animated rbc’s physiology 451 renal physiology dr. michael fill, lecturer [email protected]
TRANSCRIPT
Lecture 2
Renal Blood Flow, Filtrationand Clearance
Basic Renal Processes
1. Filtration (F)2. Reabsorption (R)3. Secretion (S)
Excretion = F + S - R
Urine FormationAfferent Arteriole Efferent Arteriole
Glomerulus
Bowman’sCapsule
RenalTubule
PeritubularCapillary
Conceptual Point :Filtration is the most basic “mode” of renalsubstance handling.
- solutes need pass the filter barrier- no specific transport processes- if there is no reabsorption or secretion,
then the substance will be excreted.
There are very few “filtered-only” solutes.Most are also reabsorbed and/or secreted.
Some Examples: Substances that are Filtered then Reabsorbed
>99.9%799.5∼0.5800Glucose mM/day
>99.9%4,498∼24,500HCO3 mM/day
99.3%19,85015020,000Cl mM/day
99.4%24,85015025,000Na mM/day
99.2%178.5∼1.5180H2O L/day
% of filtered loadreabsorbed
Amount Reabsorbed
Amount Excreted
Amount Filtered
Substance, units
This “filtered then almost completely reabsorbed” scenario is certainly not the case for all solutes.
Some Important Renal Physiology Numbers
Renal Blood Flow RBF 1.1 L/min
Renal Plasma Flow RPF 625 ml/min
RPF = RBF x (1 – hematocrit) typical hematocrit is ~0.43, so RPF is 1.1x0.57.
Glomerular Filtration Rate GFR 125 ml/min
Urine Flow Rate 1 ml/min
Filtration Fraction GFR/RPF 20%
20% of plasma entering a glomerulus is filtered. Thus, 20% of any freely-filtered solute present enters Bowman’s space.
Note that values given above can vary in different circumstances.Also remember that RBF far exceeds what kidney cells need to stayalive so RBF can vary dramatically without affecting kidney cell vitality.
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body
Fluid Filtration Reabsorption
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Glomerular Capillaries
There is net filtration along entire length of the
glomerular capillaries
Most Capillaries in Body
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body Glomerular Capillaries
Point #2: Glomerular Capillarieswork at higher pressure. (This is because efferent arteriole is usually smaller diameter than theafferent arteriole)
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body Glomerular Capillaries
Point #3: Hydrostatic pressure isconstant in glomerular capillaries.(Most capillaries have high resistance so pressure drops. The multiple parallel loops provide very low resistance.)
Glomerular Filtration
The renal circulation traverses 2 capillary beds: glomerular & peritubular
Most Capillaries in Body Glomerular Capillaries
Point #4: COP (colloid oncotic pressure) increases in glomerularcapillaries. (This is because a hugeamount of fluid exits the blood leaving plasma proteins behind.)
Hydrostatic pressure insideBowman’s Capsule is low &constant.
Net Filtration Pressure
Summary of forces driving glomerular filtration
Net Filtration Pressure (NFP) NFP = PGC – (πGC + PBS)
where,PGC is average glomerular capillary
hydrostatic pressure.πGC is average plasma oncotic pressure
PBS is average hydrostatic pressure inside
Bowman’s capsule Thus,
NFP = 55 – (30 + 15) or 10 mm Hg
GFR of course depends on this valuebut not just this value
GFR = Kf x NFP
Filtration Coefficient: - Fluid permeability of Glom.Caps. (i.e. the size of holes in filter) - Surface area of Glom.Caps. (i.e. the numerous parallel loops
in glomerulus)
Main Point :Glomerular capillaries are specialized for filtration. No reabsorption of fluid occurs in the glomerular capillaries.
Factors that Influence GFR
GFR = Kf x NFP
Glomerular permeability & surface area
Hydrostatic & oncotic pressures
Renal Artery Stenosis reduced hydrostatic pressure in glomerularcapillaries will reduced GFR
Nephritic Disease reduced number of working nephrons, lesssurface area for filtration and reduced GFR
Sympathetic Stimulation decreased afferent arteriole diameter will decrease hydrostatic pressure in glomerulus, reducing GFR.mesangial cell contraction will decrease the available surface area for filtration and decrease GFR.
Starvation (or renal disease) decreased plasma protein content lowers plasma oncotic pressure and this will increase GFR.
Blood Pressure (MAP) increased/decrease hydrostatic pressure in glomerular capillaries will increase/decrease GFR.
Kidney Stone could increase hydrostatic pressure in Bowman’s capsule reducing GFR
2001
Kidney’s Resist Changes in GFR (and RBF)
Autoregulation : intrinsic property of the kidney (no nerves/hormones needed)
can be over-ridden by extrinsic factors (nerves/hormones)
1.1 L/min
125 ml/min
Mechanisms: 1) myogenic (relatively minor in kidneys)
2) tubuloglomerular feedback
Tubuloglomerular Feedback
Juxtaglomerular Apparatus (JGA)
Juxtaglomerular Apparatus (JGA)
Macula Densa
Macula Densa: Cells sense fluid flow in distal tubule (involving NaCl & swelling) & secrete vasoconstriction agent (probably ATP). This agentdiffuses to nearby afferent arteriole influencing GFR.
Note: Granular cells secrete renin which is involved in generating extra-renal angiotensin II.
(renin does not contribute to renal autoregulation)
Tubuloglomerular Feedback
Concept of Clearance (traditionally difficult to understand)
Clearance is just a way to quantify renal handling of a substance.
Clearance is defined as the volume of plasma “cleared” of a substance by the kidneys per minute. ( ml/min )
Clearance of a substance is often used to evaluate renal function.
First…. we will define clearance in words.
Volume of Plasma Cleared
Now….Let’s see how we can calculate clearance.
Concept of Clearance
To calculate clearance of substance X (CX),
first need to calculate amount of X excreted in urine per unit time.
amount of X excreted = UX · V
Urine volume per minute (ml/min)
Urine X concentration
then simply divide this by the plasma X concentration…
CX = you will need to remember this formulaUX · V
PX
This formula is convenient because UX, PX and V are easily measured.
Now….Let’s apply this to the real world.
Concept of Clearance
To calculate clearance of substance X (CX),
first need to calculate amount of X excreted in urine per unit time.
amount of X excreted = UX · V
Urine volume per minute (ml/min)
Urine X concentration
then simply divide this by the plasma X concentration…
CX = you will need to remember this formulaUX · V
PX
This formula is convenient because UX, PX and V are easily measured.
Now….Let’s apply this to the renal world.
Inulin Clearance
Inulin: polysaccharide, not a naturally occurring substance in bodyfreely filtered but not reabsorbed or secreted ….so all inulin
that is filtered will end up in the urine
CINULIN is the “gold standard” for measuring GFR
Volume filteredis volume cleared.
GFR = CINULIN =UINULIN · V
PINULIN
V = urine produced in ml/min UINULIN = urine inulin concentration PINULIN = plasma inulin concentration
The main clinical drawback here is that inulin must be continuously infused while urine is collected (this is usually a day or so).
PAH Clearance
PAH: para-aminohippurate is also not naturally in the bodyit is freely filtered and robustly secreted….so both filtered and
secreted PAH will end up in the urine
CPAH is clinically used to estimate RPF
RPF = CPAH =UPAH · V
PPAH
V = urine produced in ml/min UPAH = urine PAH concentration PPAH = plasma PAH concentration
Cleared volume much larger thanfiltered volume.
So large in fact that it “effectively” approaches
RPF
Recall that…. RPF = RBF x (1- 0.43) so…. RBF =CPAH
0.57hematocrit
Creatinine Clearance
Creatinine: produced from creatine metabolism in muscleproduction rate usually very constant (if muscle mass constant)
freely filtered and not reabsorbed …little bit is secreted (this makes it a good but imperfect substitute for inulin)
CCR is clinically used to routinely access GFR
“GFR” = CCR =UCR · V
PCR
V = urine produced in ml/min UCR = urine CR concentration PCR = plasma CR concentration
There is a nice inverse relationship betweenPCR and “GFR”
Normal PCR = 1 mg/dl
PCR
If GFR drops by 50%, then PCR doubles ( 2 mg/dl ).
Creatinine Clearance
Creatinine: produced from creatine metabolism in muscleproduction rate usually very constant (if muscle mass constant)
freely filtered and not reabsorbed …little bit is secreted (this makes it a good but imperfect substitute for inulin)
CCR is clinically used to routinely access GFR
“GFR” = CCR =UCR · V
PCR
V = urine produced in ml/min UCR = urine CR concentration PCR = plasma CR concentration
There is a nice inverse relationship betweenPCR and “GFR”
Normal PCR = 1 mg/dl
50% GFRThus, a single PCR value can be used to roughly estimate GFR.