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POM > Blood cell abnormalities > Flashcards

Blood cell abnormalities Flashcards

1
Q

Name one cause of reduced synthesis of haem?

A

Iron deficiency

Anaemia of chronic disease

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2
Q

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

A

Thalassemia

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3
Q

What are some mechanisms of anaemia?

A

Reduced production of RBS/ haemoglobin in bone marrow

loss of blood from body

Reduced survival of red blood cells

Pooling of red blood cells in a large spleen

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4
Q

What is microcytic anaemia? What are the causes?

A

Small RBCs usually also hypochromic

Haem - iron deficiency

Can be caused by
blood loss - menstrual or hookworm
diet - vegetarian
absorption - coeliac disease or H.pylori gastritis
increased requirement - pregnancy or infancy

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5
Q

What are the 3 stages of iron depletion?

A

Iron depletion - storage iron reduced

Iron deficiency - low serum ion and transferrin saturation

iron deficiency anaemia - low haemoglobin and haematocrit

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6
Q

What are some clinical features of microcytic anaemia?

A

Pallor fatigue breathlessness
Failure of intellectual development in children
Features of underlying causes - Spoon nails (koilonychia) are soft nails that look scooped out
angular cheilitis

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7
Q

What is macrocytic anaemia?

A

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

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8
Q

What are some causes of macrocytic anaemia?

A
  • megaloblastic erythropoiesis
    delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow

A megaloblast is an abnormal bone marrow erythroblast
It is larger than normal and shows nucleocytoplasmic dissociation

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)

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9
Q

Why does an increased proportion of red blood cells lead to increased MCV?

A

Young red cells are about 20% larger than mature red cells so if there is an increased proportion of young red cells (polychromasia/reticulocytes) in the circulation, the average cell size (MCV) will be increased

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10
Q

What is seen on a blood film for those with megalobastic anaemia?

A

Tear drop cells
Hypersegmented neutrophils
Oval macrocytes

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11
Q

What is normocytic anaemia? what are the causes?

A

Normal staining and size of red blood cells but low Hb overall

Recent blood loss - GI bleeding trauma

Failure of production of red blood cells - early stages of iron deficiency, bone marrow failure or supression (chemo), bone marrow infiltration (leukaemia),

Pooling of red cells in the spleen - hypersplenism -cirrhosis, splenic sequestration in sickle cell anaemia

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12
Q

What is anaemia of chronic disease?

Give some examples of common causes

A

Usually an underlying inflammatory aspect to the disease

Rheumatoid arthritis 
Autoimmune diseases
Malignancy 
Kidney disease 
Infections such as TB or HIV
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13
Q

What is the pathogenesis of anaemia of chronic disease?

A

Cytokines like TFNa and interleukins from the chronic condition lead to a decrease in erythropoietin production and prevent normal flow of iron from duodenum to red blood cells - hepcidin influences this

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14
Q

What are some lab clues for someone with anaemia of chronic disease?

A

High C-reactive proteins (unlike iron deficiency)

High ferritin

Low transferrin

acute phase proteins increase

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15
Q

What is polychromasia and how can this be seen?

When do you usually have a high count?

A

Blue tinge to cells due to higher ribosomal RNA in young RBCS in addition to the normal pink

Haemolytic anaemia and recent blood loss

also as a response to treatment with iron, vitamin B12 and folic acid

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16
Q

What is polycythaemia and what is usually increased during this?

A

Too many red cells in the circulation

Hb, RBC and Hct are all increased compared with normal subjects of the same age

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17
Q

What is pseudo-polycythaemia?

A

Reduced plasma volume

higher concentration in blood

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18
Q

What can cause true polycythaemia?

A

Blood doping or overtransfusion

Increased EPO either appropriate or inappropirate

Independent of erythropoietin

19
Q

What is leukaemia? How does it arise?

A

Bone marrow disease resulting in overspill of abnormal cells into the blood

Arises as a result of mutation in a precursor of myeloid or lymphoid cells

19
Q

What is leukaemia? How does it arise?

A

Bone marrow disease resulting in overspill of abnormal cells into the blood

Arises as a result of mutation in a precursor of myeloid or lymphoid cells

20
Q

What is leukaemia? How does it arise?

A

Bone marrow disease resulting in overspill of abnormal cells into the blood

Neoplasm or cancer that arises as a result of mutation in a precursor of myeloid or lymphoid cells

21
Q

How is a leukaemia different to usual cancers?

A

Affected cells are not mobile - they circulate in blood and migrate into tissues

Difficult to apply the concepts of local invasion/metastasis that are usually used

Formation of localised tumour mass does not usually occur

22
Q

What is an acute leukaemia and give two examples?

A

Profound pathological effects - fatal in a matter of days, weeks or months

Acute lymphoblastic leukaemia (ALL)
Acute myeloid leukaemia (AML)

23
Q

What is an chronic leukaemia and give two examples?

A

Less impairment of function, takes a couple of years to be fatal

Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)

24
Q

Why does leukaemia occur?

A

Number of mutations in a primitive cells that has a growth or survival advantage

The single cell gives rise to clones that replace normal cells

Mutations can be in proto-oncogenes and in tumour supressor genes

25
Q

Why is polycythaemia classed as a as a myeloproliferative neoplasm

A

Polycythaemia can lead to ‘thick blood’– more technically known as hyperviscosity, which can lead to vascular obstruction

Blood can be removed (venesection) to reduce the viscosity
Drugs can be given to reduce bone marrow production of red cells

26
Q

What types of mutations in oncogenes contribute to leukaemias?

A

point mutations;

(ii) internal tandem duplication of parts of genes;
(iii) formation of fusion genes;
(iv) dysregulation when a gene comes under the control of the promoter or enhancer of another gene;
(v) somatic hypermutation subsequent to a translocation.

27
Q

What abnormal behaviours do leukaemic clones undergo?

A

Growth without dependance on growth factors

Continued proliferation without maturation

Failure to undergo normal cell death

Independent, immature, immortal (kinda)

28
Q

What mutations can occur in tumour suppressor genes?

A

deletion of the gene

inactivation through mutation.

29
Q

What can cause mutations leading to acute lymphoblastic anaemia?

A

Usually unknown
Mutagenic drugs
exposure to irradiation or chemicals in utero
Delayed exposure to common pathogen(s)

  • usually mutations before birth causing leukaemia in infants
30
Q

What can cause mutations leading to acute myeloid leukaemia?

A

Irradiation
Mutagenic drugs or chemicals - benzene, cigarette smoke

  • usually multiple sequential mutations either spontaneous or due to mutagenic agents
31
Q

What can cause mutations leading to chronic myeloid leukaemia?

A

Usually unknown

Rarely radiation or mutagenic drugs

32
Q

What can cause mutations leading to chronic lymphoid leukaemia?

A

Unknown but some families are predisposed

33
Q

What occurs in acute myeloid leukaemia?

A

In AML cells continue to proliferate but no longer mature

Mutations 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

  • build up of more immature cells or myeloblasts in bone marrow that spread to the blood
  • failure of production of normal functioning cells ie neutrophils, monocyes, erythrocytes, platelets
34
Q

What is the difference between acute and chronic myeloid leukaemia?

A

Whereas in AML there is a failure of production of end cells, in CML there is increased production of end cells

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

35
Q

What occurs in chronic myeloid leukaemia?

A

In CML cell functions arent as seriously affected

  • cells proliferate independent of external growth signals and alter interactions with stroma
  • reduced apoptosis so cells survive longer and leukaemic clone expands progressively

Translocation between chromosomes 9 and 22 in a HSC causing fusion of the BCR-ABL1 protein (philadelphia chromosome formation) - signalling between cell surface and nucleus occurs

Gives the cell growth and survival advantage

36
Q

What are direct symptoms of leukaemia ?

A 
Accumulation of abnormal cells leading to 
leukocytosis
bone pain (acute)
hepatomegaly (enlarged liver)
Splenomegaly 
Lymphadenopathy
37
Q

What are some indirect symptoms of leukaemia?

A

Fatigue, lethargy and pallor - anaemia

Fever and infections - neutropenia

Bruising and petechiae - thrombocytopenia

Bone pain - bone marrow expansion

Abdominal enlargement due to hepatomegaly (enlarged liver) and Splenomegaly

Swelling and lumps due to lymphadenopathy

38
Q

What can help treat chronic myeloid leukaemia?

A

Philadelphia chromosome inhibited by specific tyrosine kinase inhibitors, leading to remission and potentially cure of the disease

39
Q

What is usually associated with acute lymphoblastic leukaemia?

A

Normally present in children

Leukocytosis - with lymphoblasts in blood - larger size

High nuclei to cytoplasmic ratio and prominent nuclei

Anaemia (normocytic)

Neutropenia - often absent
Thrombocytopenia -often absent

40
Q

What are some treatment options for those with acute lymphoblastic anaemia?

A

supportive - Red blood cells, platelets, antibiotics

Systemic chemotherapy - drugs
Intrathecal chemotherapy- given into the fluid around the spinal cord during a lumbar puncture.

41
Q

What is a characteristic of CLL in a blood film?

A

Smear/smudge cell

42
Q

What are essential investigations to diagnose leukaemia?

A

Full blood count and film

Characterise profile of b and T cells using flow cytometry

Sample of bone marrow for cytogencis analysis on blood to look for markers ie philadelphia chromosome

43
Q

What is the main characteristic for acute myleloid leukaemia?

A

Increase in all granulocytes and their precursors - left shift

Abdominal discomform

POM (42 decks)

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