haematology and haemopoeisis Flashcards
what is haematology?
the study of blood;
diagnosis and monitoring of diseases of the blood and blood-forming organs.
how is a full blood count measured?
measured on automated analysers
what is included in a full blood count?
red blood cell count (RBC), white blood cell count(WBC), platelets and mean cell volume (MCV)
what is the mean cell volume?
the average size of a red blood cell
what are the calculated parameters of haematological tests?
haematocrit (HCT)/packed cell volume (PCV); mean cell haemoglobin (MCH); mean cell haemoglobin concentration (MCHC)
what are some common haematological tests?
blood films; erythrocyte sedimentation rate (ESR); plasma viscosity; coagulation screen; haemoglobin-variant detection; molecular testing and point of care testing
what is measured in haematinic assays?
Iron, ferritin, B12 and folic acid
what are some pathology disciplines that overlap with haematology?
blood transfusion, immunology, clinical biochemistry, microbiology, histopathology, cytology, genetics, stem cell laboratories
what is haemopoiesis?
the process by which the cellular elements of blood are formed
what are the components of blood?
red blood cells, white blood cells and platelets.
what is the primary function of red blood cells?
to carry oxygen
what is the primary function of white blood cells?
prevention and recovery from disease
what is the primary function of platelets?
function in blood clotting
what is the most numerous type of cell in the blood?
red blood cell
what is the normal range of RBC in the blood?
4.0-5.5x10^12/ L
what is the size of RBC?
6.7-7.7 micrometer diameter
what do RBCs contain?
haemoglobin
what do RBCs do?
carry oxygen from lungs to tissues; transport carbon dioxide from tissues to lungs
how long do RBCs last?
110-120 days
what are the least numerous cell type found in the blood?
white blood cells
what is total white blood count normal range?
3.5-10x10^9/l
what are the 5 types of white blood cells?
lymphocytes, neutrophils, eosinophils, basophils, monocytes
what are granulocytes?
cells that contain granules in their cytoplasm
which white blood cells are granulocytes?
neutrophils, eosinophils, basophils
what is the normal range of neutrophils in the blood?
1.5-7.5x10^9/L
what is the function of neutrophils?
fight against bacterial infection
how many lobes present in the nucleus of mature neutrophils?
3 lobes
what is the half-life of neutrophils in circulation?
7 hours
morphology of the granules in neutrophils?
fine faint granules
what is the normal range of eosinophils in the blood?
0.03-0.60x10^9/l
how many lobes in the nucleus of eosinophils?
2 lobes
morphology of the granules in eosinophils?
coarse orange granules
functions of eosinophils?
release histamine in allergic reactions and regulate hypersensitivity reactions
which WBC is the effector cell for antibody-dependent damage to parasites?
eosinophils
what is the normal range for basophils in the blood?
0.01-0.15x10^9/L
how many lobes in the nucleus of basophils?
2 lobes
morphology of the granules in basophils?
dark coarse azurophilic granules
what is special about the granules in basophils?
they contain enzymes
what are the functions of basophils?
moderate inflammatory responses; release heparin and proteases
are lymphocytes a type of granulocyte?
no
what is the normal range of lymphocytes in the blood?
1.2-3.5x10^9/l
what are the functions of lymphocytes?
fight viral infection and produce antibodies
where are lymphocytes found?
circulate between blood and lymphatic system?
what is the life span of a lymphocyte?
variable life span from a few hours to 4-5 years in the circulation
what is the nucleus like in lymphocytes?
circular
what is the normal range for monocytes?
0.2-0.8x10^9/l
what are the functions of monocytes?
fight bacterial infections; phagocytose bacteria and cells coated with antibodies
what is important about monocytes?
they are the precursors of tissue macrophages
what is the life span of monocytes?
70 hours
which of the WBCs are phagocytic?
neutrophils and monocytes
what is the normal range of platelets in the blood?
150-400x10^9/L
what is the structure of platelets like?
small discoid structures
size of platelets?
0.3-0.5 micrometers diameter
what is the lifespan of platelets in circulation?
7-10 days
when are platelets important?
blood clotting (haemostasis)
what do platelets do?
form plug at the site of injury (primary haemostasis); initiate secondary haemostasis
what is the site of haemopoiesis in a 2-week embryo?
yolk sack
what is the site of haemopoiesis in a 12-16 week embryo?
liver and spleen
what is the site of haemopoiesis at birth?
bone marrow, all bones
what is the site of haemopoiesis in an adult?
proximal ends of long bones, flat bones such as sternum, pelvis and vertebrae
which marrow is active?
red bone marrow
which marrow is inactive
yellow bone marrow
what does haemopoiesis involve?
proliferation, differentiation and apoptosis
how is haemopoiesis regulated?
by growth factors
what are the 2 main classes of growth factors?
colony stimulating factors
interleukins
what do growth factors do?
regulate haemopoiesis
inhibit apoptosis
what are haemopoietic growth factors?
glycoproteins
where are haemopoietic growth factors produced?
stromal cells, t-lymphocytes, liver and kidney
what does the bone marrow produce?
> 1million RBC per minute; similar number of WBC and platelets
what is a haemopoietic stem cell (HSC)?
a cell which gives rise to all other blood cells
where are HSCs derived from?
mesoderm - found in early stages of embryonic development
where are HSCs located?
located in the bone marrow
what markers are present on the HSC?
CD34+
what does a HSC look like?
a small lymphocyte
what are some features of a haemopoietic stem cell?
has the ability to self renew; can find its way back to the bone marrow
what is erythropoiesis?
red blood cell production
what regulates erythropoiesis?
erythropoietin - EPO (hormone)
where is EPO produced?
in the kidney
How is EPO production stimulated?
as blood passes through the kidney –> low oxygen levels are detected - this indicates low RBC –> kidney is signalled to produce EPO.
what stops the production of EPO?
when the blood passes through the kidney and there is sufficient oxygen, the kidney is instructed to stop producing EPO.
what is the earliest erythroid precursor in the bone marrow?
pronormoblast
why can red blood cells pass through the capillary microbules?
due to their flexible membrane (biconcave disc)
what is the cause of RBC death?
loss of the enzymes which maintained shape and flexibility.
where are RBCs destroyed?
bone marrow, spleen and liver
what happens to the cellular content from the destroyed RBC?
the cellular content (proteins, lipid and iron) are recycled
what happens to the breakdown products of haemoglobin?
they are excreted through liver, faeces and urine
what are granulocytes and monocytes produced from?
common myeloid precursor cells
how are granulopoiesis and monopoiesis regulated?
the combined actions of haemopoietic growth factors
what does IL-3 regulate?
the production of neutrophils, monocytes and basophils
what is GM-CSF?
granulocyte-macrophage colony-stimulating factor
what does IL-5 regulate?
production of eosinophils
stages of the development of granulocytes?
myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band forms –> mature granulocyte
what are the stages of monocytopoiesis?
monoblast –> promonocyte –> marrow monocyte –> blood monocyte (–> tissue macrophage)
how long do blood monocytes last in circulation?
20-40 hours
what is the morphology of blood monocytes?
they have variable morphology
what sort of nucleus is present in blood monocytes?
mononuclear
what is the function of blood monocytes?
phagocytose and destroy bacteria
how is lymphopoiesis regulated?
by IL1, 2, 4, 6 and 7
steps of lymphopoiesis?
lymphoblast –> prolymphocyte –> large lymphocyte –> small lymphocyte
what are the 2 types of lymphopoiesis?
B lymphopoiesis and T lymphopoiesis
where do B cells mature?
in the bone marrow
where do T cells mature?
in the thymus
what are B lymphocytes responsible for?
humoral immunity
what do B lymphocytes do?
carry surface receptors which recognise and bind foreign antigen; trigger cell proliferation into plasma cells; secreter antibodies
what are T cells responsible for?
cellular immunity
what is important for T cell activation?
antigen specificity
how are T cells activated?
antigen must be processed and presented by macrophages for activation to occur
what are the 5 main subsets of T lymphocytes?
T helper, T memory, T regulatory, T cytotoxic and Natural killer cells
what is thrombopoiesis?
platelet development
how is thrombopoiesis regulated?
by thrombopoietin
what do platelets interact with to form initial barrier to blood loss?
von Willibrands factor
how do platelets support coagulation?
they provide a negatively charged lipid surface
what are some functions of platelets?
localise thrombus formation, promote vasoconstriction, promote vessel repair
what are the stages of thrombopoiesis?
megakaryoblast –> promegakaryocyte –> megakaryocyte –> platelets
what is endomitotic replication?
replication of DNA without nuclear or cell division
what happens to cells after cycles of endomitosis?
cells become progressively larger with each complete cycle of endomitosis
what is the result of endomitosis?
large uninucleate cells with 64n DNA content
what happens in the cytoplasm of mature megakaryocyte?
a large number of platelets are produced
what happens to the platelets in the cytoplasm of megakaryocytes?
rapidly discharged directly into the bone marrow
what happens to the bare nucleus of megakaryocytes?
phagocytosed by macrophages
how long does thrombopoiesis take?
2-3 days
how many platelets does a megakaryocyte produce?
each megakaryocyte produces 2000-7000 platelets
what are the steps of primary haemostasis?
platelet activation, platelet adhesion, platelet aggregation
when is secondary haemostasis needed?
when platelet plug is not sufficient to stem blood loss and needs to be reinforced.
how does secondary haemostasis reinforce primary haemostasis?
by a series of biochemical reactions
what does secondary haemopoiesis do?
transform soluble fibrinogen to insoluble fibrin.
what does insoluble fibrin do?
intertwines with cellular components of the forming thrombus = forms a supporting scaffold
