Introduction Flashcards
What are the components and products of blood?
Plasma
- Clotting or coagulation factors
- Albumin
- Antibodies
Buffy coat
- Platelets
- White cells or leucocytes
Red blood cells
What function of blood is are the RBC’s responsible?
Gas exchange: oxygen and carbon dioxide
What function of the blood is the plasma responsible for?
- Nutrient transport
- Waste transport
- Message transport
What are the functions of the blood?
- Transport
- Maintenance of vascular integrity
- Protection from pathogens
What function of blood are the platelets and clotting factors responsible for?
Prevention of leaks
What function of blood are the anticoagulants and fibrinolytics responseible for?
Prevention of blockages
What function of blood are the granulocytes and monocytes responsible for?
Antigen recognition and antibody formation
What are the mechanisms of pathogenesis of haematological abnormalities?
High levels
- Increased rate of production
- Decreased rate of loss
Low levels
- Decreased rate of production
- Increased rate of loss
Altered function
What are stem cells?
- Totipotent cells which self-renew
- Home to marrow niche
- The undergo binary fission and flux through differentiation pathways to amplify numbers. This is regulated by hormones and growth factors
Where is bone marrow located?
In most bones in children or in the axial skeleton of adults/elderly
What does bone marrow look like?
Stroma and sinusoids
What differentiation doe RBC undergo?
- Erythroblast
- Reticulocyte
- Erythrocyte
What is the reticulocyte count?
A measure of red blood cell production
Where is erythropoietin made and what trigger it?
Made in the kidney in response to hypoxia
What are the consequences of anaemia?
Poor gas transfer and as a result dyspnoea and fatigue
What can cause anaemia?
Decreased production
- Deficiency in haematinics such as iron, folate or vit B12
- Congenital: thalassaemia
Increased loss
-Bleeding, haemolysis
What is the function of platelets?
Haemostasis and immunity
What regulates platelet production?
Thrombopoietin
Where is thrombopoiten produced?
Liver
What is thrombopoietin production regulated by?
Platelet mass feedback
What is the lifespan of platelets?
7 days
What platelet agonists are used therapeutically?
- Romiplostim
- Eltrombopag
What pathologies are linked to platelets?
Thrombocytosis
- Myeloid malignancies
- Reactive
Thrombocytopenia
- Marrow failure
- Immune destruction
Altered function
-Aspirin, clopidogrel, abciximab
What is the function of neutrophils?
To ingest and destroy pathogens, especially bacteria and fungi
What is the lifespan of neutrophils?
1-2 days
What is the speed of response of neutrophils?
Few hours
How are neutrophils regulated?
Regulated by immune responses including macrophages and IL-17
What stimulates production of neutrophils?
Granulocytes colony stimulating factor and interleukins
What are the stages in neutrophil differentiation?
- Blast
- Promyelocyte
- Myleocyte
- Metamyelocyte
- Neutrophil
What is neutrophilia?
High number of neutrophils in the blood
What can cause neutrophilia?
Infection
-Left shift, toxic granulation
Inflammation
-Eg. MI, postoperative, rheumatoid arthritis
When G-CSF is used therapeutically
- Neutropenia
- Mobilisation of stem cells
What is neutropenia?
Low number of neutrophils in the blood
What can cause neutropenia?
Decreased production
- Drugs
- Marrow failure
Increased consumption
- Sepsis
- Autoimmune
Altered function
-Chronic granulomatous disease
Some individuals from Sub-Saharan Africa have natural neutropenia
What system do monocytes belong to?
The Reticuloendothelial System
What is the function of monocytes?
To ingest and destroy pathogens, especially bacteria ad fungi
What can monocytes differentiate into?
- Macrophages
- Dendritic cells
What is the lifespan of macrophages?
- Lifespan of many months
- Some populations of macrophages self-maintaining
What is the lifespan of dendritic cells?
Weeks
Name the myeloid cells.
- Monocytes
- Macrophages
- Neutrophils
- Basophils
- Eosinophils
- Erythrocytes
- Megakaryocytes
What are eosinophils involved in?
- Parasitic infection
- Allergies
What type of markers do lymphocytes possess?
CD markers
What is lymphocytosis?
Increase in the number of lymphocytes in the blood
Give examples of causes of lymphocytosis.
- Infectious mononucleosis
- Pertussis
What is lymphopenia?
Decrease in the number of lymphocytes in the blood
Give examples of causes of lymphopenia.
- Usually post-viral
- Lymphoma
What are the subtypes of lymphocytes?
- B cells
- T cells
- Natural killer cells
What do B cells do?
Make antibodies
What do T cells do?
Help, cytotoxic and regulatory cells
Where are lymphocytes produced?
Bone marrow
-B mature in the bone marrow and T cells In the thymus
Where do lymphocytes circulate?
In the blood, lymph and lymph nodes
What do lymphocytes differentiate into?
Differentiate into effector cells in secondary lymphoid organs (lymph nodes or mucosal associated lymphoid tissue)
What does each naïve B and T cell have?
A unique surface receptor
What are antibodies?
Produced by B cells, they are adaptors between pathogens and clearance systems. They are also known as immunoglobulins
What is the function of antibodies?
- Opsonisation
- Fix complement
- Block binding
How is antibody diversity created?
- Combinatorial diversity within each chain
- Junctional diversity
- Combinatorial diversity between chains
What does mistakes in antibody diversity lead to?
Lymphoid malignancies
Briefly describe the maturation of B cells.
- Immature B cells from in the bone marrow.
- Naïve B cells can centre of lymph node follicles and undergo somatic hypermutation to become memory B cells or plasma cells
What is positive and negative selection that occurs 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
What happen to B cells that undergo positive selection?
They are exported to the periphery
What do class I HLA display?
Displays internal antigens on all nucleated cells
What do class II HLA display?
Displays antigens eaten by professional antigen presenting cells
What variation in HLA is there?
Constant within, variation between individuals
What is the role of HLA?
Immune cells read HLA barcodes on cells to help identify self vs non-self cells or infected vs uninfected cells
Give examples of system disease which affect the blood?
- Rheumatoid arthritis
- Anaemia of chronic disease
- Iron deficiency
- Folate deficiency
- Immune haemolysis
- Neutrophilia
- Immune thrombocytopenia
- Cytopenias secondary to medication
- Felty syndrome
What blood disorders are linked to the hepatic system?
- Anaemia
- Deficient clotting factors
What blood disorders are linked to the renal system?
- Anaemia
- Haemolytic uraemic syndrome
What blood disorder is linked to the CV system?
Anaemia
What blood disorder is linked to the respirator system?
Polycythaemia
What blood disorder is linked to the GI system?
Anaemia
What pathologies can occur related to plasma?
Too much
-Paraproteins
Too little
-Clotting factors: haemophilia
Abnormal function
-Clotting factors: haemophilia
What is the normal haemoglobin range for a male?
135-170g/L
What is the normal haemoglobin range for a female?
120-160g/L
What is the normal range for platelets?
150-400 10^9/L
What is the normal range for WBC?
4-10 10^9/L
What diagnostic tools are used in haematology?
- FBC
- Clotting times for clotting factors
- Bleeding time for platelets
- (Platelet and leucocyte function tests)
- Chemical assays (iron (ferritin), B12 and folate)
- Marrow aspirate and trephine biopsy
- Lymph ode biopsy (other organ biopsy)
- Imaging
What treatments are used in haematology?
Replacement
- Blood
- Haematinics
- Coagulation factors
- Plasma exchange
Transplantation
Drugs
- Cytotoxics
- Monoclonal antibodies
- Inhibitors of cellular proliferation
- Immunosuppressants
- Inhibitors of coagulation
- Inhibitors of fibrinolysis
What is the structure of the spleen?
Red and white pulp
What can cause hypersplenism?
Pancytopenia
What can cause hyposplenism?
- Infections with encapsulated bacteria
- Red cell changes
What are the causes of splenomegaly?
- infection
- Haematological malignancy
- Portal hypertension
- Haemolytic disorders
- Connective tissue disorders
- Miscellaneous
- Storage poor disorders
What infectious causes of splenomegaly are there?
- Acute eg EBV, CMV
- Chronic bacterial eg TB, brucella, SBE
- Chronic parasitic eg malaria, leishmaniasis, schistosomiasis
What haematological malignancies can cause splenomegaly?
- Various leukaemia’s and lymphomas
- Myeloproliferative disorders
What haemolytic disorders can cause splenomegaly?
- Hereditary spherocytosis, thalassaemia, haemoglobinopathies
- Megaloblastic anaemia
- Autoimmune
What connective tissue disorders can cause splenomegaly?
- SLE
- Felty syndrome
What miscellaneous causes of splenomegaly are there?
- Sarcoid
- Malignant
- Amyloid
What storage pool disorders can cause splenomegaly?
- Niemann-Pick
- Gauchers
