Physiological indicators

Physiological parameters, such as heart rate, blood pressure, body temperature, serum levels of various stress hormones (e.g. cortisol) and immunological functions (e.g. suppression of lymphocyte activity) can be used to assess welfare.1 Measurement of many of these parameters requires invasive monitoring techniques. However, where instrumentation, such as a heart rate transmitter, has already been implanted for experimental purposes, data that can help to assess welfare can be obtained with no additional adverse effects for the animal.

Values will fluctuate within ‘normal’ limits for any one animal. Extreme fluctuations are indicative of changes in welfare state.2 Changes may occur due to environmental, husbandry or experimental events. In these cases, comparing measurements in individual animals before and after the event, or between ‘treated’ and ‘control’ animals, can help to infer whether welfare is affected.3 Note there is often high variance between animals according to, for example, their age, sex, dominance status and the stability of the social group.4

Although relative changes are often more informative than absolute values, it is possible to compare single values from individual animals with ‘normal’ ranges for the species published in the literature, or with colony records held by the institution. Reference values are given in the tables below. ‘Normal’ parameter ranges can vary between institutions (e.g. due to the characteristics of the colony animals, and local practices for sample collection and analysis), so it is worthwhile to develop a baseline for your facility. The animals used to create this baseline should be in good physical condition (see Health indicatorsand neither pregnant nor lactating (unless in a breeding facility).

Other sources of information include the APV Nonhuman Primate Formulary and Internet Primate Aging Database.

Haemodynamic parameters of macaques

For a more extensive table, see: Extended table of haemodynamic parameters (Excel download).

Measurement ParametersA ParametersB
Heart rate 95 – 235 bpm (mean weight 7.6 kg) 120 – 180 bpm (rhesus and cynomolgus)
125 – 240 bpm (mean weight 5.3 kg)
Cardiac output 500 – 3300 mL/min (mean weight 7.6 kg)
350 – 1700 mL/min (mean weight 5.3 kg)
Stroke volume 4.7 – 16.7 mL (mean weight 7.6 kg)
2.8 – 10.6 mL (mean weight 5.3 kg)
Systolic artery pressure 68 – 172 mm/Hg (mean weight 7.6 kg)
122 – 194 mm/Hg (mean weight 5.3 kg)
Diastolic artery pressure 60 – 108 mm/Hg (mean weight 7.6 kg)
81 – 121 mm/Hg (mean weight 5.3 kg)
Arterial pH 7.2 – 7.48 7.36 – 7.42 (rhesus)
Venous pH 7.34 – 7.54
Blood volume 44.3 – 66.6 mL/kg
Plasma volume 30 – 48.4 mL/kg
Extracellular fluid volume 121 – 295 mL/kg
Total blood water 628 – 721 mL/kg
Whole blood haemoglobin 11.2 – 14.6 gm/100mL 12 – 13.1 g/dl (rhesus)
11 – 12.4 (cynomolgus)
Haematocrit 38 – 45% 38.3 – 49.6 (rhesus)
33.1 -37.5 (cynomolgus)
Temperature 37.8 – 39 oC 38.7 -39.8 (rhesus)
38.7 – 39.8 (cynomolgus)

A Rhesus macaques: Max Planck Institute for Biological Cybernetics

B Primate Products Inc.

 

 

Respiratory parameters of macaques

Measurement Parameters A
Dead space 7 – 26 mL
Lung compliance 9 – 27 mL/mmHg
Respiratory quotient 76 – 78%
Tidal volume 28 – 65 mL
Respiration rate 27 – 56 1/min
Minute volume 756 – 3640 mL/min
Arterial O2 saturation 85 – 93%
Arterial O2 content 14 – 18% volume
Arterial O2 tension 65 – 94 mmHg
Arterial CO2 content 50 – 67% volume
Arterial CO2 tension 28 – 42 mmHg
Arterial-venous O2 difference 4.5- 6%
O2 consumption 55 – 85 mL/min (weight 3 – 4.5 kg)

A: Rhesus macaques: Max Planck Institute for Biological Cybernetics

 

Blood test values of macaques

(Reproduced from Tasker 2012)

Measurement ParametersA ParametersB ParametersC ParametersD
White blood count 6.828 x 106/L 4.2 – 8.1 x 103/L (rhesus) 11.9 x 106/µL
11 – 12.5 x 103/L (cynomolgus)
Red blood count 5.511 x 103/L 4.95 – 6.4 x106/L (rhesus) 3.56 – 6.95 x 106/L 6.5 x 106/L
5.3 – 6.3 x106/L (cynomolgus)
Haemoglobin 12.589 g/dL 71 – 75 fL (rhesus) 12.22 g/dL
Mean corpuscular volume 72.511 fL 59 – 66 fL (cynomolgus)
Mean corpuscular haemoglobin 22.878 pg 22.8 – 24.5 pg (rhesus)
16.6 – 22.6 pg (cynomolgus)
Mean corpuscular haemoglobin concentration 31.533% 31 – 33.4 g/dL (rhesus)
25.8 – 32.8 g/dL (cynomolgus)
Red blood cell distribution width 12.857%
Haemoglobin distribution width 1.93 g/dL
Platelet blood test 290.78 x 103/L
Mean platelet volume 9.714 fL
Platelet distribution width 39.3%
Procalcitonin 0.26%
Neutrophils 56.22% 26 – 52% (rhesus) 5 – 88%
35 – 61% (cynomolgus)
Lymphocytes 34.98% 39 – 72% (rhesus) 38-58%
34 – 56% (cynomolgus)
Monocytes 4.92% 1 – 4% (rhesus) 0 – 11% 0.81 x 103/µ L
0.4 – 3% (cynomolgus)
Eosinophils 2.94% 0 – 4% (rhesus and cynomolgus) 0 – 14% 0.34 x 103/µ L
Basophils 0.2% 0 – 0.4% (rhesus) 0 – 6% 0.034 x 103/µ L
0 – 0.2% (cynomolgus)
Large unstained cells 0.744%
Lithium 2.058 x 103/µ L
Mean peroxidase index -13.878 x 103/µ L
White blood cell FLAGS 4666.67
Sodium 146.33 mEq/L 142 – 149 mEq/L (rhesus)
142 – 150 mEq/L (cynomolgus)
Potassium 4.08 mEq/L 3.3 – 3.7 mEq/L (rhesus)
3.3 – 3.9 mEq/L (cynomolgus)
Chloride 107.17 mEq/L 104 – 110 mEq/L (rhesus)
109 – 119 mEq/L (cynomolgus)
Glucose 55 mg/dL 38 – 89 mg/dL (rhesus) 46 – 178 mg/dL
48 – 69 mg/dL (cynomolgus)
Phosphorous 5.15 mg/dL 1.4 – 6.4 mg/dL (rhesus)
3.8 – 5.4 mg/dL (cynomolgus)
Cholesterol 122 – 154 mg/dL (rhesus) 108 – 263 mg/dL
106 – 148 mg/dL (cynomolgus)
Calcium 9.6 mg/dL 8.7 – 10.9 mg/dL (rhesus)
8.5 – 9.3 mg/dL (cynomolgus)
Platelets 260 – 361 x 103/µl (rhesus) 109 – 597 x 103/mm3 430 x 103/µl
300 – 512 x 103/µl (cynomolgus)
Magnesium 1.38 – 1.6 mg/dL (rhesus)
Total protein 6.4 – 7 g/dL (rhesus)
7.2 – 8 g/dL (cynomolgus)
Serum protein 4.9 – 9.3 g/dL
Albumin 2.8 – 5.2 g/dL
Globulin 1.2 – 5.8 mg/dL
Blood urea nitrogen 8 – 40 mg/dL
Total bilirubin 0.1 – 2 mg/dL

A Rhesus macaques: Max Planck Institute for Biological Cybernetics

B Rhesus and cynomolgus macaques: Primate Products Inc.

Wolfensohn & Honess (2005) Handbook of Primate Husbandry and Welfare

D Cynomolgus macaques: Schurman and Smith (2005)

E Cynomolgus macaques: Tasker (2012)


 

Blood types of macaques

(Source: Primate Products Inc.)

Blood type Rhesus Cynomolgus
A Rare Present
B Common Present
AB Rare Present
O Likely present Present

 

Haematology and clinical chemistry parameters and their physiological function

(Reproduced from Tasker 2012)

HAEMATOLOGY

Abbreviation Parameter Physiological function, uses and other considerations
HB Haemoglobin concentration Found in erythrocytes and carries oxygen. Helps to evaluate RBC mass.5 Used as a measure of anaemia.6
RBC Red blood cell count Known as erythrocytes. Largest number of cells in the blood. Erythrocyte survival time is approximately 85 – 100 days in macaques.7 Effects on erythrocyte parameters typically reflect a change in the balance between RBC production and RBC loss.8 Changes in plasma volume through dehydration or volume expansion can indirectly affect erythrocyte parameters.9
PCV Packed cell volume Measure of percentage of red blood cells in a sample of spun whole blood.10 Used to estimate the degree of dehydration; the more dehydrated, the higher the PCV.11
RETA Reticulocytes Immature red blood cells. Develop and mature in bone marrow and circulate for a short period in blood before developing into mature red blood cells. Normal reticulocyte count is less than 1% in monkeys.12
RABS Absolute reticulocytes As above.
MCV Mean cell volume Measure of average red blood cell volume. MCV varies in cynomolgus monkeys depending on origin; larger in animals of Chinese/Vietnamese origin.13
MCH Mean corpuscular haemoglobin The average mass of hemoglobin per red blood cell in a sample of blood.14
MCHC Mean cell haemoglobin concentration Measure of the concentration of hemoglobin in a given volume of packed red blood cells. MCHC is lower in monkeys than other commonly used species in the laboratory.15
HDW Haemoglobin distribution width Measure of the heterogeneity of the red cell hemoglobin concentration.
RDW Red cell distribution width Measure of the variation of RBC width (volume).
PLT Platelets Known as thrombocytes, they are important for blood coagulation (clotting), as they stimulate vasoconstriction and fibrin formation.16 Decreased platelet count is associated with prolonged bleeding, e.g. from small wounds of venepuncture sites.17
PCT Platelet distribution
MPV Mean platelet volume Measure of the average size of platelets found in blood.
PDW Platelet distribution width Measure of variation – an indication of variation in platelet size which can be a sign of active platelet release.
PT Prothrombin time Prothrombin is a pre-cursor for thrombin18 Prothrombin activator splits the enzyme thrombin from Prothrombin. Thrombin is essential for clotting. Small changes are considered not to be biologically meaningful.19
APTT Activated partial thromboplastin time A measure of coagulation mechanism by evaluating the intrinsic pathway. Responsible for converting prothrombin to thrombin, goes on to convert fibrinogen to fibrin.20 Small changes are considered not to be biologically meaningful.21
WBC White blood cell count Often termed leukocyte. Normally total white blood cell count is lower than RBC22 Important measure of immune function. Excited or frightened animals may have physiological leucocytosis (increased WBC count) due to endogenous catecholamine release, concurrently neutrophilia and lymphocytosis can occur.23 The quantitative determination of total and differential (see next row) WBC are included.24
N Neutrophils Most common WBC.25 Granular leukocyte (granulocyte). Measure of immune function. Primary function is phagocytosis of small particles and integral to inflammation. Principal cell type found in peripheral blood.26 Stress-induced leukocyte response may include mature neutrophila (no immature neutrophils).27
L Lymphocytes Second most common WBC.28 Non-granular leukocyte. Measure of immune function. Responsible for a wide variety of immune system functions. Principle cell type found in peripheral blood. Stress-induced leukocyte response may include lymphopenia (decreased numbers).29
M Monocytes Non-granular leukocyte. Measure of immune function. Primary function is phagocytosis and ingestion of large particles, processes antigens and present them to lymphocytes in a more antigenic form. Usually only present in very low numbers.30 Stress-induced leukocyte response may include monocytosis.31
E Eosinophils Granulocyte. Measure of immune function. Stress-induced leukocyte response may include eosinopenia (decreased numbers). Present in low numbers.32
B Basophils Granulocyte. Usually only present in very low numbers.33 Measure of immune function.34
LUC Large unstained cells Cells that have not taken up the stain during processing of blood and blood smears, therefore not red or white blood cells

CLINICAL CHEMISTRY

Abbreviation Parameter Physiological function, uses and other considerations
AST Aspartate aminotransferase AST in blood derived from heart (cardiac muscle) (predominantly), liver, skeletal muscle.35 Used in conjunction with ALT to identify site of tissue damage.36
ALT Alanine aminotransferase ALT in blood derived from liver.37 Highest activity in liver followed by cardiac muscle and kidney.38 Can be high due to liver damage or liver cell damage may be markedly increased in animals that struggle during restraint thought to be through secondary iatrogenic muscle injury with handling or intramuscular injection of anaesthetic agents or sedative.39
ALP Alkaline phosphatase Measurement represents joint enzyme activity – may be higher in juvenile growing animals.40 Fairly non-specific enzymes, widely distributed in tissues difficult to interpret changes.41
Gamma GT Gammaglutamyltransferase Highest concentrations found in the kidney, pancreas and liver.42 Used as an indicator for cholestasis.
Na Sodium Electrolytes help to maintain fluid balance, pH, membrane potentials, muscular functions and nerve conduction etc. Sodium is the major cation in serum and the principal determinant of extracellular fluid volume.43 Potassium is major intracellular cation, and is maintained in a narrow concentration range in serum, it is essential for muscle contraction.44
K Potassium
Cl Cholride
Ca Calcium Involved in neuromuscular activity, bone formation, coagulation.45
IN PHOS Inorganic phosphorous Essential for cell metabolism.46 Similar functions to calcium, but more sensitive renal excretion and may serve as an indicator of renal function.47 Levels vary with age; they are higher in very young animals.
T PROT Total protein Plasma proteins consist of Albumins and Globulins.48 Total protein is a measure of all the different proteins in plasma.49 Involved in binding and transport of substances in the blood. Important for maintaining osmotic pressure and associated with immunity and disease resistance. Hyperproteinemia is associate with dehydration.50
ALB Albumin Most abundant plasma protein.51 Functions include binding and transportation of substances, maintaining osmotic pressure and preventing large fluctuations in pH by acting as a buffer.52 Plasma proteins including Albumin indicate synthetic activity of the liver. Cellular damage reduces protein synthesis and the levels of plasma proteins decreases reflecting chronic liver damage.
GLOB Globulin Heterogenic set of proteins with a number of functions (e.g. transport proteins, mediate inflammation, and immunoglobulins), important for immune function.53
AG RATIO Albumin/globulin Albumin/globulin After hepatocellular damage (e.g. liver damage) reduction in Albumin accompanied by a relative increase in gamma GT producing obvious effects on the albumin/globulin ratio.54
TOT CHOL Total Cholesterol Cholesterol is a precursor for steroid hormones.55 Essential for cell membranes and a constituent of bile as it is required for the biosynthesis of bile acids. Endogenous it is produced by the liver.56 Exogenous may be present in diet. Serum cholesterol is relatively stable.57 Serum cholesterol and triglycerides may increase with age58
GLUC Glucose Serum glucose reflects numerous factors; stress and excitement may produce significant elevations of serum glucose.59 Hyperglycaemia may be due to stress or feeding the animal prior to venipuncture.60 The practice of fasting animals prior to venepuncture reportedly decreases the variability that accompanies post ingestion/digestion/intestinal absorption of glucose. (Hall 2007))
UREA Urea Urea nitrogen principally used to assess renal function.61 Urea nitrogen is formed in the liver.62 Urea and creatinine normally filtered from plasma by kidneys and therefore offers an indication of renal clearance.63
T BILI Total bilirubin Bilirubin is a breakdown product of heam from RBC destruction.64 The liver is responsible for metabolising spent RBCs and conjugating haem65 making it a useful as an indicator of liver damage.66
HCRE Creatinine Used as an indicator for renal function.67 Formed in the muscle. Is a non-protein nitrogenous waste material.68 Creatinine kinase activity is highest in the skeletal muscle, cardiac muscle and brain.69 It may be markedly increased in animals that struggle during restraint.70 as a result of secondary iatrogenic muscle injury with handling or intramuscular injection of anaesthetic agents or sedatives.
TRIGS Triglycerides Fatty acid precursors, that have a large number of functions in the body e.g. in cell membranes.71

 

Sources of variation in blood parameters by category and with examples for macaques

(Reproduced from Tasker 2012)

A range of factors have been found to affect clinical chemistry and haematological blood parameters in macaques.

Sources of variation in blood parameters

References (in alphabetical order; see Tasker 2012): 1: Andrade et al 2004; 2: Bonfanti et al. 2009; 3: Capitanio et al. 1996, 1998; 5: Chen et al. 2002; 6: Drevon-Gailet et al. 2006; 7: Giuletti et al. 1991; 8: Guzman & Radi 2007; 9: Hall 2007; 10: Hall & Everds 2003; 11: Hassimoto et al. 2004; 12: Hopper & Cray 2007; 13: Ives & Dack 1956; 14: Kim et al. 2005a; 15: Kim et a.  2005b; 16: Koga et al. 2005; 17: Landi & Kissinger 1994; 18: Lee et al. 2010; 19: Liu et al. 2008; 20: Loeb 1989; 21: Loomis et al. 1980; 22: Lugo-Roman et al. 2009; 23: Mason 1972; 24: Matsumoto et al. 1980; 25: Matsuzawa & Nagai 1994; 26: Matsuzawa et al. 1993; 27: Nam et al. 1998; 28: Pace et al.1996; 29: Perretta et al. 1991; 30: Riley & Cornelius 1989; 31: Ruys et al. 2004; 32: Schuurman & Smith 2005; 33: Segerstrom & Laudenslager 2009; 34: Sugimoto et al. 1986; 35: Terao 2005; 36: Terao et al. 2002; 37: Verlangieri et al.1985; 38: Wall et al. 1985; 39: Wolford et al. 1986; 40: Xia et al. 2009; 41: Yoshida 1981; 42: Yoshida et al. 1987a; 43: Yoshida et al. 1989; 44: Yoshida et al. 1992; 45: Yoshida et al. 1990; 46: Yoshida et al. 1987b; 47: Yoshida et al. 1994; 48: Yoshida et al. 1986a; 49: Zeng et al. 2010.

 


  1. Line et al. 1989; Reinhardt et al. 1990; Wolfensohn & Honess 2005 

  2. Tasker 2012 

  3. Kaplan et al. 1982 

  4. Kaplan et al. 1982; Sapolsky 2004 

  5. Hall & Everds 2008 

  6. Hall 2007 

  7. Hall 2007 

  8. Hall & Everds 2008 

  9. Hall & Everds 2008 

  10. Hall 2007 

  11. Hall 2007 

  12. Hall 2007 

  13. Hall 2007 

  14. Frandson & Spurgeon 1992 

  15. Hall 2007 

  16. Hall 2007 

  17. Hall 2007 

  18. Frandson & Spurgeon 1992 

  19. Hall 2007 

  20. Hall 2007 

  21. Hall 2007 

  22. Frandson & Spurgeon 1992 

  23. Hall 2007 

  24. Hall 2007 

  25. Frandson & Spurgeon 1992 

  26. Hall 2007 

  27. Hall 2007 

  28. Frandson & Spurgeon 1992 

  29. Hall 2007 

  30. Hall 2007 

  31. Hall 2007 

  32. Hall 2007 

  33. Hall 2007 

  34. Frandson & Spurgeon 1992 

  35. Frandson & Spurgeon 1992 

  36. Hall 2007 

  37. Frandson & Spurgeon 1992 

  38. Loeb 1989 

  39. Hall 2007 

  40. Loeb 1989 

  41. Evans 1996 – cardiotoxicity 

  42. Evans 1996 – cardiotxicity 

  43. Hall 2007 

  44. Hall 2007 

  45. Hall 2007 

  46. Frandson & Spurgeon 1992 

  47. Evans 1996 – lipids 

  48. Frandson & Spurgeon 1992 

  49. Hall 2007 

  50. Hall 2007 

  51. Frandson & Spurgeon 1992 

  52. Woodman 1996 

  53. Hall 2007 

  54. Woodman 1996 

  55. Frandson & Spurgeon 1992 

  56. Woodman 1996 

  57. Hall 2007 

  58. Loeb 1989 

  59. Loeb 1989 

  60. Hall 2007 

  61. Loeb 1989 

  62. Stonard 1996 

  63. Hall 2007 

  64. Frandson & Spurgeon 1992 

  65. Woodman 1996 

  66. Hall 2007 

  67. Loeb 1989 

  68. Hall 2007 

  69. Loeb 1989 

  70. Hall 2007 

  71. Woodman 1996 

Show Buttons
Hide Buttons