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82 Cardiovascular observations (III)
Table 4.8 Blood hormone tests
Plasma component Normal test result Normal test result Notes where applicable
(SI units)
Adrenocorticotropic < 120 pg/mL < 26 pmol/L There is some diurnal
hormone (ACTH) variation
Adrenaline < 60 pg/dL < 330 pmol/L
Antidiuretic hormone 1–5 pg/mL 0.9–4.6 pmol/L
(ADH)
Calcitonin < 19 pg/mL < 19 ng/L
Cortisol 5–25 µg/dL (8 a.m.) 138–690 nmol/L There is some diurnal
3–16 µg/dL (4 p.m.) 83–442 nmol/L variation
Erythropoietin (EPO) 5–36 mIU/mL 5–36 IU/L
Follicle-stimulating Male 1.42–15.4 mIU/L
1.4–15.4 IU/L
Variations according to
hormone (FSH) Female 1.37–9.9 mIU/L
1.3–9.9 IU/L
gender and female
(follicular)
ovarian cycle
1.09–9.2 mIU/L (luteal)
1.0–9.2 IU/L
6.17–17.2 mIU/L
6.1–17.2 IU/L
(ovulation)
19.3–100.6 mIU/L
19.3–100.6 IU/L
(postmenopausal)
Growth hormone < 10 ng/mL < 10 µg/L Fasting
Insulin 5.0–20 µU/mL 34.7–138.9 pmol/L Fasting
Insulin-like growth 130–450 ng/mL 130–450 µg/L
factor
Luteinising hormone Male 2.0–12.0 mIU/L
2.0–12.0 IU/L
(LH) Female 2.0–15.0 mIU/L
2.0–15.0 IU/L
(follicular)
22.0–105.0 mIU/L
22.0–105.0 IU/L
(ovulation)
0.6–19.0 mIU/L (luteal)
0.6–19.0 IU/L
16.0–64.0 mIU/L
16.0–64.0 IU/L
(postmenopausal)
Noradrenaline 110–410 pg/mL 650–2,423 nmol/L
Oestradiol (E2) Male < 20 pg/mL
< 184 pmol/L
Female 20–350 pg/mL
73–1,285 pmol/L
(follicular)
150–750 pg/mL
551–2,753 pmol/L
(ovulation)
30–450 pg/mL (luteal)
110–1,652 pmol/L
< 59 pg/mL
< 218 pmol/L
(postmenopausal)
Parathyroid hormone 10–50 pg/mL 10–50 ng/L
Progesterone Male 0.13–0.97 ng/mL 0.4–3.1 nmol/L
Female 0.1–0.7 ng/mL 0.5–2.2 nmol/L
(follicular)
2–25 ng/mL (luteal) 6.4–79.5 nmol/L
Prolactin 1–25 ng/mL 1–25 µg/L Non-lactating
Testosterone Male 300–1,200 ng/dL 10.4–41.6 nmol/L
Female < 85 ng/dL < 2.95 nmol/L
Thyroid tests
Thyroid-stimulating 0.5–5.0 µIU/mL 0.5–5.0 mIU/L
hormone (TSH)
T
total
3
80–200 ng/dL 0.9–2.8 nmol/L
T free (FT4)
4
0.9–2.3 ng/dL 12–30 pmol/L
T total
4
5.5–12.5 µg/dL 71–160 nmol/L
Thyroxin-binding 10–26 µg/dL 129–335 nmol/L
globulin
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Cardiovascular observations (III) 83
stressful situations. High levels may be due to a pituitary gland tumour producing too
much ACTH or an adrenal cortex tumour producing too much cortisol. Low levels occur
in Addison disease or a pituitary disorder producing inadequate ACTH.
Test: Erythropoietin (EPO). This hormone stimulates red blood cell production from
the bone marrow. It is produced by the kidneys when blood oxygen levels are low. The
release of EPO promotes new erythrocyte production – and therefore additional hae-
moglobin in circulation – to improve oxygen-carrying capability. The test would help
to determine the reasons for the presence of polycythaemia (excessive red cells in cir-
culation) or anaemia (low haemoglobin level in the blood possibly due to low red cell
numbers).
Test: Follicle-stimulating hormone (FSH). This is a hormone produced by the anterior
pituitary gland. It stimulates the development of ova in ovaries and sperm in testes. FSH
blood levels drop naturally in women during pregnancy and may be raised normally after
menopause. Abnormal levels have to be seen in the context of age, gender and stage of
life (e.g. puberty and menopause). Levels may become abnormal due to poor diet, pitui-
tary tumours, alcohol or drug abuse and for genetic reasons.
Test: Growth hormone. This is another anterior pituitary hormone. The test is not rou-
tine but may be requested to help assess poor growth and development in children and
adolescents or problems concerning muscle bulk or bone density in adults. It may help
to assess pituitary activity.
Test: Insulin. This hormone is produced by the beta-cells of the Islets of Langerhans in
the pancreas. Its role is to lower blood glucose levels (glucagon is the hormone that raises
blood glucose levels). Insulin promotes glucose uptake into cells. Low insulin blood lev-
els are seen in type 1 diabetes and may also be present in some patients with type 2 dia-
betes (Chapter 8). Blood insulin levels are tested when blood glucose levels are abnormal
(e.g. hyperglycaemia, high blood glucose, or hypoglycaemia, low blood glucose). The test
for C-peptide may also be requested when investigating blood glucose levels (Figure 4.2
and Table 4.2, and see C-peptide test, page 69).
Test: Insulin-like growth factor-1. This hormone regulates the function of growth hor-
mone in children and continues to have an anabolic function in adults (see growth hor-
mone, earlier). It has a similar structure to insulin, and blood levels relate closely with the
levels of growth hormone, making it a useful additional test for growth problems.
Test: Luteinising hormone (LH). This is a hormone produced by the anterior pituitary
gland and acts on the ovaries, causing ovulation and acts on the testes to produce tes-
tosterone. Measurement of the blood level is done when problems occur with the repro-
ductive system, e.g. investigating the causes of early or late puberty, low testosterone or
potential infertility.
Test: Noradrenaline. Like adrenaline, this hormone is produced by the adrenal medulla
during stress and has similar functions (see adrenaline blood test, page 81).
Test: Oestradiol (E2). This is the most potent of several oestrogen hormones produced
by the ovaries. There is a natural variation in oestrogen level across the 24 hours (i.e. a
diurnal variation). Oestrogen has several functions, many of which relate to the female
reproductive system and secondary sexual characteristics (e.g. breast formation). Blood
oestrogen is tested as part of assessment of the female reproductive system, especially for
ovarian function.
Test: Parathyroid hormone (PTH). This hormone is produced by the parathyroid gland.
It regulates blood calcium levels. Low PTH allows calcium to be stored in bone and
raised PTH causes a release of calcium from bone. It can be done at the same time as
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84 Cardiovascular observations (III)
the calcium and phosphorous blood tests (see page 76) as part of an assessment of bone
calcium density or to investigate parathyroid function.
Test: Progesterone. This hormone is produced by the ovaries, mostly over the second
half (days 15 to 28) of the ovarian cycle (i.e. after ovulation). One week after ovulation,
progesterone levels should peak, and this is usually the time when the test is done. Pro-
gesterone prepares the uterus for pregnancy should the ovum become fertilised. It is likely
to be part of a group of tests that will assess ovarian function.
Test: Prolactin. This is a hormone from the anterior pituitary gland that promotes breast
milk production during lactation. The blood levels are low during the time when women
are not breastfeeding and also in males. High levels at inappropriate times may indicate
a benign tumour of the pituitary gland called a prolactinoma that produces too much
prolactin.
Test: Testosterone. This is mostly produced by the testes and is the main androgen
hormone. It is essential for sperm production and the secondary sexual characteristics,
including muscle- and bone-building and male libido. Testosterone peaks during the
teens and early twenties and gradually declines with age. Low testosterone production
(hypogonadism) may cause low sperm count, erectile dysfunction, low libido and many
other physical problems concerning body growth and sexual development.
Test: Thyroid-stimulating hormone (TSH). This is another hormone produced by the
anterior pituitary gland. It stimulates the thyroid gland to produce thyroid hormone, a
combination of two hormones: T
3
(triiodothyronine) and T
4
(tetraiodothyronine; Fig-
ure 4.6). Thyroid hormone is mostly transported in the blood by a globulin protein.
T3
T3 T4
TISSUE CELLS
FEEDBACKFEEDBACK THYROID
TSH
ANT.
PITUITARY
TRH
HYPOTHALAMUS
__
__
T4
conversion
to T3
Figure 4.6 Thyroid hormone circulation and feedback.
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Cardiovascular observations (III) 85
Together, T
3
and T
4
promote metabolism and are very important for growth and develop-
ment. The related tests are for T total (the full amount of T in circulation), T free (FT4;
3 3 4
the amount of T
4
in circulation that is not bound to protein) and T
4
total (the full amount
of T
4
, bound and unbound, in circulation). The test for thyroxin-binding globulin is to
measure the amount of globulin available for transporting thyroid hormone in circulation.
The combination of these tests is used to assess for possible thyrotoxicosis (also called
hyperthyroidism), which is excessive thyroid hormone in circulation. It may be primary
(i.e. caused by the thyroid gland itself producing too much thyroid hormone) or second-
ary (caused by an anterior pituitary problem producing too much TSH). It is vital to dis-
tinguish between these two causes of hyperthyroidisms so that treatment can be targeted
at the correct gland. Hypothyroidsim (also called myxoedema) is low thyroid hormone
levels in circulation.
Clotting factors (Figure 4.7 and Table 4.9)
Blood needs to clot to prevent bleeding to death (called exsanguination) at the time of
injury.
There is a clotting mechanism involving the chemical interactions between a number
of proteins and other factors, which ultimately results in a solid clot (called a thrombus;
Table 4.9, Figure 4.7).
Some of these factors may be in low quantity or even missing in some conditions, and
this makes the clotting mechanism fail, causing a haemorrhage that is difcult to control.
Blood tests are available to check the levels of these factors (Table 4.9). Also shown are
the results of some coagulation times (partial thromboplastin time, PTT, activated partial
thromboplastin time, aPTT, and prothrombin time, PT). They are an indication of how
fast blood will clot (shown in seconds). PTT over 100 seconds and aPTT over 70 seconds
suggest a high risk of bleeding.
As prophylaxis in some cardiac disorders (e.g. rheumatic heart disease) or following
heart surgery, drugs are often used to prevent thrombus formation. Anticoagulants are
Table 4.9 Blood clotting factors
Clotting factor Normal test result Normal test result Notes where applicable
(SI units)
Activated coagulation
time (ACT)
Antithrombin
Bleeding time
Coagulation factor I
(brinogen)
Coagulation factor II
(prothrombin)
Partial thromboplastin
time (PTT)
Activated partial
thromboplastin time
(aPTT)
Prothrombin time (PT)
80–160 secs
21–30 mg/dL 210–300 mg/L
2–9 mins
150–400 mg/dL 1.5–4.0 g/L
70–130%
60–70 secs
30–40 secs PTT with added activator
to speed the reaction
and results in a narrow
time range
10–20 secs
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Intrinsic pathway Extrinsic pathway
XII XIIa TF + VIIa VII
XI XIa
VIIIa + IXa IX
X Xa + Va
VIII Prothrombin
XIII XIIIa Fibrinogen Fibrin
Thrombin
V
Stable
in clot
86 Cardiovascular observations (III)
Figure 4.7 Blood clotting mec hanism via the intrinsic (caused by internal damage to blood vessels)
and extrinsic (caused by external injury to tissues) pathways. The factors are numbered
in Roman numerals (e.g. X, etc.) where ‘a’ is the activated form (e.g. Xa). Thrombin is a
key component that activates VII to VIIa, XIII to XIIIa and brinogen to brin, the main
substance of the clot.
mostly given by mouth on a long-time basis and work best on the venous side of the
circulation where the blood is moving slowly. Included are the vitamin K antagonists
(Table 4.10). Vitamin K is essential for blood clotting and vitamin K antagonists prevent
this from acting.
Other anticoagulant drugs (e.g. the heparins) are given by subcutaneous or intravenous
injection when required to act quickly. The heparins are divided into heparin (unfraction-
ated) and the low molecular weight heparins (Table 4.10). Unfractionated heparin acts
rapidly but has a shorter duration of action than the low molecular weight heparins.
Immunity (Table 4.11)
The immune system involves specialised blood cells and their protein products, plus
chemical agents, all dedicated to protecting the body against foreign organisms (called
antigens) such as bacteria and viruses. The system involves killing any agents that have
gained entry to the body. The cells are leukocytes (white blood cells), of which the lym-
phocytes are shown in Table 4.11 (other leukocytes are in Table 4.14). Lymphocytes bear-
ing receptors called CD4 and CD8 (CD = cluster differentiation) are important regarding
the human immunodeciency virus (HIV). Tests for CD4 and CD8 lymphocytes are used
to assess and monitor the immune system in response to HIV infection and treatment.
Other immune system elements are listed in Table 4.11. These include the immuno-
globulins (Ig; antibodies). There are ve classes of antibodies IgA, IgG, IgM, IgD and IgE.
They are proteins that are specically against certain antigens. The last two (IgD and IgE)
are naturally low in quantity, but the levels would rise if their specic antigens entered the
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Cardiovascular observations (III) 87
Table 4.10 Anticoagulant drugs
Drug Possible side effects Use and other notes
Acenocoumarol Rare but could include liver Vitamin K antagonists.
damage, loss of appetite.
Phenindione Urine discolouration, kidney Vitamin K antagonists.
damage, reduce white cell
count, hepatitis.
Warfarin sodium Liver malfunction. Vitamin K antagonists.
Heparin (unfractionated) Adrenal malfunction, Venous thrombosis and
hypokalaemia, pulmonary emboli. For
thrombocytopenia. injection or infusion.
Bemiparin sodium Epidural haematoma. Deep vein thrombosis. Low
molecular weight heparin.
Dalteparin sodium Haemorrhage. Deep vein thrombosis. Low
molecular weight heparin.
Enoxaparin sodium Haemorrhagic anaemia, Deep vein thrombosis. Low
headache, hypersensitivity. molecular weight heparin.
Tinzaparin sodium Anaemia. Deep vein thrombosis. Low
molecular weight heparin.
Table 4.11 Blood immunity tests
Plasma component Normal test result Normal test Notes where applicable
result (SI units)
CD4 lymphocyte count 500–1,500/mm
3
CD4/CD8 ratio 0.9–2.0
CD8 lymphocyte count 150–1,000/mm
3
Complement component 1,200–1,500 µg/dL 1.2–1.5 g/L
C3
Complement component 350–600 µg/dL 0.35–0.60 g/L
C4
Hepatitis A Negative Antiviral hepatitis A
antibodies
Hepatitis B HBsAg negative = no Three tests needed to
current infection; conrm status:
immune status depends HBsAg (surface antigen);
on HBsAb (anti-HBs) HBsAb (anti-HBs);
being positive HBcAb (anti-HBc)
Hepatitis C Negative (non-reactive) Antiviral hepatitis C
antibodies; further tests
are available to search
for the viral antigen
Human Negative HIV antibodies
immunodeciency
virus (HIV) test
IgA 0–83 mg/dL (< 1 year), 0–0.83 g/L 15% of all antibodies in
then rises with age until blood
50–350 mg/dL (adult) 0.5–3.5 g/L
IgG 231–1,411 mg/dL 2.31–14.11 g/L 80% of all antibodies in
(< 1 year), then rises blood
with age until 600–1,560 6.0–15.6 g/L
mg/dL (adult)
(Continued)
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88 Cardiovascular observations (III)
Table 4.11 (Continued)
Plasma component Normal test result Normal test Notes where applicable
result (SI units)
IgM 0–145 mg/dL (< 1 year), 0–1.45 g/L 5% of all antibodies in
then varies with age blood
until 54–222 mg/L 0.5–2.2 g/L
(adult)
IgD 0.5–3.0 mg/dL 5–30 mg/L 0.2% of all antibodies in
blood
IgE 0–1,500 µg/L 0–1.5 mg/L Trace quantity in blood
Prostate-specic antigen 0–4 ng/mL 0–4 µg/L Figure given for males
(PSA)
Rheumatoid factor < 30 IU/mL < 30 kIU/L
body. The complement system (C3 and C4 are shown) is a blood-based chemical cascade
that, if activated, results in killing antigens (see type II reaction, Chapter 15, page 330).
Blood tests for specic diseases look for either antibodies created to ght that disease
(e.g. hepatitis A and HIV) or a combination of both antibodies and viral antigen (e.g.
hepatitis B, hepatitis C).
Test: Prostate-specic antigen (PSA). This protein is produced by the cells of the pros-
tate gland. The test may show raised levels in males with benign prostate hyperplasia
(BPH) and those with prostate cancer. These are two different disorders. In BPH, the
word benign indicates that it is not cancer, and hyperplasia is an enlargement of the gland
due to extra cell growth. Because PSA is raised in both conditions, additional assessment
is required, including physical examination and taking into account the risk factors, to
exclude or conrm the presence of prostate cancer.
Test: Rheumatoid factor (RF). This antibody is found in the blood of about 80% of
those with rheumatoid arthritis. It is not normally found in blood. About 20% of people
without rheumatoid arthritis are RF-positive (false positives), so it is not 100% reliable.
The antibody attacks the body’s own tissues, causing inammation, particularly in the
smaller joints of the ngers in older people.
Blood gases (Table 4.12)
Blood carries the gases oxygen to the tissues and carbon dioxide to the lungs (Chapter 5).
PO
2
is the partial pressure of oxygen and PCO
2
is the partial pressure of carbon dioxide
(Chapter 5). The letter ‘a’ indicates in arterial blood (Table 4.12). Venous blood gives dif-
ferent values that are of little clinical signicance.
Test: PaO
2
is the partial pressure of oxygen in arterial blood.
Test: PaCO
2
is the partial pressure of carbon dioxide in arterial blood.
Test: O
2
saturation. This means the amount of oxygen carried by the haemoglobin
inside the red blood cells. Arterial blood should be close to 100%.
Test: pH.
5
This is the acid-base scale for indicating the acidity or alkalinity of a uid.
The scale runs from strong acidity at pH 1, neutral at pH 7 and strong alkaline at pH 14
(Chapter 8, Figure 8.14, page 173). Blood pH is stabilised at pH 7.4, with very little toler-
ated movement up or down. Carbon dioxide concentrations in circulation have a signi-
cant impact on blood pH values (see respiratory acidosis, Chapter 5).
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Cardiovascular observations (III) 89
Table 4.12 Blood gases
Blood gas Normal result Notes
PaO
2
80–100 mmHg Arterial blood
PaCO
2
35–42 mmHg Arterial blood
O
2
saturation of Hb 94–100%
pH
7.35–7.45 Arterial blood
Table 4.13 Blood toxin tests
Toxin Normal result Notes where applicable
Arsenic (As) Negative
Cadmium (Cd) Negative
Chromium (Cr) Negative
Drugs (e.g. alcohol, Negative Time limits apply to all drug screening since
barbiturates, opiates, they are eliminated by the kidneys, thus
amphetamines etc.) reducing the blood level; this also makes
urine a useful means of screening
Lead (Pb) Negative
Mercury (Hg) Negative
Blood tests for toxic substances (Table 4.13)
Toxic substances (Table 4.13) will be eliminated as quickly as possible to minimise the
damage they could do. Elimination may include processing by the liver and removal
from the blood by the kidneys, making these organs the most susceptible to toxic dam-
age. The brain is also susceptible to those toxins capable of crossing the blood-brain
barrier. Screening for toxins must be done as soon as possible before the blood level falls
(Table4.13). Urine is also a useful substance to screen for toxins (Chapter 8).
Test: Arsenic. This is most toxic in its inorganic form (i.e. not chemically bound to an
organic substance). Exposure may be through ingestion or during industrial processes using
arsenic. Severe exposure can cause red cell destruction (haemolysis), shock and rapid death.
Test: Cadmium. This is used in several industrial processes. It is highly toxic and inhaled
cadmium dust is dangerous to the lungs and kidneys, causing renal failure. Cadmium
compounds are also carcinogenic.
Test: Chromium. Concentration of chromium inside cells damages DNA and inhaled
chromium dust is carcinogenic. Especially dangerous is hexavalent chromium (chromium
6) as part of a larger compound. This damages multiple organs and body systems and
can be carcinogenic. The use of chromium in several industrial processes may mean that
workers in this environment could be exposed if not properly protected.
Test: Lead. Lead poisoning is now established and can be prevented in industries using the
metal. Lead is toxic in two ways: (1) it binds to enzymes and mimics other metals, becom-
ing substituted for other metals in metabolic processes, e.g. during haemoglobin production
leading to anaemia; (2) the brain is particularly susceptible to lead poisoning by passing
through the blood-brain barrier which disturbs neuronal development in children. It also
disrupts the normal release of the neurotransmitters dopamine and glutamate in the brain.
Test: Mercury. Mercury is a metal that is liquid at room temperature. It is poorly
absorbed through the digestive tract and skin, but mercury vapour is easily absorbed
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90 Cardiovascular observations (III)
through the lungs when inhaled. It is quickly transported to the brain and affects multiple
cognitive functions, particularly in children. It inhibits brain development by preventing
myelin sheath formation and causes neurological birth defects in foetuses.
Blood cells
The cells in blood are:
• red blood cells (RBCs, also called erythrocytes)
• white blood cells (WBCs, also called leucocytes)
• platelets (or thrombocytes; Figure 4.8; Bain 2017).
Erythrocytes carry haemoglobin (Hb), which accounts for about 33% of the cell weight
and gives blood its red colour. Haemoglobin binds the gases oxygen and carbon diox-
ide (Chapter 5). Like all blood cells, erythrocytes are developed in bone marrow, but as
Stem cell
B-cellT-cell
lymphocytes
Monocyte
Neutrophil
Eosinophil
Basophil
Erythrocytes Platelets
Proerythroblast
Megakaryoblast
Myeloblast Monoblast Lymphoblast
Macrophage
Figure 4.8 Blood cells derived from bone marrow stem cells.
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Cardiovascular observations (III) 91
mature cells they have no nucleus, and therefore their survival in circulation is limited to
about 120 days. They are continually being replaced by new ones.
White cells are nucleated and last longer. Their role is to ght infection, part of the
body’s defence strategy. Several kinds of WBCs exist: lymphocytes, which use various
mechanisms to kill invading organisms (antigens are foreign organisms, i.e. anything that
provokes an immune reaction), and monocytes, which are phagocytic (i.e. they engulf
and destroy antigens). Lymphocytes and monocytes are agranulocytes, i.e. there are no
granules in their cytoplasm. There are various types of granulocytes, i.e. they do have
granules in their cytoplasm. The types of granulocytes are neutrophils, eosinophils and
basophils, and these release important chemicals as part of the defensive role. Platelets
are cell fragments, being the breakdown product of larger cells called megakaryocytes
(Figure 4.8). They help to control blood loss following injury to blood vessels either by
blocking small holes in the vessel wall if the injury is microscopic or by triggering the
blood-clotting mechanism.
Blood tests (cells, Table 4.14)
The normal numbers of blood cells (red, white and platelets) are shown Table 4.14.
Table 4.14 Blood cell tests. The normal average number of blood cells varies between the different
types
Blood cell Normal test result Normal test result Notes where applicable
(SI units)
Basophils 0–200 per µL 0–0.2 × 10
9
per L
Eosinophils 0–450 per µL 0–0.45 × 10
9
per L
Erythrocyte (red blood Male 4.6–6.0 × 10
6
4.6–6.0 × 10
12
cells) count perµL per L
Female 3.9–5.5 × 10
6
3.9–5.5 × 10
12
per µL per L
Erythrocyte Male 0–22 mm/hour Under 50-year-old
sedimentation rate Female 0–29 mm/hour female < 20 mm/hour
(ESR) Under 50-year-old male
< 15 mm/hour
Glycosylated 4.0–5.6%
haemoglobin or
HbA1c
Glucose-6-phosphate 10.0–14.0 U/g Hb 0.65–0.9 U/mol
dehydrogenase Hb
(G-6-PD)
Haematocrit (packed Male 41–50% 0.41–0.50
cell volume, PCV) Female 35–45% 0.35–0.45
Fraction of 1
Haemoglobin (Hb) Male 13.5–17.5 g/dL 135–175 g/L
Female 12.0–15.5 g/dL 120–155 g/L
Child 12–14 g/dL 120–140 g/L
Newborn 14.5–24.5 g/dL 145–245 g/L
Haemoglobin-binding 40–180 mg/dL 0.4–1.8 g/L
protein, haptoglobin
(HPT)
Lymphocytes 1,000–4,800/µL 1.0–4.8 × 10
9
/L
(Continued)
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