Volume 47 | Issue 2 Article 9

1985 Hypercalcemic Nephropathy in the Dog Ellen H. Hikes Iowa State University

Wallace B. Morrison Iowa State University

Follow this and additional works at: https://lib.dr.iastate.edu/iowastate_veterinarian Part of the Nephrology Commons, and the Small or Companion Animal Medicine Commons

Recommended Citation Hikes, Ellen H. and Morrison, Wallace B. (1985) "Hypercalcemic Nephropathy in the Dog," Iowa State University Veterinarian: Vol. 47 : Iss. 2 , Article 9. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol47/iss2/9

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Hypercalcemic Nephropathy in the Dog Ellen B. Hikes, DVM· Wallace B. Morrison, DVM··

INTRODUCTION base status of the animal. Calcium is a functionally important ion and The ratio of ionized calcium to protein­ coenzyme in most all of the body systems. Be­ bound calcium is altered by fluctuations in sides its structural role in bone, calcium is in­ acid-base balance. Alkalosis decreases the per­ volved in muscle contraction, the blood coag­ centage of ionized calcium by increasing the ulation system, enzyme activity, nerve protein-bound fraction. Acidosis increases the impulse transmission, hormone release and percentage of ionized calcium.3.6·lI Approxi­ membrane permeability.I-3 Calcium metabo­ mately one-half of the calcium bound is to lism is regulated primarily by parathyroid protein, primarily albumin. Interpretation of hormone (PTH), calcitonin (CT), and vi­ total calcium depends on concurrent values tamin D (1,25-dihydroxycholecalciferol).1.1.4 for serum albumin and total protein. 9 A posi­ The release of these hormones is controlled by tive linear relationship exists between total the concentration of calcium in the plasma. 5 serum calcium and both serum total protein Exact regulation of calcium in extracellular and albumin. J.ll In order to obtain more fluid is necessary to maintain normal body complete information about serum ionized function. calcium concentration, a correction formula The skeleton contains approximately 99 for total serum calcium was derived on the percent of the body's calcium stores. Only one basis of serum concentrations of albumin and percent of the total calcium is found outside total protein. The formula for calculating total the skeleton and one-tenth of one percent in serum calcium based on albumin concentra­ the extracellular fluid. 4 •6 The extracellular tions is: pool of calcium is readily available for rapid Adjusted calcium (mg/dl) = exchange with intracellular stores.6 •7 Total Calcium (mg!dl)-Albumin (g/dl)+3.5 serum calcium (extra-cellular calcium) is The correction formula based on total serum present in three forms; protein-bound (50 %), protein concentration is: complexed (10%) and ionized calcium Adjusted calcium (mg/dl) = Calcium (mg! (40 % ).8 Ionized calcium is the biologically ac­ dl)-OA [Total Serum Protein (g/dl)] +3.3 tive fraction.6.9 In most cases, total serum cal­ The correction formulas account for the ef­ cium, not just ionized calcium, is measured fects of the quantity of protein,3.9 but not for due to the technical equipment required. the effects of acid-base fluctuations on protein­ Measurement of ionized calcium alone re­ binding of calcium. Calcium-adjustment for­ quires that blood be collected anaerobically mulas can determine whether hypocalcemia and analyzed soon after collection.3.l0 Ionized or a hypercalcemia are masked by abnormal calcium values usually parallel changes in to­ serum protein concentration.' Hypoproteine­ tal calcium. It is necessary to interpret total mia can decrease the measured calcium, and serum calcium results in the context of the hyperproteinemia will increase measured cal­ plasma albumin concentration and the acid- cium.6 As serum protein concentrations de­ crease, more calcium is ionized and then re­ moved from the serum by CT regulatory ·Dr. Hikes is a 1985 graduate of the College ofVeteri­ mechanisms. This results in an absolute de­ nary Medicine at Iowa State University. •• Dr. Morrison is an assistant professor of Veterinary crease in serum calcium. Albumin is the most Clinical Sciences at.Iowa State University. important calcium binder, binding approxi-

122 Iowa State University veterinarian mately 90 percent of the protein-bound cal­ PATHOGENESIS OF HYPERCALCEMIA cium. Therefore, it is more advantageous to Neoplasia is the most common cause of hy­ use the correcting formula based on albumin percalcemia in the dog, with lymphosarcoma rather than total protein. 3.6 the most commonly involved tumor. 5•10 Can­ The normal total serum calcium value for cer-associated hypercalcemia, formerly re­ the mature dog is approximately 10.0 mg/dl ferred to as pseudohyperparathyroidism, may (9.4-12.2 mg/dl) with variations due to diet be due to tumor metastases to the bone, con­ and analytical method.6.8·1o It is not unusual current parathyroid hyperplasia, or production to see young, rapidly growing dogs with val­ of bone-resorbing factors by neoplastic cells. 13 ues approaching 12.0 mg/dl. General values Hypercalcemia associated with tumors is usu­ for young dogs are approximately 11.1 ± 0.4 ally caused by a malignant tumor of non­ mg/dl (to.5 to 11.5 mg/dl).13 Older dogs parathyroid origin secreting a factor or factors (greater than eight years of age) may have which mimic the action of PTH.5 •6 •11.15 There normal serum calcium values of 9.0 mg/dl.s is no evidence radiographically or at necropsy There appears to be no breed- or sex-related of bone metastasis in this syndrome. Labora­ differences in total serum calcium concentra­ tory findings in cases of lymphosarcoma may tion. The total serum calcium concentration show hypercalcemia, normo- or hypophospha­ represents a balance between intestinal ab­ temia, azotemia, hypercalcinuria, hyperphos­ sorption, bone resorption and accretion, and phaturia, and hyposthenuria. 11 The changes in renal excretion and reabsorption. Hypercalce­ calcium and phosphorus result from the action mia exists when serum calcium levels rise of PTH-like substances, but these substances above the normal value of 12 mg/d1.4.5.10.11 are not inhibited by increases in serum cal­ Persistent hypercalcemia is indicated by in­ cium.1u5 It should be noted that it is impor­ creased serum calcium concentration on two tant to measure and interpret serum calcium or more consecutive determinations and may and phosphorus together, because their regula­ indicate the presence of parathyroid, renal or tion and control are interrelated.6 Studies have neoplastic disease.1.13•14 Table 1 lists the dif­ identified several hypercalcemic factors pro­ ferential diagnoses of symptomatic hyper­ duced by tumors: parathyroid hormone-like calcemia in order of most likely occur­ peptides,15 prostaglandin El,16 osteoclast-ac­ rence. 10.11•13 tivating factor15 and non-vitamin D sterols.4 The chemical substances produced by tumors and the mechanisms by which hypercalcemia is induced are apparently different for different types of tumors.11 Adenocarcinomas derived from apocrine glands of the anal sac are also an important cause of hypercalcemia in older fe­ male dOgs.6.10.17 Other neoplasms which may TABLE 1. be involved in this syndrome include testicular Differential Diagnosis interstitial cell tumors and carcinoma of the 1. Malignancy: Cancer-associated hypercalcemia mammary gland, stomach, thyroid and Lymphosarcoma lung.5.10.11.15 Adenocarcinoma (apocrine glands of the anal sac) Hypoadrenocorticism (canine Addison's dis­ Other (Multiple myeloma, mammary tumors) ease) results in hyperkalemia, hyponatremia 2. Hypoadrenocorticism and hypochloridemia due to decreased produc­ 3. Renal failure tion of glucocorticoids and mineralocorticoids. 4. Bone lesion In approximately 25 percent of the affected Metastatic Septic - bacterial or mycotic osteomyelitis dogs, hypercalcemia will also be seen.13 The Disuse osteoporosis severity of hypercalcemia is correlated with the 5. Hypervitaminosis D severity of hypoadrenocorticism. However, the Iatrogenic - diet hypercalcemia is usually mild, generally less Plants - Cestrum diumum 13 111 Solanum malacoxylon than 13.5 mg/dl. • The exact cause of the Trisetum jlavescens rise in calcium levels is unknown. Several 6. Primary hyperparathyroidism mechanisms have been proposed, and the most Adenoma likely explanation involves diminished renal Adenocarcinoma excretion of calcium due to increased tubular

JiJI. 47, No. 2 123 reabsorption of calcium. IS Hypercalcemia as­ dogs with chronic renal failure, calcium levels sociated with hypoadrenocorticism usually of­ are 12.0 mg/dl or greater. IO The pathogenesis fers a good prognosis because it is corrected of hypercalcemia induced by primary renal dis­ following adequate corticosteroid therapy for ease is not fully understood, and several mech­ the hypoadrenocorticism. anisms have been proposed: a) decreased ex­ Primary and secondary bone tumors and cretion of calcium by the diseased kidney; b) septic osteomyelitis are uncommon causes of decreased renal tubular degradation of PTH; hypercalcemia in the dog, but are seen more c) PTH-induced hypercitricemia which in­ often in man as a mechanism of hypercalce­ creases complexed calcium; d) overcompensa­ mia. 19 Primary or secondary bone tumors may tion by the parathyroid gland; and e) exagger­ cause hypercalcemia via osteolysis of the bone. ated response to vitamin D with resultant It has been hypothesized that there is increased increase in intestinal absorption of calcium. 10 resorption of bone without adequate compen­ It now appears that the parathyroid glands-and satory urinary excretion of calcium.13 Asso­ increased concentration of PTH are important ciated with changes in calcium are normal or in pathogenesis of hypercalcemia associated moderately elevated serum phosphorus and al­ with chronic renal failure. 13 kaline phosphatase. 4 •1o These changes are the Acute renal failure and hypercalcemia in result of either mechanical destruction by the man may often be preceded by rhabdomyoly­ infiltrating tumor or by bone-resorbing factors sis. 4 •20 Rhabdomyolysis and associated hyper­ such as prostaglandins or osteoclast-activating calcemia is rarely observed in dogs. In man, factor. 4 Primary tumors which may produce rhabdomyolysis will cause an acute tubular ne­ hypercalcemia include osteosarcoma and crosis.10 The causes of rhabdomyolysis in man multiple myeloma. 4 Mammary gland, liver, include traumatic, drug-induced, association lung and prostate carcinomas have the highest with malignant hyperthermia or idiopathic.21 incidence of secondary bone tumors in the In a case reported in a dog, traumatic damage dog.ll Bacterial and mycotic osteomyelitis (his­ to muscle resulted in dystrophic calcification of toplasmosis, coccidioidomycosis and blastomy­ the muscle.4 Damaged muscle is the site for cosis) may also produce a hypercalcemic calcium deposition during the oliguric phase of state. 13 Bone changes are due to either sepsis acute renal failure. 20 During the diuretic and inflammation resulting in bone destruc­ phase, the sequestered calcium is released from tion; or production of bone-resorbing factors. 10 the tissues leading to hypercalcemia and hy­ Primary hyperparathyroidism is uncommon perphosphatemia.lo.2o The release of a large in animals. Most likely findings include a amount of calcium may overwhelm the capac­ single functional adenoma of the parathyroid ity of the kidneys to excrete calcium. gland, which results in production of an excess amount of PTH. Blood chemistry findings in­ Clinical Signs clude marked elevation of serum calcium, a Hypercalcemia causes a variety of clinical decrease in phosphorus and an increase in signs because it affects four major body sys­ serum alkaline phosphatase activity.6 There are tems: renal, gastrointestial, nervous and mus­ usually radiographic changes indicating de­ cular. The structural and functional effects of mineralization, subperiosteal areas of cortical hypercalcemia depend upon the underlying bone resorption, loss of lamina dura dentes, cause and the duration and severity of the hy­ soft tissue mineralization and bone cystS. 4 •6 •10 percalcemia. Gastrointestinal dysfunction is the result of Primary Renal Disease decreased contractility of the smooth muscle. Primary renal disease, chronic or acute, can This may cause anorexia, vomiting and consti­ cause' a hypercalcemic condition. However, it pation.4 •6 •15 Constipation may also result from is often difficult to establish if the hypercalce­ reduced food and water intake and dehydra­ mia is the cause of renal disease or the result of tion. Polydipsia and polyuria are also potential renal dysfunction. 6 Hypercalcemia is not a signs of hypercalcemia due to ADH inhibition classic finding in chronic renal failure. Serum at the collecting tubules of the renal medulla. biochemistries show a normal to low calcium, The nervous system is affected because hy­ increased phosphorus and increased serum percalcemia depresses the excitability of nerv­ concentrations of PTH.20 These dogs are usu­ ous tissue and suppresses lower motor neuron ally azotemic. 13 In five to ten percent of the activity.10,15 Behavioral changes, depression,

124 Iowa State University veterinarian muscle twitching, or seizures may be seen. 10.16 by hypercalcemia. Since a fall in plasma cal­ Depression is the most common neurologic cium will cause an increase in PTH secretion change seen in dogs. In severe cases, a dog and concomitant increase in active vitamin D, may be in a stupor or coma. Mild or chronic the kidney has an important role in the regula­ hypercalcemia may produce no neurologic ab­ tion of serum calcium concentration. 19.22 normalities. 6 Short-term calcium concentration is con­ Both skeletal and cardiac muscles can be af­ trolled primarily by the effect of PTH on bone fected. There is a general muscular weakness resorption. Long-term control results from the due to a decrease in muscle tone and there may effect of PTH on reabsorprtion of calcium from be specific cardiac changes due to the hyper­ kidney tubules and absorption of calcium via calcemia. Mild hypercalcemia may cause only the gastrointestinal mucosa. 23 In the kidney, hypertension.20.21 With moderate to severe hy­ most of the serum calcium in the glomerular percalcemia, there may be arrhythmias, short­ filtrate is reabsorbed in the proximal tubules ening of the Q-T interval, and prolongation of and ascending limb of the loop of Henle. 19.2J.24 the P-R interval seen on electrocardio­ In the distal tubules and collecting tubules the grams. 19.21 In severe cases, premature ventric­ reabsorption of calcium becomes selective. ular contractions or ventricular tachycardia This is most likely the site for independent reg­ may be seen.4 Cardiac and renal tissues may ulation of calcium. 23 Parathyroid hormones also undergo mineralization. Hypertension, will stimulate tubular calcium reabsorption documented in man but not yet in dogs, may and decrease phosphate reabsorption by activa­ be the result of hypercalcemic nephropathy, tion of adenyl cyclase, to increase production but is also seen when renal function is normal. of cyclic AMP. Parathyroid hormone has also Proposed mechanisms for hypertension in­ been shown to alter renal blood flow and glo­ clude: a) direct or indirect effect of calcium on merular filtration rate. 7 peripheral resistance; b) increased cardiac out­ put due to the positive inotropic effect of cal­ HYPERCALCEMIC NEPHROPATHY cium; or c) changes in the renin-angiotensin Increases in calcium can cause both struc­ system. 21 tural and functional changes in the kidney. One of the earliest clinical manifestations of NORMAL KIDNEY FUNCTION AND hypercalcemia is hyposthenuric polyuria with a CALCIUM compensatory polydipsia. The urine is hypos­ The kidney is intimately involved in the reg­ thenuric because calcium interferes with the ulation of serum calcium. Calcium absorption normal response of the collecting tubules to and excretion are under the influence of hor­ antidiuretic hormone (ADH), thereby causing monal regulation. The amount of calcium in impairment of renal concentrating ability. One extracellular fluid, cells, and bone is primarily mechanism of calcium interference with ADH dependent on the amounts absorbed in the in­ shows calcium damaging ADH receptors in the testine and excreted by the kidney.19 Main­ collecting tubules. This results in a decrease of tenance of serum calcium levels is controlled by ADH-binding. 1O Calcium also disrupts as­ PTH, vitamin D, and target organ activity. sembly of cytoplasmic microtubules. It is pos­ Parathyroid hormone is secreted in response to tulated that these tubules are necessary to fluctuations in ionized calcium and acts on bring forth the hydrosmotic effects of ADH. bone and the kidney. Parathyroid hormone is With a decrease in these microtubules, water also important in the formation of 1,25-dihy­ movement from the collecting duct lumen to droxycholecalciferol (1,25(OH)2D3) from 25- the interstitium is impeded.25 The result is a hydroxycholecalciferol (25(OH)D3) by the re­ hyposthenuric polyuria that is resistant to the nal cortex. 19 1,25-dihydroxycholecalciferol is effects of exogenous ADHI5.9 indicating that the active form of vitamin D at the intestine the hyposthenuria is renal in origin. 15 where it promotes absorption of calcium and Calcium is antagonistic to the adenyl cy­ phosphate. This compound also has a role in clase-cyclic AMP system .. Hypercalcemia de­ both bone resorption and bone deposition. creases cyclic AMP formation (via adenyl cy­ Without vitamin D, there is a decrease in the clase) in the distal convoluted tubules and effect of PTH on bone resorption. Renal ac­ collecting ducts.4 •26 A decrease in cyclic AMP tivation of vitamin D is increased by PTH or a decreases the response to ADH. Calcium also decrease in plasma phosphate. It is suppressed inhibits the Na-K ATPase required for active

Vol. 47, No. 2 125 transport of sodium or chloride into the renal necrotic epithelial cells. These cells form casts medullary interstitum. 10 This can result in in­ which may become mineralized and obstruct hibition of active transport of sodium chloride the tubular lumen. Obstruction by calcium into the interstitium from the thick ascending concretions predisposes to infection and focal limb of the loop of Henle and the distal tubules pyelonephritis. lo• ll Calcified cellular debris and collecting ducts. 25 With diminished so­ may cause obstructive atrophy of nephrons.27 dium chloride reabsorption, there is a decrease Damage to tubular basement membranes and in water reabsorption. Increased urine flow cast formation markedly diminishes the ability and sodium chloride loss, lead to hypovole­ of the kidney to regenerate.4 mia.25 The decreased response to ADH pre­ As hypercalcemic damage progresses, there vents urea accumulation in the inner medulla, is increased mineralization of tubular epithe­ which contributes to the concentrating defect. 19 lium and basement membranes. Pathologic During this phase of polyuria and polydipsia, changes can be seen interstitially and within there is no elevation of blood urea nitrogen the tubules. These changes affect the distal tu­ (BUN) or creatinine. If azotemia is present it bules and collecting ducts.21 The reversibility may be due to; prerenal factors such as dehy­ of renal damage depends on the extent of renal dration from anorexia, vomiting, or water mineralization, the presence of intact tubular diuresis; or, renal factors such as a decrease in basement membranes and adequate numbers renal perfusion or intrarenal hydronephrosis. 10 of remaining viable nephrons. 6 Advanced Renal failure initially can result from pre­ stages of severe or prolonged hypercalcemia dominately prerenal factors, but if hypercalce­ are characterized by mineralization throughout mia persists, the renal failure may be due pri­ the renal parenchyma, glomerular capillaries, marily to acquired intrinsic renal tubular Bowman's capsules and walls of vessels. 12.15 lesions.5 Effects of hypercalcemia on the kidney Eventually, there is fibroblastic proliferation may range from mild and reversible damage to and inflltration with chronic inflammatory severe and progressive damage. Injury to renal cells. 21 This leads to interstitial scarring and tubular epithelium may be due to the direct calcification, the hallmark of irreversible dam­ toxic effect of increased calcium in serum and age. 19 filtered tubular fluid. Calcium may also cause As mentioned previously, polyuria and poly­ vasoconstriction of renal vessels (afferent arteri­ dipsia are often the earliest recognized clinical oles) resulting in ischemia and decreased renal signs. Hypercalcemia affects the glomerulus by blood flow. 10.15 causing a decrease in glomerular flltration rate. Initial injury results in focal degeneration in The decrease in G FR may be the result of cal­ the ascending loop of Henle, distal convoluted cium-associated changes in glomerular capil­ tubule and collecting duct. Medullary struc­ lary permeability or volume contraction sec­ tures (loops of Henle and collecting ducts) are ondary to fluid losses. 6 A decrease in GFR may involved first; probably because of higher me­ also be due to an increase in PTH.24 Hyper­ dullary calcium concentrations.19 Earliest calcemia affects the loop of Henle by inhibiting changes are at the intracellular level: mito­ calcium and magnesium reabsorption. In the chondrial distortion and injury in tubular epi­ distal tubules and collecting ducts there is selec­ thelial cells. Calcification begins with deposi­ tive impairment of calcium reabsorption24 in tion of calcium-phosphorus complexes in the addition to the effects of calcium on ADH. As mitochondria. These complexes disrupt cell damage progresses, renal insufficiency be­ function and can lead to cell necrosis. lo Base­ comes apparent. There is a continued decrease ment membranes also become thickened and in GFR with a subsequent increase in BUN mineralized. A significant amount of tubular and creatinine levels. With progressive reduc­ damage may occur without histologically de­ tion in GFR, there is an increase in serum monstrable precipitates of calcium.ll In the phosphorus and a decrease in urine calcium early stages of hypercalcemia, glomeruli are concentration. not involved. If tubular basement membranes In determining renal involvement and estab­ have not been damaged, the chances for rever­ lishing a diagnosis and a plan for treatment, it sal of renal damage are good, assuming the is necessary to evaluate several biochemical cause of the hypercalcemia can be identified tests. Serum calcium should be repeated to rule and eliminated.4 out sample errors or changes due to the age of Cast formation results from desquamated, the dog and concentrations of albumin and

126 Iowa State University veterinarian protein. 13 A complete blood count, complete Once the serum calcium is restored to normal, serum chemistries, and electrolytes are helpful treatment of the primary problem is indicated. in ruling on several of the differential Management of concomitant renal failure diagnoses. Chemistries should include serum includes maintenance of adequate fluid and phosphorus, BUN, creatinine and serum alka­ electrolyte balance, prevention of dehydration line phosphatase. A urinalysis can reveal gluco­ due to diuretic use, and correction of acid-base suria and proteinuria due to decreased tubular imbalances.4 •10 By maintaining adequate renal function, besides measuring specific gravity.' perfusion, the chances of ischemic damage to Other tests which are helpful in establishing a nephrons is decreased. No therapy will elimi­ diagnosis include radiographic exam, electro­ nate renal lesions already present. If the hyper­ cardiographic exam and possible biopsy. Table calcemia can be controlled and the dog kept 2 lists laboratory results and gross findings for alive long enough, tubular damage may be re­ the differential diagnosis of hypercalcemia. paired by regeneration and functional adapta­ tion. 10

TABLE 2. Differential Diagnosis of Hypercalcemia by Laboratory Tests and Gross Findings.tO Serum Serum Bone Soft Tissue Parathyroid Disease Calcium Phosphorus SAP Lesion Mineralization Lesion Primary hyper- Severe, Adenoma thyroidism High Low Elevated generalized Moderate Carcinoma Normal or Mild, Inactivity Malignancy High Low slightly elevated generalized Moderate or atrophy Osteolytic Normal or Moderately Focal, Inactivity bone tumor High high elevated muItifocai Moderate or atrophy Vitamin D Mild or intoxication High High Normal absent Moderate Atrophy

TREATMENT REFERENCES Fluid volume expansion is the best sympto­ 1. Turnwald, GH: Pseudohyperparathyroidism in a Dog Caused by Lymphosarcoma: A Case Report. 13 matic treatment for hypercalcemia. Since The Southwestern ~t 32(2):115-120, 1978. many of the effects of hypercalcemia are accen­ 2. Capen, CC; Martin SL: Calcium- Regulating Hor­ tuated by dehydration, disturbances in fluid mones and Diseases of the Parathyroid Glands. in Ettinger SJ (ed): Textbook of ~terinary Internal Medicine. balance should be corrected in all cases. 4,10 Second edition. Philadelphia, W. B. Saunders Com­ Fluid therapy with 0.9 percent sodium chloride pany. 1983. 3. Finco, DR: Interpretations of Serum Calcium Con­ intravenously will promote urinary excretion centration in the Dog. Comp on Cont Educ 5(9):778- of calcium.:n In cases of mild hypercalcemia 787, 1983. (less than 14 mg!dl), fluid replacement may be 4. Drazner, FH: Hypercalcemia in the Dog and Cat. jAVMA 178(12):1252-1256, 1981. all that is necessary to decrease serum calcium. 5. MacEwen, EG; Siegel, SD: Hypercalcemia: A Para­ When calcium levels are greater than 14 mgt neoplastic Disease. ~t Cliniu of N Amer 7(1):187- 194, 1977. dl, diuretics such as furosemide or ethacrynic 6. Chew, DJ; Meuten, DJ: Disorders of Calcium and acid are effective as calciuretic agents. It is im­ Phosphorus Metabolism. ~t Clinics of N Amer portant to maintain adequate extracellular 12(3):411-438. 7. Raisz, LG: Bone Metabolism and Calcium Regula­ fluid volume while using these diuretics. tion. In Avioli, LV, Krane, SM (eds): Metabolic Bone Thiazide diuretics should not be used because Disease, vol. 1. New York, Academic Press, Inc. they reduce urinary excretion of calcium.11 1977. 8. Chew, DJ: Electrolytes and Osmolality. In Fenner, Glucocorticoids may be effective in lowering WR (ed): Quick Reference to Veterinary Medicine. Phila­ serum calcium concentration by blocking cal­ delphia, J. B. Lippincott Company. 1982. 9. Meuten, DJ; Chew, DJ, Capen, CC; Kociba, GJ: cium absorption from the small intestine and Relationship of Serum Total Calcium to Albumin increasing the renal excretion of calcium.4 In and Total protein in Dogs. jAVMA 180(1):63-67. cases where the calcium levels exceed 16 mgt 1982. 10. Chew, DJ; Capen, CC: Hypercalcemic Nephropa­ ell, sodium bicarbonate given intravenously thy and Associated Disorders. In Kirk, RW (ed): may reduce the toxic effects of the calcium. Current ~t Therapy VII Small Anim Prac. Pp. 1067- fiJI. 47, No. 2 127 1072. Philadelphia, W. B. Saunders Company. 1980. Third edition. New York, McGraw-Hill Book C()m­ 11 . Weller, RE: Cancer-Associated Hypercalcemia in pany. 1980. Companion Animals. Comp on Cont Educ 7(7):639- 21. Parfitt, AM; Kleerekoper, M: Clinical Disorders of 646, 1984. Calcium, Phosphorus, and Magnesium Metabolism. 12. O sborne, CA; Stevens, JB: Pseudohyperparathy­ In Maxwell, MH, Kleeman, CR (cds): Clinical Disor­ roidism in the Dog. jAVMA 162(2):125-134, 1973. ders of Fluid and Electrolyte Metaholism. Third edition. 13 . Meuten, DJ: Hypercalcemia. ~t Clinics of N Amer New York, McGraw-Hill Book Company. 1980. 14(4):891-910, 1984. 22. Michell, AR: Physiology of the Mammalian Kidney. 14. Weller, RE: Paraneoplastic Disorders in Companion In Hall, LW (ed): ~terinary Nephrology. London, Wil­ Animals. Comp on Cont Educ 4(5):423-428, 1982. liam Heinemann Medical Books Ltd. 1983, 15. Osborne, CA; Stevens, JB: Hypercalcemic Ne­ 23 . Guyton, AC: Regulation of Blood Volume, Extracel­ phropathy. In Kirk RW (ed): CUTTent ~t Therapy VI lular Fluid Volume, and Extracellular Fluid Compo­ Small Anim Prac Pp. 1080-1087. Philadelphia, W. B. sition by the Kidneys and by the Thirst Mechanism. Saunders Company. 1979. In the textbook of Medical Physiology. Sixth edition. 16 . Morrison, WB: Paraneoplastic Syndromes of the Philadelphia, W. B. Saunders Company. 1981. Dog. JAVMA 175:559-561, 1979. 24. Sutton, RAL, Dirks, JH: Renal Handling of Cal­ 17. Meuten, DJ; Cooper, BJ; Capen CC; Chew, DJ; cium, Phosphate and Magnesium. In Brenner,_BM Kociba, GJ: Hypercalcemia Associated with an Ade­ and Rector, Jr. FC (eds). The Kidney. Second edition. nocarcinoma Derived from the Apocrine Glands of Philadelphia, W. B. Saunders Company. 1981. the Anal Sac. ~t Pathol 18:454-471 , 1981. 25 . Benabe, JE; Martinez-Maldonado, M: Hyper­ 18. Peterson, ME; Feinman, JM: Hypercalcemia Asso­ calcemic Nephropathy. Arch Intern Med 138:777-779, ciated with Hypoadrenocorticism in Sixteen Dogs. 1978. jAVMA 181(8):802-804, 1982. 26. Grauer, GF: The Differential Diagnosis of Polyuric­ 19 . Agus, ZS; Goldfarb, S; Wasserstein, A: Disorders of Polydipsic Diseases. Camp of Cant Educ 3(12):1079- Calcium and Phosphate Balance. In Brenner BM 1086, 1981. and Rector, Jr. FC (eds): The Kidney. Second edition. 27 . Cotran, R: Tubulointerstitial Diseases. In Brenner, Philadelphia, W. B. Saunders Company. 1981. BM alid Rector, Jr., FC (eds): The Kidney. Second 20. Epstein, FH: Signs and Symptoms of Electrolyte edition. Philadelphia, W. B. Saunders Company. Disorders. In Maxwell, MH, Kleeman, CR (eds): 1981. Clinical Disorders of Fluid and Electrolyte Metabolism. MODEL 300 SUPER CHUTE

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128 Iowa State University veterinarian