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1 COMPLETE CHEMISTRY PANEL INTERPRETATION GUIDE Scrll dwn r click n the fllwing parameters t quickly access cntent CHEM15/17: GLU BUN CREA BUN/CREA P Ca TP ttal prtein ALB GLOB ALB/GLOB ALT ALP (ALKP) GGT TBIL CHOL AMYLASE LIPASE - Fllw-up test UPC

2 Glucse Descriptin Glucse is the basic nutrient fr tissues and is btained by diet, glycgenlysis and glucnegenesis. Glucse is tightly regulated in the nrmal animal. Cellular uptake is stimulated by insulin. Neurns, RBCs and renal tubular epithelial cells d nt require insulin fr glucse uptake. Values Belw Reference Range Hypglycemia Cmmn Causes Beta cell tumr (insulinma) Severe exertin (hunting dg hypglycemia) Hepatic disease Sepsis Idipathic r puppy hypglycemia (small breed dgs) Hypadrencrticism Paraneplastic syndrme Starvatin (mild decrease nly) Drugs that may decrease glucse measurement Insulin Beta blckers (prpranll) Antihistamines Spirnlactne Anablic sterids (nly in diabetic animals) Artifacts that may mdify glucse values include Lipemia (increased value) Failure t spin and separate sample within 30 minutes f cllectin (decreased value) Related Findings Elevated liver enzymes (ALT, AST, ALP, GGT) Inflammatry leukgram with sepsis (elevated r decreased WBC with left shift) Hypadrencrticism-lymphpenia, lw sdium and high ptassium

3 Weakness Other Labratry Tests CBC ALT, AST, ALP, GGT Electrlyte panel Amended insulin:glucse rati Values Abve Reference Range Hyperglycemia Cmmn Causes Diabetes mellitus Stress (cat) Pst-prandial (mild increase nly) Hyperadrencrticism Renal failure Acute pancreatitis Diestrus Drugs which may elevate glucse values include Gluccrticids Diuretics Megestrl acetate Prgesterne Epinephrine Salicylates Asparaginase Related Findings Plyuria/Plydipsia Weight lss Vmiting Weakness Other Labratry Tests Fructsamine Urinalysis Reference

4 Duncan JR, Prasse KW, Mahaffey EA. Veterinary Labratry Medicine, 3rd ed. Iwa State University Press: Ames, Ia; 1994.

5 Bld Urea Nitrgen (BUN) Descriptin Urea is frmed exclusively in the liver frm ammnia, and excreted mainly by the kidney. BUN readily diffuses int bld and all bdy water in similar cncentratin. Sme urea is passively reabsrbed frm the tubules back int the bld, but mst is excreted. Urea als cntributes t the smtic gradient in medulla, imprtant in medullary washut syndrme. There is an inverse relatinship between BUN and glmerular filtratin, and between BUN and tubular urine flw rate. Nt specific fr primary renal disease Affected by larger number f extrarenal factrs than is creatinine, such as ther diseases, sme chemicals and drugs, diet, and cnditin f serum (e.g., lipemia) Values Belw Reference Range Cmmn Causes Chrnic hepatic insufficiency Cngenital prtsystemic shunts, cirrhsis Severe PU-PD Hyperadrencrticism, diabetes insipidus, psychgenic Increased excretin Overhydratin, late pregnancy Drugs Diuretics, crticsterids, salt in diet, aminglycsides, amphtericin B, grwth hrmne Artifacts (falsely decreased) High cncentratins f sdium fluride and sdium citrate; chlramphenicl; lipemia (severe) Lw-prtein diet Related Findings Urine specific gravity Lw in PU/PD, increased excretin, sme drugs Serum bile acids High in cngenital and acquired hepatic atrphy (shunts and cirrhsis) Dexamethasne suppressin and ACTH stimulatin tests Lack f suppressin and/r high, respectively, with hyperadrencrticism Other Labratry Tests

6 CBC May see hemcncentratin Infectius disease tests FeCV, FeLV, FIV, Ehrlichia, Rcky Muntain sptted fever, Cccidiides Pre- and pstprandial bile acids T rule ut chrnic hepatic insufficiency due t cngenital r acquired atrphy and shunts Hepatic bipsy Fr definitive diagnsis f chrnic hepatic insufficiency Adrenal crtical tests Fr crtical hyperplasia r neplasia Urinalysis Specific gravity may help differentiate between decreased prductin and increased excretin Water deprivatin test May be useful in sme cases t determine if tubules can cncentrate the filtrate Values Abve Reference Range Cmmn Causes Renal Renal parenchymal disease due t glmerular disease, tubular dysfunctin, necrsis, fibrsis Prerenal Shck, dehydratin, pr cardiac utput, recent high-prtein meal, gastrintestinal hemrrhage, catablism f bdy tissues (fever, trauma) Pstrenal Urinary utflw tract disease due t bladder r ureteral rupture, r ureteral r urethral bstructin Related Findings Creatinine May be nrmal r lw if nnrenal cause f increased BUN; increased with renal r pstrenal causes f increased BUN Urine Issthenuric r inadequate cncentratin suggest primary renal disease Serum phsphrus Elevated in primary renal disease Albumin Albuminuria and hypalbuminemia in glmerulpathy Parathyrid hrmne increase

7 Renal pseudhyperparathyridism CBC Hemgram may shw mild t mderate nnregenerative anemia (decreased erythrpetin). Calcium Levels increase acutely in sme cases, and decrease in sme cases f ethylene glycl txicity Other Labratry Tests Creatinine May help differentiate between primary renal and prerenal disease Urinalysis Check specific gravity and prtein, casts, bacteria, crystal Electrlytes Help rule ut hypadrencrticism and metablic acidsis References Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. WB Saunders: Philadelphia, Pa; 1994.

8 Creatinine Descriptin Creatinine riginates frm nnenzymatic cnversin f creatine in muscles, ccurring at a generally cnstant and unifrm daily rate. Values are nt significantly affected by mild catablism r diet. Nt altered by as many nnrenal factrs as BUN, therefre, it is mre specific in evaluating renal disease than is BUN. It is freely filtered by glmeruli. Clearance frm plasma t urine is used t apprximate glmerular filtratin rate (GFR), which yields infrmatin n renal functin. It is nt reabsrbed by tubules; therefre, it is less affected by factrs affecting urine flw rate than BUN. Values Belw Reference Range Cmmn Causes Pregnancy Causes increased cardiac utput, thereby increasing GFR Marked muscle wasting Especially if BUN and serum phsphrus are high Other Labratry Tests Bilirubin High bilirubin values may cause artifactual decrease, depending n methdlgy used. Values Abve Reference Range Cmmn Causes Decreased GFR Prerenal, renal r pstrenal causes Acute mysitis and severe muscle trauma Uncertain significance False increase Bilirubin >10 mg/dl, hemglbin, lipemia, ascrbic acid, BSP, PSP, cephalsprins, barbiturates, acetacetate, fructse, glucse Feeding cked meat Mild increase <1 mg/dl Nephrtxic drugs May increase serum creatinine Related Findings BUN Cncurrently increases with decreased glmerular filtratin f renal, prerenal r pstrenal causes Serum phsphrus

9 May be increased in severe prerenal aztemia Urine specific gravity Used t differentiate between prerenal, renal r pstrenal causes; usually nrmal in prerenal aztemia and issthenuric in renal aztemia Other Labratry Tests Serum phsphrus BUN T help assess the status f the GFR and rule ut acute muscle disease Urine specific gravity T help distinguish between renal and prerenal aztemia Serum electrlytes T help evaluate fr hypadrencrticism, chrnic bld lss, renal disease Serum calcium T evaluate fr hypercalcemic nephrpathy Albumin T evaluate if there is albumin lss Glucse T rule ut hypersmlar diabetes mellitus Radigraphs, ultrasund T evaluate kidneys fr fcal r diffuse abnrmalities Renal bipsy When indicated by abve tests, t arrive at a definitive diagnsis, plan treatment, establish prgnsis Reference Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis By Labratry Methds. WB Saunders: Philadelphia, Pa; 1994.

10 Bld Urea Nitrgen: Creatinine Rati (BUN:CREA) Descriptin Rati f bld urea nitrgen value t creatinine value Originally thught t be f value in differential diagnsis f aztemia Pssible differences in tubular resrptin and diffusin rate and effects f diet and prtein metablism between the tw cmpunds There are t many variables fr the rati t be used as a diagnstic parameter Values Belw Reference Range Cmmn Causes Acute mysitis and severe muscle trauma Pssibly high dietary prtein ingestin Artifactually elevated creatinine due t bilirubin, hemglbin, lipemia, ascrbic acid, penicillins, cephalsprins, barbiturates Related Findings Nrmal bld urea nitrgen Other Labratry Tests Urine myglbin Urinalysis: t classify aztemia if present Values Abve Reference Range Cmmn Causes Significant muscle lss and pregnancy (due t decrease creatinine) Gastrintestinal hemrrhage Other Labratry Tests Urinalysis: helps differentiate between renal and nnrenal aztemia CBC: may shw mild t mderate nnregenerative anemia in renal aztemia References Duncan JR et al. Duncan and Prasse's Veterinary Labratry Medicine: Clinical Pathlgy, 4th ed. Ames, Ia: Iwa State University Press; Kanek JJ et al. Clinical Bichemistry f Dmestic Animals, 5th ed. San Dieg, Ca: Academic Press; Stckham SL et al. Fundamentals f Veterinary Clinical Pathlgy, 1st ed. Ames, Ia: Iwa State University Press; Willard, MD et al. Small Animal Clinical Diagnsis by Labratry Methds, 4th ed. St. Luis, M: Elsevier; 2004.

11 Phsphrus Descriptin Imprtant cmpnent f ATP Depletin may affect brain, RBC and skeletal muscle cells Severe hypphsphatemia (< 1.0 mg/dl) is mst ften seen with diabetic ketacidsis Values Belw Reference Range Hypphsphatemia Cmmn Causes Increased urinary excretin Diabetes mellitus ketacidsis Hypercalcemia f malignancy Phsphate-binding antacids Renal failure (hrse) Translcatin frm extracellular fluid (ECF) t intracellular fluid (ICF) Bicarbnate administratin Insulin therapy, hyperinsulinism IV glucse administratin Other Diagnses Decreased intestinal absrptin Decreased dietary intake Malabsrptin syndrme Phsphate-binding agent Steatrrhea Vitamin D deficiency Increased urinary excretin Diuretics Eclampsia, milk fever Fancni syndrme (renal tubular defects) Hyperadrencrticism Hyperaldsternism Primary hyperparathyridism Translcatin frm extracellular fluid (ECF) t intracellular fluid (ICF)

12 Respiratry and metablic alkalsis Vmiting and/r diarrhea Other Labratry Tests Cytlgy and/r histlgy f tissue specimens Fecal flatatin FeLV/FIV Serum PTH Ttal T4, Free T4, T3 suppressin test TLI, cbalamin, flate Urinalysis Vitamin D metablites (especially chlecalciferl) Values Abve Reference Range Hyperphsphatemia Cmmn Causes Hypervitaminsis D Chlecalciferl rdenticides Renal failure Prerenal and pstrenal aztemia Rhabdmylysis Yung, grwing animals Other Diagnses Drugs Hemlysis, in vitr Hyperthyridism Diet excess Neplasia with stelytic bne lesins Jasmine txicity Labratry errr Nutritinal secndary hyperparathyridism Phsphate enema, phsphate-cntaining fluids Primary hypparathyridism Other Labratry Tests Serum PTH Urinalysis

13 Ttal T4, Free T4, T3 suppressin test Skeletal radigraphs References Duncan JR, Prasse KW, Mahaffey EA. Veterinary Labratry Medicine, 3rd ed. Ames, Ia: Iwa State University Press, Tilley LP, et al. The 5-Minute Veterinary Cnsult: Canine and Feline. Williams & Wilkins: Baltimre, Md; Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. 3rd ed. WB Saunders: Philadelphia, Pa; 1999.

14 Calcium Descriptin Cntrlled by PTH and vitamin D, and their interactins with bne, kidneys, intestines and parathyrid glands Ttal calcium cncentratin: 50% inized, 40% prtein-bund and 10% cmplexed with bicarbnate, citrate, lactate, phsphate Inized calcium is the active frm and is available t tissues; prtein-bund frm is nt. Only the inized and cmplexed frms can be filtered by the kidneys. Values Belw Reference Range Hypcalcemia Cmmn Causes Eclampsia Dg, hrse, ewe Parturient paresis Cw Ethylene glycl txicity Dg, cat Hypalbuminemia Iatrgenic Fllwing bilateral thyridectmy/thyrid surgery Renal failure Renal secndary hyperparathyridism Labratry errr Other Diagnses Alkalemia (especially in ruminants) Bicarbnate treatment fr salicylate txicity Blister beetle pisning (hrse) Factitius (e.g., EDTA) Hypercalcitnism Hypmagnesemic tetany (ruminant) Hypvitaminsis D assciated with excess phsphrus Intestinal malabsrptin (dg)

15 Malabsrptin syndrme Nutritinal secndary hyperparathyridism Pancreatitis (acute/necrtizing) Primary hypparathyridism Transprt tetany (sheep) Other Labratry Tests Pancreatic tests Amylase, lipase, TLI CBC Serum and urine ethylene glycl cncentratins Peak between 1 and 6 hurs after ingestin Serum magnesium Serum smlality Serum PTH Urinalysis Values Abve Reference Range Hypercalcemia Other Diagnses Ingestin f calciferl (chlecalciferl)-cntaining rdenticides Factitius Lipemia, pstprandial Granulmatus diseases such as blastmycsis Rare Hemcncentratin; hyperalbuminemia Hypervitaminsis D Hypadrencrticism Iatrgenic (rare) Excessive supplementatin Excessive ral phsphate binders Ostelytic bne lesins (rare) Hypertrphic stedystrphy Multiple myelma

16 Ostemyelitis Plant txicity Jasmine, Cestrum sp., Slanum sp. Primary hyperparathyridism Renal failure Hrse, cw, uncmmn in dg Yung animal, large breed Other Labratry Tests Cytlgy and/r histlgy f tissue specimens Inized calcium Serum PTH Serum PTH-related prtein (PTHrp) Urinalysis Reference Duncan JR, et al. Veterinary Labratry Medicine; Clinical Pathlgy. 3rd ed. Iwa State University Press: Ames, Ia; Tilley LP, et al. The 5 Minute Veterinary Cnsult; Canine and Feline. Williams & Wilkins: Baltimre, Md; Willard MD, et al. Small Animal Clinical Diagnsis by Labratry Methds. 3rd ed. WB Saunders: Philadelphia, Pa; 1999.

17 Ttal Prtein Descriptin Sum f albumin and glbulin (serum) and fibringen (plasma) The prteins in the bld cnsist f albumin, fibringen, cagulatin prteins, and glbulins (t include immunglbulins and acute-phase prteins). Ttal prtein is typically measured n serum and cnsists f albumin, fibringen and glbulins. The primary difference between plasma prtein and serum ttal prtein is the absence f cagulatin prteins and fibringen in the serum. Mst prteins are prduced by the liver, and immunglbulins by lymphid tissue (plasma cells). Values Belw Reference Range Hypprteinemia Cmmn Causes Decreased prductin: Intestinal malabsrptin Malnutritin Liver disease, atrphy, fibrsis Immundeficiency disease Failure f passive transfer Excrine pancreatic insufficiency Increased lss: Renal disease Prtein-lsing glmerulpathy/renal disease Severe exudative skin disease External hemrrhage Prtein-lsing enterpathies Infiltrative intestinal neplasia Related Findings Prteinuria Elevated renal functin tests and liver enzymes Decreased TLI Other Labratry Tests Renal functin tests (BUN, creatinine, urinalysis, urine prtein:creatinine rati) Liver functin/enzyme tests (ALT, AST, albumin, bile acids) CBC

18 Intestinal/Skin bipsies Albumin/Glbulin rati Prtein electrphresis Bdy fluid analysis Values Abve Reference Range Hyperprteinemia Cmmn Causes Dehydratin Chrnic inflammatin Abnrmal glbulins (Ehrlichia, lymphma, plasma cell myelma) Intravascular hemlysis Hyperbilirubinemia Lipemia Related Findings Hemcncentratin Hemlysis Plyclnal, mnclnal gammpathies Other Labratry Tests Serum prtein electrphresis may have plyclnal r mnclnal gammpathy Albumin may be lw r high Fibringen may be high, especially in large animals CBC may see hemcncentratin Survey radigraphs Bence Jnes prtein Bne r sft tissue bipsy if plasma cell myelma suspected Infectius disease tests FeCV, FeLV, FIV, Ehrlichia, Rcky Muntain sptted fever, Cccidiides References Willard MD, et al. Small Animal Clinical Diagnsis by Labratry Methds. WB Saunders: Philadelphia, Pa; 1994.

19 Albumin Descriptin Imprtant regulatr f smtic equilibrium Prduced by the liver Carrier fr several cmpunds (especially calcium) Values Belw Reference Range Hypalbuminemia Cmmn Causes Decreased prductin Liver disease, atrphy, fibrsis/cirrhsis Primary r secndary intestinal malabsrptin Malnutritin (dietary r parasitic) Excrine pancreatic insufficiency Increased lss Renal disease, prteinuria Severe exudative skin disease/trauma External hemrrhage Prtein-lsing enterpathies Infiltrative enterpathies (neplastic, Jhnes) Related Findings Liver enzymes and functin tests May be elevated (inflammatin, neplasia, necrsis) Renal functin tests May be elevated (renal disease) r lw (hepatic insufficiency) Urine May cntain increased prtein Serum calcium May be lw Other Labratry Tests Hepatic functin tests, enzymes and bipsy Renal functin tests, bipsy Urinalysis, including prtein/creatinine rati Abdminal/Thracic tap fr fluid analysis (if applicable) TLI Cagulatin tests Intestinal bipsy Values Abve Reference Range Hyperalbuminemia Cmmn Causes

20 Dehydratin Labratry errr Related Findings Hemcncentratin (dehydratin) Calcium May be falsely high Hyperbilirubinemia Overprductin f albumin des nt ccur Other Labratry Tests Bilirubin Ttal prtein Hemgram Reference Willard MD, et al. Small Animal Clinical Diagnsis by Labratry Methds. Philadelphia, Pa: W.B. Saunders and C., 1994.

21 Albumin:Glbulin Rati (A:G Rati) Descriptin This arithmetic value (rati f serum albumin t glbulin cncentratins) has been used t aid in the interpretatin f ttal prtein values. The rati will remain nrmal if bth fractins are unifrmly altered. It ccurs with hyperprteinemia (dehydratin) and hypprteinemia (e.g., verhydratin, acute bld lss, exudative skin disease, gastrintestinal disease). The rati will be decreased r increased if an alteratin f ne fractin predminates. Nte: See interpretive guides fr Albumin and Glbulin. Values Belw Reference Range Decreased A/G rati Cmmn Causes Decreased albumin Increased glbulin Values Abve Reference Range Increased A/G rati Cmmn Causes Increased albumin Decreased glbulin References Duncan JR et al. Duncan and Prasse's Veterinary Labratry Medicine: Clinical Pathlgy, 4th ed. Ames, Ia: Iwa State University Press; Kanek JJ et al. Clinical Bichemistry f Dmestic Animals, 5th ed. San Dieg, Ca: Academic Press; Stckham SL et al. Fundamentals f Veterinary Clinical Pathlgy, 1st ed. Ames, Ia: Iwa State University Press; Willard, MD et al. Small Animal Clinical Diagnsis by Labratry Methds, 4th ed. St. Luis, M: Elsevier; 2004.

22 Alanine Amintransferase (ALT) Descriptin ALT is a cytslic enzyme that catalyzes the reversible transaminatin f L-alanine and 2-xglutarate t pyruvate and glutamate. The enzyme is almst exclusively fund within hepatcytes, but als in very small amunts in muscle. As a result, serum increases are highly specific fr hepatcyte injury in dgs and cats. The hepatcyte level f ALT in hrses, ruminants and pigs is very lw, and hence ALT is f limited value in these species. Values Belw Reference Range Cmmn Causes The hepatcyte level f ALT in hrses, ruminants and pigs is very lw, and ALT is f limited value in these species. Values Abve Reference Range Cmmn Causes Primary hepatcellular and biliary system diseases Infectius diseases: ICH, FIP, leptspirsis, septicemia, hepatic abscess, chlangihepatitis Txic insult Aflatxicsis, pyrrlyzidine alkalids, idisyncratic drug reactins Neplasia Lymphsarcma, bile duct carcinma, metastatic neplasia Obstructive disease Chlangitis, pancreatitis, neplasia, bile duct fibrsis Trauma Chrnic active hepatitis Strage disrders Cpper strage disease Metablic disrders Diabetes mellitus, hyperadrencrticism, ketsis, hepatic lipidsis, feline hyperthyridism Drug therapy Crticsterids, barbiturates Severe skeletal mypathy Related Findings Other hepatic enzymes

23 AST, ALP, GGT, GLDH may als be elevated Bilirubin May be increased due t chlestasis, prtsystemic shunts Chlesterl Elevated with chlestatic disease Glucse High in cases f diabetes mellitus CBC May have evidence f inflammatry disease, anemia, leukemia, stress Other Labratry Tests Hepatic bipsy Fr definitive diagnsis f underlying primary hepatbiliary disease Adrencrtical functin tests T diagnse hyperadrencrticism Amylase, lipase, TLI T assess fr the pssibility f pancreatitis References Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. 2nd ed. WB Saunders: Philadelphia, Pa; Duncan JR, Prasse KW, Mahaffey EA. Veterinary Labratry Medicine: Clinical Pathlgy. 3rd ed. Iwa State University Press: Ames, Ia; 1994.

24 Alkaline Phsphatase (ALKP) Descriptin Alkaline phsphatase refers t a grup f enzymes that catalyze the hydrlysis f phsphate esters at an alkaline ph in vitr. Little is knwn abut their intracellular functin, but these are membrane-bund and present in mst tissues in the bdy. High activities are present in the liver, bne, intestine, kidney and placenta. Intestinal, renal and placental isenzymes have extremely shrt half-lives, and are nt respnsible fr significant increases in serum ALP. Changes in the serum level f ALP can be attributed t bne and hepatic isenzymes. The hepatic ALP is fund mainly in canalicular cell membranes, and is released as a result f biliary disease and increased hydrstatic pressure in the biliary system. In the dg, a sterid-induced isenzyme is prduced in the liver n expsure t gluccrticids, cntributing t serum ALP increases. In cats, the hepatic isenzyme has a shrt half-life, and even minr increases shuld be cnsidered significant. In ruminants and hrses, the serum ALP levels are highly variable, and are f limited diagnstic use. GGT, GLDH and AST are f mre use in large animals. Values Belw Reference Range Cmmn Causes Nt clinically significant Artifact assay perfrmed n EDTA r xalate plasma Values Abve Reference Range Cmmn Causes Chlestasis Intra- r extra-hepatic chlestasis Primary hepatcyte injury See ALT Bile duct bstructin Ascending infectin Neplasia Pancreatitis Fibrsis Abscessatin

25 Intestinal freign bdy Crticsterid excess (dgs nly) Hyperadrencrticism Exgenus gluccrticids Increased steblastic activity in bne Yung animals increased steblastic activity leads t increases up t 3 4 times the basal level expected in mature animals. Bne disease Bne neplasia Rickets Fractures Hyperparathyridism Drug therapy Anticnvulsants/Barbiturates Miscellaneus Neplasia Related Findings Hepatic enzymes (ALT, AST, GGT) Increased with primary hepatcellular r chlestatic disease Bilirubin Often increased due t chlestasis Nte that elevatins f ALP will precede elevatins in bilirubin. Chlesterl Increased with chlestasis r endcrine disease, but may be decreased with hepatic insufficiency r prtsystemic shunts Amylase, lipase, TLI May be increased in cases f pancreatitis Hemgram May indicate the presence f inflammatin, r a stress leukgram in cases f crticsterid excess Other Labratry Tests Urinalysis T check fr bilirubinuria, and as part f the screen fr hyperadrencrticism Other hepatic enzymes

26 The pattern f change ften helps t further define the likely cause Hepatic bipsy Adrencrtical functin tests T assess fr pssible hyperadrencrticism References Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. 2nd ed. WB Saunders: Philadelphia, Pa; Duncan JR, Prasse KW, Mahaffey EA. Veterinary Labratry Medicine: Clinical Pathlgy. 3rd ed. Iwa State University Press: Ames, Ia; 1994.

27 Gamma-Glutamyl Transferase (GGT) Descriptin GGT is invlved in glutathine metablism and is mainly assciated with the micrsmal membranes f hepatcyte canalicular surfaces, bile duct epithelium and renal cnvluted tubular epithelial cells. The activity f serum GGT parallels the activity f ALP. Fr detectin f hepatbiliary disease, GGT has a higher specificity and lwer sensitivity than ALP in dgs. The ppsite is seen in cats, except fr hepatic lipidsis. GGT is less influenced than ALP by secndary hepatic disease and enzyme-inducing drugs; generally GGT will nly be mildly increased. GGT des nt tend t increase after increased steblastic activity in yung, grwing animals, bne disease and acute hepatic necrsis, as des ALP. GGT is mre useful in hrses and ruminants due t its narrw reference range and the high variability f ALP activity in these species. The use f ALP and GGT tgether increases the predictive value fr hepatic disease. Values Belw Reference Range Cmmn Causes Nt clinically relevant Values Abve Reference Range Increased serum GGT Cmmn Causes Intrahepatic (bile canaliculi) and extrahepatic (cmmn bile duct) chlestasis Crticsterid excess (dgs nly) Hyperadrencrticism Exgenus gluccrticid drugs Drug therapy Anticnvulsant/Barbiturates Primary hepatcyte injury See ALT Nephrtxicses (e.g., aminglycsides) will cause increased urine GGT Related Findings Other hepatic enzymes may als be increased with primary chlestatic (ALP) r hepatcellular (ALT, AST) disease. Bilirubin is ften increased due t chlestasis. Chlesterl is increased with chlestasis r endcrine disease, but may be decreased with hepatic insufficiency r prtsystemic shunts.

28 Amylase, lipase and TLI may be increased in cases f pancreatitis. A hemgram may indicate the presence f inflammatin, r a stress leukgram in cases f crticsterid excess. The latter may als cause an increase in glucse cncentratin. Bile acids may be increased if the hepatic functin is impaired. BUN, albumin and glucse serum cncentratins may be decreased with chrnic hepatbiliary disease. Other Labratry Tests Adrencrtical functin tests CBC Hepatic cytlgy and histlgic examinatins Hepatic imaging Other liver chemical parameters, hepatic functin tests/parameters Urinalysis Urine GGT:creatine rati References Duncan JR, et al. Veterinary Labratry Medicine: Clinical Pathlgy. 3rd ed. Iwa State University Press: Ames, Ia; Tilley L.P, et al. The 5 Minute Veterinary Cnsult: Canine and Feline. Williams & Wilkins: Baltimre, Md; Willard MD, et al. Small Animal Clinical Diagnsis by Labratry Methds. 3rd ed. WB Saunders: Philadelphia, Pa; 1999.

29 Bilirubin Descriptin Bilirubin is a waste prduct resulting frm catablism f heme in a variety f hemprteins, mainly erythrcyte hemglbin. A small amunt is als prduced by the breakdwn f hepatic cytchrme P-450, tryptphan pyrrlase and myglbin. Hemglbin is brken dwn t heme, irn and glbin mainly within macrphages. The heme mlecule is further degraded t biliverdin and then t bilirubin (uncnjugated) befre release back int the circulatin. On leaving the cell, the uncnjugated bilirubin binds t albumin, is transprted t the liver and bund by receptrs within the hepatcyte membrane. Bilirubin disassciates frm albumin, and is taken int the cell by carrier-mediated transprt. The bilirubin is then cnjugated with glucurnic acid, which renders bilirubin water-sluble. Cnjugated bilirubin is secreted int bile canaliculi t be excreted int the intestinal tract via the bile duct. Resident bacteria cnvert cnjugated bilirubin t urbilingen, which is then excreted via the feces. The serum levels f bilirubin are prprtinal t the rate f hemglbin breakdwn, subsequent remval frm the serum by hepatcytes and excretin int the intestinal tract. Mst methds f bilirubin assay are based n the diaz reactin. With the additin f reagent, clr develps rapidly (direct reactin). After additin f alchl, further clr develpment ccurs (indirect reactin). The direct-reacting cmpnent is equivalent t cnjugated bilirubin, and the indirect reactin gives a measurement f the ttal serum bilirubin. The difference between these tw results gives a derived value f uncnjugated bilirubin. The prprtins f direct and indirect bilirubin fractins have been investigated in rder t differentiate between hemlytic r chlestatic disease. Hwever, the prprtins vary greatly and are f limited clinical use. Values Belw Reference Range Cmmn Causes Nt clinically significant. Values Abve Reference Range Bilirubinemia Cmmn Causes Liver disease Hepatcellular injury Txic injury Ascending bacterial chlangitis Neplasia Chlestatic disrders Pancreatitis Neplasia Bile duct rupture Reduced hepatic mass Prt-systemic shunt Cirrhsis Neplasia Acute hemlytic disease Artefact Hemlysis f sample Lipemia

30 Related Findings PCV, red cell indices and erythrcyte mrphlgy May indicate the presence f hemlytic disease Liver enzymes Will be elevated in cases f hepatcyte injury and chlestasis, see ALT and ALP Amylase, Lipase may be elevated in cases f pancreatitis Bilirubinuria Will precede and accmpany elevatins in cnjugated bilirubin Other Labratry Tests Hepatic bipsy Fr definitive diagnsis f hepatcellular disease r chrnic insufficiency Cmbs test T assess fr the presence f anti-erythrcyte antibdies as part f immune-mediated hemlytic anemia Abdmincentesis T rule ut the presence f bile peritnitis References Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. 2nd ed. WB Saunders: Philadelphia, Pa: Kanek JJ. Clinical Bichemistry f Dmestic Animals. 4th ed. Academic Press: San Dieg, Ca; Duncan JR, Prasse KW, Mahaffey EA. Veterinary Labratry Medicine: Clinical Pathlgy. 3rd ed. Iwa State University Press: Ames, Ia; 1994.

31 Chlesterl Descriptin The ttal amunt f serum chlesterl is under clse hmestatic cntrl. It is influenced by dietary intake, prductin in the liver frm fatty acids, tissue utilizatin and hepatic uptake, metablism and excretin as bile acids int the gastrintestinal tract. Values Belw Reference Range Hypchlesterlemia Cmmn Causes Decreased uptake Lw-fat diet Intestinal malabsrptin/maldigestin Severy malnutritin Decreased prductin Hepatic insufficiency such as with cirrhsis, prtsystemic shunts Related Findings Lw BUN, hypalbuminemia Als due t hepatic insufficiency, r severe intestinal disease with malassimilatin Bilirubin May be elevated with hepatic insufficiency CBC Mild, nnregenerative anemia due t chrnic disease Other Labratry Tests Fecal examinatin, TLI, intestinal bipsy T assess fr pssible maldigestin/malabsrptin syndrmes Pre- and pstprandial bile acids T assess fr hepatic insufficiency as a result f cngenital r acquired atrphy r prtsystemic shunts Values Abve Reference Range Hyperchlesterlemia Cmmn Causes Hyperlipidemic states Pst-prandial Increased fat mbilizatin

32 Diabetes mellitus, starvatin/hyperlipidemia in hrses, hyperadrencrticism, steatitis in cats Decreased fat catablism Hypthyridism Primary idipathic hyperlipidemias Liver and biliary system diseases with chlestasis See ALP, bilirubin Miscellaneus Pancreatitis Nephrtic syndrme Glmerulnephritis Related Findings Glucse Increased with diabetes mellitus, and ccasinally with hyperadrencrticism, pancreatitis Prteinuria, hypalbuminemia and edema Characteristic f nephrtic syndrme Pancreatitis Inflammatry leukgram with pancreatitis, Hyperadrencrticism Stress leukgram with hyperadrencrticism Bilirubin, ALT, AST, ALP, GGT Increased with primary hepatcellular r chlestatic disrders Amylase, lipase, TLI Elevated with pancreatitis Other Labratry Tests Fructsamine, beta-hydrxybutyrate T assess fr the presence f diabetes mellitus Urinalysis Prteinuria with nephrtic syndrme, glycsuria with diabetes mellitus T4 T definitively diagnse hypthyridism Adrencrtical functin tests T assess fr pssible hyperadrencrticism

33 References Willard MD, Tvedten H, Turnwald GH. Small Animal Clinical Diagnsis by Labratry Methds. 2nd ed. WB Saunders: Philadelphia, Pa; Kanek JJ. Clinical Bichemistry f Dmestic Animals. 4th ed. Academic Press: San Dieg, Ca; 1989.

34 Amylase Descriptin Amylase is a calcium-dependent metallenzyme that catalyzes the hydrlysis f cmplex carbhydrates. Amylase is synthesized in an active frm. The pancreas secretes alkaline fluid that prevents acid-induced denaturatin f the enzyme and prvides an ptimal envirnment fr enzyme activity. Tissue surces: pancreas, stmach, kidney, small intestine, uterus, thers Serum amylase activity des nt decrease prprtinally as the functinal excrine pancreatic tissue mass decreases in excrine pancreatic insufficiency (EPI); therefre, amylase is f n value as a marker f EPI. Values Belw Reference Range Decreased amylase Cmmn Causes Acute pancreatitis (cats) Other Labratry Tests CBC Urinalysis Bilirubin Hepatic enzymes Glucse May be increased with necrtizing pancreatitis May be decreased with feline suppurative pancreatitis Calcium Chlesterl Tryglyceride Lipase Trypsin-like immunreactivity (TLI) Values Abve Reference Range Increased amylase Cmmn Causes Pancreatitis (3 4-fld increase in amylase cncentratin, dgs and hrses) Pancreatic acinar cell damage Pancreatic duct bstructin

35 Gastritis Gastritis neplasia Hepatic disease Renal disease (up t 2.5-fld increase in amylase cncentratin, dgs) Decreased glmerular filtratin rate (GFR), aztemia Related Findings Crticsterids d nt reliably increase serum amylase cncentratin. If the measured amylase cncentratin f abdminal fluid exceeds that f serum, differential diagnses include pancreatic disease and intestinal rupture. Other Labratry Tests CBC Urinalysis Hepatic enzymes Glucse May be increased with necrtizing pancreatitis May be decreased with feline suppurative pancreatitis Calcium Chlesterl Tryglyceride Lipase Canine pancreatic lipase immunreactivity (c-pli) Trypsin-like immunreactivity (TLI) References Willard MD, Twedt DC, Tvedten H, Turnwald GH, eds. Gastrintestinal, pancreatic and hepatic disrders. In: Small Animal Clinical Diagnsis by Labratry Methds. 3rd ed. WB Saunders: Philadelphia, Pa; Brbst DF, Kanek JJ, Harvey JW, Bruss ML, eds. Pancreatic functin. In: Clinical Bichemistry f Dmestic Animals. 5th ed. Academic Press: New Yrk; Strmbeck DR, Guilfrd WG, Center SA, Strmbeck DR, Williams DA, Meyer DJ, eds. Small and large intestine: Nrmal structure and functin. In: Strmbeck s Small Animal Gastrenterlgy. 3rd ed. WB Saunders: Philadelphia, Pa; Williams DA, Guilfrd WG, Center SA, Strmbeck DR, Meyer DJ, eds. The pancreas. In: Strmbeck s Small Animal Gastrenterlgy. 3rd ed. WB Saunders: Philadelphia, Pa; 1996.

36 Lipase Descriptin Lipase activity is used as a marker f pancreatitis. The sensitivity and the specificity f the assay is dependent upn the methdlgy used. Increased specificity can be attained if the values are greater than three-fld f the upper end f the nrmal reference range, unless baseline data is established fr the individual patient's lipase values. Hwever, even fllwing this guideline, there are significant numbers f pancreatitis cases that will nt have a significant increase in lipase activity. Lipase may riginate frm pancreatic r nnpancreatic surces, such as the gastrintestinal mucsa, which makes it difficult t interpret increases f lipase activity less than three-fld abve the high end f the reference range. Extra-pancreatic factrs that influence lipase cncentratin include: Gluccrticids therapy in which lipase increases five-fld withut cncurrent increases in amylase activity Renal disease r severe dehydratin with which there is decreased lipase clearance by the kidneys (up t three-fld increase) Liver disease Values Belw Reference Range Cmmn Causes Nt clinically significant. Values Abve Reference Range Cmmn Causes Acute pancreatitis magnitude f increase desn't reflect severity f disease Drug therapy crticsterids, heparin Hepatic disease Kidney disease Neplasia pancreatic adencarcinma, gastric carcinma Related Findings In cats with acute pancreatitis, lipase cncentratin desn't increase t levels seen in dgs and, in fact, sme cats have an increase in lipase withut cncurrent increases in amylase cncentratin. Other Labratry Tests CBC, bichemistry prfile and urinalysis Abdminal ultrasund Spec cpl Test, canine pancreatic lipase immunreactivity (cpli) Feline pancreatic lipase immunreactivity (fpli) Histpathlgy Reference Williams DA, ed. The Pancreas. Strmbecks' Small Animal Gastrenterlgy. 3rd ed. WB Saunders: Philadelphia, Pa; 1996.

37 Urine Prtein:Creatinine Rati (UPC) Descriptin The urine prtein:creatinine (UPC) rati is a simple and rapid test fr the detectin and quantificatin f prteinuria. Unlike ther qualitative and semi-quantitative tests, the UPC rati is nt affected by urine cncentratin and vlume. The urine prtein:creatinine rati ffers the accuracy f 24-hur urine prtein measurements withut the need t perfrm the 24-hur urine cllectin. The urine prtein:creatinine rati is btained by dividing the prtein cncentratin [UPRO] (mg/dl) by the creatinine cncentratin [UCRE] (mg/dl). The result is a unitless rati. Apprpriate interpretatin f urine prtein:creatinine rati results requires that yu first lcalize the prtein lss t the kidneys and then determine persistence. Lcalizatin Causes f prteinuria can be prerenal r pstrenal. It is imperative that prerenal and pstrenal causes f prteinuria are ruled ut befre assessing yur UPC value. This can be dne by examining the patient s histry and clinical signs, bichemical prfile, CBC and cmplete urinalysis (including urine sediment examinatin and determinatin f urine specific gravity). Prerenal: evaluate fr Bence Jnes prteinuria, myglbinuria, hemglbinuria Pstrenal: evaluate urine sediment fr signs f hemrrhage, inflammatin, infectin and neplasia Renal: determine level f aztemia Persistence Determinatin f persistence f prteinuria is necessary t rule ut transient elevatins f urine prtein. Determine persistence f prteinuria as needed given the level f aztemia and ther clinical signs. In questinable cases, the 2004 ACVIM Frum Cnsensus Statement (Small Animal): Assessment and Management f Prteinuria in Dgs and Cats recmmends repeating the UPC rati n three r mre ccasins, at least tw weeks apart. Evaluatin Once yu have addressed lcalizatin and determinatin f persistence, yu shuld evaluate yur urine prtein:creatinine rati results in light f the patient s level f aztemia. The fllwing ranges are in accrdance with the recmmendatins frm the 2004 ACVIM Frum Cnsensus Statement (Small Animal): Assessment and Management f Prteinuria in Dgs and Cats. Nnaztemic and persistent prteinuria with inactive urine sediment (dgs and cats): UPC <0.5 n significant prteinuria UPC 0.5 <1.0 requires further mnitring UPC 1.0<2.0 prteinuria UPC 2.0 significant prteinuria Aztemic dgs and persistent prteinuria with inactive urine sediment (dgs): UPC <0.5 n significant prteinuria UPC 0.5 significant prteinuria Aztemic cats and persistent prteinuria with inactive urine sediment (cats): UPC <0.4 n significant prteinuria UPC 0.4 significant prteinuria Once renal disease is established, yu shuld determine if any underlying cause is present and address that as needed. Ptential beneficial ancillary tests include: radilgy, ultrasngraphy, bld pressure evaluatin, infectius disease testing, endcrine testing and autimmune testing. The urine prtein:creatinine rati can be used as a prgnstic indicatr, with higher ratis crrelating t a wrsening prgnsis. Hwever, it is wrth nting that in severe cases f chrnic renal disease, the urine P:C rati may decrease. This is due t the

38 fact that as plasma creatinine increases and the number f functining nephrns decreases, the amunt f urinary prtein lss is reduced. Mre inf n UPC

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