Laboratory testing in feline liver and renal disease
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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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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

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


Hepatic lobule anatomy

Hepatic Lobule Anatomy


Hepatic portal anatomy

Hepatic Portal Anatomy


Hepatic lobule anatomy1

Hepatic Lobule Anatomy


Hepatocyte enzyme distribution

Hepatocyte Enzyme Distribution


Transaminases dehydrogenases

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


Cholestatic enzyme markers

Cholestatic Enzyme Markers


Laboratory testing in feline liver and renal disease

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


Laboratory testing in feline liver and renal disease

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


Bilirubin metabolism excretion

Bilirubin Metabolism & Excretion


Bilirubin in cats

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


Bilirubin assay interference

Bilirubin Assay Interference


Liver function tests

Liver Function Tests

  • Endogenous

  • Albumin, urea, Glucose, Cholesterol, Coagulation Factors, NH3


Bleeding disorders in feline liver disease

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


Liver function tests1

Liver Function Tests


Bile acids in cats

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%


Red cell changes in liver disease

Red Cell Changes In Liver Disease

  • Immune Mediated Haemolytic Anaemia

  • Normocytic normochromic anaemia

  • Microcytosis without anaemia

  • Acanthocytes

  • Red Cell Parasites


White cell changes in liver disease

White Cell Changes In Liver Disease

White cell

  • Inflammatory/toxic changes

  • Lymphoproliferative disease

  • Infiltrative conditions


Common feline liver diseases

Common Feline Liver Diseases

The big 5

  • Cholangiohepatitis:

    • acute, chronic, lymphocytic

  • Hepatic lipidosis

  • Pancreatitis

  • Hepatic neoplasia

  • Extrahepatic bile duct obstruction


Acute cholangiohepatitis

  • 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


Histopathology of acute cholangiohepatitis

Histopathology of Acute Cholangiohepatitis


Toxic band neutrophils in acute cholangiohepatitis

Toxic Band Neutrophils In Acute Cholangiohepatitis


Chronic cholangiohepatitis

  • 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


Lymphocytic cholangitis

  • 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


Hepatic lipidosis

 

  • 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


Histopathology of hepatic lipidosis

Histopathology Of Hepatic Lipidosis


Liver aspirate cytology

Liver Aspirate Cytology


Nasogastric feeding

Nasogastric Feeding


Feline pancreatitis biliary tract disease

Feline Pancreatitis / Biliary Tract Disease


Feline pancreatitis

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


Feline pancreatitis1

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%


Extrahepatic bile duct obstruction

 

  • 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


Feline hepatic neoplasia

Feline Hepatic Neoplasia

Primary - rare

  • Hepoatocellular carcinoma

  • Cholangiocellular carcinoma

    Metastatic - common

  • Lymphoma

  • Myeloproliferative disease

  • Mast cell neoplasia

  • Haemangiosarcoma


Feline hepatic neoplasia1

Feline Hepatic Neoplasia

  • Variable clinical and physical signs

  • Biochemical abnormalities - variable

  • Differentiate from bile duct adenomas, hepatic cysts


Reactive induced hepatic changes

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


Systemic infections involving the liver

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


Making the diagnosis

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


Luna granville

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 )


Luna granville1

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)


Luna granville2

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.


Tom morrison

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 )


Laboratory testing in feline liver and renal disease

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 )


Tom morrison progression

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 )


Smokey bridges

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 155.0mmol/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 )


Laboratory testing in feline liver and renal disease

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 * 6.1nmol/L Low (15.0 -50.0 )


Pinta ibarra

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/LLow (21.0 -39.0 )

Globulin 38 g/L (15.0 -57.0 )

Albumin Globulin ratio * 0.5 Low (0.6 - 1.5 )

Sodium 153.0mmol/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 )


Pinta ibarra1

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 )


Pinta ibarra2

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


Feline chronic renal disease

Biochemistry

Azotaemia

Potassium

Calcium

Urinalysis

Retained concentrating ability

Leucocyte dipstick response

Crystaluria significance

Feline Chronic Renal Disease

What’s different about cats?


Feline chronic renal disease1

Mild

Moderate

Marked

Feline Chronic Renal Disease

Azotaemia

Urea mmol/l

20

35

50

Creatinine umol/l

250

350

500


Feline chronic renal disease2

High renal tubular flow promotes potassium loss

Potassium depletion is only poorly reflected in serum concentration

Hypokalaemia exacerbates renal insufficiency

Anorexia, vomiting, depression, muscle weakness can all reflect hypokalaemia

Hyperkalaemia in CRF is a poor prognostic sign

Feline Chronic Renal Disease

Potassium


Feline chronic renal disease3

Total calcium comprises 3 components

Usually serum calcium is normal in CRF

10% of cats have increased total calcium in CRF

Phosphate restricted diets may increase calcium

Feline Chronic Renal Disease

Calcium


Urine specific gravity in cats

Concentrating ability is retained later in cats

USG 1.030 need not exclude renal disease

Urine Specific Gravity In Cats

  • Measure on cat USG scale

  • Dipstick SG scale is useless


Urinary tract infection in cats

Increasingly common with age

Need not be associated with leuconuria

Leucocyte dipstick gives false positive

Urinary Tract Infection In Cats


Boric acid tubes

Boric Acid Tubes


Crystaluria in cats

Alkaline urine

Cooled urine

Concentrated urine

May dissolve in boric acid

Struvite

Oxalate

Crystaluria In Cats

  • Acidic urine

  • Cooled urine

  • Concentrated urine


Making the diagnosis in feline renal disease

Making The Diagnosis In Feline Renal Disease

  • Need blood and urinalysis

  • Complete the renal profile

  • Urine best examined/prepared whilst still fresh

  • Sediment and culture required

  • Serial measurements are valuable for monitoring progression/response to treatment


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