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Laboratory Testing in Feline Liver and Renal Disease

Laboratory Testing in Feline Liver and Renal Disease. Shropshire Veterinary Association 24th February 2005. Nick Carmichael. BVM&S, BSc VetSci(Hons), Diploma VCS (Syd), Diploma RC Path, Diplomate ECVCP, MRCVS. Feline Liver Disease. Liver anatomy - what matters clinically

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Laboratory Testing in Feline Liver and Renal Disease

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  1. Laboratory Testing in Feline Liver and Renal Disease Shropshire Veterinary Association 24th February 2005 Nick Carmichael BVM&S, BSc VetSci(Hons), Diploma VCS (Syd), Diploma RC Path, Diplomate ECVCP, MRCVS

  2. Feline Liver Disease • Liver anatomy - what matters clinically • Liver enzymes - what they mean • Liver function tests • FBC changes in liver disease - how they help • Common feline liver disease patterns • Primary Vs secondary liver changes • Putting it together

  3. Hepatic Lobule Anatomy

  4. Hepatic Portal Anatomy

  5. Hepatic Lobule Anatomy

  6. Hepatocyte Enzyme Distribution

  7. Transaminases & Dehydrogenases • ALT • AST • GLDH Measure integrity of cell membranes Degree of increase correlates with number of hepatocytes involved AST increases correlate with more severe hepatocelullar injury

  8. Cholestatic Enzyme Markers

  9. Liver Enzymes In Cats Hepatocellular ALT: High Low ALP 1/2 life: 66 hours 6 hours Steroid induced ALP: Yes No Bilirubinuria: Normal Abnormal Cholangiohepatitis: Rare Common

  10. Diagnostic Profiles Contains grouped tests related to organ function Tests provide complimentary information Tests included relate to a presenting sign Assists in localisation/ narrowing of the DDx Screens Contains a single test per organ Single most sensitive test included Test array is fixed Provides yes/no information regarding normality Screens Vs Profiles

  11. Bilirubin Metabolism & Excretion

  12. Bilirubin In Cats • Measures uptake and excretion of bilirubin • Exclude prehepatic jaundice • Intra- or post-hepatic cholestasis • Direct/indirect bilirubin NBG • Bilirubinuria is ALWAYS abnormal in cats

  13. Bilirubin Assay Interference

  14. Liver Function Tests • Endogenous • Albumin, urea, Glucose, Cholesterol, Coagulation Factors, NH3

  15. Bleeding Disorders In Feline Liver Disease Abnormalities of PT and PTT • Common, usually mild increase PTT only • PTT <100 secs • Vitamin K dependant coagulopathy on EHBDO • Increased PTT and PT

  16. Liver Function Tests

  17. Bile Acids In Cats Detect • Presence of diffuse morphologic change • Significant functional impairment • Best test for portosystemic shunt • Fasting bile acids sensitivity = 49% • Bile acid stimulation test sensitivity = 81%

  18. Red Cell Changes In Liver Disease • Immune Mediated Haemolytic Anaemia • Normocytic normochromic anaemia • Microcytosis without anaemia • Acanthocytes • Red Cell Parasites

  19. White Cell Changes In Liver Disease White cell • Inflammatory/toxic changes • Lymphoproliferative disease • Infiltrative conditions

  20. Common Feline Liver Diseases The big 5 • Cholangiohepatitis: • acute, chronic, lymphocytic • Hepatic lipidosis • Pancreatitis • Hepatic neoplasia • Extrahepatic bile duct obstruction

  21. T.Bilirubin, ALT, ALP, AST, GGT, bile acids  Acute Cholangiohepatitis Clinical features • Often young to middle aged cats, male • Non specific clinical signs • Fever, depression, dehydration • Acute illness with pyrexia • Inflammatory leucogram

  22. Histopathology of Acute Cholangiohepatitis

  23. Toxic Band Neutrophils In Acute Cholangiohepatitis

  24. T.Bilirubin, ALT, ALP, AST, GGT, bile acids, mild NR anaemia, lymphocytosis  Chronic Cholangiohepatitis Clinical features • Often middle aged - older cats • Non specific clinical signs • Often concurrent pancreatic and small intestinal inflammation “Triaditis” • Can progress to biliary cirrhosis

  25. T.Bilirubin, ALT, ALP, AST, GGT, bile acids, hyperglobulinemia  Lymphocytic Cholangitis Clinical features • Young to middle aged cats, often persians • Usually BAR and afebrile • Abdominal effusion with high protein count • Differentiate from FIP

  26.   • T.Bilirubin, ALT, ALP, AST, bile acids, but not GGT Hepatic Lipidosis Clinical features • Usually >2yrs old, obese, indoor cats • Preceded by partial/complete anorexia • Jaundice, vomiting, dehydration • Can have encepalopathy:depression, ptyalism • Cytology can help confirm diagnosis

  27. Histopathology Of Hepatic Lipidosis

  28. Liver Aspirate Cytology

  29. Nasogastric Feeding

  30. Feline Pancreatitis / Biliary Tract Disease

  31. Feline Pancreatitis Clinical features • Vague and non specific • Lethargy, anorexia, dehydration • Vomiting & abdominal pain less common 30% • May have abdominal mass 23%, dyspnoea 20% • May have concurrent bowel/biliary tract disease • 40% of cats with lipidosis have pancreatitis

  32. Feline Pancreatitis Laboratory findings • +/- inflammatory leucogram • Mild liver enzymes and bilirubin elevations • Amylase and lipase usually WNL • fTLI sensitivity 30%, specificity 83% • fPLI sensitivity 70%, specificity 83%

  33.   • ALT, ALP, GGT, T. Bilirubin, bile acids Extrahepatic Bile Duct Obstruction • Causes • stricture/fibrosis, neoplasia, inspisated bile, bile stones • Clinical signs • Anorexia, depression, vomiting, icterus, hepatomegally • Acholic faeces, vitamin K responsive coagulopathy, absence of urobilinogen

  34. Feline Hepatic Neoplasia Primary - rare • Hepoatocellular carcinoma • Cholangiocellular carcinoma Metastatic - common • Lymphoma • Myeloproliferative disease • Mast cell neoplasia • Haemangiosarcoma

  35. Feline Hepatic Neoplasia • Variable clinical and physical signs • Biochemical abnormalities - variable • Differentiate from bile duct adenomas, hepatic cysts

  36. Reactive/Induced Hepatic Changes Liver changes without significant liver disease • Endocrine disease • hyperthyroidism, Diabetes mellitus • Bystander hyperbilirubinaemia • dehydration, sepsis, anorexia • Reactive/secondary hepatopathies • hypoxia, endotoxaemia, ?lymphocytic portal hepatitis

  37. Systemic Infections Involving The Liver • Feline Infectious Peritonitis • Clinical signs, profile changes, FCoV, cytology • Toxoplasmosis • Clinical signs, profile changes, toxoplasma IgM &IgG • Imported diseases • Cytauxzoonosis, Hepatozoonosis

  38. Making The Diagnosis • Is primary liver disease likely? • Check an appropriate profile including a FBC • If liver changes are present • Rule out extrahepatic causes of the changes • Bile acid stimulation test (if not icteric) • For triaditis add PLI, folate and cobalamin • Consider cytology if appropriate • Often laparotomy & biopsy recommended

  39. Signalment: 15yrs, DSH, MN History: Long term vomiting, weight loss. Recent anorexia and hypersalivation. Very weak. Luna Granville Biochemistry Total protein * 50 g/L Low (54.0 -80.0 ) Albumin * 17 g/L Low (21.0 -39.0 ) Globulin 33 g/L (15.0 -57.0 ) Albumin Globulin ratio * 0.5 Low (0.6 - 1.5 ) Sodium 145.0 mmol/L (125 -160 ) Potassium * 2.7 mmol/L Low (3.6 -6.0 ) Na:K ratio * 54 High (32 -41 ) Chloride * 115 mmol/L Low (117 -140 ) Total calcium 2.15 mmol/L (2.0 -3.0 ) Phosphate * 0.93 mmol/L Low (1.2 -2.6 ) Urea 6.1 mmol/L (4.0 -12.0 ) Creatinine 99 umol/L (80.0 -180.0) Alk Phos * 994 U/L High (0.0 -50.0 ) ALT * 299 U/L High (0.0 -40.0 ) Gamma GT 8 U/L (0.0 -10.0 ) Total bilirubin * 49 umol/L High (0.0 -10.0 ) Bile acids * 77.9 umol/L High (0.1 - 5.0 ) Glucose * 11.8 mmol/L High (3.5 -6.6 ) CK * 209 U/L High (0.0 -152.0) Cholesterol 4.3 mmol/L (1.5 -6.0 )

  40. Signalment: 15yrs, DSH, MN History: Long term vomiting, weight loss. Recent anorexia and hypersalivation. Very weak. Luna Granville Biochemistry Feline TLI * 346.7 High (12 -82 ) Alk Phos * 435 U/L High (0.0 -50.0 ) ALT * 280 U/L High (0.0 -40.0 ) Endocrinology B12 1040 ng/L (240 - 1200) Folate * 5.9 ug/L Low (8.0 - 20.5)

  41. Signalment: 15yrs, DSH, MN History: Long term vomiting, weight loss. Recent anorexia and hypersalivation. Very weak. Luna Granville Haematology RBC * 3.01 x10^12/L Low (5.5 -10.0 ) Hb * 5.4 g/dl Low (9.0 -17.0 ) HCT * 15.1 % Low (27.0 -50.0 ) MCV 50.0 fl (40.0 -55.0 ) MCH 17.8 pg (13.0 -21.0 ) MCHC 35.5 g/dl (30.5 -36.5 ) Platelets * 162 x10^9/L Low (170 -650 ) WBC * 19.61 x10^9/L High (4.0 -15.0 ) Neutrophils 63% 12.35x10^9/L (2.5 -12.5 ) Lymphocytes * 37% 7.26x10^9/L High (1.5 -7.0 ) Monocytes 0.% 0.00 x10^9/L (0.0 -0.8 ) Eosinophils 0.% 0.00 x10^9/L (0.0 -1.5 ) Nucleated RBC's 0.20 10^9/L (0.0 -4.0 ) PT * 13.7 Seconds High (8.0 -13.0 ) APTT * 28.4 Seconds High (12.0 -25.0 ) Haematologist Comment: Red cells appear normochromic with increased anisocytosis (+) and poikilocytosis (+). There is no evidence of increased polychromasia despite the presence of occasional late normoblasts. No abnormal white cells were seen and platelets appeared in adequate numbers on the smears and of normal morphology. There was no evidence of platelet clumping on the EDTA smear.

  42. Signalment: 15yrs, male, DSH History: Exploratory laporotomy confirms mass developing in one of the liver lobes Tom Morrison Biochemistry Total protein 80 g/L (54.0 -80.0 ) Albumin 24 g/L (21.0 -39.0 ) Globulin 56 g/L (15.0 -57.0 ) Albumin Globulin ratio * 0.4 Low (0.6 - 1.5 ) Sodium 156.0 mmol/L (125 -160 ) Potassium 4.7 mmol/L (3.6 -6.0 ) Na:K ratio 33 (32 -41 ) Chloride 124 mmol/L (117 -140 ) Total calcium 2.35 mmol/L (2.0 -3.0 ) Phosphate 1.27 mmol/L (1.2 -2.6 ) Urea * 15.1 mmol/L High (4.0 -12.0 ) Creatinine 160 umol/L (80.0 -180.0) Alk Phos * 178 U/L High (0.0 -50.0 ) ALT * 185 U/L High (0.0 -40.0 ) Gamma GT 6 U/L (0.0 -10.0 ) Total bilirubin 6 umol/L (0.0 -10.0 ) Bile acids * 5.2 umol/L High (0.1 - 5.0 ) Glucose 5.8 mmol/L (3.5 -6.6 ) CK 57 U/L (0.0 -152.0) Cholesterol 2.8 mmol/L (1.5 -6.0 )

  43. Signalment: 15yrs, male, DSH History: Exploratory laporotomy confirms mass developing in one of the liver lobes Tom Morrison Haematology RBC 8.87 x10^12/L (5.5 -10.0 ) Hb 13.4 g/dl (9.0 -17.0 ) HCT 45.9 % (27.0 -50.0 ) MCV 52.0 fl (40.0 -55.0 ) MCH 15.1 pg (13.0 -21.0 ) MCHC * 29.2 g/dl Low (30.5 -36.5 ) Platelets 512 x10^9/L (170 -650 ) WBC 13.90 x10^9/L (4.0 -15.0 ) Neutrophils 73% 10.15 x10^9/L (2.5 -12.5 ) Lymphocytes 19% 2.64 x10^9/L (1.5 -7.0 ) Monocytes 1% 0.14 x10^9/L (0.0 -0.8 ) Eosinophils 6% 0.83 x10^9/L (0.0 -1.5 ) Basophils 1% 0.14 x10^9/L (0.0 -0.2 ) Haematologist Comment Red cells appear normocytic and normochromic. White cells appear of normal morphology and unremarkable. Platelets appear of normal morphology and in adequate numbers on the smears with no evidence of platelet clumping on the EDTA smear. Thank you for the fresh film sent with Tom's request. Endocrinology Total T4 34.8 nmol/L (15.0 -50.0 )

  44. Signalment: 15yrs, male, DSH History: Exploratory laporotomy confirms mass developing in one of the liver lobes ..1 Month Later Tom MorrisonProgression Biochemistry Total protein 75 g/L (54.0 -80.0 ) Albumin 24 g/L (21.0 -39.0 ) Globulin 51 g/L (15.0 -57.0 ) Albumin Globulin ratio * 0.5 Low (0.6 - 1.5 ) Urea * 23.4 mmol/L High (4.0 -12.0 ) Creatinine 144 umol/L (80.0 -180.0) Alk Phos * 393 U/L High (0.0 -50.0 ) ALT * 144 U/L High (0.0 -40.0 ) AST 30 U/L (0.0 -69.0 ) GLDH 6 U/L (0.0 -10.0 ) Gamma GT 8 U/L (0.0 -10.0 ) Total bilirubin 3 umol/L (0.0 -10.0 ) Bile acids * 5.9 umol/L High (0.1 - 5.0 ) Glucose 4.9 mmol/L (3.5 -6.6 ) Cholesterol 2.9 mmol/L (1.5 -6.0 )

  45. Signalment: 8yrs, Female, DSH History: Acute inappetence, lethargy, polyuria. Slight weight loss. Mucosae pale. Smokey Bridges Biochemistry Total protein 80 g/L (54.0 -80.0 ) Albumin * 18 g/L Low (21.0 -39.0 ) Globulin * 62 g/L High (15.0 -57.0 ) Albumin Globulin ratio * 0.3 Low (0.6 - 1.5 ) Sodium 155.0 mmol/L (125 -160 ) Potassium 5.5 mmol/L (3.6 -6.0 ) Na:K ratio * 28 Low (32 -41 ) Chloride 118 mmol/L (117 -140 ) Total calcium * 1.83 mmol/L Low (2.0 -3.0 ) Phosphate 1.77 mmol/L (1.2 -2.6 ) Urea * 25.5 mmol/L High (4.0 -12.0 ) Creatinine * 246 umol/L High (80.0 -180.0) Alk Phos 7 U/L (0.0 -50.0 ) ALT 31 U/L (0.0 -40.0 ) Gamma GT 6 U/L (0.0 -10.0 ) Total bilirubin * 32 umol/L High (0.0 -10.0 ) Bile acids * 6.2 umol/L High (0.1 - 5.0 ) Glucose 5.4 mmol/L (3.5 -6.6 ) CK 139 U/L (0.0 -152.0) Cholesterol 5.0 mmol/L (1.5 -6.0 )

  46. Signalment: 8yrs, Female, DSH History: Acute inappetence, lethargy, polyuria. Slight weight loss. Mucosae pale. Smokey Bridges Haematology RBC * 11.43 x10^12/L High (5.5 -10.0 ) Hb 16.8 g/dl (9.0 -17.0 ) HCT * 54.4 % High (27.0 -50.0 ) MCV 48.0 fl (40.0 -55.0 ) MCH 14.7 pg (13.0 -21.0 ) MCHC 30.8 g/dl (30.5 -36.5 ) Platelets * 140 x10^9/L Low (170 -650 ) WBC * 42.00 x10^9/L High (4.0 -15.0 ) Neutrophils * 94% 39.48 x10^9/L High (2.5 -12.5 ) Bands * 2% 0.84 x10^9/L High (0.0 -0.3 ) Lymphocytes * 2% 0.84 x10^9/L Low (1.5 -7.0 ) Monocytes * 2% 0.84 x10^9/L High (0.0 -0.8 ) Eosinophils 0.% 0.00 x10^9/L (0.0 -1.5 ) Haematologist Comment Red cells appear normocytic and normochromic. Marked leucocytosis with a mild left shift and toxic changes within neutrophils. Mild lymphopenia with occasional enlarged reactive lymphocytes. Mild monocytosis. Platelets appear mildly reduced and of normal morphology. Endocrinology Total T4 * 6.1 nmol/L Low (15.0 -50.0 )

  47. Signalment: 11yrs, FN, DLH History: Straining to urinate. Cervical mass. Pinta Ibarra Biochemistry Total protein 58 g/L (54.0 -80.0 ) Albumin * 20 g/L Low (21.0 -39.0 ) Globulin 38 g/L (15.0 -57.0 ) Albumin Globulin ratio * 0.5 Low (0.6 - 1.5 ) Sodium 153.0 mmol/L (125 -160 ) Potassium 4.4 mmol/L (3.6 -6.0 ) Na:K ratio 35 (32 -41 ) Chloride 121 mmol/L (117 -140 ) Total calcium 2.18 mmol/L (2.0 -3.0 ) Phosphate 2.21 mmol/L (1.2 -2.6 ) Urea 11.6 mmol/L (4.0 -12.0 ) Creatinine * 73 umol/L Low (80.0 -180.0) Alk Phos * 113 U/L High (0.0 -50.0 ) ALT 38 U/L (0.0 -40.0 ) Gamma GT 8 U/L (0.0 -10.0 ) Total bilirubin * 16 umol/L High (0.0 -10.0 ) Bile acids 0.1 umol/L (0.1 - 5.0 ) Glucose * 7.7 mmol/L High (3.5 -6.6 ) CK 119 U/L (0.0 -152.0) Cholesterol 3.7 mmol/L (1.5 -6.0 )

  48. Signalment: 11yrs, FN, DLH History: Straining to urinate. Cervical mass. Pinta Ibarra Haematology RBC 6.79 x10^12/L (5.5 -10.0 ) Hb 10.3 g/dl (9.0 -17.0 ) HCT 32.1 % (27.0 -50.0 ) MCV 47.0 fl (40.0 -55.0 ) MCH 15.2 pg (13.0 -21.0 ) MCHC 32.2 g/dl (30.5 -36.5 ) Platelets 347 x10^9/L (170 -650 ) WBC 8.53 x10^9/L (4.0 -15.0 ) Neutrophils 71% 6.06 x10^9/L (2.5 -12.5 ) Lymphocytes 27% 2.30 x10^9/L (1.5 -7.0 ) Monocytes 1% 0.09 x10^9/L (0.0 -0.8 ) Eosinophils 1% 0.09 x10^9/L (0.0 -1.5 ) Haematologist Comment Red cells appear normocytic and normochromic. White cells appear of normal morphology and unremarkable. Normal platelets morphology and numbers - there is some evidence of platelet clumping on th EDTA smear which may have reduced the absolute count somewhat. Thanks for the fresh blood film sent with Pinta's submission. Endocrinology Total T4 * 94.1 nmol/L High (15.0 -50.0 )

  49. Signalment: 11yrs, FN, DLH History: Straining to urinate. Cervical mass. Pinta Ibarra Microbiology Urine creatinine 16.90 mmol/L Urine protein 1.33 g/L Urine protein:creatinine 0.79 (0.0 -1.0 ) Specific gravity 1.034 Urine biochemistry pH 7 Protein * ++ Glucose Negative Ketones Negative Urobilinogen Negative Bilirubin Negative Haemoglobin * ++++ Urine sediment RBCs 10-20 /hpf WBCs *20-30 /hpf Epithelial Occasional epithelial seen Crystals None seen Casts None seen Urine culture * >100,000 colonies of coagulase negative Staph Marbofloxacin Sensitive Enrofloxacin Sensitive Cephalexin Sensitive Synulox Sensitive Tribrissen Sensitive Clindamycin Sensitive

  50. Biochemistry Azotaemia Potassium Calcium Urinalysis Retained concentrating ability Leucocyte dipstick response Crystaluria significance Feline Chronic Renal Disease What’s different about cats?

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