Module prepared by Ben WoodmanSmith Medical Student Cardiff University Steve Allen Professor of Paediatrics and International Health College of Medicine Swansea University Ann Benton Consultant Haematologist ABMU Health Board Swansea ID: 208568
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Slide1
Module 1 | Anaemia an introduction
Module prepared by:
Ben Woodman-Smith; Medical Student, Cardiff University
Steve Allen; Professor of Paediatrics and International Health, College of Medicine, Swansea University
Ann Benton; Consultant Haematologist, ABMU Health Board, Swansea Slide2
Contents
1.0. Introduction anaemia
1.1. How to use this module
1.2. Learning outcomes
The red cell life cycle2.0. The erythrocyte: an overview2.1. Erythropoiesis2.2. The red cell membrane2.3. Haematinics2.4. Red cell metabolism2.5. Haemoglobin and oxygen transport2.6. Ageing and death of the red blood cell.Quiz 1 Anaemia; an overview3.0. Defining anaemia.3.1. Prevalence of anaemia3.2. Clinical features of anaemiaQuiz 2Classifying Anaemia4.0. Classification of anaemia4.1. Red cell indices4.2. Morphological classification4.3. Aetiological classification of anaemia. Interpretation of Blood film5.0. Basic interpretation of a blood film.5.1. Anaemia: essential bites Quiz 3GlossaryReferences
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 metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.5.1. Anaemia cardsQuiz 3.6.0. Glossary7.0. References
please click on contents to repeat a section.
Please click here to move
forwards
or
backwards
through the moduleSlide3
| Introduction
Welcome to the anaemia module!
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/dlAnaemia 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 it’s clinical features, interpret blood results and respond with appropriate management. 1.1Contents1. 1Introduction 1.2 use this module1.3 Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1
3.0. Defining anaemia.
3.1. Prevalence3.1. Clinical features
Quiz 2 4.0.
Classifying anaemia 4.1. red cell indices.
4.2. Morphological classification4.3. 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.
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.
Prevalence3.1. Clinical features
Quiz 2 4.0.
Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3
. Aetiological classification 5.0. Blood film: a basic
interpretation.5.1. Anaemia cardsQuiz 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.Slide4
| how to use this module
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.1.2Contents1. 1Introduction 1.2 use this module1.3 Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia
4.1. red cell indices.4.2. Morphological classification4.3. 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.
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 classification4.3. Aetiological
classification 5.0. Blood film: a basic interpretation
.5.1. Anaemia cardsQuiz 3.
6.0. Glossary
7.0. References
please click on contents to repeat a section.Slide5
| how to use this module
| how to use this module
1.2
Information within red boxes is considered core knowledge
Information within the green boxes is considered useful knowledge
KEYInformation within the grey boxes is considered optional to gain a broader understanding of anaemia and its causes.
Key point!
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.
Contents
1. 1Introduction
1.2 use this module1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis
2.3. Red
cell membrane
2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.
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
essential bites.
These cards are designed to provide some essential information on key anaemias. These are accessible throughout the module.Slide6
| learning outcomes (L.O.)
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 macrophagesRenal system (erythropoietin)Functional DNA (globin genes)Nutrition (Iron, B12, Folate, amino acids)Link the components of red cell structure to red cell development and functioncomponents of haemoglobin moleculemetabolic pathways active in red blood cellsfeatures of red cell membraneLink 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
1.3
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 metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.
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.
L.O. We
will place these objectives along the route to help direct your learning….Slide7
| the erythrocyte: an overview
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. Contents page2.1. The erythrocyte: an overview. 2.1Welcome to section one. An erythrocyte is a fully developed red blood cell!Slide8
| the erythrocyte: an overview
Contents page
2.1
*L.O. Link the components of red cell structure to red cell development and functionImage: scanning electron microscope of red blood cellTo achieve these functions the red cell has several unique properties….
Strength: it has a strong but flexible membrane able to withstand the recurrent
shear forces involved in the circulation of blood.
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.
Biconcave shape
:
increases surface area
available for
gaseous exchange.
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. 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 short (120 days).START HEREFINISH HERESlide9
Kidney
Bone marrow
Red blood cells in circulation
erythropoietin
Stem cells
Erythroid precursors
An
erythrocyte is a fully developed, mature red blood
cell.
The adult human
makes
approximately 10
12
new erythrocytes every day by the process of erythropoiesis. This is a complex
process that occurs within the bone marrow.
B
efore
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. As with much human physiology, this system works via a feedback mechanism.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.| Erythropoiesis Contents page2.1. The erythrocyte: an overview.2.2. Erythropoiesis
2.2
2
.
EPO stimulates stem
cells
within the bone
marrow which differentiate into
erythroid
precursors.
3. EPO continues
to
stimulate primitive erythroid cells (red blood cells) in the bone marrow and induce maturation.
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.
START HERE
FINISH HERE
List the key components of
erythropoiesis
(red cell production)
LOSlide10
| 2.2. Erythropoiesis
Contents page
2.1
. The erythrocyte: an overview.2.2. Erythropoiesis
2.2Key point! 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.Key point! Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO. It’s 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.
Hypoxia is the major stimulant for increased EPO production
Kidney
Bone marrow
erythropoietin
Erythroid precursors
Stem cells
Kidney
Bone marrow
erythropoietin
Erythroid precursors
Stem cellsSlide11
|Red cell precursors and the sequence of
e
rythropoiesis
Contents page
2.1. The erythrocyte: an overview.2.2. Erythropoiesis 2.2Anaemia 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.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.Key point! Key point!
marrow
3.5
Erythrocyte
: after 1 week the mature erythrocyte emerges with no organelles and high haemoglobin content.
Sequence: amplification and maturation of the erythrocyte
Pronormoblast
:
This is the earliest
and largest
cell with a
large nucleus
and
no haemoglobin.
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
.
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.
bloodSlide12
|haematinics
V
itamin
B
12 (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 B12. 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.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 marrowAssessing haematinic status is key to the investigation of the cause of anaemiahaemoglobin deficiency;
Click here see all key causes.
iron life cycle;Click here to see the key stages
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.
Click here to see a schematic diagram of vitamin B
12 absorption
2.4
Contents page
2.1
. The erythrocyte: an overview.2.2. Erythropoiesis2.3. The red cell membrane2.4 Haematinics
Erthropoiesis
is also regulated by the availability of
haematinics
“
Check the
haematinics” this is a phrase used frequently
on the hospital ward!Slide13
|haematinics in haemoglobin
Iron
Protoporphyrin
Globin
Haem
HaemoglobinThalassaemiaIron deficiencyChronic inflammationMalignancyClick here to returnChronic 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.
2.4Slide14
|haematinics: the normal iron cycle
Click here to return
2.4
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 …..
Erythroid bone marrow (normoblasts)
Reticuloendothelial system;
Spleen & macrophages
Duodenum
Serum transferrin
Fe
Red blood cells
Liver
Iron
is a key constituent of haemoglobin
(60-70% of total body iron is stored here) and it’s 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).
2.
Iron
is then attached to a
protein,
transferrin
in
the
serum (plasma),
where it is transported to the bone marrow for haemoglobin synthesis.
1.
Iron is absorbed from the
small
intestine
in the ferrous state (Fe
2+
; approx. 1mg/day).
3.
Dying
red
cells are
recycled by macrophages in the spleen and iron is recycled into the plasma for
further use.
Soluble transferrin receptors,
sTfR
are on the red cell surface. These can be measured and are increased in iron deficiency.
A
n iron deficiency profile.
Serum Iron:
Reduced
Serum total iron-binding capacity (TIBC):
Increased- the body works hard to bind free iron.
Serum ferritin:
Reduced-since iron stores are low
Serum soluble transferrin receptors:
Increased-since red cells attempt to absorb more iron.
In iron deficient states, bone marrow iron is reduced.
START
Some iron binds to
apoferritin
to form ferritin, a storage compound.Slide15
There are a number of key steps in the absorption of Vitamin
B12. The two key locations
are the stomach and the terminal ilium. Dietary vitamin B12 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. Vitamin B12 deficiency can take up to two years to develop as the body has sufficient stores for this period.
Distal ileum
Site of B
12
absorption
Oesophagus
Stomach
IF
Intrinsic factor
Vitamin B
12
ingested
|haematinics: vitamin B
12
Pernicious anaemia
: the leading cause of B
12
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
B
12-IF complex for absorption in the distal
ileum. 2.4
Click here to return
Causes of vitamin B12 deficiency
Pernicious anaemia
Inadequate intake
Poor absorptionSlide16
| the red cell structure
The red 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.
2.3There are 4 red cells proteins of importance: Contents page2.1. The erythrocyte: an overview.2.2. Erythropoiesis2.3. The red cell membrane 2.1Inherited 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.
ankyrin
Protein 4.1
actin
spectrin
Key point!
Click next
slide
to see flow
diagram
Link the components of
red cell structure to red cell development and function
LOSlide17
reduced spectrin synthesis
dysfunctional spectrin
a
bnormal spectrin gene
Spectrin malfunction within erythrocyte membrane
Erythrocytes are exposed to high sheer forces within the microcirculationCytoskeleton function impaired; cell loses ability to deformSpherocyte: a small, more rigid, spherical erythrocyte resultsCells are either destroyed within the microcirculation or detected and removed by the reticuloendothelial system of the spleenHaemolysis; premature red cell death occurs causing anaemiaflow diagram: the process of spherocytosis in hereditary spherocytosisSlide18
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 pathwayWith no cell organelles and no mitochondria the fully developed erythrocyte relies on this aerobic pathway to gain energy (ATP) for the cell.2.5 Contents page2.1. The erythrocyte: an overview.2.2. Erythropoiesis2.3. The red cell structure 2.3.1. Cell membrane 2.3.2. DNA synthesis2.4. Red cell metabolism
Glucose
Glucose- 6-P
Fructose-6-P
Lactate
Pyruvate kinase
Glucose-6-phosphate dehydrogenase
NAPD
NADPH+H
+
2GSH
H
2
O
O-GSSGHexose monophosphate shuntEmbden-Meyerhof glycolytic pathwayRibulose 5-P6-PG
Key point: Oxidant stress!
CLICK HERE
ADP
ADP
ATP
ATP
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).
Pyruvate kinase deficiency:
In
rare circumstances there are defects within the critical glycolytic enzymes. 95% of these defects are associated with
p
yruvate
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 metabolism
Key point!
Slide19
Glucose
Glucose- 6-P
Fructose-6-P
Lactate
Pyruvate kinase
Glucose-6-phosphate dehydrogenaseNAPDNADPH+H+ 2GSHH2OO-GSSGHexose monophosphate shuntEmbden-Meyerhof glycolytic pathway
Ribulose 5-P
6-PG
Oxidant stress!
ADP
ADP
ATP
ATP
Red cell functioning adequately under normal conditions
Drugs:
e.g.
antimalarials
Fava beans
Infection
Red cell cannot produce enough NADPH via the HMP shunt
Inadequate amounts of GSH to combat oxidant stress
Oxidant damage to cell membrane
Reduced red cell survival
Haemolytic
anaemia
!
RETURNSlide20
| haemoglobin and O
2
transport
A
key function of a red cell is to carry and deliver oxygen to the tissues and return CO2
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. It’s waste products are also released when a red cell is destroyed prematurely and are therefore a valuable indicator of haemolysis. Contents page2.1. The erythrocyte: an overview.2.2. Erythropoiesis2.3. The red cell structure 2.3.1. Cell membrane 2.3.2. DNA synthesis2.4. Red cell metabolism2.5. Haemoglobin and O2 transport 2.6
2,3-DPG
o
xyhaemoglobin
deoxyhaemoglobin
A molecule called
2,3 – Diphosphoglycerate (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
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.
GLOBIN CHAIN
A normal adult haemoglobin (Hb A) molecule consists
of
4
polypeptide
(
globin
)
chains:
12
12.
Haemoglobinopathies
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 it’s 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.
Key point!
Oxygen (O
2
)Slide21
|
haemoglobin
in foetal haemoglobin
2,3-DPG
o
xyhaemoglobin
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 HbA
2
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.
RETURN
2.6Slide22
|haemoglobin and the oxygen dissociation curve
Contents page
2.1
. The erythrocyte: an overview.
2.2. Erythropoiesis2.3. The red cell structure 2.3.1. Cell membrane 2.3.2. DNA synthesis2.4. Red cell metabolism2.5. Haemoglobin and O2 transport
PO
2
(mm Hg)
Hb saturation (100%)
50
50
CO
2
pH
2,3-DPG
CO
2pH2,3-DPG
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 molecule’s affinity for O
2.
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.
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 CO
2 levels and with HbF.
A shift to the
right
indicates
a decreased affinity for O
2. 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.
2.6Slide23
|ageing and death
Haemolytic anaemias;
This is an important group of anaemias.
T
here are many important causes of premature red cell death resulting in anaemia and the increased products of haemolysis within the blood circulation and beyond.
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.Haemolysis: any process that shortens the red blood cell lifespan to less than 120 days.A red cell shows signs of deterioration and reduced glycolytic rate from around 100 days of the cell’s 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. 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. 2.7
Contents
1. 1Introduction
1.2 use this module
1.3 Learning outcomes
2.1. The erythrocyte
2.2. Erythropoiesis2.3. Red cell
membrane2.4. Haematinics
2.5. Red cell metabolism2.6. Haemoglobin2.7. 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 classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.Slide24
Haemoglobin
Haem
Unconjugated bilirubin
C
onjugated in the liver
to
the
diglucuronide
, water-soluble form that is secreted in the bile and then converted
to stercobilinogen
.
Liver
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
.
3
. Bilirubin
Heamolysis
results in excess
bilirubin
causing jaundice (typically lemon yellow
colour
) and pigment gallstones.
Globin
Iron
Attaches to transferrin
F
Is metabolized to amino acids
Red blood cell
Investigating haemolysis
Lactic
acid
dehydrogenase (LDH)
Reticulocyte count
Bilirubin
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.
3. LDH
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).
Flow diagram: products of red cell destruction.
The protoporphyrin of haem is metabolised to the yellow
pigment
bilirubin, which is bound to albumin in the plasma.
S
tercobilinogen is
excreted in the faeces
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
.Slide25
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
.
true / false
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!
c
lick to check answersSlide26
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 statesFalse! 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 leftFalse! It would shift to the right. All these factors would cause haemoglobin (Hb) to have a reduced affinity for O2 and increase O2 release
fom Hb.
Vitamin B
12
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 B
12
are key building blocks of haemoglobin
False!
Vitamin
B
12
and folate are key building blocks of DNA.
Chronic anaemia and malignancy prevent haem productionTrue! Chronic anaemia and malignancy block iron from being incorporated into the haem molecule.A deficiency in folate causes a macrocytic megaloblastic anaemiaTrue! 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 α2
β2).
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.
true / falseSlide27
What exactly is anaemia
?Anaemia is defined as haemoglobin concentration less than the normal reference range. Reference
ranges differ according to age, sex and altitude. However, in general, anaemia is defined as Hb concentrationFor adult males < 13.5 g/dl
For
adult women < 11.5 g/dlAs well as reduced [Hb], anaemia is usually accompanied by a reduction in the number of red cells (red cell count) and packed cell volume (PCV). However this is not always the case.
Red cell count and PCV may be normal in some patients with lower than normal haemoglobin levels (and hence anaemic). The total circulating haemoglobin concentration is therefore determined by….the circulating plasma volume the total circulating haemoglobin mass. The following circumstances should therefore be taken in to consideration…… Welcome to section 2! | defining anaemia| Dehydration |Reduced plasma volume may mask anaemia.| Pregnancy or splenomegaly |These can produce an increase in plasma volume reducing the apparent haemoglobin concentration even though circulating haemoglobin levels are normal. | Acute significant blood loss |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.
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes
2.1. The
erythrocyte
2.2. Erythropoiesis2.3. Red cell membrane
2.4. Haematinics
2.5.
Red cell metabolism2.6. Haemoglobin
2.7. Ageing and death
Quiz 1
3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.
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.Slide28
| prevalence
Anaemia is thought to affect
1.62 billion people on a daily
basis (WHO
); this is 24% of the world’s 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 nationsA complex interaction of socio-economic conditions, nutritional deficiencies and co-existing 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. 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.
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 metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.Slide29Slide30Slide31Slide32
|clinical features of anaemia
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. Contents1. 1Introduction 1.2 use this module1.3 Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics
2.5. Red cell metabolism2.6. Haemoglobin2.7. 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 classification4.3
. 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
blood’s
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;
2.
The skin
A common sign is generalised
pallor due
primarily to vasoconstriction with redistribution of blood to key areas (brain, myocardium).Slide33
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 O2 dissociation curve of haemoglobin and the cardiovascular system to adapt
.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.Age: The elderly are less tolerable of anaemia mainly as a result of an inability to increase cardiac output. Co-existent disease - often cardiac or pulmonary disease.|clinical features of anaemiaIn 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;Slide34
| clinical features of anaemia
General
symptoms and
signs
Contents
1. 1Introduction 1.2 use this module1.3 Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell
membrane2.4. Haematinics2.5.
Red cell metabolism2.6. Haemoglobin2.7. 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
Weakness and lethargy
Shortness of breath: particularly on exercise.
Headaches
Palpitations
Confusion and symptoms of cardiac failure in elderly
Some specific
s
igns
Click images
for explanation of signs!
General SignsSlide35
| clinical features of anaemia
This is a list of general symptoms and signs; we will cover more specific clinical features as we progress through the module.
Signs:
P
allor
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 aloneRETURNSlide36
| clinical features of anaemia
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
(spoon-shaped nails). This is specific to iron deficiency.RETURNSlide37
| clinical features of anaemia
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.RETURNSlide38
| clinical features of anaemia
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 B
12
and folate deficiency.RETURNSlide39
| clinical features of anaemia
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.
RETURNSlide40
| clinical features of anaemia
This is a list of general symptoms and signs; we will cover more specific clinical features as we progress through the module.
Signs
RETURN
Peripheral oedema. A general sign.Slide41
| clinical features of anaemia
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!RETURNSlide42
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.
true / false
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!
c
lick to check answers
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. Haematinics2.5. Red cell metabolism
2.6. Haemoglobin2.7. 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 classification4.3. Aetiological classification
5.0. Blood film: a basic interpretation.
Quiz 3.6.0
. Glossary7.0. References
please click on contents to repeat a section.
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.Slide43
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
glosso-pharyngeal webbing.
True!
Click here to continue moduleSlide44
Welcome to section 3!
|classification of anaemia
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 classificationThis is a practical and clinically useful classification for establishing a differential diagnosis of anaemia.
It is done by examining red cells in a blood stained smear and by automated measurements of red cell indices
Aetiological classification
This classification is based on cause and illuminates the pathological process underlying anaemia
.
*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.
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.Quiz 3.
6.0. Glossary7.0. References
please
click on contents to repeat a section.Slide45
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)
a small red blood cell. Normocytic (MCV of 80-99fL) a normal size red blood cell. Macrocytic (MCV > 99fL) 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 B12 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). |red cell indicesRDW: Red cell distribution width; an index of the variation in sizes of the red cell population within an indiviual. T
his 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
These are the key measures of red cell indices. They relate to the haemoglobin content and size of the red blood cells. Slide46
|interpretation of red cell indices
Microcytosis
&
hypochromia
Normocytosis & normochromiaMicrocyticabnormally 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.Hypochromichypochromic cells due to a failure of haemoglobin synthesis.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.
Normocytic
Many processes causing anaemia do not effect the cell size or haemoglobin concentration within cells.
N
ormocytic
normochromic
anaemia develops when there is a decrease in the production of normal red blood cells.
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 productionMacrocytosis & megaloblastosisMacrocytic 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.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!
Alcohol | Liver disease | hypothyroidism | Hypoxia | cytotoxic drugs | pregnancy
|
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. Slide47
| morphological classification of anaemia
Anaemia type
Red cell indices
Common examples
M
icrocytichypochromic
MCV < 80 fl
MCH < 27 pg/L
Iron deficiencyThalassaemia
Sideroblastic
Normocyticnormochromic
Macrocytic
MCV > 98
fl
Folate deficiency B12deficiency
normal
Haemolysis
Chronic disease
Marrow infiltration
Megaloblastic
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. Haematinics2.5.
Red cell metabolism2.6. Haemoglobin2.7. Ageing and death
Quiz 1 3.0. Defining anaemia.
3.1. Prevalence3.1. Clinical features
Quiz 2 4.0. Classifying anaemia
4.1. red cell indices.4.2. Morphological classification4.3. 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.Slide48
|aetiological classification of anaemia
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 ProductionInsufficient 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.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 lifespanThis 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.Pooling: Hypersplenism.
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 metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. 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.Slide49
Reduced bone marrow erythroid cells
aplastic anaemia
Leukaemia or malignancy
|classification of anaemia based on pathology
Loss of red cells due to bleeding
Increased destruction of red cells (haemolytic anaemiaFailure of production of red cells by the bone marrowDilution of red cells by increased plasma volume (e.g. hypersplenism)Nutritional (haematinic) deficiencyIronvitamin B12folateIneffective red cell formation Chronic inflam.Thalassaemiarenal diseaseimmuneNon-immuneAutoimmune warmAutoimmune coldAdverse drug reactionHaemolytic disease of the newborn
Malaria
Burns
Mechanical heart valve
HypersplenismPNH
Abnormal red cell membrane
Abnormal haemoglobin
Abnormal red cell metabolism
Sperocytes
Elliptocytes
Thalassaemia
Sickle cell anaemia
Pyruvate kinase deficiency
G6PD deficiency
Inherited /
inside the cellAcquired /outside cell
anaemia
|classification of anaemia based on pathology
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.Slide50
|blood film: a basic interpretation
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.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
Please click on
each cell
to see the blood film and
it’s causes.
Please click
here to compare blood films
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.Slide51
Normal red blood film
Microcytic hypochromic
Macrocytic megaloblastic
Target cells
Bite cells
ElliptocyteFragmentsFragments‘Pencil’ cells
Malaria
StomatocyteSickle cell
Spherocyte
AcanthocyteSlide52
|anaemia essential bites
R.C.I: a microcytic hypochromic anaemia
Epi
: this is the
most
common cause of anaemia worldwide affecting around 500million daily.Aet: 1. The most common cause of iron deficient anaemia is BLOOD loss 2. reduced intake (diet) 3. Increased demand (pregnancy) 4. Malabsorption (coeliac, gastrectomy) FBC, ferritin, serum iron, TIBC, serum transferrin saturation. Endoscopy/colonoscopy if suspected blood loss.Si/Sy. Koilonychia, sore tongue, angular stomatitis, Plummer-Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Tx. Treat underlying cause, give ferrous sulphate until Hb and MCV normal (4-6months).iron deficieny
R.C.I.:
a
microcytic hypochromic anaemiaEpi: One
of the most common autosomal inherited disorders. Common in Mediterranean, Africa and middle east. Gene carriers are protected from
p.falciprum malaria.Path: Reduced beta globin (of haemoglobin) production. Ineffective erythropoiesis
and haemolysisIX. blood film, Hb electropheresis
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 haemopoisis).
Tx. For major Thalassaemia treat with repeated blood transfusion and iron chelation.
Β
-
Thalassaemia
R.C.I.:
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.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: Bone pain, if chronic haemolysis- jaundice and pigment gallstones. Txt Supportive; analgesia, fluids and antibiotics if required. Sickle cell disease
Epi
: the
most common cause of a naemia worldwide affecting around
500million daily.Aet: pernicious anaemia, malabsorpion,
post total gastrectomyIx. B
12MCV
platelets. IF antibodies, folate levels 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 no oral form.
Vitamin B12 & Folate deficiency
Epi
:
Aet: increased consumption (pregnancy),
dietary deficiency, folate antagonist (drugs eg; methotrexate).Ix. folate
MCV transferrin saturation. Endoscopy/ colonoscopy if suspected blood loss.
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 no oral form.
Path
G6PD is a key enzyme in the hexose monophosphate shunt. An important funtion of the shunt is maintain a health haemoglobin by removing oxidant stresses. Wihtout the enzyme, Hb
breakdown resulting in haemolytic aneamia.
Aet: X-linked
Ix. Direct assay during haemolysisSi/Sy:
Koilonychia, sore tongue, angular stomatitis, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless
gastritis. Rx Avoid precipitants of oxidative stress; drugs (anti-malarials, analgesics), fava beans.
Tx. Blood transfusion if required.
G6PD deficieny
Epi
: the
most
common cause of anaemia worldwide affecting 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, Plummer
- Vinson
syndrome (dysphagia due to oesophageal web),
painless
gastritis.
Txt
Treat
underlying cause, give ferrous sulphate until Hb and MCV
normal
.
Hereditary spherocytosis;
Microcytic anaemia
Macrocytic anaemia
Haemolytic anaemias
Epi
: the
most
common cause of anaemia worldwide affecting 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, Plummer- Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Txt
Treat underlying cause, give ferrous sulphate until Hb and MCV normal.
Aquired Haemolytic anaemias;
KEY
R.C.I.
Red Cell Indices
Epi. Epidemiology
Aet. AetiologyIx. Investigations
Si/Sy.
Signs and Symptoms
Path.
Pathology
Tx.
Treatment
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.Slide53
Well done!
You have come to the end of the
third and final
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!click to check answersMicrocytosis is MCV < 90fLThe 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
true / false
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes
2.1. The erythrocyte2.2. Erythropoiesis2.3. Red
cell membrane2.4. Haematinics
2.5. Red cell metabolism2.6. Haemoglobin
2.7. Ageing and death Quiz 1
3.0. Defining anaemia.3.1.
Prevalence3.1. 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
. Glossary7.0. References
please
click on contents to repeat a section.Slide54
Microcytosis
is M
CV < 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 >99fLTrueBoth 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 moduleSlide55
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
Blood film
RBC
morphology:
normocytic
,normochromic.
return
Definitions
Normocytic:
A cell with an MCV within the normal range
Normochromic:
concentration of anaemia is within the normal range
The biconcave red cell when stained shows a classical central area of pallor on a blood film.Slide56
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
Blood film
RBC
morphology:
Microcytic hypochromic.
Explanation
Red cells are smaller and lighter than normal and displaying a typical ‘area of central pallor’.
Cause
Iron deficient anaemia
Thalassaemia
returnSlide57
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte
2.2. Erythropoiesis2.3. Red
cell structure2.3.1. Cell membrane2.3.2 DNA synthesis
2.4. Red cell metabolism2.5.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
5.0 Blood film: a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. QuizA 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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
macrocytic ,megaloblastic (More oval)
Cause
Macrocytic:
Macrocytic megaloblastic:
Liver disease
Vitamin B
12
Alcoholism Folate
Slide58
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte
2.2. Erythropoiesis2.3. Red cell structure
2.3.1. Cell membrane2.3.2 DNA synthesis
2.4. Red cell metabolism2.5.Haemoglobin2.6 O
2 dissociation curve
3.0. Defining anaemia.3.1. Prevalence
3.2 Clinical features 4.0.
Classifying anaemia 4.1. red cell indices4.2.
Morphological 4.3 Aetiological classification
5.0 Blood film: a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. QuizA 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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
target cell
Extra: it is also possible to see one neutrophil and two platelets.
Cause
Target cells are found in peripheral blood films in a number of conditions.
Liver disease (obstructive jaundice).
Thalassaemia major.
Sickle cell anaemia.Slide59
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket/blister cell.
Explanation:
Oxidant damage
Cause:
G6PD deficiencySlide60
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Elliptocyte
. Blood film shows characteristic elliptical (elongated) red cells.
Causes
Hereditary elliptocytosis: due to a defective cell membrane protein (Spectrin, band 4.1).Slide61
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Elliptocyte.
Causes
Hereditary elliptocytosis
Blood film
RBC
morphology:
Fragments
Cause
Disseminated Intravascular Coagulation (DIC)
Microangiopathy
TTP
Burns
Cardiac valvesSlide62
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Tear drop poikilocyte
Definition: Poikilocyte; an individual cell of abnormal shape
Cause
Myelofibrosis
Extramedullary haemopoiesisSlide63
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
“
Pencil” cell.
These are thin elongated cells. Often occur alongside microcytic hypochromic cells, poikilocyte and occasional target cells.
Explanation
Iron deficiencySlide64
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte
2.2. Erythropoiesis2.3. Red cell structure
2.3.1. Cell membrane2.3.2 DNA synthesis
2.4. Red cell metabolism2.5.Haemoglobin2.6 O
2 dissociation curve
3.0. Defining anaemia.3.1. Prevalence
3.2 Clinical features 4.0.
Classifying anaemia 4.1. red cell indices4.2.
Morphological 4.3 Aetiological classification
5.0 Blood film: a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. QuizA 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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Ring-forms in P.falciprum Intracellular malarial parasite
Explanation
A certain amount of haemolysis occurs with all types of malarial infection. It can lead to DIC and intravascular haemolysis.
Malaria:
Transmitted by the mosquito
t
his disease causes up to 3 million deaths a year and is a
major cause of anaemia within the tropics
!
See malaria module for more information.Slide65
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Stomatocyte
Explanation
Liver disease
AlcoholismSlide66
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Sickle cell
Explanation
In
sickle cell anaemia
the red blood cell undergoes a “sickling” process due the cell containing haemoglobin S.
In a deoxygenated state this haemoglobin undertakes a permanent conformational change creating large polymers. As a result these cells become rigid and unable to deform. The red cell eventually looses its cell membrane and becomes damaged as it travels through the circulation changing into the sickled shape we see. This eventually leads to an early cell death (hemolysis). Slide67
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte
2.2. Erythropoiesis2.3. Red cell structure
2.3.1. Cell membrane2.3.2 DNA synthesis
2.4. Red cell metabolism2.5.Haemoglobin2.6 O
2 dissociation curve
3.0. Defining anaemia.3.1. Prevalence
3.2 Clinical features 4.0.
Classifying anaemia 4.1. red cell indices4.2.
Morphological 4.3 Aetiological classification
5.0 Blood film: a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. QuizA 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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
Micro-
Spherocyte.
This slide shows spherocytes caused by
hereditary spherocytosis
. They sit amongst larger polychromatic red cells.
Cause |
Explanation
A
bnormality
of cytoskeleton proteins. These cells are excessively permeable to sodium influx. Cell looses membrane on passage through reticuloendothelial
system.
Red cell osmotic fragility is characteristically increased.Slide68
|blood film: a basic interpretation
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis
2.3. Red cell structure2.3.1.
Cell membrane2.3.2 DNA synthesis2.4. Red cell metabolism2.5
.Haemoglobin2.6 O2
dissociation curve 3.0. Defining anaemia
.3.1. Prevalence3.2 Clinical features
4.0. Classifying anaemia
4.1. red cell indices4.2. Morphological
4.3 Aetiological classification 5.0 Blood film:
a basic interpretation.
5.0
. Blood film: a basic interpretation.
6.0.
Glossary
7.0. Quiz
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.Please click on each cell to see the blood film, causes and explanation.
Normal red cell
Microcytic hypochromic
Macrocyte
Target cell
Basket case
Elliptocyte
Fragments
Tear drop poikilocyte
Pencil cell
Stomatocyte
Sickle cell
Spherocyte
Acanthocyte
Malarial parasite
return
Blood film
RBC
morphology:
basket cell.
Explanation
Oxidant damage
G6PD deficiency
Blood film
RBC
morphology:
“Prickle” cell or small echinocytes. Especially prominent in postsplenectomy patients.
Definition: Echinocyte:
cell with abnormal blunt or sharp projections on surface. Can be up to 30 projections per cell.
Explanation
Pyruvate kinase deficiencySlide69
|glossary
Anaemia
:
a
haemoglobin
concentration in peripheral blood below normal r ange for sex and ageHaemoglobin: a metalloprotien inside a red blood cell that is responsible for oxygen delivery. It is composed of four globulin chains each containing an iron containing haem group.Macrocytic: Red cells of average volume (MCV) above normal.
Mean cell volume: the average volume of circulating red cellsMean Corpuscular
Haemoglobin (MCH): The average haemoglobin
content of red blood cells.Microcytic:
red cells of average volume (MCV) below normalNormoblast:
nucleated red cell precursor normallyy found in the bone marrow
Poikilocytosis: variation in shape of peripheral blood red cells
Reticulocyte: a non-nucleated young red blood cell still containing RNA. Can be found in the peripheral blood and bone marrow.
Stem cell: resides in the bone marrow and by division and differentiation gives rise to all the blood cells
Sickle cell disease: an inherited disorder of haemoglobin of varying severity. The name arises from the deformed shape of the red blood cell takes when the abnormal haemoglobin
inside them polymerizes at low oxygen concentrations.
Thalassaemias
: a spectrum of inherited disorders of
haemoglobin
where there is an
inbalance in globin chain production.Contents1. 1Introduction 1.2 use this module1.3 Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.
5.1. Anaemia cardsQuiz 3.
6.0. Glossary
7.0. References
please click on contents to repeat a section.Slide70
|references and links
Contents
1. 1Introduction
1.2 use this module
1.3
Learning outcomes 2.1. The erythrocyte2.2. Erythropoiesis2.3. Red cell membrane2.4. Haematinics2.5. Red cell metabolism2.6. Haemoglobin2.7. Ageing and death Quiz 1 3.0. Defining anaemia.3.1. Prevalence3.1. Clinical features Quiz 2 4.0. Classifying anaemia 4.1. red cell indices.4.2. Morphological classification4.3. Aetiological classification 5.0. Blood film: a basic interpretation.5.1. Anaemia cardsQuiz 3.6.0. Glossary7.0. Referencesplease click on contents to repeat a section.Slide71
R.C.I: a microcytic hypochromic anaemia
Epi
: this is the
most
common cause of anaemia worldwide affecting around
500million people.Aet: 1. The most common cause of iron deficient anaemia is blood oss 2. reduced intake (diet) 3. Increased demand (pregnancy) 4. Malabsorption (coeliac, gastrectomy)Ix. FBC, ferritin, serum iron, TIBC, serum transferrin saturation. Endoscopy/colonoscopy if suspected blood loss.Si/Sy. Koilonychia, sore tongue, angular stomatitis, Plummer-Vinson syndrome (dysphagia due to oesophageal web), painless gastritis. Tx. Treat underlying cause, give ferrous sulphate until Hb and MCV normal (4-6months).iron deficient anaemia; an overviewColon cancermicrocytic hypochromic blood film.
ReturnSlide72
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 haemolysisIx. 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. β-thalassaemia major requires repeated blood transfusion and iron chelation.Β-ThalassaemiaReturnSlide73
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. Electrophoresis, haemoglobin solubility test.Si/Sy: Bone pain, jaundice, pigment gallstones, leg ulcers, dactylitis in infants. Txt Supportive; analgesia, fluids and antibiotics during crises. Sickle cell disease (HbSS); an overviewDactylitis in a childBlood film: sickle cellsReturnSlide74
path
: Vitamin B
12
binds to IF intrinsic factor in the stomach and is absorbed in the terminal ileum
Aet:
Pernicious anaemia, malabsorpion, post total gastrectomyIx. B12MCV platelets. IF antibodies. Check folate levels. 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 no oral form.Vitamin B12 deficiency Aet: increased consumption (pregnancy), dietary deficiency, folate antagonist (drugs eg; methotrexate, alcohol).Ix. serum folate, red cell folate.
MCV Si/Sy: Jaundice.
Weight loss. GI disturbances. Glossitis.
Txt. Folic acid supplementation. Exclude Vitamin B12
deficiency first.
Folate deficiency
Glossitis
.
Blood film; Microcytic hypochromic
ReturnSlide75
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 activitySi/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.G6PD deficient anaemia; an overviewDrugsFava beansReturnSlide76
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; spherocytes Increased osmotic fragility. negative antiglobulin test.Si/Sy: asymptomatic. Jaundice, splenomegaly General features of anaemiaTxt Give ferrous sulphate , ferritin if deficiencyHereditary spherocytosis; an overviewReturnBlood filmSlide77
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 2nd line. Vaccination against H. Influenza, Men C and Pneumococcus.Autoimmune haemolytic anaemia; an overviewThese anaemias can be split into ‘warm’ and cold’ types. This is dependent on the temperature at which the antibody reacts with the body.COLDAet: Associated with the production of autoantibodies of IgM and are removed early by the reticuloendothelial system. Usually self-limiting.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 of skin), Reynaud's phenomenon
. Txt
Remove precipitants, keep patient warm, consider immunosuppression.
Return