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C R Kleeman

Publications and source records attributed to C R Kleeman.

At least 55 records · Page 3Linked to original sources
PubMed1980

Role of growth hormone in experimental phosphorus deprivation in the rat.

The demands of growth are known to exacerbate the effect of phosphorus deprivation (PD). We examined whether changes associated with PD could be prevented in young rats in which growth and growth hormone (GH) were eliminated by hypophysectomy (HPX) and whether PD in normal intact rats (INT) was associated with increased secretion of GH. INT or thyroxine- and ACTH-replaced HPX rats were fed one of the three diets: 0.31% P (NP); 0.027% P (LP), and 0.31% P, pair-fed with LP-mates (NP-PF). The results indicate that HPX did not qualitatively alter several physiologic responses to PD: (a) serum and urinary phosphorus (P) decreased and urinary calcium (Ca) increased; (b) net intestinal Ca retention fell and duodenal sac uptake of 45Ca rose; and (c) external P balance was restored and duodenal sac uptake of 32P-phosphate increased. Only the hypercalcemia seen in INT, LP rats was prevented by HPX. In INT rats serum immunoassayable GH levels, measured in single samples, were not different between different dietary groups while pituitary bioassayable GH was reduced in both LP and NP-PF rats when compared to the NP rats. Thus, except for hypercalcemia, the physiologic responses associated with PD are not prevented by the elimination of growth and GH, and the development of these responses in INT rats was not associated with a consistent or specific alteration in GH secretion.

Animals↗
PubMed1980

The clinical physiology of water metabolism. Part III: The water depletion (hyperosmolar) and water excess (hyposmolar) syndromes.

Hyperosmolality occurs when there are defects in the two major homeostatic mechanisms required for water balance-thirst and arginine vasopressin (AVP) release. In this situation hypotonic fluids are lost in substantial quantities causing depletion of both intracellular and extracellular fluid compartments. Patients with essential hypernatremia have defective osmotically stimulated AVP release and thirst but may have intact mechanisms for AVP release following hypovolemia. Hyperosmolality can also be seen in circumstances in which impermeable solutes are present in excessive quantities in extracellular fluid. Under these conditions there is cellular dehydration and the serum sodium may actually be reduced by water drawn out of cells along an osmotic gradient. Hyposmolality and hyponatremia may be seen in a variety of clinical conditions. Salt depletion, states in which edema occurs and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may all produce severe dilution of body fluids resulting in serious neurologic disturbances. The differential diagnosis of these states is greatly facilitated by careful clinical assessment of extracellular fluid volume and by determination of urine sodium concentration. Treatment of the hyposmolar syndromes is contingent on the pathophysiology of the underlying disorder; hyponatremia due to salt depletion is treated with infusions of isotonic saline whereas mild hyponatremia in cirrhosis and ascites is best treated with water restriction. Severe symptomatic hyponatremia due to SIADH is treated with hypertonic saline therapy, sometimes in association with intravenous administration of furosemide. Less severe, chronic cases may be treated with dichlormethyltetracycline which blocks the action of AVP on the collecting duct.

Adenocarcinoma↗
PubMed1980

Kidney stones.

The prevalence of kidney stones has steadily risen during this century; passage of a calculus and a positive family history increase the probability of recurrence. Findings from recent studies on the cause of renal calculi have stressed crystallization and crystal aggregation of stone minerals from supersaturated urine, rather than excessive organic matrix. Absence of normal urine inhibitors of calcium salts is also stressed. Formation of calcium oxalate stones is the major problem. Therapy with decreased calcium and oxalate intake, thiazides, phosphate salts and allopurinol in various combinations has substantially decreased the prevalence of recurrent stones. The rationale for the use of allopurinol is that uric acid salts enhance the tendency for calcium oxalate to crystallize from supersaturated urine. The hypercalciuria seen in 30 percent to 40 percent of patients with oxalate stones is usually caused by intestinal hyperabsorption of calcium. Although patients with uric acid calculi constitute only a small fraction of those in whom stones form, they represent a group in whom good medical therapy, based on sound physiologic principles, has proved extremely successful. Renal tubular syndromes lead to nephrocalcinosis and lithiasis through hypercalciuria, alkaline urine and hypocitraturia, the latter an inhibitor of calcium salt precipitation. Recent advances in surgical techniques are discussed, including the rationale for removing staghorn calculi. The ileal ureter and coagulum pyelolithotomy deserve special emphasis.

Acidosis, Renal Tubular↗
PubMed1979

Causes of hypercalcemia.

Hypercalcemia is most commonly seen in normal infants as the result of normal rapid bone growth. The most common causative diseases are malignant disease and hyperparathyroidism. A variety of pharmacologic agents, especially vitamin D and its metabolites and thiazide diuretics, can elevate serum calcium levels. Hypersensitivity to vitamin D appears to be a cause of hypercalcemia in infants and in patients with granulomatous disease, such as sarcoidosis. Ingestion of escessive amounts of calcium, especially with alkali, may also cause hypercalcemia, as may prolonged immobilization, particularly under conditions of rapid bone turnover.

Adult↗
PubMed1979

Management of hypercalcemia.

Hypercalcemia calls first for supportive measures, eg, adequate hydration, movement or mobilization of the patient to the greatest amount tolerated, and reevaluation of drugs being taken. When immediate lowering of the serum calcium level is not clinically mandatory, oral administration of furosemide, corticosteroid, or phosphorus should be considered. In acute emergencies, saline loading and parenteral furosemide therapy should be tried first, except in a patient with renal failure and congestive heart failure, in whom peritoneal dialysis or hemodialysis should be used instead. Calcitonin can be given for the first 12 to 24 hours to lower serum calcium concentration until a definitive management plan is formulated. Corticosteroid, if not contraindicated, should be started as soon as possible. In severe primary hyperparathyroidism with hypophosphatemia, phosphorus can be given intravenously until oral phosphate therapy can be established. Surgery, of course, should be performed as soon as possible. In most cases of neoplasia, mithramycin given according to a recommended schedule is safe and frequently effective. In desperate cases, additional use of prostaglandin synthesis inhibitors probably now is justified by empirical observations. All of these therapeutic measures are used only to stabilize electrolyte balance so that the primary cause of the hypercalcemia can be treated.

Adrenal Cortex Hormones↗
PubMed1979

Normophosphatemic phosphate depletion in growing rat.

To study the influence of phosphate depletion (PD) on the serum, urinary, bone, and soft tissue phosphorus, we studied growing rats given a high-phosphorus (HP), normal-phosphorus (NP), or low-phosphorus (LP) diet. We obtained the following results. a) With an LP diet, animals did not grow but developed the characteristic biochemical changes of PD. b) The NP rats had an unexplained accelerated rate of growth, and developed all the biochemical changes of PD, although they were normophosphatemic. c) Bone P and Ca were significantly lower in the LP and NP rats compared to the HP rats, suggesting that minerals were mobilized from bone to support soft tissue P needs. d) Soft tissue P was not different in HP, NP, and LP rats, confirming previous observations that soft tissue P is maintained even in PD. We conclude that 1) the physiologic adaptation to PD may occur in growing rats on an apparently normal phosphorus diet when the metabolic demand is unusually high, e.g. accelerated growth; 2) the evolution of the biochemical parameters of PD in the face of normophosphatemia suggest a sensor mechanism sensitive to change in dietary P concentration.

Animals↗
PubMed1979

Effect of phosphorus depletion on intestinal calcium and phosphorus absorption.

Intestinal calcium (Ca) hyperabsorption is a well-documented feature of experimental phosphorus depletion (PD). To further evaluate the effect of PD on Ca absorption we studied metabolic balance and in vitro everted duodenal sac uptake of Ca and phosphorus (P) in weanling male rats. Animals were assigned to three dietary groups: normal, 0.3% P ad libitum (NP); low, 0.03% P ad libitum (LP); and normal, 0.3% P but pair-fed with assigned LP mates (NP-PF). Results indicate that although PD led to an early but unsustained increase in 45Ca uptake by the everted duodenal sac in vitro, net intestinal Ca retention is consistently decreased in rats on the LP diet compared with rats eating either the NP or NP-PF diet. The reduction in net intestinal Ca absorption is reflected by an increase in fecal Ca, both in absolute quantities and in proportion to dietary Ca intake. The initial negative P balance after the initiation of the LP diet was promptly, albeit precariously, corrected. This was associated with a sustained increase in duodenal 32P uptake in vitro and virtual cessation of growth. Because the biosynthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its accumulation in intestinal mucosa have been reported to increase with PD, our study represents an example in which the physiological interrelationship between the activity of 1,25(OH)2D3 and intestinal Ca absorption may be dissociated.

Animals↗
PubMed1979

Influence of dietary magnesium in experimental phosphate depletion: bone and soft tissue mineral changes.

We studied weanling rats fed 0.06% (group 1) and 0.10% (group II) magnesium (Mg) during phosphate depletion (PD) in order to evaluate the role of Mg in the bone, soft tissue, and serum changes of PD. The following results were obtained: 1) serum Mg remained stable in the face of a negative Mg balance; 2) the hypercalcemic and hypercalciuric response to PD was the same in both groups; 3) bone Mg content was decreased with PD in both groups and was associated with a significant decrease in bone calcium and phosphorus. We conclude that: 1) the hypomagnesemia of PD is dependent mainly on the dietary intake of Mg; 2) the hypercalcemia and hypercalciuria of PD are not caused by primary changes in Mg homeostasis; 3) low-dietary Mg during PD may cause a defect in soft tissue utilization of P in the growing rat.

Animals↗
PubMed1979

Interaction of somatostatin with PTH and AVP: renal effects.

Six conscious intact dogs were studied to evaluate the interactions of somatostatin (SRIF) with exogenous antidiuretic hormone arginine vasopressin (AVP). SRIF administration caused a significant increase in free water clearance compared to a vehicle-treated group: -0.91 (+/- 0.41 SD) ml/min to 0.21 (+/- 0.32 SD) ml/min in the experimental group (P less than 0.01) versus 0.21 (+/- 0.81 SD) ml/min to -0.21 (+/- 0.68 SD) ml/min in the control (P greater than 0.5). Six conscious, thyroparathyroidectomized dogs were studied to test the interaction of SRIF and parathyroid extract (PTE). There were no significant changes in the phosphaturic and hypocalciuric effects of PTE with SRIF administration. We conclude that acute systemic SRIF administration interferes with the antidiuretic action of AVP, probably at the renal-tubular level, but does not antagonize the renal actions of PTE.

Animals↗
PubMed1979

Transient hypoaldosteronism after renal allotransplantation.

Studies were performed to investigate the nature of the hyperkalemia and hypokaliuria observed in two patients after renal allotransplantation in both of whom the graft was functioning and urinary output was adequate. In the first patient, examinations in the upright position revealed low values for plasma renin activity and plasma aldosterone. The second patient showed similar findings, and, in addition, an angiotensin II (Hypertensin) infusion was ineffective in stimulating aldosterone secretion during the hyperkalemic state. In both patients, short-term administration of 9 alpha-fluorohydrocortisone caused kaliuresis with a definite decrease in serum potassium. There was a spontaneous correction of the biochemical and hormonal abnormalities six weeks after transplantation and the response to an angiotensin II infusion normalized. We suggest that the hyperkalemia in both of these patients was due primarily to the transient failure of the renin-angiotensin system of the transplanted kidney.

Adult↗
PubMed1979

Mannitol.

Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction.

Acute Kidney Injury↗
PubMed1979

The clinical physiology of water metabolism. Part I: The physiologic regulation of arginine vasopressin secretion and thirst.

Water balance is tightly regulated within a tolerance of less than 1 percent by a physiologic control system located in the hypothalamus. Body water homeostasis is achieved by balancing renal and nonrenal water losses with appropriate water intake. The major stimulus to thirst is increased osmolality of body fluids as perceived by osmoreceptors in the anteroventral hypothalamus. Hypovolemia also has an important effect on thirst which is mediated by arterial baroreceptors and by the renin-angiotensin system. Renal water loss is determined by the circulating level of the antidiuretic hormone, arginine vasopressin (AVP). AVP is synthesized in specialized neurosecretory cells located in the supraoptic and paraventricular nuclei in the hypothalamus and is transported in neurosecretory granules down elongated axons to the posterior pituitary. Depolarization of the neurosecretory neurons results in the exocytosis of the granules and the release of AVP and its carrier protein (neurophysin) into the circulation. AVP is secreted in response to a wide variety of stimuli. Change in body fluid osmolality is the most potent factor affecting AVP secretion, but hypovolemia, the renin-angiotensin system, hypoxia, hypercapnia, hyperthermia and pain also have important effects. Many drugs have been shown to stimulate the release of AVP as well. Small changes in plasma AVP concentration of from 0.5 to 4 muU per ml have major effects on urine osmolality and renal water handling.

Adolescent↗
PubMed1979

The clinical physiology of water metabolism. Part II: Renal mechanisms for urinary concentration; diabetes insipidus.

The renal reabsorption of water independent of solute is the result of the coordinated function of the collecting duct and the ascending limb of the loop of Henle. The unique juxtaposition of the ascending and descending portions of the loop of Henle and of the vasa recta permits the function of a counter-current multiplier system in which water is removed from the tubular lumen and reabsorbed into the circulation. The driving force for reabsorption is the osmotic gradient in the renal medulla which is dependent, in part, on chloride (followed by sodium) pumping from the thick ascending loop of Henle. Urea trapping is also thought to play an important role in the generation of a hypertonic medullary interstitium. Arginine vasopressin (AVP) acts by binding to receptors on the cell membrane and activating adenylate cyclase. This, inturn, results in the intracellular accumulation of cyclic adenosine monophosphate (AMP) which in some fashion abruptly increases the water permeability of the luminal membrane of cells in the collecting duct. As a consequence, water flows along an osmotic gradient out of the tubular lumen into the medullary interstitium. Diabetes insipidus is the clinical condition associated with either a deficiency of or a resistance to AVP. Central diabetes insipidus is due to diminished release of AVP following damage to either the neurosecretory nuclei or the pituitary stalk. Possible causes include idiopathic, familial, trauma, tumor, infection or vascular lesions. Patients present with polyuria, usually beginning over a period of a few days. The diagnosis is made by showing that urinary concentration is impaired after water restriction but that there is a good response to exogenous vasopressin therapy. Nephrogenic diabetes insipidus can be identified by a patient's lack of response to AVP. Nephrogenic diabetes insipidus is caused by a familial defect, although milder forms can be acquired as a result of various forms of renal disease. Central diabetes insipidus is eminently responsive to replacement therapy, particularly with dDAVP, a long lasting analogue of AVP. Nephrogenic diabetes insipidus is best treated with a combination of thiazide diuretics as well as a diet low in sodium and protein.

Body Water↗
PubMed1978

High concentration of sweat calcium, magnesium and phosphate in chronic renal failure.

Sweat collected from the forearm of chronic renal failure and control patients, after iontophoretic stimulation with pilocarpine, was analyzed for Na, K, Cl, Mg, phosphate and urea. Concentrations of Ca, Mg and phosphate in sweat from chronic renal failure patients were significantly elevated (p less than 0.05) as compared to controls, while the concentrations of Na, K, and Cl were normal. The mean sweat rates and apparent skin conductivities were lower in uremics, but not significantly different from controls (0.05 less than p less than 0.10). Tentatively it is concluded that the increase of Ca, Mg and phosphate in uremic sweat is due to an increase in the secretion of these electrolytes in the secretory portion of the sweat gland, while the reabsorptive duct is normal.

Calcium↗