animated rbc’s physiology 451 renal physiology dr. michael fill, lecturer [email protected]

Animated RBC’s

PHYSIOLOGY 451

RENAL PHYSIOLOGYDr. Michael Fill, Lecturer

[email protected]

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 Capillaries

There is net filtration along entire length of the

glomerular capillaries

Most Capillaries in Body



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)




Point #3: Hydrostatic pressure isconstant in glomerular capillaries.(Most capillaries have high resistance so pressure drops. The multiple parallel loops provide very low resistance.)




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.

animated rbc’s physiology 451 renal physiology dr. michael fill, lecturer [email protected]

Documents