Edward J. Lennon

The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis.

Acute acid loads have been shown to titrate extraand intracellular buffers (1, 2). The state of titration of these buffers is reflected by the level of serum bicarbonate. With sustained acid loading, serum bicarbonate ultimately stabilizes at some reduced level despite continuing acid retention, indicating that an additional buffer system is titrated. It has been suggested that such additional quantities of buffer could arise from the slow dissolution of bone mineral during chronic metabolic acidosis (3). The present metabolic balance studies were carried out to study further the relationship between acid retention and calcium balance during chronic ammonium chloride acidosis.

Studies of the Mechanism by Which Chronic Metabolic Acidosis Augments Urinary Calcium Excretion in Man

We carried out clearance studies in nine healthy adults and four patients with hypoparathyroidism before and after inducing stable metabolic acidosis with either NH(4)Cl or acetazolamide. Clearances were repeated in seven normal subjects and three of the patients 3 days after stopping these agents.During acidosis in the normal subjects, serum ultrafilterable calcium concentration rose significantly, but inulin clearance fell to a greater extent, so that the calculated filtered load of calcium fell significantly. Despite this, urinary calcium excretion rose. Urinary calcium excretion remained elevated in the recovery studies when the serum ultrafilterable calcium concentration and filtered load of calcium had returned to control levels. Evidence is presented indicating that the increased calcium excretion which occurred during acidosis and recovery clearances was not due to natriuresis or to increased excretion of complexing anions. The comparable results in the four patients with hypoparathyroidism, two of whom also had hypothyroidism, suggest that the capacity to alter secretion rates of parathyroid hormone, thyrocalcitonin or both is not a critical determinant of the augmented rates of calcium excretion during acidosis.We conclude that metabolic acidosis produces increased urinary calcium excretion by causing decreased renal tubular calcium reabsorption. Evidence is presented which suggests that this is a direct effect of metabolic acidosis on metabolic processes within renal tubular cells.

The Effect of Treatment of Acidosis on Calcium Balance in Patients with Chronic Azotemic Renal Disease

Small but statistically significant negative calcium balances were found in each of eight studies in seven patients with chronic azotemic renal disease when stable metabolic acidosis was present. Only small quantities of calcium were excreted in the urine, but fecal calcium excretion equaled or exceeded dietary intake. Complete and continuous correction of acidosis by NaHCO(3) therapy reduced both urinary and fecal calcium excretion and produced a daily calcium balance indistinguishable from zero. Apparent acid retention was found throughout the studies during acidosis, despite no further reduction of the serum bicarbonate concentration. The negative calcium balances that accompanied acid retention support the suggestion that slow titration of alkaline bone salts provides an additional buffer reservoir in chronic metabolic acidosis. The treatment of metabolic acidosis prevented further calcium losses but did not induce net calcium retention. It is suggested that the normal homeostatic responses of the body to the alterations in ionized calcium and calcium distribution produced by raising the serum bicarbonate might paradoxically retard the repair of skeletal calcium deficits.

Defense of Hydrogen Ion Concentration in Chronic Metabolic Acidosis: A New Evaluation of an Old Approach

Excerpt The interpretation of disturbances in acid-base metabolism requires knowledge of the hydrogen ion concentration of body fluids and the state of the buffers that defend this concentration. C...

The incidence of skin reactivity to insulin in diabetic patients

Abstract Skin tests for the presence of skin reactivity to insulin were done on 168 diabetics and 20 nondiabetic individuals. The individuals were divided into 4 groups. Group I consisted of diabetics on insulin, Group II consisted of diabetics formerly on insulin, Group III consisted of diabetics who had never received insulin, and Group IV consisted of nondiabetic controls. Group I demonstrated 53 per cent with skin reactivity; Group II, 18.6 per cent; Group III, 10 per cent; and Group IV, none. There was no positive correlation with age, duration of diabetes, control, or history of allergic disease.

Insulin allergy and insulin resistance: Report of a case☆

Abstract A case is presented of a patient who exhibited local and generalized urticarial reactions, presumably due to insulin, associated with increasing insulin requirements and a delayed hypoglycemic response to intravenously administered insulin. The presence of skin-sensitizing antibodies to insulin of various animal species was demonstrated. Insulin-binding (blocking?) antibody was also demonstrated. Administered labeled insulin was largely retained intravascularly, the insulin space approximating the plasma volume. The role of insulin-binding antibody in retaining insulin within the vascular space was related to the diminished physiologic response to insulin. The significance of these immune phenomena in the genesis of frequently observed cases of relative insulin resistance is discussed.

The Diagnosis and Treatment of Toxic Nodular Goiter

Because toxic nodular gaiter occurs frequently in elderly persons who have associated degenerative diseases, it presents unusual problems in diagnosis and treatment. The difficulty in diagnosis may be compounded by the sporadic function of the toxic thyroid nodule with fluctuating clinical and laboratory findings.The pathogenesis of toxic nodular gaiter is reviewed, as are the clinical picture, laboratory findings, and choice of therapy. In general, surgical resection is the most effective definitive form of therapy, but it carries a significant risk which must be evaluated carefully.