Intro to Haematology Flashcards
What is the role of Haematology?
The investigation of blood and bone marrow
The management of disorders of blood and bone marrow
Both involve interactions with other organs
What components makes up blood?
Plasma;
- Clotting or Coagulation Factors
- Albumin
- Antibodies
Buffy Coat;
- Platelets
- White Cells or Leucocytes
Red Blood Cells
What are the functions of the blood?
- Transport
- Maintenance of Vascular Integrity
- Protection from Pathogens
What is involved in Transport?
Gases;
- Oxygen and carbon dioxide (In Red Cells)
- Nutrients
- Waste
- Messages
(These are in Plasma)
What is involved in Maintenance of Vascular Integrity?
Prevention of leaks - Platelets and clotting factors
Prevention of blockages - Anticoagulants and fibrinolytics
What is involved in Protection from Pathogens?
Phagocytosis and killing -Granulocytes/monocytes
Antigen recognition and antibody formation - Lymphocytes
What is this?
Oral sepsis in neutropenia
What is this?
Severe candidal infection in an immunocompromised patient
What causes Haematological abnormalities?
High levels;
- Increased rate of production
- (Decreased rate of loss)
Low levels;
- Decreased rate of production
- Increased rate of loss
Altered function
Where do our Blood Cells come from?
Bone marrow makes all blood cells from pluripotent stem cells
What are the features of Stem Cells
- 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’
Where is Bone Marrow Stored?
Bones: most in children, axial in elderly
What does Bone Marrow look like?
Stroma and sinusoids (blood vessels)
Pink bone, white fat, spaces between haematopoietic cells
Label this blood film
Biconcave discs with central pallor (RBC’s)
How do RBC’s develop?
Erythroblast–>reticulocyte–>erythrocyte
What is Erythropoietin?
Erythropoietin - made in kidney in response to hypoxia
Hence why ones with kidney impairment are anaemic
Why is a Reticulocyte count used and what does a high or low count show?
Reticulocyte count - a measure of red cell production
High - Bleeding?
Low - Bone marrow issues?
What is Polycythaemia and when is it seen?
Too many RBC’s - In Myeloid Malignancies
What are the Causes of Anaemia?
Poor gas transfer:
- Dyspnoea
- Fatigue
Decreased production (Deficiency in ‘haematinics’);
- Iron
- Folate
- Vitamin B12
Congenital:
- Thalassaemias
Increased loss
- Bleeding
- Haemolysis
What are the features of Red blood cells?
Microcytes, macrocytes
Polychromasia
Burr cells in renal failure etc
Can make ~10g/L/day
What are the features of Platelets?
Function=haemostasis (and immune) (Part of primary haemostatic response)
Production regulated by thrombopoietin
- Produced in liver
- Regulation by platelet mass feedback
Lifespan =7 days
What Pathologies can be caused by Platelets?
Thrombocytosis (Too many platelets);
- In Myeloid Malignancies
- ‘Reactive’
Thrombocytopenia (Not enough platelets);
- Marrow failure
- Immune destruction: ITP
Altered function;
- Aspirin
- Clopidogrel
- Abciximab
What is this?
Non blanching Petechiae rash from Thrombocytopenia
What is this from?
Significant blood blisters - single platelets count
Very Very Low Platelets (Thrombocytopenia)
What is Polychromasia?
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.
What is this and the causes?
Microcytic, hypochromic red cells in Iron Deficiency
What does a Low MCV suggest?
Low MCV microcytic;
- Small and pale
- Iron deficiency most common cause
What does a High MCV suggest?
Macrocytic;
- B12 or folate deficiency (neutrophils can see)
What is this?
Macrocytic Red Cells in Folate Deficiency
What is this?
Sickle cells & target cells in sickle cell disease
What is this?
Schistocytes (fragmented cells) in haemolytic uraemic syndrome
What is this and what does it do?
Megakaryocytes make Platelets
What is this and its significance?
Platelets, beginning to clump is INSIGNIFICANT, it just makes platelet counts harder.
What are the features of Neutrophils?
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
Was is the different between these 5 Neutrophils?
1). Blast (Acute Myeloid Leukemia)
2). Promyelocyte
3). Myelocyte
4). Metamyelocyte
5). Neutrophil
What is Neutrophillia?
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
What is Neutropenia and its features?
Not enough neutrophils
Decreased production
- Drugs
- Marrow failure
Increased consumption
- Sepsis
- Autoimmune
Altered function
- eg chronic granulomatous disease
What is this cell and its function?
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
What is this cell and its function?
Eosinophil (Another Myeloid Cell)
- Parasites
- Allergies
What is this cell?
Basophil (Another Myeloid Cell)
What is this cell and its function?
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?)
Label these cells
Where do Leucocytes live?
In the Peripheral blood
What are the Subtypes of Lymphocytes?
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)
What is unique about the T and B cell receptors?
Each naïve T and B cell has unique surface receptor
*Red bit is specific and can change, specific for specific type of antigen
What are antibodies?
Adaptors between pathogens and clearance systems: opsonisation
- ‘Kiss of death’
How do Antibodies create different receptors?
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
What is Repertoire Diveristy and when can it go wrong?
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)……….
How do B Cells mature and at what stages can defects occur?
How does Positive and negative selection within a Leukocyte occur?
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
What is Human leucocyte Antigen: HLA?
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
Name some conditions that affect the Blood?
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).
How can diseases in Different Systems affect the Blood?
Hepatic
- Anaemia, deficient clotting factors
Renal
- Anaemia, haemolytic uraemic syndrome
Cardiovascular
- Anaemia
Respiratory
- Polycythaemia
Gastrointestinal disease
- Anaemia
What conditions can too much plasma cause?
Paraproteins in the Blood
What conditions can too little plasma cause?
Problems with Clotting factors: haemophilia
What can Abnormal function in the Plasma cause?
Clotting factors: von Willebrand disease
What Diagnostic tools should you use for blood investigations in order of 1st line onwards?
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
What is Ferritin?
The protein that carries Iron
What things does a Full Blood count check?
- Haemoglobin
- RBC
- Platelets
WBC
- Neutrophils
- Lymphocytes
- Monocytes
- Eosinophils
- Basophils
No ‘primitive’ cells
What Haematology Treatments are Available?
Replacement
- Blood
- Haematinics
- Coagulation factors
- Plasma exchange
Transplantation
Drugs
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis
