial to venous end). Oncotic pressure = constant
Hydraulic pressure in GFR = constant. Oncotic pressure: 25 to 35 (afferent to efferent end)
Compare the filtration fraction in the glomerular capillaries to the filtration fraction in typical capillaries, explaining why the former is much higher
Filtration FRACTION is higher in glomerular capillaries
Higher filtration in kidneys because glomerular capillaries have higher filtration coefficient, Kf, from capillaries being highly fenestrated
Define the features of albumin and the filtration barrier that result in a normal filtration fraction for albumin of less than 0.1%, explaining why a low albumin filtration fraction is important
Albumin has a hard time filtering because it is larger than 5000 Da and it is negatively charged
It’s important that albumin has a low filtration fraction, otherwise so much of it would be filtered out and lost - and the liver wouldn’t be able to keep up because it makes only a little bit of albumin daily
Describe the size and charge selectivities of the glomerular capillaries
Easiest to filter: positive charged
Hardest to filter: negative charged
molecules <5000 Da = “freely filtered”
Where is the location of SIZE selectivity in the GFR filtration barrier?
Slits between foot process of podocytes
Layer 3 of filtration barrier
What is the location of the CHARGE selectivity in the filtration barrier?
Surface of capillary endothelium
Basement membrane
Surface of podocytes (epithelial cells of Bowman’s capsule)
= all 3 layers of filtration barrier
What does the surface of the filtration barrier contain to help with charge selectivity?
Glycoproteins to repel large anions
What are podocytes?
Epithelial cells of Bowman’s capsule
Define autoregulation and describe two mechanisms for autoregulation of RBF and GFR
Autoregulation: changes in BP lead to changes in RVR to maintain a relatively constant RBF
Mechanisms:
(1) Myogenic response: increased pressure in lumen stretches the vessel wall and activates cation channels to depolarize and activate LTCC to trigger SM contraction and thereby increase RVR
(2) Tubuloglomerular feedback (TGF): macula densa monitor solutes and will send signals to afferent arterioles to regular RBF and GFR
How can kidneys regulate RBF and GFR?
Via changes to RVR
Given that both RBF and GFR are autoregulated, identify the major site of the changes in RVR
Afferent arteriole
What does TGF do in response to increased NaCl delivery?
1) macula densa will constrict afferent arterioles to increase their resistance, thereby increasing RVR (to decrease RBF) and decreasing P(GC) (to decrease GFR)
2) main mediator triggered by increased absorption of NaCl is Adenosine, which acts as vasoconstrictor in kidneys
Which autoregulation mechanism is slower to respond?
TGF
What does TGF do in response to decreased NaCl delivery?
Macula densa decreased reabsorption of NaCl will trigger vasodilation by PGs to dilate the afferent arteriole and decrease its resistance
List the sequence of events that occur in the auto regulatory response to a change in BP
Inc. Renal perfusion pressure (from inc. mean arterial pressure) leads to:
(1) Inc. RBF, Inc. GFR
(2) Inc. stretch of AA and triggering of myogenic response to contract SM in AA to increase its resistance and inc RVR (to drop RBF) and drop hydraulic pressure of glomerular capillary (to decrease GFR)
(3) TGF response takes place with more sodium chloride delivered to macula densa, which respond with release of increased adenosine mediators to contribute to construction of SM in AA
What is the effect of different NaCl delivery to macula densa on renin secretion?
More NaCl = inhibition of Renin secretion = dec. Ang II
Less NaCl = PGs stimulate renin secretion = inc. Ang II
With aid of Starling equation for GFR, describe clinical conditions and interventions that can change the GFR
Kf: from contraction/relaxation of mesangial cells in ECM
(Ex: kidney + systemic diseases)
P(GC): paracrines can change R(AA) or R(EA)
(Ex: hormones (Ang II, ADH, ANP) and sympathetic stimulation
P(BS): can increase with urinary tract obstruction
Pi(GC): inc. oncotic pressure from rise in plasma proteins
(Ex: multiple myeloma)
Predict the acute effect (short term response) on RBF and GFR of decreased solute reabsorption in each of the following nephron segments:
Proximal tubule
Thick ascending limb
Distal nephron
PT
More salt comes to macula densa = dec. GFR
Thick AL
More salt comes to macula densa = dec. GFR
(But with loop diuretic, macula densa sees no solute coming to it and it would increase GFR)
Distal nephron
Nothing - it’s located beyond macula densa
Describe the regulation of RBF and GFR by sympathetic division, appreciating these effects occur only @ high levels of nerve traffic
Initiated during BRR response to drop in BP
High levels of nerve traffic = vasoconstriction
Inc. resistance of AA
= Inc. RVR = dec. RBF
Also = dec. P(GC) = dec. GFR
(Dec. in RBF contributes to GFR from flow dependence)
What is the kidney and its vasculature innervated by?
ONLY the sympathetic division of ANS
How does RPF act as an indirect regulator of GFR?
RPF affects how oncotic pressure rises
With inc. RPF, GFR goes up because higher net filtration pressure
When RPF is higher, oncotic pressure rises more slowly
Describe the regulation of RBF and GFR by adenosine
Constricts afferent arterioles
Important mediator in TGF for when BP increases
Describe regulation of RBF and GFR by Ang II
Constricts AA and EA
Inc. RVR = dec. RBF
Inc. resistance of EA vs. AA = “interesting consequences” for GFR
Contracts mesangial cells = dec. Kf
Promotes retention of Na and water
(Inc. Na reabsorption in PT)
(Inc. aldosterone secretion = inc. Na reabsorption in CNT, CD)
What effect do low levels of sympathetic nerve traffic and intermediate levels have on regulation of RBF and GFR?
Low levels
Inc. Na reabsorption in PT
Intermediate
Inc. renin secretion
What effect does ADH have on RBF and GFR regulation?
Antidiuretic (inc. water permeability of CNT, CD)
Vasoconstriction
Dec. blood flow to medulla (promote formation of concentrated urine)
What effect does atrial natriuretic peptide (ANP) have on RBF and GFR regulation?
Natriuretic effects (dec. Na reabsorption in CD)
Vasodilation
Dilates AA = dec. RVR = inc. RBF
Dec. R(AA) = inc. P(GC) = inc. GFR
What effect do prostaglandins have on RBF and GFR regulation?
Preferentially vasodilation AA
Modulate or counteract vasoconstrictors
What increases synthesis of PGs?
Ang II
Sympathetic stimulation
What can be the result of inhibition of PG synthesis by NSAIDs?
Renal vasoconstriction with most significant effects in patients with volume depletion or poor renal perfusion
What is the effect of NO on RBF and GFR regulation?
Modulates or counteracts vasoconstrictors
What increases synthesis of NO?
Ang II
Describe the changes in RBF and GFR that occur during pregnancy, following a protein-rich meal, and after removal of one kidney
Pregnancy
Inc. RBF and GFR (hormone mediated)
Protein-rich meal
Inc. RBF, GFR
(Inc. AA’s in TF may stimulate Na reabsorption by cotransport in PT = dec. delivery of NaCl to macula densa)
Removal of one kidney
Drop in GFR but will return to majority of baseline at long term
