Chronic metabolic acidosis, particularly in patients with CKD, has different adverse effects, primarily on the musculoskeletal system:
Bone Disease: Chronic acidosis can lead to bone demineralization and osteomalacia, as the body buffers excess acid by leaching calcium from bones. This can exacerbate pre-existing bone diseases and lead to fractures.
Muscle Wasting: Chronic acidosis accelerates muscle protein degradation, leading to muscle atrophy and weakness. This process is particularly concerning in elderly patients, as it can reduce mobility and increase the risk of falls.
Growth Retardation in Children: Acidosis interferes with growth hormone and insulin-like growth factor, stunting growth in children with chronic metabolic acidosis.
Worsening of CKD: Chronic acidosis accelerates the progression of CKD by promoting fibrosis and inflammation in the kidneys. This can further impair renal function and exacerbate acidosis in a vicious cycle.
Impaired Glucose Tolerance: Chronic metabolic acidosis reduces insulin sensitivity, leading to glucose intolerance and potentially contributing to the development of type 2 diabetes.
Reduced Albumin Synthesis: Acidosis inhibits albumin production, contributing to hypoalbuminemia and exacerbating protein-energy wasting in patients with chronic illnesses.
Increased β2-Microglobulin Production: Metabolic acidosis stimulates the production of β2-microglobulin, which can accumulate in tissues and lead to amyloidosis, further complicating CKD and other chronic conditions.
| Domain | Acute | Chronic |
|---|---|---|
| Predominant systems | Cardiovascular, neurologic, immune, metabolic | Musculoskeletal, metabolic, renal |
| Cardiovascular | Impaired myocardial contractility and reduced cardiac output, particularly below pH 7.1; arterial vasodilation with hypotension and shock; ventricular arrhythmias; resistance to infused catecholamines | — |
| Oxygen delivery | Bohr-effect shift of the oxygen-hemoglobin dissociation curve, decreasing hemoglobin's affinity for oxygen | — |
| Neurologic | Mental confusion, lethargy, and even coma, though brain pH is only minimally affected | — |
| Immune function | Reduced bactericidal activity of leukocytes and a dampened immune response | — |
| Glucose handling | Interference with insulin receptor binding, impairing glucose metabolism and causing hyperglycemia | Reduced insulin sensitivity, glucose intolerance, and potential contribution to type 2 diabetes |
| Cellular energy and survival | pH-dependent glycolytic enzymes such as 6-phosphofructokinase slow, decreasing energy production; apoptosis is promoted | — |
| Bone, muscle, and growth | — | Bone demineralization and osteomalacia from calcium buffering, with fracture risk; accelerated muscle protein degradation causing atrophy and weakness; growth retardation in children through interference with growth hormone and IGF |
| Kidney and plasma proteins | — | Accelerated CKD progression through renal fibrosis and inflammation; inhibited albumin synthesis; increased β2-microglobulin production, which can accumulate and lead to amyloidosis |
