red cell abnormalities

Question 1

what is anaemia

Answer 1

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

Question 2

anaemia mechanism

Answer 2

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

Question 3

cause of anaemia

Answer 3

either a condition causing reduced synthesis of haem or one causing reduced synthesis of globin

Question 4

Can you name one cause of reduced synthesis of haem?

Answer 4

iron deficiency

Question 5

What do you call a condition in which there is an inherited defect leading to reduced synthesis of globin ?

Answer 5

thalassemia

Question 6

cell size and anaemia

Answer 6

Microcytic – usually also hypochromic
Normocytic – usually also normochromic
Macrocytic – usually also normochromic

Question 7

microcytic anaemia

Answer 7

A microcytic anaemia is one in which average cell size is decreased

Question 8

common causes of microcytic anaemia

Answer 8

Defect in haem synthesis

Defect in globin synthesis (thalassaemia)

Question 9

Defect in haem synthesis

Answer 9

Iron deficiency

Anaemia of chronic disease*

Question 10

Defect in globin synthesis (thalassaemia)

Answer 10

Defect in α chain synthesis (α thalassaemia)

Defect in β chain synthesis (β thalassaemia

Question 11

iron deficiency causes

Answer 11

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

Question 12

maccrocytic anaemia

Answer 12

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

Question 13

megaloblast

Answer 13

an abnormal bone marrow erythroblast

It is larger than normal and shows nucleocytoplasmic dissociation

Question 14

megaloblastic anaemia causes

Answer 14

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

Question 15

causes of macrocytic anaemia

Answer 15

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)

Question 16

if proportion of young RBC increase, what happens to MCV

Answer 16

it increases

Question 17

difference between polychromasia and reticulocytosis

Answer 17

the presence of presenting them is different

reticulocyte needs a stain to appear blue

Question 18

polychromatic

Answer 18

presence of red cells with a blue tinge to the cytoplasm; they are young red cells, newly released from the bone marrow

Question 19

reticulocytosis

Answer 19

presence of increased numbers of young red cells, recognised by a specific reticulocyte stain

Question 20

normocytic anaemia

Answer 20

Recent blood loss

Failure of production of red cells

Pooling of red cells in the spleen

Question 21

recent blood loss e.g.

Answer 21

Gastrointestinal haemorrhage, trauma

Question 22

failure of production of RBC e.g.

Answer 22

Early stages of iron deficiency
Bone marrow failure or suppression (e.g. chemotherapy)
Bone marrow infiltration (e.g. leukaemia)

Question 23

Pooling of red cells in the spleen e.g.

Answer 23

Hypersplenism, e.g. liver cirrhosis

Splenic sequestration in sickle cell anaemia

Question 24

polychythaemia

Answer 24

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

Question 25

pseudo polycynthaemia

Answer 25

reduced blood plasma

Question 26

true polycynthaemia

Answer 26

total volume increase in RBC in the circulation
blood doping or over transfusion
appropriately increased erythroprotein
inappropriate erythroprotein synthesis or use
independent of erythroprotein

Question 27

blood doping

Answer 27

presence of cells of 2 different blood groups

Question 28

appropriate increase of erythropoietin

Answer 28

during high altitude or during patient hypoxia

Question 29

inappropriate increase of erythropoietin

Answer 29

administered erythropoietin haematologically or during renal tumour

Question 30

independent of erythropoietin

Answer 30

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

Question 31

how to reduce polycythaemia vera

Answer 31

Blood can be removed (venesection) to reduce the viscosity

Drugs can be given to reduce bone marrow production of red cells

Question 32

cause and mechanism:
A patient with an abdominal mass?

A breathless cyanosed patient

A patient with an enlarged spleen

A young healthy athlete

Answer 32

carcinoma of kidney- inappropriate erythropoietin synthesis
hypoxia- appropriately increased erythropoietin
polycynthaemia vera- abnormal bone marrow function
very suspicious-blood doping and erythropoietin use

Question 33

polycythaemia notes

Answer 33

nose and lips blue= hypoxia therefore cynosis

Question 34

undesirable effects of polycythaemia from hypoxia

Answer 34

hyper viscosity and therefore more probe to thrombosis

Question 35

what is leukaemia

Answer 35

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

Question 36

term for leukaemia in a benign way

Answer 36

chronic leukaemia-disease go on for a long time

Question 37

term for leukaemia in a malignant way

Answer 37

acute leukaemia-disease very aggressive and death results rapidly

Question 38

classification of leukaemia

Answer 38

Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)

Question 39

causes of leukaemia

Answer 39

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

Question 40

important leukaemogenic mutations

Answer 40

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

Question 41

Identifiable causes of leukaemogenic mutations include

Answer 41

Irradiation
Anti-cancer drugs
Cigarette smoking
Chemicals—benzene

Question 42

somatic mutation can be beneficial in what way?

Answer 42

reversion of abnormality in cell to normal phenotype

Question 43

characteristics of acute myeloid leukaemia

Answer 43

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

Question 44

difference between acute and chronic leukaemia

Answer 44

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

Question 45

characteristics of chronic myeloid leukaemia

Answer 45

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

Question 46

disease characteristics of leukaemia

Answer 46

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

Question 47

example of chronic leukaemia

Answer 47

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

Question 48

example of chronic leukaemia 2

Answer 48

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

Question 49

example of acute lymphoblastic leukaemia haematological

Answer 49

haematological
Leucocytosis with lymphoblasts in the blood
Anaemia (normocytic, normochromic)
Neutropenia
Thrombocytopenia
Replacement of normal bone marrow cells by lymphoblasts
high nuclear cytoplasmic ratio

Question 50

example of acute lymphoblastic leukaemia clinical

Answer 50

enlarged liver spleen lymph nodes and testis

refer to pictures on slideshow

Question 51

leukaemogenic mechanisms

Answer 51

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

Question 52

treatment of acute lymphoblastic leukaemia

Answer 52

Supportive:Red cells,Platelets,Antibiotics
Systemic chemotherapy
Intrathecal chemotherapy