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Haematology > Introduction: The Scope of Clinical Haematology > Flashcards

Introduction: The Scope of Clinical Haematology Flashcards

1
Q

What are the blood components?

A

Plasma - about 1/2

  • clotting/coagulation factors
  • albumin
  • antibodies

Buffy coat

  • platelets
  • white cells/leucocytes

Red blood cells

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2
Q

What are the functions of blood?

A

Transport

  • gases, oxygen and CO2 in red cells
  • nutrients, waste, communication in plasma

Maintenance of vascular integrity

  • prevention of leaks - platelets and clotting factors
  • prevention of blockages - anticoagulants and fibrinolytic agents

Protection from pathogens

  • phagocytosis and killing - granulocytes/monocytes
  • antigen recognition and antibody formation - lymphocytes
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3
Q

What is the pathogenesis of haematological abnormality?

A

High levels - increased rate of production, decreased rate of loss

Low levels (more common) - decreased rate of production, increased rate of loss

Altered function

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4
Q

Where are blood cells made? What are they derived from?

A

In the bone marrow
Derived from stem cells

Lymphocyte stem cells split off very early

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5
Q

What are the types of WBC?

A 
Neutrophils
Monocytes
Basophils
Eosinophils
Lymphocytes
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6
Q

What are the types of myeloid cells?

A 
Erythrocytes
Platelets
Neutrophils
Monocytes
Basophils 
Eosinophils
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7
Q

What are the features of stem cells?

A

Totipotent
Self-renewal
Home to marrow niche - CSCR4

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8
Q

As stem cells divide, what do they go through?

A

Binary fission and flux through differentiation pathways

Amplify numbers

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9
Q

What is flux regulated by?

A

Hormones, growth factors

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10
Q

What kind of cells make up most of the bone marrow?

A

Fat cells

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11
Q

Where in the bone marrow do stem cells usually lie?

A

Near the bone, moving closer to the centre as they differentiate
In most bones in children and axial bones in the elderly

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12
Q

What are the histological features of bone marrow?

A

Stroma and sinusoids

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13
Q

What is the normal RBC shape?

A

Bi-concave

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14
Q

What are erythroblasts known as when they are released into the circulation?

A

Reticulocytes (immature RBC)

These then become erythrocytes

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15
Q

What are reticulocytes useful for?

A

Can provide a good measurement of how many RBCs are being produced in around 24 hours

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16
Q

Where is erythropoietin made?

A

In the kidney in response to hypoxia

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17
Q

What haematological abnormality might develop in chronically hypoxic people?

A

Polycythaemia

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18
Q

What are the causes of anaemia?

A

Decreased production

  • deficiency in haematinics e.g. iron, B12, folate
  • thalassaemia

Increased loss

  • bleeding
  • haemolysis
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19
Q

How many RBCs can be made per day?

A

Around 10g/L/day

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20
Q

What are platelets formed from?

A

Megakaryocytes

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21
Q

What are the functions of platelets?

A

Haemostasis and immune functions

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22
Q

What regulates the production of platelets?

A

Thrombopoietin - produced in liver, regulation by platelet mass feedback

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23
Q

What is the lifespan of platelets?

A

7 days

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24
Q

What are the platelet pathologies?

A

Too many

  • thrombocytosis
  • myeloid malignancies, reactive

Thrombocytopenia
- marrow failure, immune destruction

Altered function
- aspirin, clopidogrel, abciximab etc.

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25
Q

What is the function of neutrophils?

A

To ingest and destroy pathogens, especially bacteria and fungi

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26
Q

What are neutrophils regulated by?

A

Immune responses - macrophage, IL-17

27
Q

What is the lifespan of neutrophils?

A

1-2 days

28
Q

What is the speed of response of neutrophil?

A

A few hours

29
Q

When are neutrophils raised?

A

Infection

  • G-CSF
  • left shift, toxic granulation

Inflammation
- post-operative, MI, RA

30
Q

What are the causes of neutropenia?

A

Lowered

Racial - more common in certain populations

Decreased production

  • drugs
  • marrow failure

Increased consumption

  • sepsis
  • autoimmune

Altered function e.g. chronic granulomatous disease

31
Q

What is the function of the monocytes?

A

To ingest and destroy pathogens, especially bacteria and fungi
Subset of monocytes migrate into tissues and become macrophages, main function is to migrate into tissues where they can differentiate into macrophages and survive for many months

32
Q

What is the lifespan of macrophages?

A

Many months

33
Q

What is monocytosis associated with?

A

Usually associated with neutrophilia

Mycobacterial inflections

34
Q

What is monocytopenia associated with?

A

Mycobacteria in hairy cell leukaemia

35
Q

What is the main role of eosinophils?

A

Historically main role was in fighting off parasitic infections, more commonly now in allergy

36
Q

What is lymphocytosis associated with?

A

Infectious mononucleosis

Pertussis

37
Q

What is lymphopenia associated with?

A

Usually post-viral

Lymphoma

38
Q

What are the subtypes of lymphocytes?

A

B cells
T cells
Natural killer cells

39
Q

Where are lymphocytes produced?

A

Produced in bone marrow

40
Q

Where do B and T cells mature?

A

B cells mature in bone marrow

T cells mature in thymus

41
Q

What do lymphocytes differentiate into in secondary lymphoid organs?

A

Effector cells

42
Q

What are the regions of the B/T cell receptor?

A

Variable region at the top and constant region at the bottom

43
Q

What are the roles of antibodies?

A

Adaptors between pathogens and clearance systems
Opsonisation
Fix complement
Block binding
IgG immunoglobulin most common, but many other types

44
Q

What happens in the creation of a receptor chain gene?

A

Shuffling of exons at a time when lymphocytes are differentiating
In gremlin DNA, 4 common enzymes are seen, joined up together in a random fashion (recombination)

45
Q

What are the types of repertoire diversity and what do mistakes in these processes cause?

A

Combinatorial diversity
Junctional diversity
Combinational diversity

Mistakes in processes cause lymphoid malignancy

46
Q

What is the positive and negative selection in the bone marrow?

A

If the 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
B cells that survive this selection are exported to the periphery

47
Q

What are the classes of human leucocyte antigen (HLA)?

A

Class I - displays internal antigens on all nucleated cells

Class II - displays antigens eaten by professional antigen-presenting cells

48
Q

What do HLA molecules help cells to identify?

A

Self vs non-self cells or uninfected vs infected cells

49
Q

Give examples of blood disorders that occur due to systemic diseases

A 
Anaemia of chronic diseases 
Iron deficiency 
Folate deficiency 
Immune haemolysis 
Neutrophilia
Immune thrombocytopenia 
Cytopenia secondary to medication 
Felty syndrome
50
Q 
Give examples of blood disorders caused by;
hepatic
renal 
cardiovascular
respiratory 
GI disease
A

Hepatic - anaemia, deficient clotting factors

Renal - anaemia, haemolytic uraemic syndrome

Cardiovascular - anaemia

Respiratory - polycythaemia

GI - anaemia

51
Q

What are the components of the full blood count?

A 
Haemglobin 
RBC
Platelets 
WBC
Neutrophils 
Lymphocytes
52
Q

What is the normal Hb range?

A

Males - 135-170g/L

Females - 120-160g/L

53
Q

What is the normal RBC range?

A

4-5 x 10^12/L

54
Q

What is the normal platelet range?

A

150-400 x 10^9/L

55
Q

What is the normal WBC range?

A

4-10 x 10^9/L

56
Q

What is the normal neutrophil range?

A

1.5-7 x 10^9/L

57
Q

What is the normal lymphocyte range?

A

1.5-4 x 10^9/L

58
Q

What is affected by plasma disorders?

A

Too much - paraproteins
Too little - clotting factors, haemophilia
Abnormal function - clotting factors, haemophilia

59
Q

What are the main haematological tests?

A 
FBC 
Clotting times for clotting factors 
Bleeding time for platelets 
Platelet and leucocyte function tests
Chemical assays - iron (ferritin), B12, folate 
Marrow aspirate and trephine biopsy 
Lymph node biopsy 
Imaging
60
Q

What is the spleen composed of?

A

Red pulp and white pulp

61
Q

What are the haematological effects of spleen disorders?

A

Hypersplenism - pancytopenia

Hyposplenism - infections with encapsulated bacteria, red cell changes

62
Q

What are the causes of splenomegaly?

A

Infectious

  • acute e.g. EBV, CMV
  • chronic bacterial e.g. TB
  • chronic parasitic e.g. malaria

Haematological - malignancy

  • leukaemias and lymphomas
  • myeloproliferative disorders

Portal hypertension

Haemolytic disorders

  • hereditary spherocytosis, thalassaemia, haemoglobinopathies
  • megaloblastic anaemia
  • autoimmune

Connective tissue disorders

  • SLE
  • Felty syndrome

Miscellaneous

  • sarcoid
  • malignancy
  • amyloid

Storage pool disorders

  • Gaucher disease
  • Niemann Pick
63
Q

What are the main haematology treatments?

A

Replacement

  • blood
  • haematinics
  • coagulation factors
  • plasma exchange

Transplantation

Drugs 
- cytotoxics
- monoclonal antibodies 
inhibitors of cellular proliferation 
- immunosuppressants
- inhibitors of coagulation
- inhibitors of fibrinolysis

Haematology (11 decks)

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