Achille Guariglia

Muscle energy metabolism in uremia

Energy-rich phosphagens were measured in 11 patients with end-stage chronic renal failure and 11 nonuremic subjects. A significant decrease of ATP, phosphocreatine, total adenine nucleotides, lactate, and energy charge was found. The present results can be referred both to glycolytic sequence disturbances and to the lack of substrates characteristic of uremia.

Uremic Acidosis and Intracellular Buffering

Skeletal muscle biopsies were performed in 16 controls and 15 non-dialysed end-stage chronic renal failure (CRF) patients presenting untreated metabolic acidosis. Intracellular bicarbonate, pH, water compartments and electrolytes were determined. In 8 of 15 patients muscle ATP and lactate were measured. Intracellular bicarbonate (HCO3i) and pH (pHi) were obtained by means of muscle total carbon dioxide method: a significant (p less than 0.001) reduction in both intracellular acid--base indexes was found in all patients (pHi 6.82 +/- 13 vs. 7.04 +/- 0.05; HCO3i 6.28 +/- 2.07 vs. 11.86 +/- 0.87). Total muscle as well as extracellular water was increased. Muscle sodium and chloride contents were also increased, while no change in potassium and magnesium was detected. A significant decrease of both muscle ATP and lactate was found. The data lead to the conclusion that chronic retention of acids in CRF results in a depletion of the muscle buffer pool and consequently in intracellular acidosis: the latter could be the main cause of the cell energy metabolism derangement described in uremia.

CELL METABOLISM RESPONSE TO CARDIOPULMONARY BYPASS IN PATIENTS UNDERGOING AORTO-CORONARY GRAFTING

The main parameters of muscle acid-base, water and energy metabolism were studied in ten patients undergoing low-flux (1.5 l/min/m2), low-pressure (40 to 60 mmHg) hypothermic (26 degrees C) cardiopulmonary bypass (CPB) for aortocoronary grafting; absolute gas exchange and haemodynamic data were also measured throughout the entire CPB period. At the end of CPB a substantial preservation of water and energy metabolic indexes was found; a condition of extracellular metabolic acidosis was apparently sustained by muscle cell anaerobic glycolysis enhancement with a consequent increase of both muscle and plasma lactate content. Subnormal cell phosphocreatine levels as well as reduced bicarbonate buffer stores and decreased intracellular pH, were detected. Direct limiting effects of hypothermia on tissue O2 delivery and muscle oxidative metabolism as well as vasoconstriction and arteriovenous shunting associated with CPB procedures are likely to be involved in the above mentioned alterations of cell metabolism.

Effects of low flux-low pressure cardiopulmonary bypass on intracellular acid-base and water metabolism

In eight patients undergoing open heart surgery for elective myocardial revascularization, extra-intracellular acid-base and water metabolism parameters were studied before and after cardiopulmonary bypass procedures. All patients presented a different degree of metabolic acidosis related to plasma lactate increase. Intracellular acid-base indexes did not change significantly, though all but one patient showed an intracellular buffers consumption. Both total muscle and extracellular water increased, while intracellular water did not change. It was concluded that low flux-low pressure perfusion CPB was related to a substantial preservation of cell integrity.

Nutritional and metabolic aspects of COPD

Derangements of cell metabolism in course of hypercapnic-hypoxemic Chronic Obstructive Pulmonary Disease (COPD) are not well defined. This seems to be surprising, should one consider that the understanding of the response of body tissues to blood gas alterations is of utmost importance in order to assess the systemic effects of the disease.

Plasma and Skeletal Muscle Free Aminoacids in Acute Renal Failure

Abnormalities in protein metabolism are well known in acute renal failure (ARF) (1, 2). When renal function is acutely reduced or completely abolished, two phenomena contribute to derange protein metabolism: first, acute protein catabolism occurs inducing negative nitrogen balance, overproduction of urea and other nitrogen catabolites; second, these latter substances accumulate in the body, due to defective renal excretion, possibly contributing through their toxic effect to enhance proteolysis. In addition, if ARF is accompanied or is caused by catabolizing events (severe bleeding, surgery, sepsis, rhabdomiolysis), a further stimulus to protein breakdown contributes to a tremendous, acute malnutrition (1, 2). It is generally thought that the severity of protein catabolism may influence the clinical course of ARF (1). Acute malnutrition in ARF may be easily demonstrated by net loss of muscle mass (1, 2) and from a biochemical point of view by severely negative balance, fall of serum proteins and finally by changes in plasma amino acids (AA) levels, with reduction of essential AA (1). However, plasma free AA concentrations are not fully representative of the whole body pool of free AA, the concentrations of which are by far higher in intracellular water (ICW) than in plasma (3). Muscle tissue is the largest homogeneous cellular tissue in the body, thus containing the largest amount of free AA. Every catabolic condition is characterized primarily by increased net muscle protein degradation, which in turn causes increased flow of free AA to other organs, mainly to the liver. Accelerated muscle proteolysis is reflected also by changes in muscle free AA concentrations, as it has been demonstrated under several conditions, such as surgical trauma, sepsis, diabetes mellitus (4, 5, 6, 7). On the other hand it has been shown that sufficient and equilibrated concentrations of cellular free AA are needed to fully regulate equilibrium between muscle protein synthesis and breakdown (8).

Intracellular Acid-Base and Energy Metabolism in Uremia: A Preliminary Study on Five Patients Before and During Dialysis Treatment

Failure of uremic patients to excrete end-products of endogenous metabolism necessarily results in a positive acid balance with consequent recruitment of both bone and soft tissue buffers.

Intracellular Acid-Base and Energy Metabolism in Oliguric Acute Renal Failure (OARF)

Acute renal failure is often associated with a condition of metabolic acidosis. However, extracellular acid-base parameters do not seem to be fully representative of the entity of retained acids, since it is the intracellular compartment which is mainly involved in buffering of the acid load (1–2).