The Continuum of Acid Stress

2021 ◽  
pp. CJN.17541120
Author(s):  
Donald E. Wesson
Keyword(s):  
Metabolic Acidosis ◽  
Acid Stress ◽  
Kidney Injury ◽  
Organ Injury ◽  
Bicarbonate Concentration ◽  
Related Condition ◽  
Chronic Metabolic Acidosis ◽  
Plasma Bicarbonate ◽  
Acid Accumulation ◽  
The Continuum

Acid-related injury from chronic metabolic acidosis is recognized through growing evidence of its deleterious effects, including kidney and other organ injury. Progressive acid accumulation precedes the signature manifestation of chronic metabolic acidosis, decreased plasma bicarbonate concentration. Acid accumulation that is not enough to manifest as metabolic acidosis, known as eubicarbonatemic acidosis, also appears to cause kidney injury, with exacerbated progression of CKD. Chronic engagement of mechanisms to mitigate the acid challenge from Western-type diets also appears to cause kidney injury. Rather than considering chronic metabolic acidosis as the only acid-related condition requiring intervention to reduce kidney injury, this review supports consideration of acid-related injury as a continuum. This “acid stress” continuum has chronic metabolic acidosis at its most extreme end, and high-acid-producing diets at its less extreme, yet detrimental, end.

Role of endothelin-1 in renal regulation of acid-base equilibrium in acidotic humans

2012 ◽  
Vol 303 (7) ◽  
pp. F991-F999 ◽  
Author(s):  
Alexandra Pallini ◽  
Henry N. Hulter ◽  
Jurgen Muser ◽  
Reto Krapf
Keyword(s):  
Metabolic Acidosis ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Endothelin 1 ◽  
Plasma Bicarbonate ◽  
Human Volunteers ◽  
Acid Base Equilibrium ◽  
Normal Human ◽  
Mineralocorticoid Activity

Endothelin-1 inhibits collecting duct sodium reabsorption and stimulates proximal and distal tubule acidification in experimental animals both directly and indirectly via increased mineralocorticoid activity. Diet-induced acid loads have been shown to increase renal endothelin-1 activity, and it is hypothesized that increased dietary acid-induced endothelin-1 activity may be a causative progression factor in human renal insufficiency and that this might be reversed by provision of dietary alkali. We sought to clarify, in normal human volunteers, the role of endothelin-1 in renal acidification and to determine whether the effect is dependent on dietary sodium chloride. Acid-base equilibrium was studied in seven normal human volunteers with experimentally induced metabolic acidosis [NH4Cl 2.1 mmol·kg body weight (BW)−1·day−1] with and without inhibition of endogenous endothelin-1 activity by the endothelin A/B-receptor antagonist bosentan (125 BID p.o./day) both during dietary NaCl restriction (20 mmol/day) and NaCl repletion (2 mmol NaCl·kg BW−1·day−1). During NaCl restriction, but not in the NaCl replete state, bosentan significantly increased renal net acid excretion in association with stimulation of ammoniagenesis resulting in a significantly increased plasma bicarbonate concentration (19.0 ± 0.8 to 20.1 ± 0.9 mmol/l) despite a decrease in mineralocorticoid activity and an increase in endogenous acid production. In pre-existing human metabolic acidosis, endothelin-1 activity worsens acidosis by decreasing the set-point for renal regulation of plasma bicarbonate concentration, but only when dietary NaCl provision is restricted.

Ventilatory response to chronic metabolic acidosis and alkalosis in the dog

1984 ◽  
Vol 56 (6) ◽  
pp. 1640-1646 ◽  
Author(s):  
N. E. Madias ◽  
W. H. Bossert ◽  
H. J. Adrogue
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Ventilatory Response ◽  
Wide Spectrum ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Plasma Bicarbonate ◽  
Oral Sodium ◽  
Chronic Change

Systematic data are not available with regard to the anticipated appropriate responses of arterial PCO2 to primary alterations in plasma bicarbonate concentration. In the present study, we attempted to rigorously characterize the ventilatory response to chronic metabolic acid-base disturbances of graded severity in the dog. Animals with metabolic acidosis produced by prolonged HCl feeding and metabolic alkalosis of three different modes of generation, i.e., diuretics (ethacrynic acid or chlorothiazide), gastric drainage, and administration of deoxycorticosterone acetate (alone or in conjunction with oral sodium bicarbonate), were examined. The results indicate the existence of a significant and highly predictable ventilatory response to chronic metabolic acid-base disturbances. Moreover, the magnitude of the ventilatory response appears to be uniform throughout a wide spectrum of chronic metabolic acid-base disorders extending from severe metabolic acidosis to severe metabolic alkalosis; on average, arterial PCO2 is expected to change by 0.74 Torr for a 1-meq/l chronic change in plasma bicarbonate concentration of metabolic origin. Furthermore, the data suggest that the ventilatory response to chronic metabolic alkalosis is independent of the particular mode of generation.

The Ventilatory Response in Diabetic Ketoacidosis

1974 ◽  
Vol 46 (4) ◽  
pp. 539-549 ◽  
Author(s):  
M. Fulop ◽  
N. Dreyer ◽  
H. Tannenbaum
Keyword(s):  
Metabolic Acidosis ◽  
Diabetic Ketoacidosis ◽  
Ventilatory Response ◽  
Hydrogen Ion ◽  
Inverse Relation ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Arterial Blood ◽  
Blood Ph ◽  
Ion Activity

1. Previous studies of the ventilatory response to metabolic acidosis have usually considered only patients with arterial blood pH above 7·10. To define the response during more severe acidaemia, arterial CO2 tension and pH were measured in fifty-three episodes of diabetic ketoacidosis, including twenty-four with pH below 7·10, and ten with pH below 7·00. 2. The relation between arterial CO2 tension, and both blood pH and plasma bicarbonate concentration, in these cases with generally severe metabolic acidaemia (mean pH 7·12 ± SD 0·13), was very similar to the relations between those variables found by others in patients with less severe acidaemia, such as that due to renal failure. 3. As arterial blood hydrogen ion activity increased, arterial CO2 tension decreased inversely, reflecting well-sustained hyperventilation, even during profound acidaemia. 4. The inverse relation between arterial CO2 tension and hydrogen ion activity suggests that during metabolic acidosis, alveolar ventilation increases in direct proportion to the increased blood hydrogen ion activity.

scholarly journals Effect of growth hormone on renal and systemic acid-base homeostasis in humans

1998 ◽  
Vol 274 (4) ◽  
pp. F650-F657 ◽  
Author(s):  
Anita Sicuro ◽  
Katia Mahlbacher ◽  
Henry N. Hulter ◽  
Reto Krapf
Keyword(s):  
Growth Hormone ◽  
Metabolic Acidosis ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Normal Subjects ◽  
Acid Excretion ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Plasma Bicarbonate ◽  
Net Acid Excretion

The effects of recombinant human growth hormone (GH, 0.1 U ⋅ kg body wt−1 ⋅ 12 h−1) on systemic and renal acid-base homeostasis were investigated in six normal subjects with preexisting sustained chronic metabolic acidosis, induced by NH4Cl administration (4.2 mmol ⋅ kg body wt−1 ⋅ day−1). GH administration increased and maintained plasma bicarbonate concentration from 14.1 ± 1.4 to 18.6 ± 1.1 mmol/l ( P < 0.001). The GH-induced increase in plasma bicarbonate concentration was the consequence of a significant increase in net acid excretion that was accounted for largely by an increase in renal [Formula: see text]excretion sufficient in magnitude to override a decrease in urinary titratable acid excretion. During GH administration, urinary pH increased and correlated directly and significantly with urinary[Formula: see text] concentration. Urinary net acid excretion rates were not different during the steady-state periods of acidosis and acidosis with GH administration. Glucocorticoid and mineralocorticoid activities increased significantly in response to acidosis and were suppressed (glucocorticoid) or decreased to control levels (mineralocorticoid) by GH. The partial correction of metabolic acidosis occurred despite GH-induced renal sodium retention (180 mmol; gain in weight of 1.8 ± 0.2 kg, P< 0.005) and decreased glucocorticoid and mineralocorticoid activities. Thus GH (and/or insulin-like growth factor I) increased plasma bicarbonate concentration and partially corrected metabolic acidosis. This effect was generated in large part by and maintained fully by a renal mechanism (i.e., increased renal NH3 production and[Formula: see text]/net acid excretion).

Distal tubule bicarbonate reabsorption during rebound metabolic alkalosis

1991 ◽  
Vol 69 (11) ◽  
pp. 1784-1788 ◽  
Author(s):  
David H. Vandorpe ◽  
Steven P. Nadler ◽  
David Z. Levine
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Distal Tubule ◽  
Bicarbonate Transport ◽  
Bicarbonate Concentration ◽  
Plasma Bicarbonate ◽  
Bicarbonate Reabsorption ◽  
Collecting Ducts ◽  
Persistent Elevation

Rebound metabolic alkalosis is a transient alkalemia that is seen during recovery from NH4Cl-induced metabolic acidosis. The persistent elevation of plasma bicarbonate concentration is the result of continuing excretion of net acid by the kidney. Bicarbonate transport by inner medullary collecting ducts has been reported by others to proceed normally (i.e., bicarbonate reabsorption continues in this segment) during rebound metabolic alkalosis. No other segmental responses have been evaluated. Since the surface distal tubule of the rat is known to both reabsorb and secrete bicarbonate in vivo, it was of interest to determine the response of this segment. Our results show that the distal tubule microperfused in vivo during rebound metabolic alkalosis continues to reabsorb significant amounts of bicarbonate, despite the presence of systemic alkalemia that we have previously shown to be associated with distal tubule bicarbonate secretion.Key words: rebound metabolic alkalosis, distal tubule, micropuncture, bicarbonate reabsorption.

scholarly journals Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease

2020 ◽  
Vol 31 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Donald E. Wesson ◽  
Jerry M. Buysse ◽  
David A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Acid Excretion ◽  
Adaptive Responses ◽  
Disease Treatment ◽  
Chronic Metabolic Acidosis ◽  
Progression Of Kidney Disease

Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.

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