red cell abnormalities Flashcards
what is anaemia
The haemoglobin concentration (Hb) is reduced
The RBC and the Hct/PCV are usually also reduced
Anaemia is usually due to a reduction of the absolute amount of haemoglobin in the blood stream Occasionally a low Hb results from an increase in plasma volume
In a healthy person, anaemia resulting from an increase in plasma volume
cannot persist because the excess fluid in the circulation is excreted
For practical purposes, anaemia can therefore be regarded as a resulting from a decrease in the absolute amount of haemoglobin in the circulation
anaemia mechanism
Reduced production of red cells/haemoglobin in the bone marrow
Loss of blood from the body
Reduced survival of red cells in the circulation
Pooling of red cells in a very large spleen
We need to distinguish the mechanism of anaemia from the cause:
The mechanism of the anaemia might be reduced synthesis of haemoglobin in the bone marrow
The cause of this could be either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin
cause of anaemia
either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin
Can you name one cause of reduced synthesis of haem?
iron deficiency
What do you call a condition in which there is an inherited defect leading to reduced synthesis of globin ?
thalassemia
cell size and anaemia
Microcytic – usually also hypochromic
Normocytic – usually also normochromic
Macrocytic – usually also normochromic
microcytic anaemia
A microcytic anaemia is one in which average cell size is decreased
common causes of microcytic anaemia
Defect in haem synthesis
Defect in globin synthesis (thalassaemia)
Defect in haem synthesis
Iron deficiency
Anaemia of chronic disease*
Defect in globin synthesis (thalassaemia)
Defect in α chain synthesis (α thalassaemia)
Defect in β chain synthesis (β thalassaemia
iron deficiency causes
Increased loss (blood loss) Commonest cause in adults,Hookworm commonest cause worldwide,Menstrual (menorrhagia) Insufficient intake Dietary,Vegetarians,Malabsorption,Coeliac disease (gluten,induced enteropathy),H. pylori gastritis Increased requirements Physiological Pregnancy Infancy
maccrocytic anaemia
A macrocytic anaemia is one in which average cell size is increased
Macrocytic anaemias usually result from abnormal haemopoiesis so that the red cell precursors continue to synthesize haemoglobin and other cellular proteins but fail to divide normally
As a result, the red cells end up larger than normal
One cause of macrocytic anaemia is megaloblastic erythropoiesis
- This refers specifically to a delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow - Megaloblasts are generally seen in the bone marrow, not the blood film
megaloblast
an abnormal bone marrow erythroblast
It is larger than normal and shows nucleocytoplasmic dissociation
megaloblastic anaemia causes
caused by a deficiency of vitamin B12 or folate
It is possible to suspect megaloblastic anaemia from the peripheral blood features but to be sure requires bone marrow examination
causes of macrocytic anaemia
Lack of vitamin B12 or folic acid (megaloblastic anaemia)
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Recent major blood loss with adequate iron stores (reticulocytes increased)
Haemolytic anaemia* (reticulocytes increased)
if proportion of young RBC increase, what happens to MCV
it increases
difference between polychromasia and reticulocytosis
the presence of presenting them is different
reticulocyte needs a stain to appear blue
polychromatic
presence of red cells with a blue tinge to the cytoplasm; they are young red cells, newly released from the bone marrow
reticulocytosis
presence of increased numbers of young red cells, recognised by a specific reticulocyte stain
normocytic anaemia
Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen
recent blood loss e.g.
Gastrointestinal haemorrhage, trauma
failure of production of RBC e.g.
Early stages of iron deficiency
Bone marrow failure or suppression (e.g. chemotherapy)
Bone marrow infiltration (e.g. leukaemia)
Pooling of red cells in the spleen e.g.
Hypersplenism, e.g. liver cirrhosis
Splenic sequestration in sickle cell anaemia
polychythaemia
specifically to too many red cells in the circulation
The Hb, RBC and Hct are all increased compared with normal subjects of the same age and gender
pseudo polycynthaemia
reduced blood plasma
true polycynthaemia
total volume increase in RBC in the circulation
blood doping or over transfusion
appropriately increased erythroprotein
inappropriate erythroprotein synthesis or use
independent of erythroprotein
blood doping
presence of cells of 2 different blood groups
appropriate increase of erythropoietin
during high altitude or during patient hypoxia
inappropriate increase of erythropoietin
administered erythropoietin haematologically or during renal tumour
independent of erythropoietin
mutation in red cells and production independently of erythropoietin
This condition is an intrinsic bone marrow disorder called polycythaemia vera
It is classified as a myeloproliferative neoplasm
Polycythaemia can lead to ‘thick blood’– more technically known as hyperviscosity, which can lead to vascular obstruction
how to reduce polycythaemia vera
Blood can be removed (venesection) to reduce the viscosity
Drugs can be given to reduce bone marrow production of red cells
cause and mechanism:
A patient with an abdominal mass?
A breathless cyanosed patient
A patient with an enlarged spleen
A young healthy athlete
carcinoma of kidney- inappropriate erythropoietin synthesis
hypoxia- appropriately increased erythropoietin
polycynthaemia vera- abnormal bone marrow function
very suspicious-blood doping and erythropoietin use
polycythaemia notes
nose and lips blue= hypoxia therefore cynosis
undesirable effects of polycythaemia from hypoxia
hyper viscosity and therefore more probe to thrombosis
what is leukaemia
Leukaemia results from a series of mutations in a single lymphoid or myeloid stem cell (bone marrow)
These mutations lead the progeny of that cell to show abnormalities in proliferation, differentiation or cell survival leading to steady expansion of the leukaemic clone
term for leukaemia in a benign way
chronic leukaemia-disease go on for a long time
term for leukaemia in a malignant way
acute leukaemia-disease very aggressive and death results rapidly
classification of leukaemia
Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
causes of leukaemia
a series of mutations in a single stem cell
oncogenic influences
Others are probably random errors—chance events—that occur throughout life and accumulate in individual cells
Loss of function of a tumour-suppressor gene can also contribute to leukaemogenesis—this can result from deletion or mutation of the gene
If there is a tendency to increased chromosomal breaks, the likelihood of leukaemia is increased
In addition, if the cell cannot repair DNA normally, an error may persist whereas in a normal person the defect would be repaired
important leukaemogenic mutations
Mutation in a known proto-oncogene
Creation of a novel gene, e.g. a chimaeric or fusion gene
Dysregulation of a gene when translocation brings it under the influence of the promoter or enhancer of another gene
Identifiable causes of leukaemogenic mutations include
Irradiation
Anti-cancer drugs
Cigarette smoking
Chemicals—benzene
somatic mutation can be beneficial in what way?
reversion of abnormality in cell to normal phenotype
characteristics of acute myeloid leukaemia
cells continue to proliferate but they no longer mature
A build up of the most immature cells— myeloblasts or ‘blast cells’—in the bone marrow with spread into the blood
A failure of production of normal functioning end cells such as neutrophils, monocytes, erythrocytes, platelets
In AML, the responsible mutations usually affect transcription factors so that the transcription of multiple genes is affected
Often the product of an oncogene prevents the normal function of the protein encoded by its normal homologue
Cell behaviour is profoundly disturbed
difference between acute and chronic leukaemia
Acute lymphoblastic leukaemia has an increase in very immature cells— lymphoblasts—with a failure of these to develop into mature lymphocytes
In chronic lymphoid leukaemias, the leukaemic cells are mature, although abnormal, T cells or B cells or natural killer (NK) cells
characteristics of chronic myeloid leukaemia
In CML, the responsible mutations usually affect a gene encoding a protein in the signalling pathway between a cell surface receptor and the nucleus
The protein encoded may be either a membrane receptor or a cytoplasmic protein
In CML, cell kinetics and function are not as seriously affected as in AML
However, the cell becomes independent of external signals, there are alterations in the interaction with stroma and there is reduced apoptosis so that cells survive longer and the leukaemic clone expands progressively
Whereas in AML there is a failure of production of end cells, in CML there is increased production of end cells
disease characteristics of leukaemia
Accumulation of abnormal cells leading to
Leucocytosis, bone pain (if leukaemia is acute), hepatomegaly, splenomegaly
lymphadenopathy (if lymphoid), thymic enlargement (if T lymphoid), skin infiltration
Lack of production of normal cells leading to
Anaemia, leucopenia, thrombocytopenia
example of chronic leukaemia
CML results from a translocation between chromosomes 9 and 22, occurring in a haemopoietic stem cell
As a result a chimaeric gene, BCR-ABL1 is formed
The gene product gives the cell a growth and survival advantage and gives rise to a leukaemic clone
refer to slides for image example
example of chronic leukaemia 2
There is an increase in all granulocytes —neutrophils, eosinophils and basophils—and their precursors
There is anaemia
There is an enlarged spleen (splenomegaly)
The BCR-ABL1 protein signals between the cell surface and the nucleus
It can be inhibited by specific tyrosine kinase inhibitors, lading to remission, and potentially cure, of the disease
example of acute lymphoblastic leukaemia haematological
haematological
Leucocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia
Replacement of normal bone marrow cells by lymphoblasts
high nuclear cytoplasmic ratio
example of acute lymphoblastic leukaemia clinical
enlarged liver spleen lymph nodes and testis
refer to pictures on slideshow
leukaemogenic mechanisms
Formation of a fusion gene
Dysregulation of a proto-oncogene by juxtaposition of it to the promoter of another gene, e.g. a T-cell receptor gene
Point mutation in a proto-oncogene
treatment of acute lymphoblastic leukaemia
Supportive:Red cells,Platelets,Antibiotics
Systemic chemotherapy
Intrathecal chemotherapy
