1. Introduction: The scope of clinical haematology Flashcards
what is the blood components and products?
what is the transport function of blood?
In blood:
- Gases - Oxygen and carbon dioxide
In plasma:
- nutrients
- waste
- messages
Functions of blood:
Maintenance of Vascular Integrity - how does blood do this?
- Prevention of leaks by clotting factors and platelets
- Prevention of blockages by anticoagulants and fibrinolytics
another function of blood is protection from pathogens, how is this done?
- Phagocytosis and killing by granulocytes/monocytes
- Antigen recognition and antibody formation by lymphocytes
Pathogenesis of haematological abnormalities/what causes haeatological abnormalities?
•High levels
- Increased rate of production
- (Decreased rate of loss)
•Low levels
- Decreased rate of production
- Increased rate of loss
•Altered function (often genetically determined and often less important)
what is Haematopoiesis?
the formation of blood cellular components
Cells in blood all made form stem cells
Leukocytes are the white blood cells
Myeloid cells are all cells but lymphocytes
what are the features of stem cells?
- totipotent - can differentiate into all those cell types
- self-renewal (can divide and maintain their numbers)
- 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’
wher eis bone marrow and what does it look like?
- Where is it? - Bones: most in children, axial in elderly
- What does it look like? - Stroma and sinusoids
what is Erythroid differentiation an dwhat governs it?
- Erythroblast–>reticulocyte–>erythrocyte
- Erythropoietin - made in kidney in response to hypoxia
what is Reticulocyte count?
a measure of red cell production
what is polycythaemia?
Polycythaemia, also known as erythrocytosis, means having a high concentration of red blood cells in your blood. This makes the blood thicker and less able to travel through blood vessels and organs
what causes anaemia?
•Decreased production:
- Deficiency in ‘haematinics’ - iron, folate, vitamin B12
- Congenital: thalassaemias
•Increased loss:
- Bleeding, haemolysis
what are the consequences of anaemia?
Poor gas transfer: dyspnoea, fatigue
you cna classify anaemia in what way?
You can classify anaemia weather the cells are big or small
- Microcytes, macrocytes
- Polychromasia (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)
- Burr cells in renal failure etc
what is the first line of defence if there is a broken blood vessel?
platelets
they clump together
what makes platelets?
Released by megakaryocytes in the bone marrow – platelets bud off from it
what is the function of platelets?
haemostasis (and immune)
platelet production is regulated by what?
•Production regulated by thrombopoietin
- Produced in liver
- Regulation by platelet mass feedback
what is the lifespan of platelets?
7 days
what are some platelet pathologies?
•Thrombocytosis (to many platelets):
- In Myeloid Malignancies: Dominic Culligan
- ‘Reactive’
•Thrombocytopenia (to few platelets):
- Marrow failure
- Immune destruction: ITP: Henry Watson
•Altered function - aspirin, clopidogrel, abciximab etc
what is the function of neutrophils?
to ingest and destroy pathogens, especially bacteria and fungi
what regulates neutrophils?
•regulation by immune responses - Macrophages, IL-17
IL-17 stimulates production of neutrophils within hours of detection of the bacteria infection
what are neutrophils lifespan and speed of response?
- Lifespan = 1-2 days
- Speed of response = few hours
what are the steps in neutrophil differentiation?
starts in marrow
Neutrophils - Production regulated by granulocyte-colony stimulating factor (G-CSF)
but what is neutrophilia?
a high number of neutrophils in the blood
what causes neutrophilia?
- Infection - Left shift (when immature neutrophils are released from the bone marrow due to an outpouring of cells, typically due to infectio), toxic granulation
- Inflammation - eg MI, postoperative, rheumatoid arthritis
- G-CSF used therapeutically:
- Neutropenia
- Mobilisation of stem cells
what are the causes of neutropenia? (abnormally low concentration of neutrophils in the blood)
- Decreased production - Drugs, Marrow failure
- Increased consumption - Sepsis, Autoimmune
- Altered function - eg chronic granulomatous disease
Monocytes-the ‘reticuloendothelial system’ - what is its function?
to ingest and destroy pathogens, especially bacteria and fungi
Subset of monocytes migrate into tissues and become macrophages or dendritic cells
what is Lymphocytosis? and its causes?
higher-than-normal amount of lymphocytes
- Infectious mononucleosis (EBV)
- Pertussis (whooping ccough)
what is •Lymphopenia and its causes?
low lymphocytes
- Usually post-viral
- lymphoma
whata re the subtypes of lymphocytes and where are they made?
•Subtypes
- B cells – make antibodies
- T cells – Helper, cytotoxic, regulatory
- NK cells (like T cells that fight viral infections)
•Produced in bone marrow - B cells mature in bone marrow, T cells in thymus
Adaptive receptor diversity:
•Each naïve T and B cell has unique what?
surface receptor
Immunoglobulins made up of light and heavy chain
T cell receptor made up of alpha and beta chain
Antibody sticks to a bug it recognises and then the rest of the immune system comes and ________ __
destroys it
what is the process of B cell maturation?
Germinal centers or germinal centres (GCs) are sites within secondary lymphoid organs – lymph nodes and the spleen – where mature B cells proliferate, differentiate, and mutate their antibody genes during a normal immune response to an infection.
what is positive and negative selection 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 are the types of Human leucocyte Antigen: HLA?
•Class I: displays internal antigens on all nucleated cells
Molecules that take antigens form within the cell and bind them and bring them to the surface so B and T cells know what is going on within the cell
That’s how cytotoxic T cells know a cell has been infected by a virus as bits of the virus are displayed on the surface
- Class II: displays antigens eaten by professional antigen presenting cells (e.g. macrophages)
- Constant within (No variation like B and T cells receptors), variation between individuals
many systemic diseases affect the blood such as what?
rheumatoid arthritis
- Hepatic - Anaemia, deficient clotting factors
- Renal - Anaemia, haemolytic uraemic syndrome
- Cardiovascular - anaemia
- Respiratory - Polycythaemia
- Gastrointestinal disease - anaemia
what are some problems with plasma?
- Too much - Paraproteins
- Too little - Clotting factors: haemophilia
- Abnormal function - Clotting factors: haemophilia
what are some different diagnostic tools that can be used?
- Full blood count (most ocmmon in haemtaology)
- Clotting times for clotting factors and platelets (Platelet and leucocyte function tests)
- Chemical Assays e.g. iron (ferritin), B12, Folate
- Marrow aspirate and trephine biopsy, Lymph node biopsy, Other organ biopsy
- Imaging
what haeatomogical treatmens is there avalible?
•Replacement:
- Blood
- Haematinics
- Coagulation factors
- Plasma exchange
- Transplantation (haematopoetic stem cell transplantation)
- Drugs:
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis
