Intro to Haematology Flashcards

1
Q

What is the role of Haematology?

A

The investigation of blood and bone marrow

The management of disorders of blood and bone marrow

Both involve interactions with other organs

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2
Q

What components makes up blood?

A

Plasma;
- Clotting or Coagulation Factors
- Albumin
- Antibodies

Buffy Coat;
- Platelets
- White Cells or Leucocytes

Red Blood Cells

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3
Q

What are the functions of the blood?

A
  • Transport
  • Maintenance of Vascular Integrity
  • Protection from Pathogens
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4
Q

What is involved in Transport?

A

Gases;
- Oxygen and carbon dioxide (In Red Cells)

  • Nutrients
  • Waste
  • Messages
    (These are in Plasma)
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5
Q

What is involved in Maintenance of Vascular Integrity?

A

Prevention of leaks - Platelets and clotting factors

Prevention of blockages - Anticoagulants and fibrinolytics

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6
Q

What is involved in Protection from Pathogens?

A

Phagocytosis and killing -Granulocytes/monocytes

Antigen recognition and antibody formation - Lymphocytes

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7
Q

What is this?

A

Oral sepsis in neutropenia

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8
Q

What is this?

A

Severe candidal infection in an immunocompromised patient

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9
Q

What causes Haematological abnormalities?

A

High levels;
- Increased rate of production
- (Decreased rate of loss)

Low levels;
- Decreased rate of production
- Increased rate of loss

Altered function

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10
Q

Where do our Blood Cells come from?

A

Bone marrow makes all blood cells from pluripotent stem cells

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11
Q

What are the features of Stem Cells

A
  • Totipotent
  • Self-renewal

Home to marrow niche
- CXCR4 (antagonist plerixafor)

  • Binary fission and flux through differentiation pathways amplify numbers

Flux regulated by hormones / growth factors
- Some used therapeutically (erythropoietin, G-CSF, thrombopoietin agonists)

  • Stem cell properties can now be ‘induced’
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12
Q

Where is Bone Marrow Stored?

A

Bones: most in children, axial in elderly

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13
Q

What does Bone Marrow look like?

A

Stroma and sinusoids (blood vessels)

Pink bone, white fat, spaces between haematopoietic cells

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14
Q

Label this blood film

A

Biconcave discs with central pallor (RBC’s)

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15
Q

How do RBC’s develop?

A

Erythroblast–>reticulocyte–>erythrocyte

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16
Q

What is Erythropoietin?

A

Erythropoietin - made in kidney in response to hypoxia

Hence why ones with kidney impairment are anaemic

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17
Q

Why is a Reticulocyte count used and what does a high or low count show?

A

Reticulocyte count - a measure of red cell production

High - Bleeding?

Low - Bone marrow issues?

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18
Q

What is Polycythaemia and when is it seen?

A

Too many RBC’s - In Myeloid Malignancies

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19
Q

What are the Causes of Anaemia?

A

Poor gas transfer:
- Dyspnoea
- Fatigue

Decreased production (Deficiency in ‘haematinics’);
- Iron
- Folate
- Vitamin B12

Congenital:
- Thalassaemias

Increased loss
- Bleeding
- Haemolysis

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20
Q

What are the features of Red blood cells?

A

Microcytes, macrocytes
Polychromasia
Burr cells in renal failure etc
Can make ~10g/L/day

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21
Q

What are the features of Platelets?

A

Function=haemostasis (and immune) (Part of primary haemostatic response)

Production regulated by thrombopoietin
- Produced in liver
- Regulation by platelet mass feedback

Lifespan =7 days

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22
Q

What Pathologies can be caused by Platelets?

A

Thrombocytosis (Too many platelets);
- In Myeloid Malignancies
- ‘Reactive’

Thrombocytopenia (Not enough platelets);
- Marrow failure
- Immune destruction: ITP

Altered function;
- Aspirin
- Clopidogrel
- Abciximab

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23
Q

What is this?

A

Non blanching Petechiae rash from Thrombocytopenia

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24
Q

What is this from?

A

Significant blood blisters - single platelets count

Very Very Low Platelets (Thrombocytopenia)

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25
Q

What is Polychromasia?

A

Polychromasia is a disorder where there is an abnormally high number of immature red blood cells found in the bloodstream as a result of being prematurely released from the bone marrow during blood formation (poly- refers to many, and -chromasia means color.) These cells are often shades of grayish-blue.

26
Q

What is this and the causes?

A

Microcytic, hypochromic red cells in Iron Deficiency

27
Q

What does a Low MCV suggest?

A

Low MCV microcytic;
- Small and pale
- Iron deficiency most common cause

28
Q

What does a High MCV suggest?

A

Macrocytic;
- B12 or folate deficiency (neutrophils can see)

29
Q

What is this?

A

Macrocytic Red Cells in Folate Deficiency

30
Q

What is this?

A

Sickle cells & target cells in sickle cell disease

31
Q

What is this?

A

Schistocytes (fragmented cells) in haemolytic uraemic syndrome

32
Q

What is this and what does it do?

A

Megakaryocytes make Platelets

33
Q

What is this and its significance?

A

Platelets, beginning to clump is INSIGNIFICANT, it just makes platelet counts harder.

34
Q

What are the features of Neutrophils?

A

Function: to ingest and destroy pathogens, especially bacteria and fungi

Interleukins (‘between white cells’) and CSFs (colony stimulating factors)
- granulocyte-colony stimulating factor (G-CSF)

Regulation by immune responses
- Macrophages, IL-17

Lifespan =1-2 days

Speed of response = few hours

35
Q

Was is the different between these 5 Neutrophils?

A

1). Blast (Acute Myeloid Leukemia)
2). Promyelocyte
3). Myelocyte
4). Metamyelocyte
5). Neutrophil

36
Q

What is Neutrophillia?

A

Too many Neutrophils

Production regulated by granulocyte-colony stimulating factor (G-CSF)

Infection
- Left shift, toxic granulation

Inflammation
- eg MI, postoperative, rheumatoid arthritis

G-CSF used therapeutically
- Neutropenia
- Mobilisation of stem cells
*To improve platelet count or before harvest stem cells to give them back to them to make more?

  • Usually get from reactive, infection, inflammatory, post op, Post MI, etc
37
Q

What is Neutropenia and its features?

A

Not enough neutrophils

Decreased production
- Drugs
- Marrow failure

Increased consumption
- Sepsis
- Autoimmune

Altered function
- eg chronic granulomatous disease

38
Q

What is this cell and its function?

A

The ‘reticuloendothelial system’

Function: to ingest and destroy pathogens, especially bacteria and fungi

Subset of monocytes migrate into tissues and become macrophages or dendritic cells
- Some populations of macrophages self-maintaining

39
Q

What is this cell and its function?

A

Eosinophil (Another Myeloid Cell)

  • Parasites
  • Allergies
40
Q

What is this cell?

A

Basophil (Another Myeloid Cell)

41
Q

What is this cell and its function?

A

Lymphocytes

Adaptive, versus innate, immune system
- Immunological memory

Surface antigens: CD markers

Lymphocytosis (Often reactive, Any infection can cause);
- Infectious mononucleosis
- Pertussis
- Lymphoproliferative disorders

Lymphopenia
- Usually post-viral
- Lymphoma - rare
(Also drugs suppressing?)

42
Q

Label these cells

A
43
Q

Where do Leucocytes live?

A

In the Peripheral blood

44
Q

What are the Subtypes of Lymphocytes?

A

Subtypes;
- B cells – make antibodies
- T cells – Helper, cytotoxic, regulatory
- NK cells

Produced in bone marrow
- B cells mature in bone marrow, T cells in thymus

Circulate in blood, lymph and lymph nodes

Differentiate into effector cells in secondary lymphoid organs (lymph nodes or mucosal associated lymphoid tissue)

45
Q

What is unique about the T and B cell receptors?

A

Each naïve T and B cell has unique surface receptor

*Red bit is specific and can change, specific for specific type of antigen

46
Q

What are antibodies?

A

Adaptors between pathogens and clearance systems: opsonisation
- ‘Kiss of death’

47
Q

How do Antibodies create different receptors?

A

Can recombine different bits of DNA with the constant bit to change and be specific for different types of antigens

Called Creation of a Receptor Chain Gene by Recombination

48
Q

What is Repertoire Diveristy and when can it go wrong?

A

Repertoire diversity is inversely related to clonality, which refers to the number and frequency of observed TCRs within a sample, and together with diversity is often used as a meter of immune response efficacy (please see Glossary section for definitions and quantification of repertoire diversity measures).

Combinatorial diversity – within each chain
- V-region combined with J- or D- then C-region

Junctional diversity
- At join, additional nucleotides added

Combinatorial diversity – between chains
- Each alpha chain pairs with a beta chain
- Each light chain pairs with a heavy chain

Mistakes cause lymphoid malignancies
- eg IgH heavy locus on chromosome 14
- t(14,18), t(8,14), t(11,14)……….

49
Q

How do B Cells mature and at what stages can defects occur?

A
50
Q

How does Positive and negative selection within a Leukocyte occur?

A

In the bone marrow if gene rearrangement results in a functional receptor the cell is selected to survive – positive selection

If the receptor recognises ‘self’ antigens - the cell is triggered to die – negative selection: tolerance

B cells that survive this selection are exported to the periphery

51
Q

What is Human leucocyte Antigen: HLA?

A

Class I: displays internal antigens on all nucleated cells

Class II: displays antigens eaten by professional antigen presenting cells

Constant within, variation between individuals

Immune cells read HLA-Barcode on cells to help identify self vs non self cells or uninfected vs infected cells
- An immune response is triggered if a infected cell is identified

52
Q

Name some conditions that affect the Blood?

A

Many systemic diseases affect the blood for example: rheumatoid arthritis causes;
- Anaemia of chronic disease
- Iron deficiency
- Folate deficiency
- Immune haemolysis
- Neutrophilia
- Immune thrombocytopenia
- Cytopenias secondary to medication

  • Felty syndrome (This disorder is generally defined by the presence of three conditions: rheumatoid arthritis (RA), an enlarged spleen (spenomelgaly) and a low white blood cell count (neutropenia).
53
Q

How can diseases in Different Systems affect the Blood?

A

Hepatic
- Anaemia, deficient clotting factors

Renal
- Anaemia, haemolytic uraemic syndrome

Cardiovascular
- Anaemia

Respiratory
- Polycythaemia

Gastrointestinal disease
- Anaemia

54
Q

What conditions can too much plasma cause?

A

Paraproteins in the Blood

55
Q

What conditions can too little plasma cause?

A

Problems with Clotting factors: haemophilia

56
Q

What can Abnormal function in the Plasma cause?

A

Clotting factors: von Willebrand disease

57
Q

What Diagnostic tools should you use for blood investigations in order of 1st line onwards?

A

1st Line;
- Full Blood Count

2nd Line;
- Clotting times for clotting factors and platelets (Platelet and leukocyte function tests?)

3rd Line;
Chemical Assays;
- Iron (Ferritin)
- B12
- Folate

4th Line;
- Marrow aspirate and trephine biopsy (bone marrow)
- Lymph node Biopsy (Lymphoma?)
- Other organ biopsy

5th Line;
- Imaging

58
Q

What is Ferritin?

A

The protein that carries Iron

59
Q

What things does a Full Blood count check?

A
  • Haemoglobin
  • RBC
  • Platelets

WBC
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils

No ‘primitive’ cells

60
Q

What Haematology Treatments are Available?

A

Replacement
- Blood
- Haematinics
- Coagulation factors
- Plasma exchange

Transplantation

Drugs
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis