Acid-alkaline balance: role in chronic disease and detoxification.
Minich Deanna M,Bland Jeffrey S
Alternative therapies in health and medicine
In conclusion, the increasing dietary acid load in the contemporary diet can lead to a disruption in acid-alkaline homeostasis in various body compartments and eventually result in chronic disease through repeated borrowing of the body's alkaline reserves. Adjustment of tissue alkalinity, particularly within the kidney proximal tubules, can lead to the more effective excretion of toxins from the body. Metabolic detoxification using a high vegetable diet in conjunction with supplementation of an effective alkalizing compound, such as potassium citrate, may shift the body's reserves to become more alkaline.
Disorders of acid-base balance.
Kellum John A
Critical care medicine
BACKGROUND:Intensivists spend much of their time managing problems related to fluids, electrolytes, and blood pH. Recent advances in the understanding of acid-base physiology have resulted from the application of basic physical-chemical principles of aqueous solutions to blood plasma. All changes in blood pH, in health and in disease, occur through changes in three variables: carbon dioxide, relative electrolyte concentrations, and total weak acid concentrations. However, while this quantitative approach has enjoyed widespread use among researchers, clinicians are reluctant to employ it. Recent advances have brought a measure of parity between the newer and the older, descriptive approach to acid-base physiology. DATA SYNTHESIS:Case-based review of the literature. CONCLUSION:Both quantitative and traditional approaches can be easily combined to result in a powerful tool for bedside acid-base analysis.
10.1097/01.CCM.0000286399.21008.64
Acid-base disorders in liver disease.
Scheiner Bernhard,Lindner Gregor,Reiberger Thomas,Schneeweiss Bruno,Trauner Michael,Zauner Christian,Funk Georg-Christian
Journal of hepatology
Alongside the kidneys and lungs, the liver has been recognised as an important regulator of acid-base homeostasis. While respiratory alkalosis is the most common acid-base disorder in chronic liver disease, various complex metabolic acid-base disorders may occur with liver dysfunction. While the standard variables of acid-base equilibrium, such as pH and overall base excess, often fail to unmask the underlying cause of acid-base disorders, the physical-chemical acid-base model provides a more in-depth pathophysiological assessment for clinical judgement of acid-base disorders, in patients with liver diseases. Patients with stable chronic liver disease have several offsetting acidifying and alkalinising metabolic acid-base disorders. Hypoalbuminaemic alkalosis is counteracted by hyperchloraemic and dilutional acidosis, resulting in a normal overall base excess. When patients with liver cirrhosis become critically ill (e.g., because of sepsis or bleeding), this fragile equilibrium often tilts towards metabolic acidosis, which is attributed to lactic acidosis and acidosis due to a rise in unmeasured anions. Interestingly, even though patients with acute liver failure show significantly elevated lactate levels, often, no overt acid-base disorder can be found because of the offsetting hypoalbuminaemic alkalosis. In conclusion, patients with liver diseases may have multiple co-existing metabolic acid-base abnormalities. Thus, knowledge of the pathophysiological and diagnostic concepts of acid-base disturbances in patients with liver disease is critical for therapeutic decision making.
10.1016/j.jhep.2017.06.023
The chemistry, physiology and pathology of pH in cancer.
Swietach Pawel,Vaughan-Jones Richard D,Harris Adrian L,Hulikova Alzbeta
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Cell survival is conditional on the maintenance of a favourable acid-base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large acid-base fluxes, which would disturb pH if uncorrected. The large cellular reservoir of H(+)-binding sites can buffer pH changes but, on its own, is inadequate to regulate intracellular pH. To stabilize intracellular pH at a favourable level, cells control trans-membrane traffic of H(+)-ions (or their chemical equivalents, e.g. ) using specialized transporter proteins sensitive to pH. In poorly perfused tumours, additional diffusion-reaction mechanisms, involving carbonic anhydrase (CA) enzymes, fine-tune control extracellular pH. The ability of H(+)-ions to change the ionization state of proteins underlies the exquisite pH sensitivity of cellular behaviour, including key processes in cancer formation and metastasis (proliferation, cell cycle, transformation, migration). Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H(+)/H(+)-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark. Through genetic instability, the cellular apparatus for regulating and sensing pH is able to adapt to extracellular acidity, driving disease progression. The therapeutic potential of disturbing this sequence by targeting H(+)/H(+)-equivalent transporters, buffering or CAs is being investigated, using monoclonal antibodies and small-molecule inhibitors.
10.1098/rstb.2013.0099
Role of Acid-Base Homeostasis in Diabetic Kidney Disease.
Khairallah Pascale,Scialla Julia J
Current diabetes reports
PURPOSE OF REVIEW:Acid-base homeostasis is impaired in chronic kidney disease (CKD) and may contribute to disease progression. Diabetes, a major cause of CKD worldwide, may exacerbate acidosis further due to differences in acid production and excretion. Here, we review the role of abnormal acid-base homeostasis in the pathogenesis and progression of diabetes and diabetic kidney disease. RECENT FINDINGS:Acidosis and dietary acid loading may contribute to the development and worsening of insulin resistance and hypertension, thereby promoting diabetes and diabetic CKD. However, although metabolic acidosis associates with progression of CKD generally, the results in diabetic CKD are mixed. Data suggests that metabolic acid production in diabetes may be higher than would be predicted based on dietary intake alone, and new observational data suggests that this higher diet-independent acid production could potentially be protective. The role of acid-base homeostasis in diabetic CKD progression is complex and must consider differences in endogenous acid production and excretion in diabetes. Ongoing observational and interventional studies in this field should consider the unique physiology of diabetes.
10.1007/s11892-017-0855-6
Acid-base disturbances in gastrointestinal disease.
Gennari F John,Weise Wolfgang J
Clinical journal of the American Society of Nephrology : CJASN
Disruption of normal gastrointestinal function as a result of infection, hereditary or acquired diseases, or complications of surgical procedures uncovers its important role in acid-base homeostasis. Metabolic acidosis or alkalosis may occur, depending on the nature and volume of the unregulated losses that occur. Investigation into the specific pathophysiology of gastrointestinal disorders has provided important new insights into the normal physiology of ion transport along the gut and has also provided new avenues for treatment. This review provides a brief overview of normal ion transport along the gut and then discusses the pathophysiology and treatment of the metabolic acid-base disorders that occur when normal gut function is disrupted.
10.2215/CJN.02450508
Acid Base Balance and Progression of Kidney Disease.
Chen Wei,Levy David S,Abramowitz Matthew K
Seminars in nephrology
A large body of work in animals and human beings supports the hypothesis that metabolic acidosis has a deleterious effect on the progression of kidney disease. Alkali therapy, whether pharmacologically or through dietary intervention, appears to slow CKD progression, but an appropriately powered randomized controlled trial with a low risk of bias is required to reach a more definitive conclusion. Recent work on urinary ammonium excretion has shown that the development of prognostic tools related to acidosis is not straightforward, and that application of urine markers such as ammonium may require more nuance than would be predicted based on our understanding of the pathophysiology.
10.1016/j.semnephrol.2019.04.009
Molecular Pathophysiology of Acid-Base Disorders.
Wagner Carsten A,Imenez Silva Pedro H,Bourgeois Soline
Seminars in nephrology
Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are mostly controlled by respiration and kidney. The kidney contributes to acid-base balance by reabsorbing filtered bicarbonate, regenerating bicarbonate through ammoniagenesis and generation of protons, and by excreting acid. This review focuses on acid-base disorders caused by renal processes, both inherited and acquired. Distinct rare inherited monogenic diseases affecting acid-base handling in the proximal tubule and collecting duct have been identified. In the proximal tubule, mutations of solute carrier 4A4 (SLC4A4) (electrogenic Na/HCO-cotransporter Na/bicarbonate cotransporter e1 [NBCe1]) and other genes such as CLCN5 (Cl/H-antiporter), SLC2A2 (GLUT2 glucose transporter), or EHHADH (enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase) causing more generalized proximal tubule dysfunction can cause proximal renal tubular acidosis resulting from bicarbonate wasting and reduced ammoniagenesis. Mutations in adenosine triphosphate ATP6V1 (B1 H-ATPase subunit), ATPV0A4 (a4 H-ATPase subunit), SLC4A1 (anion exchanger 1), and FOXI1 (forkhead transcription factor) cause distal renal tubular acidosis type I. Carbonic anhydrase II mutations affect several nephron segments and give rise to a mixed proximal and distal phenotype. Finally, mutations in genes affecting aldosterone synthesis, signaling, or downstream targets can lead to hyperkalemic variants of renal tubular acidosis (type IV). More common forms of renal acidosis are found in patients with advanced stages of chronic kidney disease and are owing, at least in part, to a reduced capacity for ammoniagenesis.
10.1016/j.semnephrol.2019.04.004
Regulation of Acid-Base Balance in Chronic Kidney Disease.
Nagami Glenn T,Hamm L Lee
Advances in chronic kidney disease
The kidneys play a major role in the regulation of acid-base balance by reabsorbing bicarbonate filtered by the glomeruli and excreting titratable acids and ammonia into the urine. In CKD, with declining kidney function, acid retention and metabolic acidosis occur, but the extent of acid retention depends not only on the degree of kidney impairment but also on the dietary acid load. Acid retention can occur even when the serum bicarbonate level is apparently normal. With reduced kidney function, acid transport processes in the surviving nephrons are augmented but as disease progresses ammonia excretion and, in some individuals, the ability to reabsorb bicarbonate falls, whereas titratable acid excretion is preserved until kidney function is severely impaired. Urinary ammonia levels are used to gauge the renal response to acid loads and are best assessed by direct measurement of urinary ammonia levels rather than by indirect assessments. In individuals with acidosis from CKD, an inappropriately low degree of ammonia excretion points to the pathogenic role of impaired urinary acid excretion. The presence of a normal bicarbonate level in CKD complicates the interpretation of the urinary ammonia excretion as such individuals could be in acid-base balance or could be retaining acid without manifesting a low bicarbonate level. At this time, the decision to give bicarbonate supplementation in CKD is reserved for those with a bicarbonate level of 22 mEq/L, but because of potential harm of overtreatment, supplementation should be adjusted to maintain a bicarbonate level of <26 mEq/L.
10.1053/j.ackd.2017.07.004