What is Metabolic Acidosis?
Disturbance in the homeostasis of the hydrogen ion concentration in the blood plasma is called metabolic acidosis. Any process that increases the serum hydrogen ion concentration is the key driver in metabolic acidosis. Metabolic acidosis is a chronic condition that works like a silent killer. The majority of patients in the Western world don’t even realize that they’ve metabolic acidosis until the damage is already done.
The Difference Between Metabolic Acidosis and Acidemia?
In metabolic acidosis, the retention of the acid in the body leads to depletion in the bicarbonate reserves of your body. There’s a slight difference between the term metabolic acidosis and acidemia. The normal blood PH level ranges between 7.35 to 7.45. When your body’s buffering capacity is too weak to maintain a normal blood PH, acidemia occurs. Metabolic acidosis is different in this case. Despite normal blood PH, you can have low-grade metabolic acidosis for years or even decades. When blood PH starts dropping, the situation is already critical and in some cases, clinicians may diagnose it as metabolic acidosis when in reality this is acidemia. This is because your body maintains normal blood PH at the expense of its bicarbonate reserves. It mainly occurs within the cells and in interstitial fluid that surrounds tissues.
Metabolic Acidosis Severity:
Metabolic acidosis is a serious health condition with no apparent signs while deep down, your blood keeps retaining acid, bicarbonate stores get depleted and various body tissues are damaged. In metabolic acidosis, your body relies on muscle, bone, and connective tissues for additional acid elimination. The symptoms of metabolic acidosis increase with age and kidney function starts deteriorating with a decreased capacity to remove acid. Metabolic acidosis can lead to nephron hypertrophy, most likely due to the adverse effects of ammonia on the kidneys. It also leads to increased loss of sodium, potassium, water, calcium, and magnesium via urine. With minerals lost from the bones particularly calcium, you’re more prone to developing osteoporosis and kidney stone formation. When your buffering capacity is unable to meet the acid load, the accumulation of acid in the cells and tissues causes cellular damage, pain, or even insulin resistance. This buffering system is a bicarbonate. When any acidic substance enters the blood, bicarbonate comes into play. The bicarbonate ions neutralize the hydronium ions and form carbonic acid and water. This carbonic acid is already a part of the blood buffering system, meanwhile, hydronium ions are removed to maintain the blood PH.
Diagnosis of Metabolic Acidosis.
The normal serum bicarbonate test is 23-30 mEq/L and the optimal range is 25 or 27-30 mEq/L. A test that shows serum bicarbonate level at or below 24 mEq/L is considered suboptimal and indicates low-grade metabolic acidosis. The low urinary citrate or high urinary ammonia further testify the metabolic acidosis. A urinary pH below 5.3 (adults) or 5.6 (children) signals metabolic acidosis in many. A pH below 6.5 indicates high acid excretion of over 40 mEq, possibly leading to acid retention in 50% of people. Even a urinary pH of 6.5 or less may suggest low-grade metabolic acidosis. Ideally, most individuals should maintain a urinary pH of approximately 6.8–7.0, indicating a near-zero net acid excretion.
Methods to Remove Extra Acid:
The human body has 4 main methods that remove acid in chronic metabolic acidosis. When proteins break down, they release H+ ions. The kidneys eliminate excess acid through ammonia production in its tubular cells. Ammonia NH3 binds with H+ to form ammonium ions. Acid can also move with phosphate out into the urine but ammonia is the main helping hand and its production in the kidneys relies on breaking down the nitrogenous amino acid glutamine, mainly sourced from skeletal muscle. While weightlifting can compensate for muscle breakdown, acidosis hampers protein synthesis and recovery. Even if muscle breakdown is counteracted by synthesis, chronic acid excretion strains the kidneys, leading to potential muscle mass loss and kidney damage over time.
The second pathway involves increased secretion of hydrogen ions in renal tubules. In mild acidosis, the kidneys' Na+/H+ ion exchanger becomes more active, eliminating H+ but reabsorbing sodium simultaneously. The impact on urinary sodium remains inconclusive, with some data suggesting increased sodium loss in urine due to potential kidney damage and reduced sodium reabsorption capacity.
The third pathway combines citrate with hydrogen ions. In the presence of more acid, citrate excretion decreases as it's reabsorbed by kidney cells, resulting in lower urinary citrate during low-grade metabolic acidosis. Citrate (citrate3−) can neutralize three protons, forming citric acid, and ultimately breaking down into water and carbon dioxide, eliminating 3H+ ions. However, reduced urinary citrate increases the risk of kidney stones. Lower citrate levels mean less binding to urinary calcium ions, leading to more soluble calcium-citrate complexes compared to oxalic acid. Low-grade metabolic acidosis leads to calcium-oxalate kidney stones. However; this condition gets better by increasing dietary bicarbonate or citrate intake.
The last buffering system includes releasing minerals (along with organic anions like phosphate and carbonate) from bones and cellular compartments. Studies in the 1960s confirmed that high dietary acid loads speed up bone breakdown. Mild acidosis improves osteoclast activity and reduces osteoblast activity ultimately increasing bone breakdown and decreasing bone building. This results in the release of calcium and phosphorus from bones, raising urine calcium levels and multiplying the risk of calcium-oxalate kidney stones.
Metabolic Acidosis Connection with Diet:
In your body, hydrogen ions (H+) represent acid and pH measures these ions on a logarithmic scale. Bases, such as bicarbonate (HCO3−) and citrate, act as hydrogen ion acceptors. Most diets result in daily acid excretion in urine, with approximately 35 mEq of bicarbonate lost in stool daily. However; during metabolic acidosis, alkali loss in stool decreases but doesn't cease. Kidneys play a vital role in bicarbonate reabsorption which decreases with age and kidney damage. Humans are considered acid-producing, alkali-losing organisms, with Western diets often nearing the threshold for acid retention. Additionally, aging accelerates acid retention due to declining kidney function and dietary choices.
Animal protein, rich in sulfur-containing amino acids, generates dietary acid, primarily sulfuric acid and hydrogen ions. Fruits and vegetables, high in organic anions like citrate, act as bases and help neutralize excessive acid in the body. Animal foods contribute to a positive potential renal acid load (PRAL), while plants have a negative PRAL. That’s why in patients with metabolic acidosis, the diet is custom-planned to promote alkalinization and reduce the intake of more acid.
When the dietary base is less, the kidneys eliminate excess acid by ammonia overproduction which is harmful to kidneys and requires muscle breakdown for nitrogen. To counter high acid intake, options include bicarbonate supplements, bicarbonate mineral waters, having a diet with more bases, and consuming fruits and vegetables. Potassium and sodium citrate post-meals can also inhibit acid. However, this solution is not advised for patients with high potassium or kidney issues.
When kidneys exceed their acid threshold (40–70 mEq/day), 1 mEq of acid is retained per 2.5 mEq over the limit. Without sufficient dietary bicarbonate, citrate, and minerals (sodium, potassium, magnesium, calcium) to neutralize excess acid, detrimental effects occur. Bones break down for bicarbonate buffering, causing mineral loss and weakened bones. Muscle and connective tissue breakdown eliminates hydrogen ions, taxing glutamine and glycine status. Kidneys suffer damage from increased ammonia production. Kidney stones may form due to citrate reabsorption and elevated calcium in urine. Cellular acid accumulation impairs enzyme function and harms all tissues.
For early diagnosis and treatment, it’s advised to look at fasting serum bicarbonate, urinary PH with a measurement after at least 4 hours of the previous meal you had, and 24-hour urinary citrate levels. After detection, adequate dietary buffers are crucial to prevent these consequences. Early detection and timely medical intervention can also save you from the damage. If you are on a keto diet due to obesity or for the sake of a healthy lifestyle, get your tests done and if needed, consult your dietitian to switch your keto diet away from acids and towards more base-containing foods, which is quite helpful in the long run.
References:
Karim Z, Attmane-Elakeb A, Bichara M. Renal handling of NH4+ in relation to the control of acid-base balance by the kidney. J Nephrol. 2002;15 Suppl 5:S128–S134. [PubMed] [Google Scholar]
Kraut JA, Madias NE. Metabolic Acidosis of CKD: An Update. Am J Kidney Dis. 2016;67:307–317. [PubMed] [Google Scholar]
Batlle D, Chin-Theodorou J, Tucker BM. Metabolic Acidosis or Respiratory Alkalosis? Evaluation of a Low Plasma Bicarbonate Using the Urine Anion Gap. Am J Kidney Dis. 2017;70:440–444. [PMC free article] [PubMed] [Google Scholar]
Kim HJ, Kang E, Ryu H, et al. Metabolic acidosis is associated with pulse wave velocity in chronic kidney disease: Results from the KNOW-CKD Study. Sci Rep. 2019;9:16139. [PMC free article] [PubMed] [Google Scholar]
Kraut JA, Kurtz I. Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005;45:978–993. [PubMed] [Google Scholar]
Chen W, Levy DS, Abramowitz MK. Acid-Base Balance and Progression of Kidney Disease. Semin Nephrol. 2019;39:406–417. [PMC free article] [PubMed] [Google Scholar]
Nagami GT, Hamm LL. Regulation of Acid-Base Balance in Chronic Kidney Disease. Adv Chronic Kidney Dis. 2017;24:274–279. [PubMed] [Google Scholar]
Kraut JA, Raphael KL. Assessment of Acid-Base Status: Beyond Serum Bicarbonate. Clin J Am Soc Nephrol. 2021;16:1429–1431. [PMC free article] [PubMed] [Google Scholar]
Hirai K, Ookawara S, Morino J, et al. Relationship between serum total carbon dioxide concentration and bicarbonate concentration in patients undergoing hemodialysis. Kidney Res Clin Pract. 2020;39:441–450. [PMC free article] [PubMed] [Google Scholar]
Bray SH, Tung RL, Jones ER. The magnitude of metabolic acidosis is dependent on differences in bicarbonate assays. Am J Kidney Dis. 1996;28:700–703. [PubMed] [Google Scholar]
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–S201. [PubMed] [Google Scholar]
Melamed ML, Raphael KL. Metabolic Acidosis in CKD: A Review of Recent Findings. Kidney Med. 2021;3:267–277. [PMC free article] [PubMed] [Google Scholar]
Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD. Nephrol Dial Transplant. 2009;24:1232–1237. [PMC free article] [PubMed] [Google Scholar]
Tabatabai LS, Cummings SR, Tylavsky FA, et al. Arterialized venous bicarbonate is associated with lower bone mineral density and an increased rate of bone loss in older men and women. J Clin Endocrinol Metab. 2015;100:1343–1349. [PMC free article] [PubMed] [Google Scholar]
Chen W, Melamed ML, Abramowitz MK. Serum bicarbonate and bone mineral density in US adults. Am J Kidney Dis. 2015;65:240–248. [PMC free article] [PubMed] [Google Scholar]
Yenchek R, Ix JH, Rifkin DE, et al. Association of serum bicarbonate with incident functional limitation in older adults. Clin J Am Soc Nephrol. 2014;9:2111–2116. [PMC free article] [PubMed] [Google Scholar]
Sebastian A, Frassetto LA, Morris RC. The acid-base effects of the contemporary Western diet: An evolutionary perspective. In: Alpern RJ, Hebert SC, eds. The kidney: physiology and pathophysiology, 2006.
Drenick EJ. The effects of acute and prolonged fasting and refeeding on water, electrolyte, and acid-base metabolism. In: Maxwell MH, Kleeman CR, Co M- H, et al, eds. Clinical disorders of fluid and electrolyte metabolism, 1972.
Tabatabai LS, Cummings SR, Tylavsky FA, et al. Arterialized venous bicarbonate is associated with lower bone mineral density and an increased rate of bone loss in older men and women. J Clin Endocrinol Metab 2015;100:1343–9.