General renal pathophysiology

Transcription

1 General renal pathophysiology 1 Relationship between plasma solute concentration and its excretion by kidneys General scheme of a feedback regulation (ig 1) 1 Relationship between plasma solute concentration and its excretion by kidneys Renal perfusion and filtration 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 () of various metabolites Plasma concentration of solutes (P X ) is disturbed by extrarenal load On the other hand, it itself interferes with individual components of (with production, supply, metabolism, and storage of a substance) P X 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 (ig ) eedback homeostasing of plasma components by kidneys on zero value (creatinine, uric acid) Controlling systems Controller Controlling organ (kidney) Direct effects of GR * = (V * U x ) With simple filtration (creatinine, inulin) More complicated instances of direct effects of (ig 8 and 9) Concentration of substances in tubular cells Control via NS, ADH, ALDO, PTH Signals to the controlling systems Indirect effects of Resorption Controlled system (plasma) K + Ca + HPO 4 - H + Substances are on a precise value (Na +, K +, H +,) homeostased above a threshold on its value (HPO -- 4, glucose in hyperglycaemia) In detail: 1 If P X rises due to enhanced X with an undisturbed renal function (normal glomerular filtration rate, GR), a new steady state is established after some time, where = P X * GR (ig 3)

2 RATIONSHIP BETWEEN PLASMA CONCENTRATION O A METABOLITE AND ITS DISCARDING BY KIDNEYS If the renal function (GR) declines with an unchanged X, a new steady state is established after some time, where = P X * flgr (ig 4) ABSORPTION, PRODUCTION, MOBILIZATION MINUS EXTRARENAL DISCARDING, DECOMPOSITION, STORING * GR * GR 3 ATER SOME TIME 95% ARE NOT ILTE- RED STEADY STATE IN WHICH = * GR 4 fl GR TIME STEADY STATE IN WHICH = * fl GR EXCRETION INDICATES HERE PRODUCTION, NOT GR 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 P CREATININE and GR is a hyperbolic one according to the equation CREATININE = P CREATININE * GR ; therefore, P CREATININE is a relatively insensitive indicator from a diagnostic point of view (ig 5) Even a direct (ie, not mediated by hormones and neural system) influence of P X 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), ig 6 and 7 left An example with a proportional resorption (urea), ig 6 and 7 right 5 eedback by means of varies according to the different behaviour of the substance in tubuli Substance filtered only *GR Excreted quantity Reabsorption Substance with proportional resorption (UREA) Resorption 50% Excreted quantity GR INULIN V * U x RATIONSHIP C x = V * U x UREA The movement along the line is not instantaneous and stops later at: = * GR 6 7 IS VALID OR ALL SUBSTANCES IN STEADY STATE

3 RESORPTION WITH SATURATION or all substances in a steady state the following eq is valid: = U X * V HIGH AINITY: EXCRETION SUBTHRESHOLD P GL 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, ig 8 T M L O W X GL AA PTH DOES NOT REGULA- TE ANYTHING, ALL LUCTUATIONS fi WILL BE UNCORRECTED RES REGULATES EECTIVY GLUCOSE 3- PO 4 - SO Resorption with a low affinity; excretion serves again as a regulator of plasma concentration, but less effectively, ig 9 LOW AINITY: T M AA URIC ACID EVERYTHING RESOR- BED, P AA DOES NOT REGULATE ANYTHING EXCR RES P X P UA REGULATES, NOT TOO EECTIVY, HOWEVER 9 Now, we could better understand how the plasma components are homeostased by a kidney (again ig ) Controlling systems Controller Controlling organ (kidney) Direct effects of GR * = (V * U x ) With simple filtration (creatinine, inulin) More complicated instances of direct effects of (ig 8 and 9) Concentration of substances in tubular cells Control via NS, ADH, ALDO, PTH Signals to the controlling systems Indirect effects of Resorption Controlled system (plasma) K + Ca + HPO 4 - H + 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 C x 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 C X * P X This amount must be discarded by the kidneys: C X * P X = U X * V This is valid regardless the ways of excretion or reabsorption Substances behave differently in the tubulus (ig 10) and accordingly, their clearance has a different relationship to GR (ig 11 13) 10

4 CLEARANCE GENERAL CASE: GLUCOSE * V C GL = P GL = GR V C x * C x = U x * V U C x = x * V < GR U x 11 1 CALCULATION O GR: 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 (ig 14 ) PAH RP P CREAT * GR = U CREAT * V U kr * V GR = P CREAT V * U PAH RP * P PAH RP * P PAH = V * U PAH OSMOL AND WATER CLEARANCE 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 ree water clearance represents a difference between the quantity of urine and the osmolal clearance A close relationship must be between both of them (ig 15) OSMOLAL CLEARANCE : C OSM * = V * V * U C OSM = OSM I = 15 C OSM = V

5 C OSM I < V > I C OSM > V < 0 < V ( 1 - ) 0 < V - V * C OSM (urine hypoosmolal, the body loses water) 1 > 0 < 1 - (urine hyperosmolal, the body retains water) free water clearance 0 < V - C OSM V > C OSM free water clearance, 0 > V - C OSM loss of water is less than loss of solutes V < C OSM The decline of osmotic clearance is in contradistinction to diuresis a sensitive sign of renal failure (ig 16) 16