Introduction to Haematology Flashcards
What are the components of blood?
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What is found in the plasma of blood?
Clotting or coagulation factors
Albumin
Antibodies
What is found in the ‘buffy coat’ of blood?
Platelets
Leukocytes
What are the functions of blood?
-
Transport
- Red cells
- Gases – oxygen and carbon dioxide
- Plasma
- Nutrients
- Waste
- Hormones (messages)
- Red cells
-
Maintenance of vascular integrity
- Platelets and clotting factors
- Prevention of leaks
- Anticoagulants and fibrinolytic
- Prevention of blockages
- Platelets and clotting factors
-
Protection from pathogens
- Granulocytes/monocytes
- Phagocytosis and killing
- Lymphocytes
- Antigen recognition and antibody formation
- Granulocytes/monocytes
What cells allows blood to achieve the function of transport?
- Red cells
- Gases – oxygen and carbon dioxide
- Plasma
- Nutrients
- Waste
- Hormones (messages)
What cells allow blood to achieve the function of maintanence of vascular integrity?
- Platelets and clotting factors
- Prevention of leaks
- Anticoagulants and fibrinolytic
- Prevention of blockages
What cells allow blood to achieve the function of protection from pathogens?
- Granulocytes/monocytes
- Phagocytosis and killing
- Lymphocytes
- Antigen recognition and antibody formation
How can haematological abnormalities be classified?
- High levels
- Increased rate of production
- Decreased rate of loss
- Low levels
- Decreased rate of production
- Increased rate of loss
- Altered function
Where does haematopoiesis happen?
Bone marrow
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What is the formation of blood cellular components called?
Haematopoiesis
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Describe the process of haematopoiesis?
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What are myeloid cells?
All cells apart from lymphocytes, which are lymphoid cells
What stem cells are found in the bone marrow/blood?
Pluripotent haematopoietic stem cell
Mesenchymal stem cells
What do mesenchymal stem cells give rise to?
- Osteoclasts
- Liver
- Skin
- Blood vessels
What are properties of stem cells?
- Totipotent
- Self-renewal
- Home to marrow niche
- CXCR4 (antagonistic plerixafor)
How do stem cells grow?
Grow by binary fission and flux through differentiation pathways to amplify numbers:
- Flux regulated by hormones/growth factors
- Some used therapeutically (erythropoietin, G-CSF, thrombopoietin agonists)
Where is bone marrow located?
Located within bones:
- In most bones in children, axial in elderly
Describe the structure of bone marrow?
- Stroma and sinusoids
Describe the erythrocyte differentiation anatomy?
- Erythroblast -> reticulocyte -> erythrocyte (red blood cell)
What is the correct name of a red blood cell?
Erythrocyte
What hormone governs the development of erythrocytes?
Hormone that governs this is erythropoietin:
- Made by kidney in response to hypoxia
Where is erythropoitin made and in response to what?
- Made by kidney in response to hypoxia
What investigation is used to measure red cell production?
Reticulocyte count
What are some pathologies related to red blood cells?
- Polycythaemia
- Too many red cells
- Anaemia
- Too few red cells
- Aetiology
- Decreased production: deficiency in haematoinics (iron, folate, B12) or congenital (thalassaemias)
- Increased loss: bleeding, haemolysis
What is the aetiology of anaemia?
- Decreased production: deficiency in haematoinics (iron, folate, B12) or congenital (thalassaemias)
- Increased loss: bleeding, haemolysis
What is the medical term for too many red cells?
Polycythaemia
How can anaemia be classified?
- Microcytes/macrocytes (big or small cells)
What terms describe big and small red cells?
- Microcytes/macrocytes (big or small cells)
How many red cells can be made per day?
Can make about 10g/L/day of red cells
What are platelets released from?
Released from megakaryocytes
What is the function of platelets?
- Haemostasis (and immune)
What hormone regulates the production of platelets?
Production regulated by thrombopoietin:
- Produced in liver
- Regulation by platelet mass feedback
Where is thrombopoietin produced and what provides regulation?
Production regulated by thrombopoietin:
- Produced in liver
- Regulation by platelet mass feedback
What is the lifespan of a platelet?
7 days
What are some pathologies related to platelets?
- Thrombocytosis
- Too many platelets
- Aetiology – myeloid malignancies such as Dominic Culligan
- Thrombocytopenia
- Too few platelets
- Aetiology – marrow failure, immune destruction (such as in ITP or Henry Watson)
- Altered function
- Aetiology – drugs (aspirin, clopidogrel, abciximab)
What is the medical term for too many platelets?
Thrombocytosis
Describe the aetiology of thrombocytosis?
- Aetiology – myeloid malignancies such as Dominic Culligan
What is the medical term for too few platelets?
Thrombocytopenia
Describe the aetiology of thrombocytopenia?
- Aetiology – marrow failure, immune destruction (such as in ITP or Henry Watson)
Describe the aetiology of altered function of platelets?
- Aetiology – drugs (aspirin, clopidogrel, abciximab)
What is the function of neutrophils?
- Ingest and destroy pathogens, especially bacteria and fungi
- Communicates with other cells
- Interleukins (between white cells)
- CSFs (colony stimulating factors) to grow more neutrophils
What chemicals do neutrophils use to communicate with other cells?
- Interleukins (between white cells)
- CSFs (colony stimulating factors) to grow more neutrophils
How is neutrophil production regulated?
Regulation by immune responses:
- Macrophages, IL-17
What is the lifespan of a neutrophil?
Lifespan is 1-2 days
Describe the process of neutrohil development?
- Blast (acute myeloid leukemia is too many of these)
- Promyelocyte
- Myelocyte
- Metamyelocyte
- Neutrophil
What hormone regulates production of neutrophils?
Production regulated by granulocyte-colony stimulating factor (G-CSF):
- Infection
- Left shift, toxic granulation
- Inflammation
- Such as in MI, postoperative, rheumatoid arthritis
- G-CSF used therapeutically
- Neutropenia
- Mobilisation of stem cells
What does G-CSF stand for?
Granulocyte-colony stimulating factor
What is the medical term for low concentration of neutrophils?
Neutropenia
Describe the aetiology of neutropenia?
- Decreased production
- Drugs
- Marrow failure
- Increased consumption
- Sepsis
- Autoimmune
- Altered function
- Such as in chronic granulomatous disease
What is the function of monocytes?
- Ingest and destroy pathogens, especially bacteria and fungi
What can a subset of monocytes do?
Subset of monocytes migrate into tissues and become macrophages or dendritic cells:
- These pick up antigens and migrate to lymph nodes
Macrophages change their name depending on what?
What tissue they are in
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Other than monocytes, what are some other myeloid cells?
- Eosinophils
- Parasites
- Allergy
- Basophils
Do lymphocytes mediate adaptive or innate immune system?
Mediates adaptive immune system rather than innate:
- Creation of immunological memory
What are lymphocytes unique surface markers?
Develop their own surface antigens:
- CD markers
What are some pathologies related to lymphocytes?
- Lymphocytosis
- Aetiology - infectious mononucleosis, pertussis
- Lymphopenia
- Aetiology – usually post-viral, lymphoma
What is the medical term for too many lymphocytes?
Lymphocytosis
Describe the aetiology of lymphocytosis?
- Aetiology - infectious mononucleosis, pertussis
What is the medical term for too few lymphocytes?
Lymphopenia
Describe the aetiology of lymphopenia?
- Aetiology – usually post-viral, lymphoma
What are the subtypes of lymphocytes?
- B cells
- Make antibodies
- T cells
- Helper, cytotoxic, regulatory
- Natural killer (NK) cells
Where are lymphocytes produced, and where do they mature?
Produced in bone marrow:
- B cells mature in bone marrow, whereas T cells mature in thymus
Where do lymphocytes differentiate into effector cells?
Differentiate into effector cells in secondary lymphoid organs:
- Lymph nodes
- Mucosal associated lymphoid tissue
Each naive T and B cell has unique what?
Unique surface receptor
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Describe the structure of immunoglobulins?
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T cell receptors are made out of what?
T cell receptor are made of alpha chain and beta chain
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What do antibodies perform?
Antibodies are adaptors between pathogens and clearance systems:
- Perform opsonisation (makes target prone to destruction by other cells)
What is opsonisation?
- Perform opsonisation (makes target prone to destruction by other cells)
What are the different kinds of antibodies?
- IgG
- IgE
- IgD
- IgM
- IgA
What does the creation of the receptor gene allow for?
Creation of receptor chain gene:
- Allows for enormous variability
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What are different ways that allow receptor diversity to be achieved?
- Combinatorial diversity – within each chain
- V-region combined with J- or D- then C region
- Junctional diversity
- At join, additional nucleotides added for further diversity
- Combinatorial diversity – between chains
- Each alpha chain pairs with a beta chain
- Each light chain pairs with a heavy chain
What is a consequence of the genetic processes allow for huge receptor diversity?
A consequence is mistakes cause lymphoid malignancies
Describe B cell maturation?
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Where does positive and negative selection of B cells occur?
Positive and negative selection occurs in the bone marrow:
- Positive selection
- If gene rearrangement results in a functional receptor the cell is selected to survive
- Negative selection
- If receptor recognises ‘self’ antigens the cell is triggered to die
What does HLA stand for?
Human leucocyte antigen
What is HLA?
Molecules that grab antigens in body and take to B or T cells
What are the different classes of HLA?
- Class I
- Displays internal antigens on all nucleated cells
- Class II
- Displays antigens eaten by professional antigen presenting cells
What are some pathologies related to plasma?
- Too much
- Paraproteins
- Too little
- Clotting factors – haemophilia
- Altered function
- Clotting factors - haemophilia
What are examples of systemic disease that affect the blood?
- Rheumatoid arthritis
- Anaemia of chronic disease
- Iron deficiency
- Folate deficiency
- Immune haemolysis
- Neutrophilia
- Immune thrombocytopenia
- Cytopenias secondary to medication
- Felty syndrome
Other examples:
- Hepatic
- Anaemia, deficiency clotting factors
- Renal
- Anaemia, haemolytic uraemic syndrome
- Cardiovascular
- Anaemia
- Respiratory
- Polycythaemia
- Gastrointestinal disease
- Anaemia
What are some diagnostic tools for haematological conditions?
- Full blood count
- Clotting factors
- Clotting times for clotting factors and platelets (platelet and leucocyte function tests)
- Chemical assays
- Iron (ferritin)
- B12
- Folate
- Biopsy
- Marrow aspirate and trephine biopsy
- Lymph node biopsy
- Imaging
- CT angiogram
- Plain film
- CT scan
What chemical assays are often used in haematology?
- Iron (ferritin)
- B12
- Folate
What biopsys are often done in haematology?
- Marrow aspirate and trephine biopsy
- Lymph node biopsy
What does a FBC measure?
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In a FBC, what are the normal ranges for:
- haemoglobin
- RBC
- platelets
- WBC
- neutrophils
- lymphocytes
- monocytes
- eosinophils
- basophils
What are different kinds of haematological treatments?
- Replacements
- Blood
- Haematinics
- Coagulation factor
- Plasma exchange
- Transplantation
- Drugs
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis
What are some drugs often used in haematology?
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis
What are some replacement therapies often used in haematology?
- Blood
- Haematinics
- Coagulation factor
- Plasma exchange