Week 11 Haematological Flashcards
Leukopoiesis
White Blood celll formation and maturation within the bone marrow
Granulated/ monocyte stage of differentiation
Differentiation into myeloid cells, leading to neutrophils, eosinophils, basophils, and monocytes/macrophages
Megakaryocytes / Platelets
Formation of megakaryocytes that produce platelets essential for blood clotting
Lymphoid development
Yields lymphocytes including B and T cells
Neutrophil: Morphology, Function, Location and Lifespan
Morphology: Polymorphonuclear with granules
Function: Phagocytosis for innate immunity
Location: circulate in blood and migrate to sites of infection
Lifespan: 6-8 hours
Monocyte : Morphology, Function, Location and Lifespan
Morphology: Kidney shaped nucleus with fine granules
Function: precursor of macrophages and dendritic
Location: circulate in blood, and migrate to tissues when needed
Lifespan: circulate for a few days, can live for months to weeks in tissuse
Eosinophil : Morphology, Function, Location and Lifespan
Morphology: bilobed nucleus with large granules
Function: defence against parasitic infections and involvement in allergies
Location: tissues and bloodstream
Lifespan: 8-12 hours
Basophils : Morphology, Function, Location and Lifespan
Morphology: bilobed nucleus large granules
Function: release histamine and other mediators involved in allergic response
Location: circulate in blood but are rare compared to other WBCs
Lifespan: hours to days
Macrophages: Morphology, Function, Location and Lifespan
Morphology: irregular shaped nucleus, abundant cytoplasm
Function: phagocytosis of pathogens and debris + antigen presentation and tissue repair
Location: lungs liver spleen ect
Lifespan: months to years
Chemotaxis
Biological process in which cells such as immune cells move in response to chemical signals or gradients
Lymphocytes
T and B cells
T cells function
Cell mediated immunity
Recognise and attach infected or abnormal host cells such as virus infected or cancer cells.
There are multiple types including CD8+ (cytotoxic), CD4+ (t helper) to Tregs (T regulatory)
B lymphocytes function
Humoral Immuntity, produce antibodies that can neutralise pathogens, mark them for destruction or enchanted phagocytosis, also antigen prevention to T cells
Leucoytosis
Abnormal increase in number of leukocytes in blood often indicating immune response to infection
Leukopeania
Decrease in total WBC count, increasing infection risk
Neutropaenia
Condition characterised by a deficiency in neutrophils, increasing risk of bacterial infections
Monocytopeadia
Reduction in number of monocytes, reducing ability to fight certain infections and inflammatory condition s
Lymph Node capsule function
Provides structural support
Lymph nodes subcapsular sinus function
Collects lymph and acts as the intital filtration site for pathogens and foreign materials
Lymph Node cortex function
Contains B cell follicle where B lymphocytes produce antibodies in response to antigens
Lymph node paracortex function
Contains T cell zones where t lymphocyte are activated and play a crucial role in cell mediate immunity
Lymph node medulla function
Contains plasma cells that produce antibodies and macrophages that phagocytise pathogens and disease
Lymphoid nodules function
Clusters of b and t lympcytes that participate in the immune response by recognising and responding to antigens
Chemokine
Subset of cytokine - attract immune cells to site of infection or inflammation
Roles of neutrophils
Phagocytosis
Degranulation - release contents into external environment
Netosis: Expulsion of nuclear material in the form of Neutrophil extracellular traps
Process of pathogen recognition
- Pathogens Exposure
- Antigen identification - by WBCs eg macrophage
- PRR binding - binding of pattern recognition receptors to pathogens surface
- Phagocytosis
- Antigen presentation
- T cell recognition - T helper cells or Cytotoxic T
B B cell recognition
Complement Action
Opsonisation - Proteins coat pathogens, making them ore susceptible to phagocytosis
Inflammation - Complement activation leads to increased Blood flow
Punching holes / lysis of membrane
IgM antibodies
Most common, long term protection
IgD Antibodies
Found in mucosal secretions
IgG Antibdies
First one produced, is a pentagon, good for agglutination
IgE antibodies
Found on surface of B cells
IgA antibodies
Allergic response and hypersentivity
AML leukaemia
Fast growing cancer of blood and bone marrow charterized by rapid proliferation of immature myeloid WBCs
ALL leukaemia
Rapidly progressive cancer of blood and bone marrow primary affecting lymphoid WBCs, most common in children
CML leukaemia
Slow gorwing, originates in myeloid WBCs, presence of Philadelphia chromosome
CLL leukaemia
Slowly progressing, effects lymphocytes, accumulation of abnormal WBCs in bone marrow
MM leukaemia
Cancer of plasma cells in bone marrow, leading to overproduction of abnormal monoclonal antibodiess and weakened bones
Leukaemia vs Lymphoma
Leukaemia = excess clonal WBCs
Lymphoma = clonal proliferation of various cell subset of lymphocytes at different stages of maturation
Lymphocyte = T cell, B cell, NKC
Indolent malignancy
Slow and non aggressive
Acute lymphoid malignancy
Progress refit and involve immature or underdeveloped cells
Clinical Features of acute leukaemia
Fatigue
Infection
Bleeding (due to increased platelets)
Heptosplenomegaly
Lymphadenopathy
Headache
Athralgia (joint pain)
Skin rashes
Clinical features of chronic leaukeamias
Fatigue
Heptosplenomegaly
Lymphadenopathy
Athragia
Complications of haematological malignancies
Organomegaly
Bleeding/brusing
Infection
Anaemia
Renal failure (due to abnormal proteins eg Immunoglobulins which can clog and damage filtration systems)
Bone pain
Risk factors for leukaemia
Chemicals/radiation
Genetic abnormality (eg Down syndrome)
Smoking
Viruses eg Epstein Barr virus
Past medical history
Family history
Roles of Bone marrow biopsy
Diagnoses - rule out leukaemia, lymphoma and myeloma
Classification - subtype and stage of malignancy ~
Staging - can see stage and potential spread
Monitoring - response to treatment/relapse
Treatment guide
Flow Cytometry markers
CD34 - immaturity
CD19 - indicative of lymphoid lineage
CD117 - indicates myeloid lineage
Binet staging system for CLL (chronic lymphocytic leukaemia)
Stage 1: fewer than three enlarged lymph node groups + no anaemia or thrombocytopenia
Stage 2: 3+ enlarged lymph node groups + no anaemia or thrombocytopenia
Stage 3: have anaemia or thrombocytopenia, enlarged lymph node groups doesn’t matter
Stages of cancer treatment
Induction: rapidly reduce cancer cells
Consolidation eliminate any remaining cancer cells
Maintenance: Lower dose long term theoapy to prevent re emergence
Allogenic Stem cell transplant infusing of healthy stem cells to replace diseased bone marrow
Development of Chronic Myeloid leukaemia
- Reciprocal translocation (between chromosomes 9 and 22) forms BCR-ABL gene
- BCR-ABL fusion genes codes for active tyrosine kinase
- Tyrosine kinase activates uncontrolled cell signalling and proliferation, particularly of Granulocytes
- Abnormal accumulation of myeloid cels in marrow and blood leds yo fatigue, splenomegaly, leukocytosis
Leakocytosis
Abnormally high WBCs
TKIs (tyrosine kinase inhibitors)
Bind to active site, name ends in -inib
Polycythaemia Vera (PV)
Blood disorder where bone marrow produces to many RBCs, WBCs, and platelets, leading to increased clotting risk
Throbocythemia (AKA ET)
Overproduction of platelets, can lead to abnormal blood clots or bleeds
Myelofibrosis
Bone marrow develops fibrosis tissue, reducing ability to produce normal cells, leading to anaemia and splenomegaly
Aplastic anaemia
Reduction of number of all blood cell types, in bone marrow
To diagnose CBC and also Bine marrow biopsy (to see reduction in heamatopoetic blood cells)
Treatment can be meds, blood transfusions, or others
