A Toxicologist's Guide to Clinical Pathology in Animals
Hematology, Clinical Chemistry, Urinalysis
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John E. Whalan
A Toxicologist’s Guide
to Clinical Pathology
in Animals
▪ Hematology
▪ Clinical Chemistry
▪ Urinalysis
John E. Whalan
Office of Research and Development
United States Environmental Protection
Agency
Washington DC, USA
Much of this Work was first published in Chinese language in 2014 by Shanghai Popular
Science Press under the title: ⭆樴≐䈑ᷜ⸲㡨樴㊯⋿ (A Guide to Clinical Pathology in
Animals).
ISBN 978-3-319-15852-5 ISBN 978-3-319-15853-2 (eBook)
DOI 10.1007/978-3-319-15853-2
Library of Congress Control Number: 2015936603
Springer Cham Heidelberg New York Dordrecht London
© Springer International Publishing Switzerland 2015
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of
the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,
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The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
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The publisher, the authors and the editors are safe to assume that the advice and information in this book
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Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.
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Preface
For many toxicologists, the evaluation of hematology, clinical chemistry, and urinalysis
data can be the most daunting part of animal toxicity studies. When dozens of
parameters are measured for each animal at regular intervals throughout a study,
there may be hundreds or even thousands of data points to consider.
What does it mean when a parameter value increases for an individual or for a
group? What does it mean when it decreases? When a parameter change is statisti-
cally significant does that mean it is biologically significant? What other parameters
can be used to strengthen a diagnosis? What is causing these changes? The answers
to these questions can be found in veterinary clinical pathology textbooks, of course,
and every toxicologist should own at least one or two; but searching for diagnostic
information in textbooks can be difficult and time consuming.
Many years ago, I began keeping a notebook of key information and diagnoses
for the clinical pathology parameters used in toxicology studies. As my notebook
grew over the years into a handbook, I shared more than 150 copies with my fellow
toxicologists. It is because of their favorable reviews and encouragement that my
handbook has now been published.
The intent of this handbook is to provide a user-friendly resource that puts the
most relevant information at your fingertips. It is written as one toxicologist to
another. I sincerely hope you find this handbook to be useful.
I wish to thank my charming wife, Chipper, for her patience and support and for
her pen drawing of a mouse. I also wish to thank my lovely daughters, Bridget and
Lorena, for their encouragement; and my grandchildren, Kathleen, Alex, and
Brooklyn, for their boundless curiosity. Finally, many thanks to Manika Power and
her colleagues at Springer Publishing who brought this book to fruition.
Washington DC, USA John E. Whalan
v
vi Preface
The views expressed in this book are those of the author, and do not necessarily
represent the views or policies of the U.S. Environmental Protection Agency.
Contents
1 The Fundamentals..................................................................................... 1
1.1 Introduction...................................................................................... 1
1.2 Routine Clinical Pathology Testing ................................................. 2
1.3 Clinical Pathology Panels ................................................................ 4
1.4 How to Evaluate Clinical Pathology Data ....................................... 5
1.4.1 Weight of the Evidence ........................................................ 5
1.4.2 What Can Go Wrong?.......................................................... 6
1.4.3 Reference Ranges ................................................................ 8
1.4.4 Statistical and Biological Significance ................................ 10
References ................................................................................................... 11
2 Hematology Highlights ............................................................................. 13
2.1 Hematopoiesis.................................................................................. 13
2.2 Erythrocytes ..................................................................................... 15
2.3 Leukocytes ....................................................................................... 17
2.3.1 Neutrophils .......................................................................... 18
2.3.2 Eosinophils .......................................................................... 20
2.3.3 Basophils.............................................................................. 20
2.3.4 Monocytes............................................................................ 20
2.3.5 Lymphocytes ........................................................................ 21
2.3.6 Differential Leukocyte Counts ............................................. 23
2.4 Thrombocytes (Platelets) ................................................................. 24
3 Blood and Urine Sampling ....................................................................... 27
3.1 Blood Sampling ............................................................................... 27
3.1.1 Hematology Sampling ......................................................... 29
3.1.2 Clinical Chemistry Sampling ............................................... 30
3.2 Blood Sampling Sites ...................................................................... 31
3.3 Urine Sampling ................................................................................ 32
vii
viii Contents
4 Species Specifics ........................................................................................ 35
4.1 Birds ................................................................................................. 35
4.2 Cats .................................................................................................. 36
4.3 Dogs ................................................................................................. 37
4.4 Guinea Pigs ...................................................................................... 38
4.5 Hamsters .......................................................................................... 38
4.6 Mice ................................................................................................. 39
4.7 Primates ........................................................................................... 40
4.8 Rabbits ............................................................................................. 40
4.9 Rats .................................................................................................. 41
5 Hematology Diagnosis .............................................................................. 43
5.1 Erythrocytes ..................................................................................... 45
5.1.1 Erythrocytes [RBC] ............................................................. 45
5.1.2 Erythrocyte Morphology...................................................... 46
5.1.3 Hematocrit [HCT, Hct, Ht, PCV] ........................................ 50
5.1.4 Hemoglobin [Hb, HB, HGB, Hgb] ...................................... 51
5.1.5 Mean Corpuscular Hemoglobin [MCH] .............................. 51
5.1.6 Mean Corpuscular Hemoglobin Concentration
[MCHC] ................................................................................. 52
5.1.7 Mean Corpuscular Volume [MCV] ...................................... 52
5.1.8 Nucleated Erythrocytes [nRBC, NRBC, NucRBC]............. 53
5.1.9 Reticulocytes [Ret, Retics] .................................................. 54
5.2 Leukocytes ....................................................................................... 55
5.2.1 Leukocytes, Total [WBC] .................................................... 55
5.2.2 Differential Leukocyte Count [Diffs] .................................. 56
5.2.3 Basophils [Basos, Bas] ........................................................ 56
5.2.4 Eosinophils [Eosins, Eos] .................................................... 57
5.2.5 Lymphocytes [Lymphs, Lym] .............................................. 58
5.2.6 Monocytes [Monos, Mon] ................................................... 59
5.2.7 Neutrophils [Neuts, Segs, N. Seg.] ...................................... 60
5.2.8 Neutrophils, Band [Bands, I. Neut., N-Band]...................... 61
5.2.9 Neutrophil: Lymphocyte Ratio [N:L Ratio]......................... 62
5.3 Hemostasis ....................................................................................... 63
5.3.1 Activated Partial Thromboplastin Time
[APTT, aPTT, PTT] .............................................................. 63
5.3.2 Bleeding Time [BT] ............................................................. 64
5.3.3 Prothrombin Time [PT, Pro Time] ....................................... 64
5.3.4 Thrombocytes (Platelets) [Thromb, Plate]........................... 65
5.4 Bone Marrow ................................................................................... 66
5.4.1 Myeloid: Erythroid Ratio [M:E Ratio] ................................ 66
Contents ix
6 Clinical Chemistry .................................................................................... 67
6.1 Alanine Aminotransferase [ALT, ALAT, SGPT, GPT, PGPT] ........ 67
6.2 Albumin [Alb].................................................................................. 68
6.3 Albumin: Globulin Ratio [A:G, A/G] .............................................. 69
6.4 Alkaline Phosphatase, Serum [ALP, AP, SAP, ALKP, Alk Phos] .... 69
6.5 Aspartate Aminotransferase [AST, ASAT, SGOT, GOT, PGOT] .... 70
6.6 Bicarbonate [Bicarb, HCO3−] ........................................................... 71
6.7 Bile Acids, Total [TBA] ................................................................... 72
6.8 Bilirubin, Conjugated (Direct) [C-Bili, CB, D-Bili]........................ 72
6.9 Bilirubin, Total [T-Bili, Bili] ............................................................ 73
6.10 Bilirubin, Unconjugated (Indirect) [U-Bili, UB, UCB, I-Bili] ........ 73
6.11 Blood Urea Nitrogen [BUN, UN] .................................................... 74
6.12 Calcium [Ca, Ca++, Ca2+, Calc] ....................................................... 75
6.13 Carbon Dioxide, Partial Pressure [pCO2, p(a)CO2] ......................... 75
6.14 Chloride [Cl, Cl−] ............................................................................. 76
6.15 Cholesterol, Total [Chol] ................................................................. 77
6.16 Cholinesterase [ChE, CHE] ............................................................. 77
6.17 Creatine Kinase [CK, CPK] ............................................................. 79
6.18 Creatinine [Creat, Cre, Cr]............................................................... 79
6.19 Fibrinogen [F, PF, FBG] .................................................................. 80
6.20 Gamma-Glutamyl Transferase [GGT, GTP].................................... 80
6.21 Globulins [GLOB] ........................................................................... 81
6.22 Glucose [GLU, Gluc]....................................................................... 82
6.23 Glutamate Dehydrogenase [GLDH, GLD, GDH] ........................... 82
6.24 Lactate Dehydrogenase [LD, LDH] ................................................ 83
6.25 Magnesium [Mg, Mg++] ................................................................... 84
6.26 Methemoglobin [metHb] ................................................................. 84
6.27 5’ Nucleotidase [5’-NT] ................................................................... 85
6.28 Oxygen, Partial Pressure [pO2, p(a)O2] ........................................... 86
6.29 pH .................................................................................................... 86
6.29.1 Metabolic Alkalosis: pH ↑ HCO3− ↑ pCO2 Normal ........... 87
6.29.2 Respiratory Alkalosis: pH ↑ HCO3− Normal pCO2 ↓ ......... 88
6.29.3 Metabolic Acidosis: pH ↓ HCO3− ↓ pCO2 Normal ............ 88
6.29.4 Respiratory Acidosis: pH ↓ HCO3− Normal pCO2 ↑ .......... 89
6.30 Phosphorus, Inorganic [P, Phos, Pi] ................................................. 89
6.31 Potassium [K, K+] ............................................................................ 90
6.32 Sodium [Na, Na+]............................................................................. 91
6.33 Sorbitol Dehydrogenase [SDH] ....................................................... 92
6.34 Total Protein [TP, T. PROT] ............................................................. 92
6.35 Triglycerides (Serum Lipoproteins) [TG, TRIG] ............................ 93
6.36 Uric Acid [UA] ................................................................................ 94
x Contents
7 Urinalysis Diagnosis .................................................................................. 95
7.1 Biliburin [Bili] ................................................................................. 96
7.2 Color ................................................................................................ 97
7.3 Glucose [GLU, Gluc]....................................................................... 98
7.4 Hemoglobin [Hb, HGB, Hgb] ......................................................... 99
7.5 Ketones ............................................................................................ 99
7.6 Occult Blood in Urine ...................................................................... 100
7.7 pH .................................................................................................... 100
7.8 Sediment .......................................................................................... 101
7.9 Specific Gravity [SG]....................................................................... 104
7.10 Total Protein [TP, T. Prot] ................................................................ 105
7.11 Turbidity .......................................................................................... 106
7.12 Urobilinogen [Urobl] ....................................................................... 106
7.13 Volume ............................................................................................. 107
8 Hematology Glossary ................................................................................ 109
9 Clinical Pathology Panels ......................................................................... 145
About the Author............................................................................................. 151
Abbreviations
ACD Acid citrate dextrose
ACTH Adrenocorticotropic hormone
ADP Adenosine 5′-diphosphate
A:G, A/G Albumin/globulin ratio
Alb Albumin
ALKP Alkaline phosphatase
Alk Phos Alkaline phosphatase
ALP Akaline phosphatase
ALT, ALAT Alanine aminotransferase
AP Alkaline phosphatase
APTT, aPTT Activated partial thromboplastin time
ASAT Aspartate aminotransferase
AST Aspartate aminotransferase
Bands Band neutrophils
Bas, Basos Basophils
Bicarb Bicarbonate
Bili Bilirubin, total
BT Bleeding time
BUN Blood urea nitrogen
Ca, Ca++, Ca2+, Calc Calcium
CB Conjugated bilirubin
CBC Complete blood count
C-Bili Conjugated bilirubin
ChE, CHE Cholinesterase
Chol Cholesterol, total
CK Creatine kinase
Cl, Cl− Chloride
CMIR Cell mediated immune response
CPK Creatine phosphokinase
Cr, Cre, Creat Creatinine
xi
xii Abbreviations
CT Clotting time
D-Bili Bilirubin, direct
DIC Disseminated intravascular coagulation
Diffs Differential leukocyte count
dL Deciliter
ECF Extracellular fluid
EDTA Ethylenediaminetetraacetic acid
Eos, Eosins Eosinophils
EPO Erythropoietin
ESR Erythrocyte sedimentation rate
F Fibrinogen
FBG Fibrinogen
FCM Flow cytometry
FDP Fibrin degradation products
Fe3+ Ferric iron
Fe2+ Ferrous iron
g/mol Grams per mole (molecular weight)
GDH Gutamate dehydrogenase
GFR Glomerular filtration rate
GGT Gamma-glutamyl transferase
GGTP Gamma-glutamyl transpeptidase
G.I. Gastrointestinal
GLD, GLDH Glutamate dehydrogenase
GLOB Globulins
GLP Good laboratory practices
GLU, Gluc Glucose
GOT Glutamic oxaloacetic transaminase
GPT Glutamic pyruvic transaminase
GTP Gamma glutamyl transpeptidase
Hb, HB Hemoglobin
Hgb, HGB Hemoglobin
HCO3− Bicarbonate
HCT, Hct Hematocrit
HSC Hematopoietic stem cell
Ht Hematocrit
I-Bili Bilirubin, indirect
ICF Intracellular fluid
I.M. Intramuscular
I. Neut Immature (band) neutrophils
I.P. Intraperitoneal
IU International units
I.V. Intravenous
K, K+ Potassium
LCFA Long-chain fatty acid
LD, LDH Lactate dehydrogenase
Abbreviations xiii
LPF Low-power field
Lym, Lymphs Lymphocytes
M Molarity
MAF Macrophage activating factor
MCH Mean corpuscular hemoglobin
MCHC Mean corpuscular hemoglobin concentration
MCV Mean corpuscular volume
M:E ratio Myeloid:erythroid ratio
MetHb Methemoglobin
Mg, Mg++, Mg2+ Magnesium
MIF Migration inhibiting factor
mL Milliliter
Mon, Monos Monocytes
MPD Myeloproliferative disorder
MPS Mononuclear phagocyte system
N Normality; nucleus
Na, Na+ Sodium
N-Band Band neutrophil
Neuts Neutrophils
N:L Neutrophil:lymphocyte ratio
5′-NT 5′-nucleotidase
NPN Nonprotein nitrogen
nRBC, NRBC Nucleated erythrocytes
N. Seg Segmented neutrophils
NucRBC Nucleated erythrocytes
ODC Ornithine decarboxylase
OECD Organisation for Economic Co-operation and Development
Osmol Osmolality
P, Pi, Phos Phosphorus, inorganic
pCO2, P(a)CO2 Partial pressure carbon dioxide
PCV Packed cell volume (hematocrit)
PF Plasma fibrinogen
PGOT Plasma glutamic oxaloacetate transaminase
PGPT Plasma glutamic pyruvic transaminase
pH pH (acidity, alkalinity)
Plate Platelets (thrombocytes)
PMN Polymorphonuclear
pO2, P(a)O2 Partial pressure oxygen
PO43− Phosphate
PP:F Plasma protein:fibrinogen ratio
Pro Time Prothrombin time
PT Prothrombin time
PTT Partial thromboplastin time
RBC Red blood cell (erythrocyte)
RES Reticuloendothelial system
xiv Abbreviations
Ret, Retics Reticulocytes
SAP Serum alkaline phosphatase
SDH Sorbitol dehydrogenase
Sed. Rate Erythroid sedimentation rate
Segs Segmented neutrophils
SG Specific gravity
SGOT Serum glutamic oxaloacetic transaminase
SGPT Serum glutamic pyruvic transaminase
SHBG Sex hormone-binding globulin
SOP Standard operating procedures
t½ Half life
T-Bili Bilirubin, total
Thromb Thrombocytes (platelets)
TBA Bile acids, total
TG Triglycerides
TP Total protein
T. PROT Total protein
TRIG Triglycerides
UA Uric acid
UB Unconjugated bilirubin
UCB Unconjugated bilirubin
U-Bili Unconjugated bilirubin
UN Urea nitrogen
Urobl Urobilinogen
WBC White blood cell (leukocyte)
