George J. Gabuzda

Renal failure in patients with cirrhosis of the liver: III. Evaluation of intrarenal blood flow by para-aminohippurate extraction and response to angiotensin

Abstract Renal functional abnormalities associated with advanced liver disease were evaluated in twenty-two patients by determining the effects of angiotensin infusions and of increasing tubular loads of para-aminohippurate (PAH) upon the extraction of PAH. Angiotensin infused intravenously produced variable changes in renal blood flow, glomerular filtration rate and urinary excretion of sodium and water, but did not alter extraction of PAH. This agent did not change the distribution of blood flow within the kidney as estimated from PAH extraction. To the extent that in some patients renal ischemia and hypoxia may have been induced, these changes also had no effect upon the extraction ratio of PAH (E PAH ). The E PAH was below normal during control periods in eight of the twenty-two patients. Reduced E PAH was associated with, but was not a consequence of, decreased renal plasma flow and glomerular filtration rate and a poor urine flow response to water administration. Chronic renal disease, tubular necrosis, renal hypoxia, excessive tubular load of PAH or low urine flow rate could not be incriminated as causes of the decreased E PAH . The decreased E PAH and associated renal functional changes noted in some patients with cirrhosis are explained best by a hemodynamic alteration involving renal cortical vasoconstriction with relative increase in medullary blood flow. Ten patients were given a PAH load. Five responded normally. In the other five changes in E PAH were consistent with the presence of a defect in ability to transport PAH.

Compartmentalization of Ascites and Edema in Patients with Hepatic Cirrhosis

Abstract Compartmentalization of ascites and nonascitic fluid was demonstrated in cirrhotic patients treated with dietary sodium restriction, diuretic therapy or paracentesis. Disparity between ascitic and nonascitic fluid absorption rates, evident during spontaneous diuresis, was exaggerated by diuretic administration. Despite rapid diuresis maximum ascites absorption rate was 930 ml per 24 hours — close to the rate of intraperitoneal saline absorption by noncirrhotic human subjects. After paracentesis ascitic fluid re-formed at as much as three and a half times the maximum absorption rate. It began to form during the paracentesis procedure and continued at a gradually decreasing rate for three to four days. The ascites formed largely by a shift of nonascitic fluid to the peritoneal cavity. However, some patients also formed ascites from retained exogenous fluid; they gained weight, and mild dilutional hyponatremia developed. Compartmentalization of ascites and edema probably causes some complications th...

Plasma renin level in hepatic cirrhosis: Relation to functional renal failure

Simultaneous measurements of various factors relative to the renin-angiotensin system were made in twenty-four patients with cirrhosis and ascites, including seven with unexplained renal failure. Mean plasma renin levels were significantly higher in the group with renal failure than in the group with normal renal function. There was a significant correlation between plasma renin and glomerular filtration rate and between plasma renin and filtered sodium load (the latter in our cases was largely determined by GFR). These data are consistent with, but do not provide direct evidence for the concept that renal arteriolar perfusion pressure is decreased in cirrhotic patients with functional renal failure and this results in renal renin release either by a direct effect or through some alteration in intrarenal sodium handling. With the patients in the supine position, renal renin release was not apparent in most of the patients studied. Plasma renin substrate was a limiting factor in in vitro angiotensin formation. There was no correlation between plasma volume or cardiac output and plasma renin level. Although this study was performed with control of many factors operative in cirrhotic patients which may importantly influence renin release, it does not adequately define the roles of many of these factors, such as alterations in the state of sodium balance or in renal handling of sodium, hepatic metabolism and posture. Until these and other factors relative to the in vivo activity of the renin-angiotensin system are more precisely defined, conclusive interpretations of the significance of plasma renin levels in cirrhosis and their relation to the abnormalities in renal function associated with advanced hepatic disease are not possible.

Pneumococcal Peritonitis in Patients with Postnecrotic Cirrhosis

Abstract Six episodes of pneumococcal peritonitis in five patients with postnecrotic cirrhosis, portal hypertension and ascites are reported. This diagnosis must be considered when fever or abdominal complaints, especially with leukocytosis, occur in patients with postnecrotic cirrhosis with ascites. Onset may be insidious. Physical examination and gross characterization of ascitic fluid were not diagnostic. Cell counts and Gram-stained smears of ascitic fluid provided first evidence of bacterial peritonitis. Adequate bacteriologic studies of blood and ascitic fluid established definitive diagnosis. Bactericidal levels of penicillin were demonstrated in ascitic fluid after a relatively small intravenous dose. Therapeutic responses to parenteral penicillin were prompt and successful with respect to the pneumococcal peritonitis. However, in four patients the peritonitis occurred as a preterminal event or was followed by other complications that caused death.

PROTEIN METABOLISM IN PATIENTS WITH CIRRHOSIS OF THE LIVER

The pathogenesis of hepatic cirrhosis is, in some measure, related to protein malnutrition. Contrariwise, established liver disease may affect nutrition, including the metabolism of protein. The purpose of this paper is to present observations relating to protein metabolism in patients with established cirrhosis of the liver. This report is a summary of published investigations concerning this aspect of nutrition in liver disease, and a presentation of data not previously reported. The presentation of data derived primarily from our laboratory is done with a full realization of the valuable contributions of others, many of which have been cited in previous publications. The data presented were obtained from the study of patients maintained on the Thorndike Metabolic Ward where specialized dietary and nursing services are available. All of the patients studied had advanced cirrhosis of the liver associated with chronic alcoholism and an inadequate dietary intake. They presented obvious clinical and laboratory evidence of parenchymatous liver disease in varying stages of activity and chronicity. In many instances the clinical diagnosis was confirmed by needle biopsy of the liver, or a t necropsy. All of the patients were allowed ad libitum ambulation on the ward, none being confined strictly to bed. None presented clinical or laboratory evidence of cardiac or renal disease, nor was any study complicated by vomiting, diarrhea, gastrointestinal bleeding, or febrile illness. Although anorexia may be a prominent symptom of liver disease, this factor does not mfluence the metabolic data presented since the patients were maintained on constant intakes of food as indicated. The methods of metabolic study, the various analytical procedures, and the clinical laboratory tests involved have been described in previous publications. Consideration of the effect of well-established cirrhosis of the liver upon the metabolism of protein is presented in the following sequence: (1) the metabolism of dietary protein; (2) the utilization and excretion of amino acids; (3) the untoward consequences of the administration of certain nitrogenous substances; and (4) finally, an evaluation of these data as they apply to the dietary management of patients with this disease.

Metabolism of ornithine and other amino acids in the cerebro-oculo-renal syndrome☆

Abstract A family of six with three male children affected with the cerebro-oculo-renal syndrome has been studied for a specific biochemical abnormality in amino acid metabolism. Oral administration of the single amino acids l-lysine, l-hydroxyproline and l-glycine did not affect the urinary amino acids excreted by the oldest affected boy. In contrast, ingestion of a comparable amount of l-ornithine resulted in intensification of the abnormal urinary amino acid pattern. Feeding the parents and sister equimolar amounts of ornithine resulted only in the mother in an abnormal urinary pattern of amino acids which resembled that of the affected male children. The data are consistent with a sex-linked mode of inheritance in this family. The syndrome described herein probably represents a variant of the cerebro-oculo-renal syndrome as originally described by Lowe.

Potentiation of Pteroylglutamic Acid by Ascorbic Acid in Anemia of Scurvy

Summary Two men with scurvy and associated anemia, while maintained on a scorbutic diet, displayed hematologic responses to 125 and 250 μg of PGA, respectively, given intramuscularly daily. A potentiation of this hematologic effect of PGA occurred on subsequent administration of 1 g of ascorbic acid daily in addition to the PGA.

Response to adrenocorticotrophic hormone in clinical scurvy.

Summary 1. Test doses of ACTH were administered to 5 patients with classical scurvy to assess their adrenal cortical activity. The test was repeated in 4 of these patients after therapy with ascorbic acid. 2. The blood eosinophil response to ACTH was that expected of individuals with normal adrenal function and did not change following treatment with ascorbic acid. 3. The urinary excretion of uric acid after ACTH was uninterpretable because of low urine volumes. 4. The blood glutathione, and the serum sodium concentrations were normal or low in these patients, but were unaltered by ascorbic acid therapy. Serum potassium concentrations were normal before and after ascorbic acid therapy. 5. To explain these evidences of normal adrenal cortical activity in scurvy, it may be postulated that either ascorbic acid is not necessary for these adrenal functions, or there was residual ascorbic acid in the adrenals of these patients.

Effect of Citrovorum Factor upon Tyrosine Metabolism in Clinical Scurvy.

Summary and Conclusions 1. A patient with scurvy excreted large quantities of tyrosyl derivatives in the urine when given 1-tyrosine orally during the scorbutic state. The tyrosyl excretion was not decreased by the intramuscular administration of 6 mg of citrovorum factor daily for 5 days, but was promptly corrected by 1 g of ascorbic acid administered orally daily. 2. Citrovorum factor in the doses indicated did not alter the abnormal capillary fragility of scurvy in 2 patients.

Kinetics of Ascites and Edema Mobilization.

Excerpt Rates of ascitic fluid absorption and edema mobilization were measured in patients with hepatic cirrhosis who were undergoing spontaneous or drug-induced diuresis. Ascites absorption rate w...