Laboratory Testing in Feline Liver and Renal Disease

1
Laboratory Testing in Feline Liver and Renal
Disease
Nick Carmichael
BVMS, BSc VetSci(Hons), Diploma VCS (Syd),
Diploma RC Path, Diplomate ECVCP, MRCVS

• Shropshire Veterinary Association
• 24th February 2005

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
Screens Vs Profiles

• 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

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 lt100 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
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
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
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
Hepatic Lipidosis

• Clinical features
• Usually gt2yrs old, obese, indoor cats
• Preceded by partial/complete anorexia
• Jaundice, vomiting, dehydration
• Can have encepalopathydepression, 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
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
Luna Granville
Signalment 15yrs, DSH, MN History Long term
vomiting, weight loss. Recent anorexia and
hypersalivation. Very weak.
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 )
NaK 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
Luna Granville
Signalment 15yrs, DSH, MN History Long term
vomiting, weight loss. Recent anorexia and
hypersalivation. Very weak.

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
Luna Granville
Signalment 15yrs, DSH, MN History Long term
vomiting, weight loss. Recent anorexia and
hypersalivation. Very weak.
Haematology RBC
3.01 x1012/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 x109/L Low (170 -650 ) WBC
19.61 x109/L High
(4.0 -15.0 ) Neutrophils 63
12.35x109/L (2.5 -12.5 )
Lymphocytes 37 7.26x109/L
High (1.5 -7.0 ) Monocytes
0. 0.00 x109/L (0.0 -0.8 )
Eosinophils 0. 0.00 x109/L
(0.0 -1.5 ) Nucleated RBC's
0.20 109/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
Tom Morrison
Signalment 15yrs, male, DSH History
Exploratory laporotomy confirms mass developing
in one of the liver lobes
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 ) NaK
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 x1012/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 x109/L (170
-650 ) WBC 13.90
x109/L (4.0 -15.0 ) Neutrophils
73 10.15 x109/L (2.5 -12.5 )
Lymphocytes 19 2.64 x109/L
(1.5 -7.0 ) Monocytes
1 0.14 x109/L (0.0 -0.8 )
Eosinophils 6 0.83 x109/L
(0.0 -1.5 ) Basophils
1 0.14 x109/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
Tom MorrisonProgression
Signalment 15yrs, male, DSH History
Exploratory laporotomy confirms mass developing
in one of the liver lobes ..1 Month Later
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
Smokey Bridges
Signalment 8yrs, Female, DSH History Acute
inappetence, lethargy, polyuria. Slight weight
loss. Mucosae pale.
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 ) NaK 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 x1012/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 x109/L
Low (170 -650 ) WBC
42.00 x109/L High (4.0 -15.0 ) Neutrophils
94 39.48 x109/L High (2.5
-12.5 ) Bands 2 0.84
x109/L High (0.0 -0.3 ) Lymphocytes
2 0.84 x109/L Low (1.5 -7.0 )
Monocytes 2 0.84 x109/L
High (0.0 -0.8 ) Eosinophils
0. 0.00 x109/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
Pinta Ibarra
Signalment 11yrs, FN, DLH History Straining
to urinate. Cervical mass.
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
) NaK 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
Pinta Ibarra
Signalment 11yrs, FN, DLH History Straining
to urinate. Cervical mass.
Haematology RBC 6.79
x1012/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 x109/L (170 -650 ) WBC
8.53 x109/L (4.0
-15.0 ) Neutrophils 71 6.06
x109/L (2.5 -12.5 ) Lymphocytes
27 2.30 x109/L (1.5 -7.0 ) Monocytes
1 0.09 x109/L (0.0 -0.8 )
Eosinophils 1 0.09 x109/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
Pinta Ibarra
Signalment 11yrs, FN, DLH History Straining
to urinate. Cervical mass.

• Microbiology
• Urine creatinine 16.90 mmol/L
• Urine protein 1.33 g/L
• Urine proteincreatinine 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

Urine culture gt100,000 colonies of coagulase
negative Staph
Marbofloxacin Sensitive Enrofloxacin
Sensitive Cephalexin Sensitive Synulox
Sensitive Tribrissen Sensitive Clindamyc
in Sensitive
50
Feline Chronic Renal Disease
Whats different about cats?

• Biochemistry
• Azotaemia
• Potassium
• Calcium

• Urinalysis
• Retained concentrating ability
• Leucocyte dipstick response
• Crystaluria significance

51
Feline Chronic Renal Disease
Azotaemia

• Mild
• Moderate
• Marked

Urea mmol/l 20 35 50
Creatinine umol/l 250 350 500
52
Feline Chronic Renal Disease
Potassium

• 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

53
Feline Chronic Renal Disease
Calcium

• 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

54
Urine Specific Gravity In Cats

• Concentrating ability is retained later in cats
• USG 1.030 need not exclude renal disease

• Measure on cat USG scale
• Dipstick SG scale is useless

55
Urinary Tract Infection In Cats

• Increasingly common with age
• Need not be associated with leuconuria
• Leucocyte dipstick gives false positive

56
Boric Acid Tubes
57
Crystaluria In Cats

• Alkaline urine
• Cooled urine
• Concentrated urine
• May dissolve in boric acid

• Acidic urine
• Cooled urine
• Concentrated urine

58
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