General renal pathophysiology

1
General renal pathophysiology

• 1. Relationship between plasma solute
  concentration and its excretion by
  kidneys
• 2. Renal perfusion and filtration

2
1. Relationship between plasma solute
concentration and its excretion by
kidneys General scheme of a
feedback regulation (Fig. 1)
1
3
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.
4
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)
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Feedback homeostasing of plasma components by
kidneys
Controlling organ (kidney)
Controlling systems
Controlled system (plasma)
Direct effects of Px
EL
.
GFR ?Px (V Ux)? With simple filtration
(creatinine, inulin) More complicated instan- ces
of direct effects of Px (Fig. 8 and 9)
K Ca2 HPO42- H . . .
Filtration
Control- ler
Resorption
Concentration of substan- ces in tubular cells
Control via N.S., ADH, ALDO, PTH
Signals to the controlling systems
2
Indirect effects of Px
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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)
2
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)
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RELATIONSHIP BETWEEN PLASMA CONCENTRATION OF A
METABOLITE AND ITS DISCARDING BY KIDNEYS
ABSORPTION, PRODUCTION, MOBILIZATION
MINUS EXTRARENAL DISCARDING, DECOMPOSITION, STORIN
G
EL
Px INDICATES HERE ONLY RELATIONSHIP
EL GFR
Px GFR
Px
.
Qf
AFTER SOME TIME
STEADY STATE
IN WHICH ? EL ? Px GFR
? EL
95 ARE NOT FILTE- RED
3
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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)
Px GFR
Px
TIME
STEADY STATE
? GFR
IN WHICH EL ? Px ? GFR
EXCRETION INDICATES HERE
PRODUCTION,
NOT GFR
4
9
These examples refer to creatinine, inulin,
glucose (above the resorption threshold) etc.,
where reabsorption or secretion of the substance
in renal tubuli is absent The 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)

5
10
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

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Feedback by means of Px varies according to the
different behaviour of the substance in tubuli
Substance filtered only
Substance with proportional resorption (UREA)
Excreted quantity
Ation
Ation
PxGFR
.
Resorption 50 Qf
.
Qf
EL
Reabsorption
Excreted quantity
?
Px
Px
The movement along the line is not instantaneous
and stops later at EL Px GFR
6
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INULIN
UREA
Px
Cx
GFR
.
V Ux
RELATIONSHIP
.
EL V Ux
IS VALID FOR ALL SUBSTANCES IN STEADY STATE
7
13
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 substance 3. 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
.
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RESORPTION WITH SATURATION
HIGH AFFINITY
EXCRETION
F
SUBTHRESHOLD PGL
TM
RES.
PTH
F L O WX
GL AA
REGULATES EFFECTIVELY ? GLUCOSE
Px DOES NOT REGULA- TE ANYTHING, ALL
FLUCTUATIONS EL ? Px WILL BE UNCORRECTED
-3
PO4-2
SO4
8
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4. Resorption with a low affinity excretion
serves again as a regu- lator of plasma
concentration, but less effectively, Fig. 9
LOW AFFINITY
EXCR.
F
TM
RES.
PX
AA URIC ACID
EVERYTHING RESOR- BED, PAA DOES NOT REGULATE
ANYTHING
PUA REGULATES, NOT TOO EFFECTIVELY, HOWEVER
9
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Now, we could better understand how the plasma
components are homeostased by a kidney (again
Fig. 2)
Controlling organ (kidney)
Controlling systems
Controlled system (plasma)
Direct effects of Px
EL
.
GFR ?Px (V Ux)? With simple filtration
(creatinine, inulin) More complicated instan- ces
of direct effects of Px (Fig. 8 and 9)
K Ca2 HPO42- H . . .
Filtration
Control- ler
Resorption
Concentration of substan- ces in tubular cells
Control via N.S., ADH, ALDO, PTH
Signals to the controlling systems
2
Indirect effects of Px
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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)

.
18
10
19
CLEARANCE
GLUKOSE
.
? V PGL
CGL ?
11
20
GENERAL CASE
Px
Cx
GFR
.
Px Cx Ux V
.
Ux V Px
.
Cx lt GFR
V
Ux
12
21
CALCULATION OF GFR
CCREAT
GFR
.
PCREAT GFR UCREAT V
.
Ukr V PCREAT
GFR
.
UCREAT V
13
22
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 )
PAH
RPF
RPF PPAH
.
V UPAH
.
RPF PPAH V UPAH
14
23
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).
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OSMOLEL AND WATER CLEARANCE
OSMOLEL CLEARANCE
.
COSM POSM V UOSM
.
V UOSM
COSM
POSM
IF
POSM UOSM
THEN
.
COSM V
15
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IF
IF
.
.
COSM lt V
COSM gt V
THEN
THEN
POSM gt UOSM
POSM lt UOSM
(urine hypoosmolal, the body loses water)
(urine hyperosmolal, the body retains water)
UOSM
1 gt
. . .
POSM
UOSM
0 lt 1 -
POSM
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UOSM
.
0 lt V ( 1 - )
POSM
. . .
.
V UOSM
.
0 lt V
POSM
COSM
free water clearance
free water clearance, loss of water is less
than loss of solutes
.
COSM
0 lt V -
.
.
COSM
V gt
COSM
0 gt V -
.
COSM
V lt
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The decline of osmotic clearance is in
contradistinction to diuresis a sensitive sign
of renal failure (Fig. 16)
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