Symptomatology,

Diagnosis & Pathology

The Full Blood Count

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 Full Blood Count FBC

The most commonly performed blood tests

Can reveal much about the status of health

Measures the number of blood cells is abnormally high or abnormally

low, or the cells themselves are abnormal.
The ranges for what is considered normal given here are typical gures. However,
different laboratories may use slightly different ranges, depending on how they
perform the measurements. Ask your doctor if you are unsure about your results.

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 Full Blood Count FBC
A full blood count measures the status of the blood, including:

Hb - amount of haemoglobin in the blood

RBC red cell count - number of red blood cells
MCV mean cell volume - the size of red blood cells

Haematocrit or PCV packed cell volume the percentage of blood made up of RBCs °
MCH average amount of Hb in individual RBCs (known as mean cell Hb) °
MCHC the Hb level in individual RBCs°
° calculated values

number of white blood cells (white cell count)

percentages of the different types of white blood cells (leucocyte differential count)
number of platelets.
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Haemoglobin - Hb
Oxygen from
the lungs
Oxygen heme
released to
Erythrocyte the tissue cells

iron heme group

α chain β chain
Haemoglobin
molecules
Oxygen
bonded with
Haemoglobin
molecules

β chain
α chain

helical shape of the globin

polypeptide molecule
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 Full Blood Count FBC
Haemoglobin (Hb)
Haemoglobin is an iron-containing compound found in the red blood cells.

The normal haemoglobin level for adult males is 130-170 g/L, adult females 120-150 g/L.

Anaemia is the most common condition caused by a de ciency of haemoglobin, due to:

inadequate production of red blood cells in the bone marrow

inadequate iron intake
inadequate folate or vitamin B12 intake
microscopic bleeding or other blood loss
blood cell destruction
a chronic illness
a defect in the haemoglobin molecule itself
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 Full Blood Count FBC

Haemoglobin (Hb)
This measurement may also detect abnormally high concentrations of haemoglobin.

chronic lung disease

an adaptation to high altitudes
polycythaemia vera - an abnormal increase in red cell production by the bone marrow
haemochromatosis
smoking

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 Full Blood Count FBC
Red cell count - RCC Complete blood count - CBC
Red cell count is an estimation of the number of red blood cells per litre of blood.

The normal red cell count for adult males is 4.5-5.5 x 1012/L, adult females 3.8-4.8 x 1012/L.

Abnormally low numbers of red blood cells may indicate

inadequate production of red blood cells in the bone marrow

anaemia as a result of blood loss
bone marrow failure
malnutrition such as iron de ciency
over-hydration by intravenous drip
mechanical damage to red blood cells

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 Full Blood Count FBC

Red cell count (RCC)

Abnormally high numbers of red blood cells may indicate anaemia as a result of blood loss

congenital heart disease

some lung diseases
Dehydration
kidney disease
polycythaemia vera

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 Full Blood Count FBC
Packed cell volume (PCV) or haematocrit (Hct)
A measure of the percentage of blood made up of RBCs performed on whole blood samples
The normal haematocrit range for adult males is 40-50%, adult females 36-46%.
A low haematocrit may indicate: centrifuge
Anaemia
blood loss
55% Plasma
bone marrow failure
Leukaemia
1% Leucocytes & Platelets
multiple myeloma
nutritional de ciency
over-hydration 44% Red blood cells
rheumatoid arthritis
low normal
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 Full Blood Count FBC

Packed cell volume (PCV) or haematocrit (Hct)

A high haematocrit may indicate:
dehydration - due to burns or diarrhoea
eclampsia - a serious condition that can occur during pregnancy
polycythaemia vera.
55% Plasma

1% Leucocytes & Platelets

44% Red blood cells

high normal 10
 Full Blood Count FBC
Mean cell volume or mean corpuscular volume (MCV)
Measures the average volume or size of RBCs
Hct
The normal MCV range for adults is 83-101 fL. (1 femtolitre = 10-15 L) MCV =
RBC

A low MCV - Microcytosis may indicate:

iron de ciency
chronic disease - rheumatoid arthritis
pregnancy
a haemoglobin disorder such as thalassaemia
anaemia due to blood cell destruction
bone marrow cancer

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 Full Blood Count FBC
Mean cell volume or mean corpuscular volume (MCV)
A high MCV, Macrocytosis, may indicate anaemia due to:

nutritional de ciencies, vitamin B12, Folate, Folic acid

bone marrow abnormalities
liver disease
hyperlipidaemia
alcoholism
lung failure
cytotoxic drugs used to treat cancers

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 Full Blood Count FBC
Mean cell haemoglobin (MCH) Hgb x 10
MCH =
RBC
A measure of the Hb level in individual RBCs

The normal MCH range for adults is 27-32 pg. (picograms/cell, 1 picogram = 10-12 g )

Low MCH may indicate:

types of anaemia where the red blood cells are abnormally small
long term blood loss

High MCH may indicate:

pernicious anaemia - vitamin B12 de ciency

lack of folic acid

hypothyroidism
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 Full Blood Count FBC
Mean cell haemoglobin concentration (MCHC) MCHC =
Hb
PVC
The MCHC is the average haemoglobin concentration in a given volume of packed red cells.

The normal MCHC range is 315-345 g/L.

Low MCHC is an indicator of:

in iron de ciency as there is less Hb in each RBC

blood loss
pregnancy
anaemias caused by chronic disease
some forms of anaemia give a normal result

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 Full Blood Count FBC
White cell (leucocyte) count
White cell count estimates the total number of white blood cells per litre of blood.

The normal white cell count for adults is 4.0-10.0 x 109/L.

An abnormal high or low white cell count can indicate many possible medical conditions and a leucocyte differential count,
which provides numbers of the different types of white cells, is usually needed to help make any diagnosis.

Abnormally high levels of white blood cells may indicate: in iron de ciency

Infection
tissue damage
Leukaemia
in ammatory diseases

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 Full Blood Count FBC
Leucocyte (white cell) differential count
Leucocyte differential count provides an estimate of the numbers of the 5 main types of white blood cells.

Neutrophils, Monocytes protect against bacteria, phagocytic activity. Neutrophils: 2.0-7.0 x 109/L
Monocytes: 0.2-1.0 x 109/L

Lymphocytes immune process, producing antibodies against foreign organisms, protecting against viruses and
ghting cancer. 1.0-3.0 x 109/L

Eosinophils kill parasites, involved in allergic responses. High numbers of eosinophils may be associated with
worm infections or exposure to substances that cause allergic reactions. Eosinophils: 0.02-0.5 x 109/L

Basophils also take part in allergic responses and increased basophil production may be associated with bone
marrow disorders or viral infection.Basophils: 0.05-0.1 x 109/L

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 Full Blood Count FBC

Platelet count
An estimation of the number of platelets per litre of blood.

Abnormally low numbers of platelets is known as thrombocytopenia, while an abnormally high level of platelets
is known as thrombocytosis.

Platelet counts are often used to monitor medications that can have toxic effects on bone marrow, or conditions
such as thrombocytopenia. They may also be used to help diagnose problems associated with abnormal bleeding
or bruising.

The normal platelet count for adults is 150-400 x 109/L.

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Liver function tests LFT

Evaluate liver biochemistry & excretory performance

indirectly - liver enzymes releases into the blood stream
aminotransferases released by injured liver cells
alkaline phosphate due to cholestasis bile stopping

directly assessing liver function by measuring hepatobiliary excretion

bilirubin
albumin

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 Liver function tests LFT

Total protein
Total protein is simply a combined measure of the concentrations of proteins in the blood.

There are 2 major types of protein:

Albumin

Globulin

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 Albumen
synthesised
by the Liver hypotonic isotonic hypertonic

•aids tissue uid homeostasis

•aids transport of insoluble molecules in blood plasma

free fatty acids - triglycerides

small molecules
such as calcium

thyroxine
Albumen protein -
584 amino acids

cortisol
unconjugated bilirubin,
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 Liver function tests LFT
Albumin
Albumin is made in the liver. Normal adult blood levels 35-55g/L

Low levels may indicate:

cirrhosis
hepatitis
starvation, poor intestinal absorption
nephrotic syndrome - kidney failure
glomerulonephritis - kidney infection
generalised infection
chronic in ammation
autoimmune disease
heart failure
pregnancy & the elderly
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 Liver function tests LFT

Albumin
Albumin is made in the liver. Normal adult blood levels 35-55g/L

High levels may indicate:

low blood pressure from blood loss

dehydration
steroid treatment

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 Globulins
some synthesised
by B Lymphocytes
Globulins are proteins that include:
•gamma globulins (antibodies) - largest portion of globulins
•many enzymes & carrier/transport proteins

some synthesised
by the Liver
immunoglobulin D - IgD Alpha 1-antichymotrypsin
immunoglobulin E - IgE
immunoglobulin G - IgG

immunoglobulin A - IgA

immunoglobulin M - IgM Transferrin

Gamma - immunoglobulins -
antibodies
Beta-2 microglobulin
 Liver function tests LFT

Globulins
Include antibodies. This measure can be raised when liver cells are damaged due to autoimmune liver damage or
to long-standing liver disease of many types, particularly when cirrhosis exists.

Normal adult blood levels 35-55g/L

Low levels may indicate:

???????????

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 Liver function tests LFT

Bilirubin
A by-product of the breakdown of heme proteins in haemoglobin of senescent RBCs that are processed
(conjugated) by the liver & eliminated from the body via the common bile duct. Gives bile its yellowish pigment.
Unconjugated (free) bilirubin is insoluble in water.

When biliary excretion is compromised bilirubin is deposited in epithelial tissue for elimination via desquamation
and is seen in the skin and mucous membrane - Jaundice.

Neonatal jaundice due to high bilirubin associated with the destruction of a HbF a different form of Hb that
combines more effectively with oxygen, used before birth.

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 Bilirubin metabolism
Red cell destruction
liver

Conjugation
free Hb in plasma
(6g daily) Albumin

Conjugated
circulating
bilirubin
conjugated bilirubin
- golden yellow

Heme protein catabolism

unconjugated free bilirubin

(indirect bilirubin)

Bone marrow
erythropoiesis (stress) Bacterial deconjugation

•Free bilirubin is fat-soluble & toxic Fecal stercobilinogen

•Conjugated bilirubin is water-soluble & non-toxic - brown in colour - 200mg daily
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 Liver function tests LFT
Bilirubin
Normal blood levels:
Total, mostly conjugated 1-2µmol/L
Conjugated Hyperbilirubinemia (direct fraction) 1-6µmol/L
Unconjugated Hyperbilirubinemia (indirect fraction) 2-13µmol/L

Hyperbilirubinemia results from one or more of the following:

Increased bilirubin production - hemolysis
Decreased liver uptake or conjugation
Decreased biliary excretion

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 Liver function tests LFT

Bilirubin
High unconjugated Hyperbilirubinemia
increased bilirubin production - hemolysis
defective liver uptake of unconjugated bilirubin
defective conjugation - Gilbert s syndrome
usually <5 times normal <100µmol/L unless there is concurrent liver injury
In cases of long-term liver illness (chronic hepatitis), the level usually stays within the normal range until
signi cant liver damage has occurred and cirrhosis is present.
In cases of short-term liver illness (acute hepatitis), elevated bilirubin levels indicate the severity of the acute
illness.

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 Liver function tests LFT

Bilirubin
High conjugated Hyperbilirubinemia
decreased bile formation
decreased bile excretion - cholestasis

High bilirubinuria
re ects conjugated bilirubin in the urine
spills into the blood due to high blood levels
excessive amounts darken the urine
indicates the presence of liver disease, the type cannot be determined

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 γ-Glutamyl Transpeptidase

GGT
Present in the cell membranes of many tissues,
including the kidneys, bile duct, pancreas, liver,
spleen, heart, brain, and seminal vesicles.
Involved in the transfer of amino acids across the
cellular membrane.

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Liver function tests LFT

γ-Glutamyl Transpeptidase GGT

An enzyme produced in bile ducts that may be elevated due to bile duct illness.

an extremely sensitive test. Raised levels may indicate:

any type of liver disease

alcohol consumption

sometimes elevated even in the case of a normally functioning liver

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 Alkaline Phosphatase
ALP
An enzyme in the cells lining the biliary ducts of
the liver.
ALP levels in plasma will rise with large bile duct
obstruction, intrahepatic cholestasis or in ltrative
diseases of the liver.
ALP is also present in bone and placental tissue,
so it is higher in growing children (as their bones
are being remodelled) and elderly patients with
Paget's disease.

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 Liver function tests LFT

ALK Phos - Alkaline Phosphatase

A family of enzymes produced in the bile ducts, intestine, kidneys, placenta and bones.

These levels may rise when disease of the bile ducts or bone disorders occur.

Increased levels suggest cholestasis

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 Alanine Transaminase

ALT
ALT is found in serum and in various bodily alanine
tissues, but is most commonly associated with the
glycogen
liver. It catalyzes the two parts of the alanine lactate
sis lactate
cycle. g ene
eo
When muscles produce lactate during times of con

tion
glu

ferm lactic
ent a
decreased oxygen, they also produce alanine.
glucose
This alanine is shuttled to the liver where it is
glucose
used to make glucose.

glycogen

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 Liver function tests LFT
ALT - Alanine Transaminase
An enzyme produced in hepatocytes that leaks into the bloodstream when hepatocytes are damaged.

A sensitive indicator of liver injury

Normal ≤40IU/L
Markedly high values >500UI/L - acute hepatocyte necrosis or injury
acute viral hepatitis
toxin or drug-induced hepatitis
Ischemic hepatitis or hepatic infarction
High levels can continue for days or weeks. The degree of elevation does not re ect the extent of injury.
Serial measurement better re ect severity & prognosis.

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 Aspartate Transaminase

AST
An important enzyme in amino acid metabolism.
Found in the liver, heart, skeletal muscle,
kidneys, brain, and red blood cells, and it is
commonly measured clinically as a marker for
liver health.
Aspartate Transaminase

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 Liver function tests LFT

AST - Aspartate Transaminase

Similar to Alanine Transaminase, but less speci c for liver disease because it is also produced in body muscle
cells.

It does tend to be higher than Alanine Transaminase in cases of alcohol-related liver disease.

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 Liver function tests LFT

Platelets
The smallest of all blood cells and are involved in promoting clotting of the blood — normally a process of
healing. In cases of chronic liver disease where cirrhosis exists, the platelet count can be lowered — although this
can occur due to many conditions other than liver disease.

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 Liver function tests LFT

Adult range or normal range

This gure allows you to compare your various LFT readings with what is considered to be the upper limit of
normal (by your particular laboratory).

To make sense when comparing results to other people s, someone s readings should be quoted as 108/45, i.e.
their actual result (108) as compared to their laboratory s normal upper limit (45).

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Glycosylated haemoglobin (HbA1c)
Formed by the attachment of glucose to hemoglobin.

The percentage of glycosylated haemoglobin in the blood re ects the average

blood sugar levels over the preceding 2 - 3 months.

The most abundant form of glycated haemoglobin is haemoglobin A1c

(HbA1c), which are signi cantly increased in diabetes.

The percentage of HbA molecules that become glycated is dependent on the

general level of glucose in the plasma over the lifetime of the molecules
(generally 3 months).

This percentage is therefore used as the standard measure of the degree of

control of hyperglycaemia in the diabetic person over this period

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 Glucose tests

Glycosylated haemoglobin (HbA1c) measurement

HbA1c <5.5% and >7.0% predicts absence or presence of Type 2 diabetes

HbA1c 6.5-6.9%, diabetes is highly probable

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 Glucose Tolerance tests
Oral Glucose Tolerance Test - OGTT
fasting PG ≥ 7.0 OGTT
A standard dose of glucose is ingested by mouth and blood levels are ≥ 11.1
checked two hours later to determine how quickly it is cleared from the HbA1c ≥ 7.0%
blood. DISEASE

fasting PG ≥ 6.1 - 7.0

The test is usually used to test for:
OGTT <7.8
HbA1c ≤5.5 - 7.0%
Type II Diabetes
PRE-DISEASE
Insulin resistance
Reactive hypoglycaemia fasting PG < 6.1
OGTT <7.8
Acromegaly - excess secretion of growth hormone
HbA1c <5.5 %
rarer disorders of carbohydrate metabolism NORMAL

mmol/L
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 Glucose Tolerance tests

Oral Glucose Tolerance Test - OGTT

Preparation

The patient is instructed to fast (water is allowed) for 8–12 hours prior to the tests.
The test should not be done during an illness, as results may not re ect the patient's glucose metabolism
when healthy.
Usually the OGTT is performed in the morning as glucose tolerance can exhibit a diurnal rhythm with a
signi cant decrease in the afternoon.

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 Glucose Tolerance tests
Oral Glucose Tolerance Test - OGTT
Procedure

A zero time (baseline) blood sample is drawn.

The patient is then given a measured dose of glucose solution to drink within 5 minutes.

Blood is drawn at intervals for measurement of glucose (blood sugar) the most important sample is the 2
hour sample and the 0 and 2 hour samples may be the only ones collected.

The WHO recommendation is for a 75g oral dose in all adults: the dose is adjusted for weight only in
children. The dose should be drunk within 5 minutes.

A variant is often used in pregnancy to screen for gestational diabetes, with a screening test of 50 grams over
one hour. If elevated, this is followed with a test of 100 grams over three hours.
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 Glucose Tolerance tests

Diabetes

symptoms of diabetes

a casual Plasma Glucose - PG level >11.1 mmol/L

fasting PG level ≥ 7.0 mmol/L

2 h PG level during an OGTT ≥ 11.1 mmol/L.

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 Oral Glucose Tolerance Curves
16
Glucose concentration (mg%)

12

0
0 1 2 3
Hours

Normal
Impared glucose tollerance
Diabeties Mellitis
 Kidney function tests
Nephron
afferent efferent
arteriole arteriole

Albumin Glomerular
1. Filtration
2. Reabsorption
capillaries 3. Secretion
Normal adult output in the urine is 15mg per day. 4. Excretion

High levels - albuminuria may indicate: Bowman s

capsule 1

kidney or bladder infections

2 Peritubular
diabetic nephropathy - kidney damage due to diabetes capillaries
glomerulonephritis - kidney infection 3

nephrotic syndrome - kidney failure

pregnancy induced high blood pressure
4 Renal vein
Urinary excretion

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 Oral Glucose Tolerance Curves
20
Glucose concentration (mg%)

15

10

0
0 1 2 3
Hours Normal
Impared glucose tollerance
Diabeties Mellitis
hyperthyroidism
Myxoedema
 Thyroid function test

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid.

TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid) or
hypothyroidism (under active thyroid), or to monitor the effectiveness of either thyroid-suppression or
hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as
atrial brillation and anxiety disorder.

A TFT panel typically includes thyroid hormones such as thyroid-stimulating hormone (TSH, thyrotropin) and
thyroxine (T4), and triiodothyronine (T3) depending on local laboratory policy.

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 Pituitary-thyroid physiology
Hypothalamus
Thyrotrophin
Somatostatin releasing
hormone
Thyroxine
T4 Triiodothyronine
T3
Pituitary
Deiodination

TSH T4 T4 T3
T3 Liver
Bound to thyroxine
binding globulin,
transthyretin & albumin

Thyroid 90% T4
10% T3

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 Follicle Stimulating Hormone
????

When is it requested?

In women and men, FSH and LH are requested as part of the investigation of infertility and
pituitary gland disorders.

FSH may also be used to determine if a woman has reached the menopause.

FSH levels also help to determine the reason a man has a low sperm count.

In children, FSH and LH may be requested when a boy or girl does not appear to be
entering puberty at an appropriate age (either too late or too soon).

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Ovarian feedback regulation
Hypothalamus
Inhibits ❶ Gonadotropin-
releasing hormone
Stimulates Anterior
pituitary

❺ ❽ Estrogen
Follicle
❸
High
estrogen ❹ Progesterone
Stimulating & inhibin
level
Hormone & ⟰⟰Estrogen
Leutenising ❷ FS,
LH
Inhibin
Hormone
surge Estrogen

❸
❻ ❼
Growing Corpus
follicle Mature
Ovulation luteum
follicle

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Testicular feedback regulation

Hypothalamus
Gonadotropin- ❶
releasing hormone
Inhibin
❺ Testis

Anterior Seminiferous
pituitary Testosterone tubule cross
section
Leutenising
❷ Hormone

Interstitial
cells ❹ Testosterone

Follicle
Stimulating
Hormone

Makes cells
receptive to
❸ Spermatogenesis

testosterone’s
stimulating
Inhibits effect
Stimulates

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 Lutenizing Hormone
????

LH is often used in conjunction with other tests (FSH, testosterone, estradiol and progesterone) in
the workup of infertility in both men and women. LH levels are also useful in the investigation of
menstrual irregularities and to aid in the diagnosis of pituitary disorders or diseases involving the
ovaries or testes.

Once a baseline urine test has been completed, further urine testing may be used to detect the
surge in LH that indicates that ovulation will occur in the next 1-2 days.

In children, FSH and LH are used to diagnose delayed and precocious (early) puberty.

LH is sometimes measured in relation to gonadotropin releasing hormone (GnRH) to distinguish

between primary or secondary disorders involving the hypothalamus, pituitary gland, or the
gonads. GnRH is the hormone produced by the hypothalamus that stimulates the pituitary to
release LH and FSH. For this test, a baseline blood sample is drawn and then the patient is given an
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 Testosterone
????

Testosterone testing is used to diagnose several conditions in men, women, and boys. These
conditions include.

delayed or precocious (early) puberty in boys;

decreased sex drive in men and women;

erectile dysfunction in men;

infertility in men and women;

testicular tumours in men;

hypothalamus or pituitary disorders; and

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 Progesterone
????

When is it requested?

Progesterone levels are measured:

As part of an infertility assessment, when a woman is having trouble getting pregnant and the
doctor wants to verify that she is ovulating normally

To determine if and when ovulation has occurred following drug therapy to induce ovulation

When symptoms, such as abdominal pain and spotting, suggest an ectopic pregnancy or threatened
miscarriage

To monitor the effectiveness of treatment when a pregnant woman requires progesterone injections
to help maintain her pregnancy

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