Renal 3 Flashcards
Glomerular Filtration Rate (GFR)
Rate of production of
Glomerular Filtrate
Plasma volume filtered into nephrons/unit time
≈
125 ml/min = 180 liters/day
Entire plasma volume is filtered every
24 min (60x/day)
Glomerular Filtration Rate (GFR) occurs via
bulk flow
Glomerular Filtration Rate (GFR)
selectivity
Unselective (except for cells, proteins, Ca++, fatty acids and other protein-bound substances)
Glomerular Filtration Rate (GFR)
regulated by
multiple systems
Filtration Fraction = GFR/RPF
Averages
20% of renal plasma flow (RPF)
Can be altered
Function of Renal Corpuscle (3)
- Bowman’s Capsule (Parietal and Visceral layers)
- Glomerular Capillaries (Glomerulus/Glomeruli)
- Bowman’s Space
Protein Free fluid filtered out of glomerulus into
Bowman’s
Space
Filtrate flows
into
Proximal
Tubule
Blood in Glomerular Capillaries separated from
Bowman’s Space by a
Filtration Barrier
Composed of Three Layers (negatively charged)
1.Capillary endothelium (Fenestrated)
2.Basal Lamina (Basement Membrane)
3.Podocytes (Visceral Layer of Bowman’s
Capsule)
Foot processes that cover outside of —, creates
basal lamina
Filtration Slits
Mesangial Cells (4)
- Modified smooth muscle cells
- Surround Glomerular Capillary loops
- Not part of filtration barrier
- Modify size of filtration slits and alter rate of
filtrate production
All substances small enough to fit through
filtration pores and slits will be
filtered
Little to no —
protein
Determinates of the Ability of a Solute to Penetrate
the Glomerular Membrane (2)
molecular size
ionic charge
Molecular size
( small molecules
filter better than large ones)
Ionic charge
(cations filter better
than anions)
Proteins are both (2), hence do not
filter well.
large and
negatively charged
Electrical properties of the
solutes:
more positive charge
higher filterability
In minimal change nephropathy
– loss of negative charge on
GBM
-proteins filtered through GBM
-proteinuria
Capillary filtration coefficient
(Kf):
product of the
permeability and surface area
of the capillaries.
NFP:
Balance of hydrostatic
and colloid osmotic forces
acting across the capillary
membrane.
GFR is high because of
high
hydrostatic pressure and high
Kf .
NFP =
10 mmHg, 125 ml/min;
180 L/day
Kf =
hydraulic conductivity x surface area
Kf = hydraulic conductivity x surface area (3)
– 400x higher than any other capillary bed
– Normally not highly variable.
– Alterations in Kf not used to regulate GFR
Diseases can — Kf
lower
Diseases can lower Kf (2)
– Thickened basement membrane: hypertension,
diabetes mellitus
– Decreased capillary surface area: glomerulonephritis.
Hydrostatic Pressures (2)
Glomerular (PG)
Bowman’s Capsule (PB)
Primary control point for GFR.
Glomerular (PG)
Determinant of GFR most subject
to physiological control.
Glomerular (PG)
Factors that influence PG (3)
- arterial pressure (effect is
buffered by autoregulation) - afferent arteriolar resistance
- efferent arteriolar resistance.
Bowman’s Capsule (PB)
Not a — regulator
of GFR (normally changes as a
function of GFR).
physiological
Bowman’s Capsule (PB)
Diseases can affect GFR via PB (2)
- Tubular Obstruction (kidney stones, tubular necrosis) - Urinary tract obstruction (prostate hypertrophy/cancer)
Glomerular Capillary Colloid Osmotic Pressure
(πG)
Increases along length
of
glomerular capillary:
– Affected by filtration
fraction.
Glomerular Capillary Colloid Osmotic Pressure
(πG)
opposes
hydrostatic pressure
Glomerular Capillary Colloid Osmotic Pressure
(πG)
GFR — along the length of capillary
decreases
factors that affect PiG
Control of GFR by Changes in PG
Hydrostatic Pressure in Glomerular capillaries can be altered by
altering the — of the afferent and efferent arterioles.
Leads to changes in —
resistance
GFR
— GFR due to increased
[plasma protein] caused
by — Filtration Fraction
decreased
increased
physical determinants: ↓ Kf → ↓ GFR
physiologic/pathophysiologic causes: (3)
Renal disease, diabetes mellitus, hypertension
physical determinants: ↑ PB → ↓ GFR
physiologic/pathophysiologic causes:
Urinary tract obstruction
physical determinants: ↑ PiG → ↓ GFR
physiologic/pathophysiologic causes: (2)
Increased [proteins]plasma, Dehydration
physical determinants: ↓ PG → ↓ GFR
physiologic/pathophysiologic causes:
?
physical determinants: ↓ MAP → ↓ PG
physiologic/pathophysiologic causes:
↓ Arterial pressure (remember that normal MAP sits at
the low end of the myogenic autoregulatory range)
physical determinants: ↓ RE → ↓ PG
physiologic/pathophysiologic causes:
↓ Angiotensin II (ACE inhibitors)
physical determinants: increase RA → ↓ PG
physiologic/pathophysiologic causes: (2)
increase Sympathetic activity, vasoconstrictor hormones
Renal Blood Flow ≈–% of total cardiac output
20
RBF =
(Pa-Pv)/
Total Renal Vascular Resistance
Kidneys tightly control RBF
-
– renal auto-regulation.
Vascular resistance regulated by
factors acting on
afferent and/or efferent arterioles (70% of total intrarenal resistance).
Blood flow in medulla
<10% of total RBF
Blood flow in medulla <10% of total
RBF
- Very low flow in vasa recta contributes to
generation of osmotic gradient for
concentration/dilution
O2 consumption reflects
ATP consumption.
ATP consumption reflects
active transport.
Primary Active Transporters (4)
Na+-K+-ATPase
H+-ATPase
H+-K+-ATPase
Ca++-ATPase
Control of RBF (and GFR) 1. Autoregulation A.Myogenic Autoregulation Function: (1) (2)
Keeps RBF and GFR relatively constant in spite of
changes in MAP
Reflex vessel constriction in response to increase MAP
Intrinsic to blood vessels
Control of RBF (and GFR) 1. Autoregulation B. Tubuloglomerular Feedback (TGF) Function: (1) (2)
Helps ensure a nearly constant delivery of Na+ and Cl- to
the distal nephron
Prevents spurious fluctuations in renal excretion
Juxtaglomerular Apparatus
- Autoregulation (Prevents
moment to moment changes in GFR)
JGA Mediates the – Response
TGF
JGA
Composed of: (2)
Juxtaglomerular cells (JG)
Macula densa cells in the wall of
TAL
Juxtaglomerular cells (JG) (2)
- Primarily in walls of afferent
arterioles - Secrete Renin
Macula densa cells in the wall of
TAL (2)
In close contact with JG cells
Sense [Na+] and [Cl-] in filtrate
Stimuli for Renin Release (3)
decrease BP
decreaseRBF
decrease NaCl Delivery to Macula
Densa (TGF Response)
Control of RBF (and GFR) (cont.)
Three levels
Autoregulation
Local Control
Systemic Control
Autoregulation (2)
A.Myogenic Autoregulation
B.Tubuloglomerular Feedback
Local Control (2)
Paracrines and Autocrines
Endothelin, Prostaglandins, NO, Bradykinin, Dopamine.
Systemic Control (3)
Sympathetic NS and Epinephrine
Renin-angiotensin system
Atrial natriuretic peptide
SNS (and circulating epinephrine) has minor role in
regulating RBF in
“normal” state.
Renal autoregulation smooths normal SNS-induced changes in (2)
arterial
pressure and cardiac output.
SNS activation by — (blood loss, cardiac events, etc) can alter RBF.
stress
SNS increases — of both afferent and efferent arterioles.
resistance
hormone or paracrine: NE/E (severe/acute disturbances) mechanism: effect on RBF: effect on GFR:
↑RA and ↑RE
↓
↓
hormone or paracrine: Endothelin
mechanism:
effect on RBF:
effect on GFR:
↑RA and ↑RE
↓
↓
hormone or paracrine: Angiotensin II
mechanism:
effect on RBF:
effect on GFR:
mainly ↑ RE
↓
↑
hormone or paracrine: PGE2, PGI2
mechanism:
effect on RBF:
effect on GFR:
↓RA
↑
↑
hormone or paracrine: Bradykinin
mechanism:
effect on RBF:
effect on GFR:
↓RA
↑
↑
hormone or paracrine: NO
mechanism:
effect on RBF:
effect on GFR:
↓RA and ↓RE
↑
↑
Other Factors that increase GFR and RBF (2)
- High Protein Diet
2. High Blood Glucose levels
Other Factors that increase GFR and RBF 1. High Protein Diet 2. High Blood Glucose levels Both lead to pronounced increases in (2)
RBF and GFR
Other Factors that increase GFR and RBF
1. High Protein Diet
2. High Blood Glucose levels
results in
reduced NaCl delivery to macula densa
Other Factors that increase GFR and RBF
1. High Protein Diet
2. High Blood Glucose levels
TGF response functions to
keep NaCl delivery to macula densa constant
Other Factors that increase GFR and RBF
1. High Protein Diet
2. High Blood Glucose levels
opposite effects seen if
PT reabsorption is reduced
Calculating the Filtered Load (Fx) of a Substance (3)
Rate at which substances enter the nephron
Units = Amt/time
Fx = (GFR) ([X]plasma)
Calculating the Excretion rate (Ex) of a substance (3)
Rate at which substances are excreted
Units = Amt/time
Ex = (Uv)([X]urine); where Uv =Urine Flow Rate
Calculating the Clearance rate (Clx) of a substance (5)
Determines the volume of blood cleared of a substance in a
given amount of time
Units = Vol./time
Clx = Ex/[X]plasma
Clinulin and Clcreatinine used as index of GFR
ClPAH used as index of RBF (Renal Blood Flow
