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Module 1 | Anaemia an introduction

Contents

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

1.0. Introduction anaemia


1.1. How to use this module
1.2. Learning outcomes

The red cell life cycle


2.0. The erythrocyte: an overview
2.1. Erythropoiesis
2.2. The red cell membrane
2.3. Haematinics
2.4. Red cell metabolism
2.5. Haemoglobin and oxygen transport
2.6. Ageing and death of the red blood cell.
oQuiz 1

Anaemia; an overview
3.0. Defining anaemia.
3.1. Prevalence of anaemia
3.2. Clinical features of anaemia
oQuiz 2
Classifying Anaemia
4.0.
4.1.
4.2.
4.3.

Classification of anaemia
Red cell indices
Morphological classification
Aetiological classification of anaemia.

Interpretation of Blood film


5.0. Basic interpretation of a blood film.
5.1. Anaemia: essential bites
oQuiz 3
Glossary
References

Please click here to move forwards or


backwards through the module

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features

Welcome to the anaemia module!

| Introduction

1.
1

Anaemia can be defined as a reduction in the haemoglobin in the blood below normal range
for age and sex. Essentially, anaemia is defined as haemoglobin (Hb) concentration:
For adult males < 13.5 g/dl
For adult women < 11.5 g/dl
Anaemia is a global public health problem affecting both developing and developed countries. It has
major consequences for human health as well as social and economic development. In 2008, iron
deficiency anaemia was considered to be among the most important contributing factors to the
global burden of disease.
Given the importance of anaemia both globally and within the UK, it is essential that any medical
student or junior doctor can understand the major causes of anaemia, recognise its clinical features,
interpret blood results and respond with appropriate management.

Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Image above: scanning electron


microscope image of red blood cells.
Image left: Global WHO map of
anaemia in preschool age children.

| how to use this module


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

1.
2

This self-directed learning (SDL) module has been designed for


medical and other health care students.
We suggest that you start with the learning objectives and try to
keep these in mind as you go through the module slide by slide, in
order and at your own pace.
Complete the true/false questions as you go along to assess your
learning.
You should research any issues that you are unsure about. Look in
your textbooks, access the on-line resources indicated at the end
of the module and discuss with your peers and teachers.
Finally, enjoy your learning! We hope that this module will be
enjoyable to study and complement your learning about anaemia
from other sources.

| how to use this module


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death

KEY
Information within red boxes is considered core knowledge

Information within the green boxes is considered useful knowledge

Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features

5.0. Blood film: a basic


interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Key point!

Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification

Information within the grey boxes is considered optional to gain a broader


understanding of anaemia and its causes.

These are placed along the way within this module. Based on the learning
objectives, these comment boxes are aimed at highlighting the important links
between the structure, physiology and life cycle of the red blood cell to the
pathological processes resulting in anaemia.

Anaemia
essential bites.

These cards are designed to provide some essential


information on key anaemias. These are accessible
throughout the module.

1.
2

| learning outcomes (L.O.)


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.

By the end of the module, you should be able to.

List the key components of erythropoiesis (red cell production)


Bone marrow stroma, haemopoietic stem cells, tissue macrophages
Renal system (erythropoietin)
Functional DNA (globin genes)
Nutrition (Iron, B12, Folate, amino acids)
Link the components of red cell structure to red cell development and function
components of haemoglobin molecule
metabolic pathways active in red blood cells
features of red cell membrane
Link the classification of anaemia to the physiology of erythropoiesis and the influence of
systemic pathology
Interpret red cell indices reported in a full blood count and correlate with red cell
morphological classification and underlying causes of anaemia
Define anaemia and know the clinical symptoms and signs to look out for
Recognize some key blood film abnormalities

6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

L.O. We will place these objectives along the route to help direct
your learning.

1.
3

| the erythrocyte: an overview


Partners in Global Health Education

Contents page
2.1. The
erythrocyte: an
overview.

2.
1

Welcome to section one.


When learning about anaemia and in fact haematology in general,
it is essential to go back to square one and understand the basics
of cell production, function and life cycle.
Within this first module we aim to tie some basic
physiology of the red blood cell to the pathological
manifestations of anaemia. If fully understood, it will
remain as a backbone for future clinical knowledge
whenever approaching an anaemic patient.

With this in mind we now look in some detail at the structure,


function and life cycle of the red blood cell. Please click here for next
slide.

An erythrocyte is a fully
developed red blood cell!

| the erythrocyte: an overview


Partners in Global Health Education

Contents page

*L.O. Link the components of red cell structure to red cell development and
function

START HERE
Function
The primary function of the erythrocyte
is the carriage of oxygen from the lungs
to the tissues and CO2 from the tissues
to the lungs.

The red cell also plays an important role


in pH buffering of the blood.

Lifespan: Because the fully


developed red blood cell has no
nucleus the cell cannot divide or
repair itself. The lifespan is
therefore relatively shortFINISH
(120 HERE
days).
Haemoglobin content: unique to
the red cell, it is this metaloprotein
molecule which is pivotal in red cell
development and Oxygen transport
due to its affinity for O2.

To achieve these functions the red


cell has several unique
properties.

Image: scanning electron microscope of


red blood cell

Biconcave shape: increases


surface area available for gaseous
exchange.

Flexibility: the red


cell is 7.8 m across
and 1.7 m thick and
yet it is able to fit
through capillaries of
only 5 m diameter.
This is in-part due to
the flexible
membrane and
shedding of the
nucleus.

Strength: it has a
strong but flexible
membrane able to
withstand the
recurrent shear
forces involved in the
circulation of blood.

2.
1

| Erythropoiesis
Partners in Global Health Education

Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis

2.
2

An erythrocyte is a fully developed, mature red blood cell. The adult human makes approximately
1012 new erythrocytes every day by the process of erythropoiesis. This is a complex process that
occurs within the bone marrow. Before an erythrocyte arrives fully functioning into the blood
stream it must develop from a stem cell through an important number of stages. This module
has simplified this process and highlights the key stages. Follow the numbered red boxes through
to the end before continuing to the next slide.

3. EPO
continues to
stimulate
primitive
erythroid cells
(red blood cells)
in the bone
marrow and
induce
maturation.
2. EPO stimulates
stem cells within
the bone marrow
which differentiate
into erythroid
precursors.

START HERE
1: Erythropoietin (EPO),
a growth factor, is
synthesized primarily (90%)
from peritubular cells of the
kidneys (renal cortex).

Macrophages surround and


supply iron to these
erythroprogenitor cells that
become erythroblastic islands.

Stem
cells

Bone marrow

Erythroid
precursors

As with much
human physiology,
this system works
via a feedback
mechanism.

Red blood cells in


circulation

erythropoietin

Kidney

FINISH HERE
4. There is no store of EPO. The production of
erythropoietin is triggered by tissue hypoxia
(oxygen tension sensed within the tubules of the
kidney) and stops when oxygen levels are normal.

LO List the key components of erythropoiesis (red cell production)

| 2.2. Erythropoiesis

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis

Stem
cells

Hypoxia is the major stimulant for increased EPO


production

Key point!

Partners in Global Health Education

Contents page

Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO.
Its absence or reduction causes anaemia through reduced red cell production. Anaemia
due to EPO deficiency will be normocytic in morphology; i.e. the red cell will be a normal
shape and size but reduced in number.

Bone marrow Erythroid

precursors

Bone marrow Erythroid

precursors

erythropoietin

erythropoietin

Kidne
y

Key point!

Stem
cells

Kidne
y

In chronic states of anaemia the opposite may occur. The chronic hypoxic state
increases production of EPO. This leads to an increase in the proportion of
erythroblasts, expansion and eventually fatty deposition within the bone marrow.
During childhood when the growth plates are still present, this expansion can lead
to bone deformities such as frontal bossing. This is seen in chronic haemolysis
such as thalassaemia.

2.
2

|Red cell precursors and the sequence of erythropoiesis

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis

Key point!

Partners in Global Health Education

Contents page

2.
2

Reticulocytes are an important cell in haematology as they increase in number following a


haemorrhage, haemolytic anaemia or from treatment of a haematinic deficiency. They provide
an excellent measure of red cell production and the age of the red cell population. In normal
blood there is usually about 1 reticulocyte : 100 erythrocytes.

marro
w

Pronormoblast: This is the earliest and largest cell


with a large nucleus and no haemoglobin.
Normoblasts: these cells go through a large
number of progressive changes.
Fundamentally
they reduce in cell size but increase the
haemoglobin concentration in the cytoplasm. The
nucleus proportionally decreases until it is extruded
before the cell is released in to the blood.
3.4. Reticulocytes: Considered the teenagers of
the the life cycle! This is the FINAL stage of
development before full maturation. These cells are
now anucleate and contain roughly 25% of the final
haemoglobin total.
They reside mostly in the
marrow but in healthy individuals a small number
can be found in the peripheral blood. They contain
some cell organelles.

blood
Sequence: amplification and
maturation of the erythrocyte

3.5 Erythrocyte: after 1 week the mature


erythrocyte emerges with no organelles and
high haemoglobin content.

Key point!
Anaemia of
chronic disease.
In individuals living
with a chronic
disease (e.g.
rheumatoid
arthritis),a complex
interaction of
inflammatory
cytokines interferes
with the red cell
lifecycle by
impairing iron
metabolism and
inhibiting red cell
precursors. The end
result is a
normocytic anaemia.

Check the haematinics this is a phrase


used frequently on the hospital ward!

|haematinics

Partners in Global Health Education

Contents page
2.1. The erythrocyte:
an overview.
2.2. Erythropoiesis
2.3. The red cell
membrane
2.4 Haematinics

haemoglobin
deficiency;
Click here see all
key causes.
iron life cycle;
Click here to see
the key stages
Click here to see
a schematic
diagram of
vitamin B12
absorption

2.
4

Erthropoiesis is also regulated by the availability of haematinics


So what exactly are the haematinics? These are the key micronutrients that must be present if a red
blood cell and its haemogoblin are to develop in a normal fashion.

These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and

folate
A deficiency in any one of these micronutrients can result in anaemia through impaired
red cell production within the bone marrow
Assessing haematinic status is key to the investigation of the cause of anaemia
Iron:
At the centre of the haem molecule is an atom of iron which binds oxygen in a reversible manner.
Haemoglobin concentration in the developing red cell is a rate limiting step for erythropoiesis. In
iron deficiency, red cells undergo more divisions than normal and, as a result, are smaller
(microcytic) and have a reduced haemoglobin content (hypochromic). Iron deficiency is the
leading cause of anaemia worldwide.
Vitamin B12 (cobalamin) and folate (pteroylglutamic acid):
These are key building blocks for DNA synthesis and essential for cell mitosis. DNA synthesis is
reduced in all cells that are deficient in either folate or vitamin B 12. The bone marrow is the factory
for blood cell production. In haematinic deficiency, DNA replication is limited and hence the number
of possible cell divisions is reduced leading to larger red cells being discharged into the blood i.e.
less DNA, less divisions and larger cells. This leads to enlarged, misshapen cells or megaloblasts in
the marrow and macrocytic red cells in the blood.

|haematinics in haemoglobin
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Iron

Click here to
return

Iron
deficiency
Chronic
inflammatio
n
Malignancy

Chronic infections and


inflammatory disorders
cause chronic anaemia as a
result of;
1. slightly shortened red
blood cell life span
2. sequestration of iron in
inflammatory cells called
macrophages
Both procedures result in a
decrease in the amount of
iron available to make red
blood cells.

Protoporphyrin

Haem

Globin

Haemoglobi
n

Thalassaemi
a

2.
4

|haematinics: the normal iron cycle


Partners in Global Health Education

An iron deficiency
profile.
Serum Iron: Reduced
Serum total ironbinding capacity
(TIBC): Increased- the
body works hard to bind
free iron.

Serum ferritin:
Reduced-since iron
stores are low

Iron deficiency can be identified best by assessing the appearances of the red cells on a blood
film. Iron indices in a blood sample are helpful to confirm a lack of iron. In order to interpret these
indices, it is vital to understand how the body handles iron ..
Iron is a key constituent of haemoglobin (60-70% of total
body iron is stored here) and its availability is essential
for erythropoiesis. In iron deficiency, there are more
divisions of red cells during erythropoiesis than normal.
As a result the red cells are smaller (microcytic) and
have a reduced haemoglobin content (hypochromic).
Red blood
cells
In iron deficient states, bone marrow
iron is reduced.

Soluble transferrin receptors,


sTfR are on the red cell surface.
These can be measured and are
increased in iron deficiency.

Erythroid bone
marrow
(normoblasts)

Some iron binds to


apoferritin to form
ferritin, a storage
compound.

Serum soluble
transferrin receptors:
Increased-since red
cells attempt to absorb
more iron.

Reticuloendothelial system;
Spleen & macrophages

Liver
2. Iron is then attached to
a protein, transferrin in
the serum (plasma),
where it is transported toSerum
transferrin
the bone marrow for
haemoglobin synthesis.

Click here to
return

2.
4

Fe

Duodenum

3. Dying red cells


are recycled by
macrophages in
the spleen and
iron is recycled
into the plasma
for further use.

1. Iron is absorbed from the small


intestine in the ferrous state (Fe2+;
approx. 1mg/day).

STAR
T

|haematinics: vitamin B12


Partners in Global Health Education

2.
4

There are a number of key steps in the absorption of Vitamin B 12. The two key locations
are the stomach and the terminal ilium. Dietary vitamin B 12 binds with intrinsic factor
(IF) in the stomach, a transport protein produced by gastric parietal cells. The B12-IF
complex then travels through the small intestine and is absorbed by special receptors in
the distal ileum. This pathway is important when considering possible causes of Vitamin
B12 deficiency.
Oesophagus
Causes of vitamin
B12 deficiency
1.Pernicious
anaemia

Stomach
IF Intrinsic factor

2.Inadequate intake
3.Poor absorption

Distal ileum
Site of B12
absorption

Click here to
return

Vitamin B12
ingested

Vitamin B12 deficiency can


take up to two years to
develop as the body has
sufficient stores for this
period.
Pernicious anaemia: the
leading cause of B12
deficiency. IgG autoantibodies
target gastric parietal cells
and its product IF causing an
atrophic gastritis. This results
in reduced secretion of
intrinsic factor and therefore
reduced B12-IF complex for
absorption in the distal ileum.

| the red cell structure


Partners in Global Health Education

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis
2.3. The red cell
membrane

L
O
red

Link the components of red cell structure to red cell development and function

The
cell possesses an outer lipid bilayer membrane and a cytoskeleton that
consists of a dense but collapsible lattice of specialised proteins. The lipid bilayer acts as
a hydrophobic skin, whereas the proteins provide the strength, deformability and the
biconcave shape of the cell.
There are 4 red cells proteins of importance:

spectrin

actin

Protein 4.1

ankyrin

Inherited disorders of erythrocyte membrane proteins result in a poorly deformable


cell of normal size (normocyte) that cannot withstand the shear forces within the
circulation. The membrane is then lost within the microcirculation creating spherical
or elliptoid cells. These cells are then trapped and destroyed by macrophages within
the spleen. This is one cause of haemolytic anaemia. Important examples are
hereditary spherocytosis or elliptocytosis due to defects in the protein spectrin.

Key
point!

Contents page

2.
3
1

Click next slide to see flow diagram

flow diagram: the process of spherocytosis in hereditary


spherocytosis
abnormal spectrin
gene

reduced spectrin
synthesis

dysfunctional
spectrin

Spectrin malfunction
within erythrocyte
membrane

Erythrocytes are
exposed to high sheer
forces within the
microcirculation

Cytoskeleton function
impaired; cell loses
ability to deform

Spherocyte: a small,
more rigid, spherical
erythrocyte results

Haemolysis;
premature red cell
death occurs
causing anaemia

Cells are either destroyed


within the microcirculation
or detected and removed
by the reticuloendothelial
system of the spleen

Key point:
Oxidant stress!
CLICK HERE

H2O

O-

|red cell metabolism

Partners in Global Health Education

Contents page

Embden-Meyerhof
glycolytic pathway

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell
membrane
2.3.2. DNA synthesis

2.4. Red cell


metabolism

2GSH

GSSG

NAPD

NADPH+H

Hexose
monophosphate shunt.

Glucose
+

Glucose- 6-P

6-PG
Glucose-6-phosphate
dehydrogenase

ADP

ATP

Key point!

This is a
sequence of
biochemical
reactions in
which glucose is
metabolised to
lactate with the
generation of 2
ATP molecules
(providing
energy for the
cell).

Fructose-6-P

Ribulose 5-P

ADP
Pyruvate kinase
ATP

2.
5

Hexose
monophosphate
shunt

Red cells require a


mechanism to detoxify
the waste products
(accumulated oxidised
substrates) of the cell.
This shunt provides this
solution. It also provides
10% of glycolysis.
However this metabolic
pathway is also
susceptible to pathology.
The glycolytic pathway
With no cell organelles
and no mitochondria the
fully developed
erythrocyte relies on this
aerobic pathway to gain
energy (ATP) for the cell.

Lactate

Pyruvate kinase deficiency: In rare circumstances there are defects within the critical glycolytic enzymes. 95% of these defects
are associated with pyruvate kinase, a key enzyme within this pathway. The result is insufficient ATP production for cell life and
therefore premature death (haemolysis).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that is relatively common. The G6PD enzyme
is a rate-limiting step within this pathway. If deficient, haemolysis occurs when the cell is placed under oxidative stress (e.g. by
oxidative drugs, fava beans, infections) creating a potentially severe anaemia. Click OXIDATIVE STRESS for more info.

Red cell functioning adequately


under normal conditions

Infection

Fava beans

Oxidant stress!

Red cell cannot produce


enough NADPH via the
HMP shunt

Drugs: e.g.
antimalarials

H2O

O-

Embden-Meyerhof
glycolytic pathway

2GSH

GSSG

Glucose
NAPD

Inadequate amounts of GSH to


combat oxidant stress

NADPH+H+

Glucose- 6-P
Oxidant damage to cell
membrane

6-PG
Glucose-6-phosphate
dehydrogenase

ADP

ATP
Fructose-6-P
Reduced red cell survival

ADP
Pyruvate kinase
ATP

Haemolytic anaemia!

Ribulose 5-P

Hexose
monophosphate
shunt

Lactate

RETURN

| haemoglobin and O2 transport


Partners in Global Health Education

Contents page

A key function of a red cell is to carry and deliver oxygen to the tissues and return CO 2
from the tissues to the lungs. As a result the red cell has developed a specialised
molecule called haemoglobin (Hb). It is important to gain a basic understanding of
its synthesis, functioning and metabolism as errors in these processes lead to a
number of anaemic states. Its waste products are also released when a red cell is
destroyed prematurely and are therefore a valuable indicator of haemolysis.

Oxygen (O2)

HAEM MOLECULE
Each individual globin combines
with one haem molecule. This
molecule contains iron and binds
oxygen in a reversible manner. A
mature red cell (an erythrocyte)
contains approximately 640
million haemoglobin molecules.

2,3DPG

oxyhaemoglobin

deoxyhaemoglobin

A molecule called
2,3
Diphosphoglycer
ate (2,3-DPG) sits
between the
chains and when
increased helps to
offload oxygen to
the
tissues.

For more information


on foetal
haemoglobin click
here

Haemoglobinopathies

Key point!

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell
membrane
2.3.2. DNA
synthesis
2.4. Red cell
metabolism
2.5. Haemoglobin
and O2 transport

GLOBIN CHAIN
A normal adult
haemoglobin (Hb A)
molecule consists of
4 polypeptide (globin)
chains: 12 12.

2.
6

Thalassaemia: reduced rate of synthesis of either or globin chains. Within this group of
inherited conditions there may be both ineffective erythropoiesis and haemolysis resulting in
a microcytic anaemia sometime also with hypochromia.
Sickle cell disease: an inheritance of two abnormal -globin genes (HbSS). The abnormality
consists of a point mutation in the globin gene. This results in Hb insolubility in its
deoxygenated state with crystallization within the red cell causing sickling of the cell and
vascular occlusion. A common problem that affects primarily the Afro-Caribbean populations.

| haemoglobin in foetal haemoglobin


Partners in Global Health Education

RETURN

2,3DPG

oxyhaemoglobin

deoxyhaemoglobin

Oxygen requirements differ at different stages of development. The foetus displays a


different type of haemoglobin to an adult. Foetal Hb (Hb F) and HbA2 still contain two
chains but instead of chains have two and chains respectively. HbF has a higher
affinity for oxygen compared to maternal HbA. This is impart due to less binding of 2,3
DPG. The change from HbF to HbA occurs at around 3-6months of age.

2.
6

|haemoglobin and the oxygen dissociation curve


Partners in Global Health Education

A shift to the left indicates an


increased affinity for O2. This
makes it easier for Hb to bind to
O2, in the lungs and conversely
more difficult for Hb to release O 2
in the tissues.. This occurs when
there is a rise in pH (alkalosis),
low CO2 levels and with HbF.

The shape of this classic sigmoid


curve will be dictated by the
number of 2,3-DPG metabolites and
CO2 and H+ ion concentration in the
red blood cell.

CO2

pH

2,3-DPG

50

2.1. The erythrocyte:


an overview.
2.2. Erythropoiesis
2.3. The red cell
structure
2.3.1. Cell
membrane
2.3.2. DNA
synthesis
2.4. Red cell
metabolism
2.5. Haemoglobin
and O2 transport

The sigmoid curve: this occurs because as O2 is unloaded the beta chains are pulled apart
and 2,3-DPG enters the space. This reduces the haemoglobin molecules affinity for O2.

Hb saturation (100%)

Contents page

2.
6

50

CO2

pH

2,3-DPG

PO2 (mm Hg)

A shift to the right


indicates a decreased
affinity for O2. This
occurs when there are
raised concentrations of
2,3-DPG, H+ ions
(acidosis) or CO2 within
the red blood cell. This
results in greater
release of O2 to the
tissues.

|ageing and death

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and
death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary

please
click on
7.0.
References

contents to repeat
a section.

2.
7
A red cell shows signs of deterioration and reduced glycolytic rate from around 100 days of
the cells cycle. Without any DNA or ribosomes, the cell is unable to generate new
enzymes (like pyruvate kinase or G6PD that we have been introduced to). These ageing
cells are eventually identified by the reticuloendothelial system. This is a system of
white blood cells that are present within the spleen, liver and lymph nodes whose main role
is to phagocytose damaged or ageing cells. The tired red cells are removed and recycled
by macrophages in the spleen and liver.
Haemolysis: any process that shortens the red blood cell lifespan to less than 120 days.

Haemolytic anaemias; This is an important group of anaemias. There are many


important causes of premature red cell death resulting in anaemia and the increased
products of haemolysis within the blood circulation and beyond.

Normally red cell degradation and recycling is managed by the reticuloendothelial system
on a daily basis without any problems. When a pathological process causes premature lysis
of the red cells, the ability of the body to clear the increased number of waste products
may be overloaded.
The next slide demonstrates the breakdown of the products of the red blood
cell.
This is an important pathway to consider whenever encountering a
haemolytic anaemia.

Flow diagram: products of red cell destruction.


1. LDH is a nucleic enzyme which
is released on red cell destruction.
The concentration of LDH is
measurable from a blood sample
and provides an indicator of
haemolysis.

Investigating haemolysis
Red blood cell

2. Reticulocyte count will be


elevated in response to the
feedback loop during anaemia.
The bone marrow increases red
cell production. Reticulocytes are
larger than mature red blood cells
causing a rise in mean cell volume
( MCV).

3. LDH
Haemoglobin

Iron

Attaches to
transferrin

Stercobilinogen is excreted in
the faeces
Some stercobilin and stercobilogen are reabsorbed from
the intestine and excreted in the urine as urobilin and
urobilinogen. Raised levels in the urine may indicate
haemolysis.

Globin

Haem

Is metabolized
to amino acids

Unconjugated
bilirubin

Liver
Conjugated in the liver to
the diglucuronide, watersoluble form that is
secreted in the bile and
then converted to
stercobilinogen.

1.Lactic acid dehydrogenase


(LDH)
2.Reticulocyte count
3.Bilirubin
The protoporphyrin of haem is
metabolised to the yellow pigment
bilirubin, which is bound to
albumin in the plasma.
Haptoglobins these proteins bind
to any free haemoglobin. These
proteins can become saturated in
a haemolytic anaemia.
Haemoglobin can then pass into
the urine causing
haemoglobinuria or converted to
haemosiderinuria.
3. Bilirubin
Heamolysis results in
excess bilirubin causing
jaundice (typically lemon
yellow colour ) and
pigment gallstones.

Well done!
You have come to the end of the first section.
We suggest that you answer Quiz 1 to assess your learning so far. Please
remember to write your answers on the mark sheet before looking at the correct
answers!
true / false
A normal red blood cell has an average lifespan of 80 days
Erythropoietin is reduced in chronic hypoxia
Iron is transported in the blood bound to apoferritin.
High affinity haemoglobin would shift the oxygen dissociation curve to the left, thus
limiting oxygen delivery to the tissues?
Vitamin B12 is absorbed in the jejunum.
Folate and vitamin B12 are key building blocks of haemoglobin.
Chronic anaemia and malignancy prevent haem production.
A deficiency in folate causes a macrocytic, megaloblastic anaemia.
Adult haemoglobin is composed of 2 alpha and 2 beta globin chains.
Increased reticulocytes is a key feature of a haemolysis.

click to check

true /

false
A red blood cell has an average lifespan of 80 days
False! A red blood cell has an average lifespan of 120 days. This is short compared to other blood cells due to the cell
having no nucleus or organelles and is thus unable to replace key enzymes and maintain cell function.

Erythropoietin (EPO) production is reduced in chronic hypoxic states


False! In chronic hypoxic states there is an increased production of EPO. This leads to an increase in the proportion of
erythroblasts, expansion and eventually fatty deposition within the bone marrow .

Iron is transported in the blood bound to apoferritin.


True! JAK 2 is a receptor for erythropoietin. A point mutation (tyrosine kinase) in this receptor is implicated in the
oncogenisis of several myeloproliferative neoplasm. (90% of Polycythemia vera patients).

A low pH, a high CO2 concentration in the blood and a high number of 2,3-DPG would shift the
oxygen dissociation curve to the left
False! It would shift to the right. All these factors would cause haemoglobin (Hb) to have a reduced affinity for O 2 and
increase O2 release fom Hb.

Vitamin B12 is absorbed in the jejunum


False! Vitamin B12 binds to intrinsic factor in the stomach, travels through the small bowel and the complex is absorbed in
the distal ileum.

Folate and vitamin B12 are key building blocks of haemoglobin


False! Vitamin B12 and folate are key building blocks of DNA.
Chronic anaemia and malignancy prevent haem production
True! Chronic anaemia and malignancy block iron from being incorporated into the haem molecule.
A deficiency in folate causes a macrocytic megaloblastic anaemia
True! Both folate and vitamin B12 are key micronutrients for DNA synthesis. Deficiencies cause a macrocytic
megaloblastic anaemia.

Adult haemoglobin is composed of 2 alpha and 2 beta chains


True! The normal adult Hb contain 4 globin chains (often notated as 22).

Increased reticulocytes is a key feature of a haemolytic anaemia


True! The cells will be elevated in response to our feedback loop during anaemia. With excessive destruction of red cells, the bone
marrow increases production.

Welcome to section 2! | defining anaemia


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining
Defininganaemia.
3.0.
anaemia.
3.1.
Prevalence
Prevalence
3.1. Clinical
features
3.1. Clinical features
Quiz 2
Quiz 2

4.0.
Classifying anaemia
4.0. red
Classifying
anaemia
4.1.
cell indices.
4.1. Morphological
red cell indices.
4.2.
4.2. Morphological
classification
classification
4.3.
Aetiological
4.3. Aetiological
classification
classification
5.0. Blood film: a basic
5.0. Blood film: a basic
interpretation.
interpretation.
5.1.
Anaemia cards
Quiz 3.
Quiz 3.
6.0. Glossary
6.0. Glossary
7.0. References
please
click on
7.0.
References

contents to repeat
a section.

| Acute significant blood


loss |

| Pregnancy or
splenomegaly |

Following acute blood loss it


may take up to a day for
the plasma volume to be
replaced and anaemia to
present. Therefore, clinical
features of shock and
reduced blood volume may
occur before a fall in
haemoglobin concentration.

These can produce an


increase in plasma volume
reducing the apparent
haemoglobin concentration
even though circulating
haemoglobin levels are
normal.

| Dehydration |

Reduced plasma volume


may mask anaemia.

| prevalence
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification

Anaemia is thought to affect 1.62 billion people on a daily basis (WHO); this is 24% of
the worlds population. Anaemia affects both developing and developed nations.
However the main causes vary according to geographical region and from country to
country. The WHO (World Health Organisation) has devised the most comprehensive
global data bank on anaemia. Women (both pregnant and non-pregnant) and children
suffer most from the condition.

Developing nations
A complex interaction of socio-economic conditions, nutritional deficiencies and coexisting disease (malaria, HIV) are key contributors to anaemia in developing nations
(particularly within the tropics).
Africa has the highest prevalence of anaemia. It occurs in 67.6% of preschool children,
57.1% of pregnant women and 47.5% of non-pregnant women.

5.0. Blood film: a basic


interpretation.
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Click here to see WHO


world map of the
prevalence anaemia in
non-pregnant women

Click here to see WHO


world map of the
prevalence of anaemia
in pre-school aged
children

Click here to see WHO


world map of the
prevalence of anaemia
in pregnant women.

|clinical features of anaemia


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Tissue hypoxia is the end result of the bloods reduced oxygen carrying capacity. The
compensatory mechanisms in response to hypoxia cause the clinical
manifestations to develop.
An anaemic individual will have the following two key compensatory mechanisms;

1. The cardiovascular system


Cardiac compensation is the major adaptation. Both stroke volume and heart rate
increase mobilizing greater volumes of oxygenated blood to the tissues. This can present
with palpitations, tachycardia and heart murmurs. Dyspnoea which occurs in severely
anaemic patients may be a sign of cardio-respiratory failure.

2. The skin
A common sign is generalised pallor due primarily to vasoconstriction with redistribution
of blood to key areas (brain, myocardium).

|clinical features of anaemia


Partners in Global Health Education

In general, a healthy individual may compensate well for anaemia and remain mostly
asymptomatic.

However many of the following symptoms and signs are observable when the following
occurs;

1.A rapid onset: Anaemia that develops over a short period of time will cause more
symptoms than more slowly progressing anaemia because there is less time for the O 2
dissociation curve of haemoglobin and the cardiovascular system to adapt.
2.Severity: Mild anaemia (Hb 9.0-11.0 g/dL) often produces no symptoms or signs. In a
young person, severe anaemia may not even present clinically. However this is
notoriously unreliable and some patients with severe anaemia may compensate well
while others with mild anaemia may present with severe symptoms.
3.Age: The elderly are less tolerable of anaemia mainly as a result of an inability to
increase cardiac output.
4. Co-existent disease - often cardiac or pulmonary disease.

| clinical features of anaemia


Partners in Global Health Education

General symptoms and signs


Click images for explanation of signs!

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

General Symptoms
Headaches

Shortness of
breath: particularly
on exercise.

Palpitations

Confusion and symptoms of


cardiac failure in elderly
Weakness and
lethargy

General Signs

Some specific signs

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs:

Pallor of mucous
membranes (most
common sign). This is a
general sign.
Beware: pallor is quite
subjective and NOT a
reliable clinical sign. Be
careful not to exclude
anaemia on the basis of
absence of pallor alone

RETURN

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs:

Nail bed; demonstrating


koilonychia (spoonshaped nails). This is
specific to iron
deficiency.

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| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs

Atrophic glossitis; red


large swollen tongue.
This is seen in both
vitamin B12 and folate
deficiency.

RETURN

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs

Angular stomitis;
fissuring at corners of
mouth. This is seen in
both vitamin B12 and
folate deficiency.

RETURN

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs

Dysphagia: pharyngeal
web (Paterson-Kelly
syndrome). This occurs
in iron deficiency.

RETURN

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs

Peripheral
oedema. A
general sign.

RETURN

| clinical features of anaemia


Partners in Global Health Education

This is a list of general symptoms and signs; we will cover more specific clinical
features as we progress through the module.
Signs

High flow murmur, bounding


pulse and/or tachycardia: All
features of a compensatory
hyperdynamic circulation.
These are general signs!

RETURN

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz
Quiz 22

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Well done!
You have come to the end of the second section.
We suggest that you answer Quiz 2 to assess your learning so far. Please
remember to write your answers on the mark sheet before looking at the
correct answers!
true / false
An adult male with a haemoglobin concentraion (Hb) < 11.5 g/dl is anaemic.
Within the developing world iron deficiency is the single most common cause of
anaemia.
The respiratory system is the main physiological compensator in anaemia.
Koilonychia, glossitis and angular stomatitis are all general signs of anaemia.

Some key signs associated with iron deficient anaemia are koilonychia and
glosso-pharyngeal webbing.

click to check
answers

An adult male will be anaemic if they have a haemoglobin of < 11.5 g/dl
on a full blood count.
False! An adult male is anaemic if [Hb] is < 13.5 g/dl. An adult female will be considered
anaemic if [Hb] is < 11.5 g/dl.
Within the developing world iron deficient anaemia is the single greatest cause of
anaemia
True!
The respiratory system is the main physiological compensator in anaemia.
False! The cardiovascular system is the major adaptor. Both stroke volume and heart rate
increase in an attempt to mobilize greater volumes of oxygenated blood to the tissues.
Koilonychia, glossitis, angular stomatitis are all general signs of anaemia.
False! Koilonychia is sign of iron deficiency. Glossitis and angular stomatits are a sign of
vitamin B12 and folate deficiency.
Some key signs associated with iron deficient anaemia are koilonychia and glossopharyngeal webbing.
True!

Click here to continue


module

Welcome to section 3!|classification of anaemia


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying
anaemia
4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary

please
click on
7.0.
References

contents to repeat
a section.

Essentially there are two ways to classify anaemia, by red cell size
(morphological classification) or by cause (aetiological classification). Both have
their purpose and both need to be fully understood to gain a rounded
understanding of anaemia.

Morphological classification

Aetiological classification

This is a practical and clinically useful


classification for establishing a differential
diagnosis of anaemia.

This classification is based on cause and


illuminates the pathological process
underlying anaemia.

It is done by examining red cells in a blood


stained smear and by automated
measurements of red cell indices

*Key point: In order to understand this classification it is essential to


understand red cell indices reported in the full blood count (FBC). There is
great reward in understanding these indices as they enable one to identify
some of the underlying processes leading to anaemia and, importantly, help
to formulate a differential diagnoses.

|red cell indices


Partners in Global Health Education

These are the key measures of red cell indices. They relate to the haemoglobin content and
size of the red blood cells.
MCV: Mean cell volume; the average volume of the red cells. MCV does not provide an indicator
of either haemoglobin concentration within the cells, or the number of red cells. It enables us to
categorize red cells into the following;
Microcytic
(MCV <80fL)
Normocytic (MCV of 80-99fL)
Macrocytic (MCV > 99fL)

a small red blood cell.


a normal size red blood cell.
a large red blood cell.

This is a key index that is used daily in medical settings across the world to categorize the type of
anaemia present.
It is reliable in most cases; one exception is when two pathologies occur at the same time such as vitamin B 12
and Iron deficiency. MCV reports average cell volume; further assessment of cell size and how this varies
within an individual can be ascertained from the red cell distribution width (RDW; see below).

MCH: Mean corpuscular haemoglobin ( normal range 26.7-32.5pg/cell): the average


haemoglobin content of red blood cells.
Cells with a reduced haemoglobin content are termed
hypochromic and those with a normal level are termed normochromic (see below).
RDW: Red cell distribution width; an index of the variation in sizes of the red cell population
within an indiviual. This will be raised if two red cell populations are present. Occasionally useful if
there is doubt about multiple causes of anaemia. A common cause for an increased RDW is the
presence of reticulocytes.

Normochromic implies normal staining of the cells in a thin blood film. The central area
of pallor is normally about 1/3 of the cell diameter
Hypochromic

indicates reduced staining with increase in the central area of pallor

|interpretation of red cell indices


Partners in Global Health Education

Microcytosis & hypochromia

Normocytosis & normochromia

Macrocytosis & megaloblastosis

Microcytic
abnormally small red blood cells.
Microcytic anemia is not caused by
reduced DNA synthesis. It is not
fully understood but is believed to
be
due
reduced
erythroid
regeneration.

Normocytic normochromic
anaemia develops when there is a
decrease in the production of normal
red blood cells.

Macrocytic megaloblastic
red blood cells have an unusual misshapen
appearance, which is due to defective
synthesis of DNA. This in turn leads to
delayed
maturation
of
the
nucleus
compared to that of the cytoplasm and the
cells have a reduced survival time.

Hypochromic
hypochromic cells due to a failure of
haemoglobin synthesis.

Normocytic
Many processes causing anaemia do
not effect the cell size or haemoglobin
concentration within cells.

In clinical practice megaloblastic anaemia is


almost always caused by a deficiency of
vitamin B12 or folate which are key
building blocks in DNA synthesis.

Pathologies;
anemia of chronic disease (some)
aplastic anemia
Haemolysis: a increased destruction (some)
Hemolysis ;or loss of red blood
pregnancy/fluid overload: an inbalance or
an increase in plasma volume compared to
red cell production

Macrocytosis:
The exact cause of the pathological
mechanisms behind these large cells is not
fully understood.. It is thought to be linked
to lipid deposition on the red cell membrane.
Alcohol is the most frequent cause of a
raised MCV!

Pathologies;
Iron deficiency; iron is an
essential building block of haem.
Failure of globin synthesis; this
occurs in the thalassemia's.
Crystallization of haemoglobin:
sickle cell disease and
haemoglobin C.

Alcohol | Liver disease | hypothyroidism |

| morphological classification of anaemia


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

Anaemia type

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features

Red cell
indices

Microcytic
hypochromi
c

MCV < 80 fl
MCH < 27 pg/L

Normocytic
normochromi
c

normal

Macrocytic
Megaloblastic

MCV > 98 fl

Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Common
examples

Iron deficiency

Haemolysis

Thalassaemia

Chronic disease

Sideroblastic

Marrow infiltration

Folate
deficiency
B12deficienc
y

|aetiological classification of anaemia


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death

This classification is based on cause and illuminates the pathogenic process


leading to anaemia.
You can look at anaemia from a production, destruction or pooling point of view.
Reduced Production
Insufficient production: If you consider the bone marrow to be the factory it
must have enough raw material (Iron, vitamin B12 and folate) to make new blood
cells. These raw material are called haematinics. If there is not enough of the raw
material (a deficiency of one or more of the haematinics), then there is insufficient
production.

Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.

Inefficient production (erythropoiesis): some problem with maturation of the


erythroid in the marrow. Occurs in bone marrow infiltration
(malignancy/leukaemia), aplastic anaemia or in the macrocytic megaloblastic
anaemia.

Destruction
Reduced Cell lifespan
This is either due to loss of red blood cells in a haemorrhage (a bleed) or the
excessive destruction of red blood cells in haemolysis. Haemolysis is an important
cause of red cell destruction and anaemia.

Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Pooling: Hypersplenism.

|classification of anaemia based on pathology


Partners in Global Health Education

Contents

anaemia

1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death

Increased
destruction of
red cells
(haemolytic
anaemia

Loss of red cells


due to bleeding

Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Inherited /
inside the
cell

Acquired /
outside cell

immune

Autoimmune
warm
Autoimmune
cold
Adverse
drug
reaction
Haemolytic
disease of
the newborn

Dilution of red
cells by increased
plasma volume
(e.g.
hypersplenism)

Nonimmun
e

Malaria
Burns
Mechanical
heart valve
Hypersplenism
PNH

Reduced bone
marrow erythroid
cells
aplastic anaemia
Leukaemia or
malignancy

Abnormal
red cell
membrane

Sperocytes

Elliptocytes

Failure of
production of
red cells by the
bone marrow

Nutritional
(haematinic)
deficiency
Iron
vitamin B12
folate

Abnormal
haemoglobin

Thalassaemia
Sickle cell
anaemia

Ineffective red cell


formation
Chronic inflam.
Thalassaemia
renal disease

Abnormal
red cell
metabolism

Pyruvate
kinase
deficiency
G6PD
deficiency

|blood film: a basic interpretation


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification

A blood film is an essential investigation in classifying and diagnosing the cause of anaemia. A blood sample
(anticoagulated venous sample) is smeared onto a glass slide, fixed and stained. Red cells are examined
along with white cells, granulocyte precursors, blast cells and platelets.
Red blood cells appear paler in the centre of the cell due to their biconcave shape. The pinkish colour one
observes in a normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour
are the key variables to observe.

Please click on each cell to see the blood film and its
causes.

Normal red
cell

Microcytic
hypochromi
c

Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Macrocyte

Tear drop
poikilocyte

Please click here to compare blood films

Target cell

Pencil cell

5.0. Blood film: a


basic
interpretation.
Quiz 3.
6.0. Glossary

please
click on
7.0.
References

contents to repeat
a section.

Spherocyte

Acanthocyte

Basket case

Malarial parasit

Normal red blood film

Elliptocyte

Stomatocyte

Microcytic hypochromic

Fragments

Sickle cell

Macrocytic megaloblastic

Fragments

Target cells

Pencil cells

Spherocyte

Bite cells

Malaria

Acanthocyte

|anaemia essential bites


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

Microcytic anaemia
iron deficieny

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.

Macrocytic anaemia
Vitamin B12 &
Folate deficiency
Epi:
common cause of a
worldwide affecting around
daily.

the most
naemia
500million

Aet:
anaemia, malabsorpion,
gastrectomy

pernicious
post total

Ix.
platelets. IF
folate levels

B12MCV
antibodies,

Si/Sy:
Gradual
deterioration, Irritability,
Loss of
memory, Painless jaundice,
Loss of
sensation , Feeling of pins
and needles in
extremities. ataxic

Txt
Intramuscular
(IM) of 1mg of
hydroxycobalamin (Vitamin B12). There is

Haemolytic anaemias
G6PD deficieny

Epi:
Aet:
consumption
dietary
folate antagonist
methotrexate).

increased
(pregnancy),
deficiency,
(drugs eg;

Ix.
folateMCV transferrin
Endoscopy/
if suspected blood

saturation.
colonoscopy
loss.

haemoglobin
breakdown

G6PD is a key enzyme in the hexose monophosphate shunt. An


important
funtion of the shunt is maintain a health
by removing oxidant
stresses. Wihtout the enzyme, Hb
resulting in haemolytic aneamia.

Aet:

X-linked

Si/Sy:
deterioration,
Loss of memory,
jaundice, Loss of
Feeling of pins and
extremities. ataxic

Txt
Intramuscular (I M) of 1mg of

Gradual
Irritability,
Painless
sensation ,
needles in

Ix.

Direct assay during haemolysis

Si/Sy:

Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to


painless gastritis.

hydroxycobalamin (Vitamin B12).

There is
no oral

Path

oesophageal web),
Rx

Avoid precipitants of oxidative stress; drugs (anti-malarials,


analgesics), fava beans.

Tx.

Blood transfusion if required.

form.

no oral
form.

Hereditary
spherocytosis;

-Thalassaemia
R.C.I.:

a microcytic hypochromic anaemia

Epi:
One of the most common autosomal inherited
disorders. Common in Mediterranean, Africa and middle east. Gene
carriers are protected from
p.falciprum malaria.
Path:
Ineffective

Reduced beta globin (of haemoglobin) production.


erythropoiesis and haemolysis

IX.

blood film, Hb electropheresis

Si/Sy.
anaemia, low MCV.

Heterozygotes: often asymptomatic, mild

Epi:

the most common cause of anaemia worldwide aff ecting around


500million daily.

Aet:

The most common cause of iron deficient anaemia is BLOOD loss


reduced intake (diet)
Increased demand (pregnancy)
Malabsorption (coeliac, gastrectomy)

Ix.

FBC, ferritin, serum iron, TIBC, transferrin


saturation. Endoscopy/colonoscopy if suspected blood

first 6 months of life,


extramedullary

Tx.

loss.
Si/Sy:

Homozygote: severe anaemia, failure to thrive in


splenomegaly, bone hypertrophy (secondary to
haemopoisis).

blood transfusion and iron

painless gastritis.

chelation.

a microcytic hypochromic anaemia

Aet:
A group of autosomal recessive genetic disorders
due to a haemoglobin chain mutation. Part of the haemoglobinopathies
that primarily affect those of
African origin (sickel cell
trait can afford some protection against malaria.

Epi:

Path:
Abnormal haemoglobin (HbS) undergo a sickling
transformation in a
deoxygenated state and a permenant
conformational change of shape. The
red cell looses its ability
to deform becoming rigid. This can cause
occlusion of small vessels.
These crises are precipitated by hypoxia,
dehydration, infection and
the cold.
IX.

Electropherisis, haemoglobin solubility test.

Si/Sy:
pigment gallstones.

Txt
required.

Bone pain, if chronic haemolysis- jaundice and

Treat underlying cause, give ferrous sulphate until Hb and MCV


normal.

Aquired Haemolytic
anaemias;

Sickle cell disease


R.C.I.:

Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),

Txt

For major Thalassaemia treat with repeated

the most common cause of anaemia worldwide aff ecting around


500million daily.

Aet:

The most common cause of iron deficient anaemia is BLOOD loss


reduced intake (diet)
Increased demand (pregnancy)
Malabsorption (coeliac, gastrectomy)

Ix.

FBC, ferritin, serum iron, TIBC, transferrin


saturation. Endoscopy/colonoscopy if suspected blood
loss.

Si/Sy:

Koilonychia, sore tongue, angular stomatitis, PlummerVinson syndrome (dysphagia due to oesophageal web),
painless gastritis.

Txt

Supportive; analgesia, fluids and antibiotics if

Treat underlying cause, give ferrous sulphate until Hb and MCV


normal.

6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

KEY

Epi. Epidemiology

Ix. Investigations

R.C.I. Red Cell Indices

Si/Sy. Signs and Symptoms

Aet. Aetiology

Path. Pathology

Tx. Treatment

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

Well done!
You have come to the end of the third and final section.

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

We suggest that you answer Quiz 3 to assess your learning. Please


remember to write your answers on the mark sheet before looking at the
correct answers!
true / false
Microcytosis is MCV < 90fL
The appearance of a hypochromic red blood cell is caused by reduced DNA
synthesis
In vitamin B12 deficiency you would expect the MCV to be >99fL
Both sickle cell anaemia and thalassaemia have abnormal haemoglobin
A macrocytic blood film may indicate excess alcohol consumption or liver disease

click to check
answers

Microcytosis is MCV < 90fL


False! Microcytosis is MCV < 80fL.
The appearance of a hypochromic red blood cell is caused by reduced DNA synthesis
False! A hypochromic film is due to reduced haemoglobin content within red blood cells.
In vitamin B12 deficiency you would expect the MCV to be >99fL
True
Both sickle cell anaemia and thalassaemia have abnormal haemoglobin

True!
A macrocytic blood film may indicate excess alcohol consumption or liver disease
True!

Click here to
return to
beginning of
module

Blood film
RBC morphology:
normocytic,normochromic.
|blood
film: a basic interpretation
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.

Definitions
Red cells appear paler in their
centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
Normocytic:
A cell with an MCV within the normal
variables to observe.
range
Normochromic:
concentration of anaemia is within
the normal
Please click on each cell to see the
bloodrange
film, causes and explanation.
The biconcave red cell when stained shows a classical central
area of pallor on a blood film.

Normal red
cell

Microcytic
hypochromi
c

Macrocyte

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film

film:
a basic
RBC morphology:|blood
Microcytic
hypochromic.
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

interpretation

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
Explanation
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
Red cells are smaller and lighter than normal and
variables to observe.

displaying a typical area of central pallor.

Please click Cause


on each cell to see the blood film, causes and explanation.

Iron deficient anaemia


Normal red
cell

Thalassaemia
Microcytic

Macrocyte

hypochromi
c

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film
RBC morphology:
macrocytic
(More oval)
|blood
film: ,megaloblastic
a basic interpretation
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.
Cause

Macrocytic
megaloblastic:
Please click on Macrocytic:
each cell to see the blood film, causes
and explanation.
Liver disease
Alcoholism

Normal red
cell

Microcytic
hypochromi
c

Vitamin B12
Folate

Macrocyte

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film

|bloodtarget
film:cell
a
RBC morphology:
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

basic interpretation

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
Extra:
it is also
possible to see
one neutrophil
andbe
twosmeared
platelets.onto a glass
investigations into anaemia. A blood
sample
(anticoagulated
venous
sample) will
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells
unique haemoglobin content. Shape, size and colour are the key
Cause
variables to observe.

Target cells are found in peripheral blood films in a number of

Please click on each


cell to see the blood film, causes and explanation.
conditions.

Normal red
cell

1.Liver disease (obstructive jaundice).


2.Thalassaemia
major.
Microcytic
Macrocyte
Target cell
3.Sickle cell anaemia.
hypochromi
c

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film

|blood film: a basic interpretation

RBC morphology: basket/blister cell.


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation:

Please click on each cell to see the blood film, causes and explanation.

Oxidant damage
Normal red
cell

Cause:
Microcytic
Macrocyte
hypochromi
c G6PD deficiency

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood filmBlood film


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

film:
a basic interpretation
RBC|blood
morphology:
basket
RBC morphology:
Elliptocyte.
Bloodcell.
film shows characteristic
A blood film can provide key elliptical
evidence(elongated)
in diagnosing
It is therefore is an essential part of all
redanaemia.
cells.
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.

Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation

Please click onCauses


each cell to see the blood film, causes and explanation.

Normal red
cell

damage
HereditaryOxidant
elliptocytosis:
due to a defective cell membrane
protein
(Spectrin,
band
4.1).
Microcytic G6PD deficiency
Macrocyte
Target cell
hypochromi
c

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

Blood film
Blood film

film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Fragments
RBC morphology: Elliptocyte.

interpretation

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Cause Explanation
Causes Please click on each cell to see the blood film, causes and explanation.
Disseminated
Intravascular
Oxidant
damage Coagulation (DIC)
Hereditary elliptocytosisMicroangiopathy
TTP
Basket case
Normal red
Microcytic
Macrocyte
Target cell
G6PD deficiency
Burns
cell
hypochromi
c Cardiac valves

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying
anaemia
4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology: Tear drop poikilocyte

interpretation

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.

Definition: Poikilocyte; an individual cell of abnormal shape

Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation

Please click on Cause


each cell to see the blood film, causes and explanation.

Normal red
cell

Oxidant damage
Myelofibrosis
Extramedullary haemopoiesis
Microcytic
Macrocyte
G6PD deficiency
hypochromi
c

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

RBC morphology:
Pencil
cell.
These
thin elongated
film:
a basic
interpretation
RBC|blood
morphology:
basket
cell. are
cells. Often occur alongside microcytic
A blood film can provide key evidence in diagnosing
anaemia. It
is therefore
is an
hypochromic
cells,
poikilocyte
andessential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
targetgranulocyte
cells.
slide, fixed and stained. Red cells are examined alongoccasional
with white cells,
precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation
Explanation

Please click on each cell to see the blood film, causes and explanation.

Iron deficiency
Oxidant damage
Normal red
cell

Microcytic G6PD deficiency


Macrocyte
hypochromi
c

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

RBC morphology:
Ring-forms
P.falciprum
film:
a inbasic
interpretation
RBC|blood
morphology:
basket
cell.
Intracellular malarial parasite

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation

Explanation
of
malarial infection. It can lead to DIC and intravascular
haemolysis.Oxidant damage

certain
of blood
haemolysis
occursand
with
all types
Please click onAeach
cell amount
to see the
film, causes
explanation.

Normal red
cell

Basket case
Microcytic
Macrocyte
Targetcauses
cell up to 3
Malaria: Transmitted
by the mosquito this disease
G6PD deficiency
hypochromi
million deaths a year and is a major cause of anaemia within the
c tropics! See malaria module for more information.

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film

|blood film: a basic interpretation

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

RBC morphology:
basket cell.
RBC morphology:
Stomatocyte

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation

Please click on Explanation


each cell to see the blood film, causes and explanation.

Normal red
cell

Oxidant damage
Liver disease
Alcoholism
Microcytic G6PD deficiency
Macrocyte
hypochromi
c

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

film:
a basic
RBC|blood
morphology:
basket
cell.
RBC morphology:
Sickle cell

interpretation

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
Explanation
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

In sickle cell anaemia the red blood cell undergoes a


sickling process due the cell containing haemoglobin S.
Explanation
Please click on each cell to see the blood film, causes and explanation.

Normal red
cell

In a deoxygenated state this haemoglobin undertakes a permanent


Oxidant damage
conformational change creating large polymers. As a result these
cells become rigid and unable to deform. The red cell eventually
Basket case
Microcytic G6PD deficiency
Macrocyte
Target cell
looses its cell membrane and becomes damaged as it travels
hypochromi
through the circulation changing into the sickled shape we see. This
c
eventually leads to an early cell death (hemolysis).

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film

RBC morphology:
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

Micro-Spherocyte. This slide shows spherocytes


caused
by hereditary
They sit amongst
|blood
film:
aspherocytosis.
basic
RBC
morphology:
basket
cell. interpretation
larger
polychromatic
red cells.

A blood film can provide key evidence in diagnosing anaemia. It is therefore is an essential part of all
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells are examined along with white cells, granulocyte precursors, blast cells.
Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Cause | Explanation

Explanation

Please click on each cell toAbnormality


see the blood
film, causesproteins.
and explanation.
of cytoskeleton
These cells

Normal red
cell

are excessively
Oxidant
damage permeable to sodium influx. Cell
looses membrane on passage through
reticuloendothelial
cell osmotic
fragility
Basket case
Microcytic G6PD
Macrocyte system. Red
Target
cell
deficiency
hypochromi is characteristically increased.
c

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Spherocyte

Acanthocyte

Malarial parasit

Blood film
Blood film

|blood film: a basic interpretation

Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell structure
2.3.1. Cell membrane
2.3.2 DNA synthesis
2.4. Red cell
metabolism
2.5.Haemoglobin
2.6 O2 dissociation
curve

3.0. Defining anaemia.


3.1. Prevalence
3.2 Clinical features

4.0. Classifying anaemia


4.1. red cell indices
4.2. Morphological
4.3 Aetiological
classification

RBC morphology:
cell. echinocytes.
RBC morphology:
Pricklebasket
cell or small
A blood film can provide key evidence
diagnosinginanaemia.
It is therefore
is an essential part of all
Especiallyinprominent
postsplenectomy
patients.
investigations into anaemia. A blood sample (anticoagulated venous sample) will be smeared onto a glass
slide, fixed and stained. Red cells
are examined
along with
cells, granulocyte
precursors, blast cells.
Definition:
Echinocyte:
cellwhite
with abnormal
blunt or sharp

projections on surface. Can be up to 30 projections per cell.

Red cells appear paler in their centre of the cell due to their biconcave. The pinkish colour one observes in a
normal blood film is a result of the cells unique haemoglobin content. Shape, size and colour are the key
variables to observe.

Explanation

Please click on Explanation


each cell to see the blood film, causes and explanation.

damage
PyruvateOxidant
kinase deficiency
Normal red
cell

Microcytic G6PD deficiency


Macrocyte
hypochromi
c

Target cell

return
Elliptocyte

Fragments

Stomatocyt
e

Sickle cell

Tear drop
poikilocyte

Pencil cell

5.0 Blood film: a basic


interpretation.

5.0. Blood film: a basic


interpretation.
6.0. Glossary
7.0. Quiz

Basket case

Spherocyte

Acanthocyte

Malarial parasit

|glossary
Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Anaemia:
Haemoglobin:
delivery. It is
haem group.

a haemoglobin concentration in peripheral blood below normal


range for sex and age
a metalloprotien inside a red blood cell that is responsible for oxygen
composed of four globulin chains each containing an iron containing

Macrocytic:

Red cells of average volume (MCV) above normal.

Mean cell volume:

the average volume of circulating red cells

Mean Corpuscular Haemoglobin (MCH):

The average haemoglobin content of red blood cells.

Microcytic:

red cells of average volume (MCV) below normal

Normoblast:

nucleated red cell precursor normallyy found in the bone marrow

Poikilocytosis:

variation in shape of peripheral blood red cells

Reticulocyte:
in the

a non-nucleated young red blood cell still containing RNA. Can be found
peripheral blood and bone marrow.

Stem cell:
the

resides in the bone marrow and by division and differentiation gives rise to all
blood cells

Sickle cell disease:


from the
haemoglobin

an inherited disorder of haemoglobin of varying severity. The name arises


deformed shape of the red blood cell takes when the abnormal
inside them polymerizes at low oxygen concentrations.

Thalassaemias:

a spectrum of inherited disorders of haemoglobin where there is an inbalance in


globin chain production.

|references and links


Partners in Global Health Education

Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes

2.1. The erythrocyte


2.2. Erythropoiesis
2.3. Red cell membrane
2.4. Haematinics
2.5. Red cell
metabolism
2.6. Haemoglobin
2.7. Ageing and death
Quiz 1

3.0. Defining anaemia.


3.1. Prevalence
3.1. Clinical features
Quiz 2

4.0. Classifying anaemia


4.1. red cell indices.
4.2. Morphological
classification
4.3. Aetiological
classification
5.0. Blood film: a basic
interpretation.
5.1. Anaemia cards
Quiz 3.
6.0. Glossary
7.0. References

please click on
contents to repeat
a section.

Partners in Global Health Education

iron deficient anaemia; an overview

Colon cancer
microcytic hypochromic
blood film.

Return

Partners in Global Health Education

-Thalassaemia
R.C.I.:

a microcytic hypochromic anaemia

Epi:
One of the most common inherited disorders. Common in
Mediterranean, Africa and Middle East.
Path: Reduced beta globin (of haemoglobin) production. Ineffective
erythropoiesis and haemolysis
Ix.

blood film, Hb electrophoresis

Si/Sy. Heterozygotes: often asymptomatic, mild anaemia, low MCV.


Homozygote: severe anaemia, failure to thrive in first 6 months
of life, splenomegaly, bone hypertrophy (secondary to extramedullary
haemopoiesis).

Tx.
-thalassaemia major requires repeated blood transfusion and
iron
chelation.

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Partners in Global Health Education

Sickle cell disease (HbSS); an overview


R.C.I.:

a microcytic hypochromic anaemia

Aet: Autosomal recessive genetic disorders due to mutation of the


gene for HbA. Affect primarily people of African origin. Sickle cell trait
(HbAS) affords strong protection against malaria.
Path: Abnormal haemoglobin (HbS) undergoes a sickling
transformation when in a deoxygenated state resulting in a permanent
conformational change of shape. The red cell looses its ability to
deform becoming rigid. This can cause occlusion of small vessels and
result in sickle cell crises precipitated by hypoxia, dehydration, infection
and the cold.
IX.

Dactylitis in a child

Electrophoresis, haemoglobin solubility test.

Si/Sy: Bone pain, jaundice, pigment gallstones, leg ulcers, dactylitis in


infants.

Txt
Supportive; analgesia, fluids and antibiotics during crises.

Blood film: sickle cells

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Vitamin B12 deficiency


path: Vitamin B12 binds to IF intrinsic
factor in the stomach and is
absorbed in the terminal ileum
Aet:
Pernicious anaemia,
malabsorpion, post total
gastrectomy

Folate deficiency
Aet:

increased consumption
(pregnancy), dietary
deficiency, folate antagonist
(drugs
eg; methotrexate,
alcohol).
Ix.

Ix.
B12MCV platelets. IF
antibodies. Check folate levels.

serum folate, red cell


folate. MCV

Si./Sy: Gradual deterioration, Irritability,


Loss of memory, Painless jaundice,
Loss of sensation , Feeling of pins
and needles in extremities,
ataxic.

Si/Sy: Jaundice. Weight loss. GI


disturbances. Glossitis.

Txt.
Intramuscular (IM) of 1mg of
hydroxycobalamin (Vitamin B12).
There is no oral form.

Txt.

Folic acid supplementation.


Exclude Vitamin B12
deficiency first.

Glossitis.

Blood film; Microcytic hypochromic

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Partners in Global Health Education

G6PD deficient anaemia; an overview


Path G6PD is a key enzyme in the hexose monophosphate shunt. An
important function of the shunt is maintain healthy haemoglobin by protection
from oxidant stress. In G6PD deficiency, haemolytic anaemia occurs.
Aet:

X-linked

Ix.

Direct assay of G6PD activity

Drugs

Si/Sy: None other than those of acute / chronic anaemia


Rx
Avoid precipitants of oxidative stress; drugs (anti-malarials,
analgesics), fava beans.
Tx.

Blood transfusion if required.

Fava beans

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Partners in Global Health Education

Hereditary spherocytosis; an overview


Epi:

1 in 5000 people in Northern Europe.

Aet:

Autosomal dominant

Path. Defective cell membrane protein (spectrin) causes a loss of cell


membrane, progressive spherocytosis and eventually premature death
(haemolysis). Increased sensitivity to infections such as parvo-virus.
Ix.

Blood film

Blood film; spherocytes


Increased osmotic fragility.
negative antiglobulin test.

Si/Sy: asymptomatic.
Jaundice, splenomegaly
General features of anaemia
Txt

Give ferrous sulphate , ferritin if deficiency

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Autoimmune haemolytic anaemia; an overview


These anaemias can be split into warm and cold types. This is dependent on the temperature at
which the antibody reacts with the body.
WARM
Aet:
associated with the production of
autoantibodies of IgG. They attach to the red cell at
body
temp and are removed early by the
reticuloendothelial
system.
Path:

Idiopathic or precipitated by drugs or autoimmune


disease, leukaemia.

IX.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Jaundice, general features, splenomegaly
Txt
Steroids, splenectomy as 2 line. Vaccination
against H. Influenza, Men C and Pneumococcus.
nd

COLD
Associated with the production of autoantibodies
of IgM and are removed early by the
reticuloendothelial
system. Usually self-limiting.
Aet:

Path:

Idiopathic or secondary to infection or

lymphoma.

IX.
Bloods: unconjugated haemoglobin, LDH,
Reticulocytes.
Positive direct antiglobulin test.
Si/Sy: Worse in cold weather, acrocyanosis (purpling
skin), Reynaud's phenomenon.
Txt
Remove precipitants, keep patient warm,
consider immunosuppression.

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