general renal pathophysiology 1. relationship between plasma solute concentration and its excretion...
TRANSCRIPT
General renal pathophysiology
• 1. Relationship between plasma solute concentration and its excretion by kidneys
• 2. Renal perfusion and filtration
1. Relationship between plasma solute concentration and its excretion by kidneys
General scheme of a feedback regulation (Fig. 1)
1
The activity of kidneys could be represented as an activity of a controlling organ, maintaining (together with lungs and gastrointestinal tract) the composition of plasma at a constant level. Homeostased levels of plasma components are deviated by disturbing influences, from the point of view of renal excretory functions, predominantly by sc. extrarenal load (EL) of various metabolites.
Plasma concentration of solutes (PX) is disturbed by extrarenal load. On the other hand, it itself interferes with individual components of EL (with production, supply, metabolism, and storage of a substance).PX is corrected by renal excretion. However, it must have a possibility to modify the excretion in a feebdback manner; this is realized by a direct, trivial manner during filtration, or indirectly by neural and hormonal feedbacks (Fig. 2)
K+
Ca2+
HPO42-
H+
.
.
.
Feedback homeostasing of plasma components by kidneys
EL
Controlling organ (kidney)
Controlling systems
Filtration
Resorption Control- ler
Controlled system (plasma)
GFR * Px = (V * Ux)With simple filtration (creatinine, inulin)More complicated instan-ces of direct effects of Px
(Fig. 8 and 9)Concentration of substan-ces in tubular cells
Control viaN.S., ADH, ALDO, PTH
Signals to the controlling systems
Indirect effects of Px2
Direct effects of Px
.
on zero value (creatinine, uric acid)
Substances are on a “precise” value (Na+, K+, H+,...)homeostased
above a threshold – on its value (HPO4
--, glucose in hyperglycaemia)
In detail:
1. If PX rises due to enhanced ELX with an undisturbed renal function (normal glomerular filtration rate, GFR), a new steady state is established after some time, where EL = PX * GFR (Fig. 3)
2
RELATIONSHIP BETWEEN PLASMA CONCENTRATIONOF A METABOLITE AND ITS DISCARDING BY KIDNEYS
EL
AFTER SOME TIME
95% ARE NOT FILTE- RED
STEADY STATE
IN WHICH EL = Px * GFR
Qf
.
ABSORPTION,PRODUCTION,MOBILIZATION MINUSEXTRARENALDISCARDING,DECOMPOSITION,STORING
Px* GFR
Px INDICATES HEREONLY RELATIONSHIP EL GFR
EL
Px
3
Px* GFR
GFRTIME STEADY
STATEIN WHICH EL = Px * GFR
EXCRETION INDICATES HERE PRODUCTION, NOT GFR
Px
4
2. If the renal function (GFR) declines with an unchanged ELX, a new steady state is established after some time, where EL = PX * GFR (Fig. 4)
5
These examples refer to creatinine, inulin, glucose (above the resorption threshold) etc., where reabsorption or secretion of the substance in renal tubuli is absentThe relationship between PCREATININE and GFR is a hyperbolic one according to the equation ELCREATININE = PCREATININE * GFR ; therefore, PCREATININE is a relatively insensitive indicator from a diagnostic point of view (Fig. 5)
Even a direct (ie., not mediated by hormones and neural system) influence of PX on the excretion of the substance X is complicated in case when the tubuli interfere with the excretion by reabsorption
1. An example without reabsorption (inulin), Fig. 6 and 7 left
2. An example with a proportional resorption (urea), Fig. 6 and 7 right
Feedback by means of Px varies according to the different behaviour of the substance in tubuli
Substance filtered only Substance with proportionalresorption (UREA)
Excretedquantity
Px*GFR
Qf
Reabsorption
EL
Px Px
Resorption 50% Qf
.
Excreted quantity
6
The movement along the lineis not instantaneous and stopslater at: EL = Px* GFR
Ation Ation
.
INULIN
IS VALID FOR ALL SUBSTANCES IN STEADY STATE
V * Ux
GFR
Px
Cx
.
7
EL = V * Ux
.
UREA
RELATIONSHIP
For all substances in a steady state the following eq. is valid:
EL = UX * V
In case of a resorption with a saturation point (threshold), renal excretion is dependent on the maximal resorption rate and on the affinity of the transporters to the substance3. Resorption with a threshold and a high affinity: everything under the resorption maximum is resorbed (glucose, some aminoacids); excretion is an effective regulator of plasma concentration in the region of bending of the resorption curve, Fig. 8
.
PTH
EXCRETION
RES.
GLAA
SUBTHRESHOLD PGL
RESORPTION WITH SATURATION
HIGH AFFINITY:
FLOWX
REGULATESEFFECTIVELY GLUCOSE
TM
8
F
Px DOES NOT REGULA-TE ANYTHING,ALL FLUCTUATIONSEL Px WILL BEUNCORRECTED
-3PO4-2
SO4
LOW AFFINITY:
TM
EXCR.
RES.
AA URIC ACID
EVERYTHING RESOR-BED, PAA DOES NOTREGULATE ANYTHING
PUA REGULATES,NOT TOO EFFECTIVELY,HOWEVER
4. Resorption with a low affinity; excretion serves again as a regu- lator of plasma concentration, but less effectively, Fig. 9
9
F
PX
K+
Ca2+
HPO42-
H+
.
.
.
EL
Controlling organ (kidney)
Controlling systems
Filtration
Resorption Control- ler
Controlled system (plasma)
GFR * Px = (V * Ux)With simple filtration (creatinine, inulin)More complicated instan-ces of direct effects of Px
(Fig. 8 and 9)Concentration of substan-ces in tubular cells
Control viaN.S., ADH, ALDO, PTH
Signals to the controlling systems
Indirect effects of Px2
Direct effects of Px
.
Now, we could better understand how the plasma components are homeostased by a kidney (again Fig. 2)
The concept of renal clearance: The effectivity of renal activity could be assesed by means of the amount of a substance which a hypothetical volume of plasma is completely got off per time interval.It is evident that a completely cleared volume of plasma Cx had to bear the same “load” as the same volume of plasma before did, therefore the amount of the substance which had to be cleared per minute is CX * PX. This amount must be discarded by the kidneys:
CX * PX = UX * V.
This is valid regardless the ways of excretion or reabsorption.Substances behave differently in the tubulus (Fig. 10) and accordingly, their clearance has a different relationship to GFR (Fig. 11 – 13)
.
PAH
RPF
RPF * PPAH
RPF * PPAH = V * UPAH
V * UPAH
.
.
14
Clearance of substances which are secreted nearly exclusively by the tubular wall (and are not filtered in the glomeruli) may directly serve as indicators of the renal perfusion, eg., PAH (Fig. 14 )
Osmolal and free water clearance:Osmolal clearance is quite analogical to the clearance concept of common metabolites a and is calculated in an analogical manner. Free water clearance represents a difference between the quantity of urine and the osmolal clearance. A close relationship must be between both of them (Fig. 15).
OSMOLEL AND WATER CLEARANCE
COSM * POSM = V * UOSM
COSM = V * UOSM
POSM
IF
POSM = UOSM
THEN
COSM = V
.
.
.
15
OSMOLEL CLEARANCE :
IF
THEN
.
POSM > UOSM
COSM < V
(urine hypoosmolal, the body loses water)
1 > UOSM
POSM
0 < 1 -UOSM
POSM
IF
THEN
.
POSM < UOSM
COSM > V
(urine hyperosmolal, the body retains water)
.
.
.
0 < V - COSM
.
V > COSM
.
0 > V - COSM
.
V < COSM
.
0 < V ( 1 - ) UOSM
POSM
0 < V V * UOSM
POSM COSM
.
..
.
.
.
free water clearance free water clearance,loss of water is less than
loss of solutes