HEMATOLOGY Flashcards
blood cells and their function
red blood cells- oxygen and carbon dioxide transport
platelets-haemotosis
neutrophils- protection from bacteria and fungi
monocytes- protection from bacteria and fungi
eosinophils- protection against parasites
lymphocytes-B cells-immunoglobulin synthesis
-T cells -protection against viruses
what is the difference of lifespan between red blood cells and platelets
red blood cells- 120 days
platelets- 10 days
What is a decrease/increase in myeloid cells
Pancytopenia/pancytosis
What is a decrease/increase in red cell count
Anaemia/ erythrocytosis
What is a decrease/increase in neutrophils
Neutropenia/neutrophilia
What is a decrease/increase in white cells
Leukopenia/leukocytosis
Whats an increase in eosinophil
Eosinophilia
What is an increase in basophils
Basophilia
Whats a decrease/increase in monocytes
Monocytopenia/monocytosis
Whats a decrease/increase in lymphocyte
Lymphopenia/lymphocytosis
Whats a decrease/increase in platelet
Thrombocytopenia/thrombocytosis
What is haematopoiesis
Is the commitment and differentiation process that leads to the formation of all blood cells from haematopietic stem cells
When does haematopoiesis take place
In the egg yolk in a fetus and in the bone marrow of an adult
What is the role of pluripotent haematopoietic stem cells
Can self renew and differentiate into a variety of cell types and the oath is determined by a range of growth factors present
What are the types of growth factors
Colony stimulating factors (CSF)- mutli CSF (IL-3) and GM-CSF (granulocyte macrophage)
EPO(erythropoietin) induces production of RBCs (red blood cells)
TPO(thrombopoietin) induces the production of megakaryocytes
what is erythropiesis
the differentiation of proerythroblast cells into mature red blood cells
describe the cells in order in erythropiesis
proerythroblst-basophlic erythroblast-polychromatphilic erythrobloast- normoblast-reticulocyte-mature erythrocyte
what is present in a normoblast
nuclear DNA, RNA in cytoplasm, its in one marrow and not in the blood
whats present in a reticulocyte
no nuclear DNA, RNA in cytoplasm and is present in blood and bone marrow
what is present in a mature RBC
no nuclear dna and no rna in cytoplasm it is present in bone marrow and blood
where is EPO produced
in the kidney in response to anoxia caused by anemia
it acts to stimulate erythropoiesis and stimulates haemoglobin synthesis
is the reticulocyte present in blood
yes and it later develops into mature blood cells within 24 to 48
what factors affect erthrocyte production
iron, vitamin B12 and folic acid
what are the reasons for thrombocytopenia
result of decreased bone marrow production usually in an enlarged spleen or an increases platelet destruction due to infection, drugs, immune mechanisms
what are the reasons for thrombocytosis
due to iron deficiency, imflammation, cancer or infection
what could be the cause of changes in leukocytes
infection, trauma, malignancy, autoimmunity, allergy and drugs
what does mean cell volume mean
how big the cells are on average
what does packed cell volume/haematocrit mean
how much of the blood volume is cells
what does mean cell haemoglobin mean
average amount of Hb per RBC
what does mean cell Hb concentration mean
conc of Hb in a given volume of RBC’s
what does red cell distribution width mean
how variable are individual cell size measurements
what is anemia
reduction in RBC Hb concentration
what are cells with low MCV called
microcytic
what are cells with high MCV called
macrocytic
what is microcytic hypochromic anemia
smaller RBC and decreased colour
what is normocytic normochromic anemia
individual rbc normal but fewer in number
what is hemolytic anemia
usually an increase in reticulocytes
what are the causes of acquired anemia
iron, folate deficiency- blood loss, anemia of chronic disease, haemolysis, marrow infiltration
what are the causes of inherited anemia
haemoglobinpathies eg thalassemia, sickle cell disease and RBC membrane defects
what is the normal reticulocyte percentage in blood
0.5-2%
what happens to reticulocyte count if anemia is caused by bleeding
reticulocyte count increases
what does a low reticulocyte number suggest
anemia due to failure of production of RBC. this could be due to iron deficiency, VitB12 deficiency, folate deficiency or kidney disease
what kind of anemia does iron deficiency cause
microcytic hypochromic anemia
how is iron recycled in the body
the iron is transported to the blood where it is carried by transferrin to the bone marrow for erythropoiesis and the destruction of RBCs leads to iron recycling
what usually causes iron deficiency
blood loss or heavy menstrual periods
what are the other causes of microcytic anemia
anemia of chronic disorders-failure of iron release to serum by macrophages
sideroblastic anemia- failure of protoporphyrin synthesis for haem ring
thalassaemias- failure of globin synthesis due to genetic defect
what is sideroblastic anemia
disordered incorporation of iron into haem within the mitochondria of developing erythroblasts
what are causes of sideroblastic anemia
hereditary- X linked
drugs-isoniazid
lead poisoning
idiopathic-common form and disease of the elderly
what causes chronic disorder anemia
typically normocytic and normochromic
pathogenesis related to decrease release of iron from macrophages to plasma and reduced RBC lifespan
what type of macrocytic anemia is there and what causes it
megaloblastic anemia caused by vit B12 and folate deficiency
how does folate or b12 deficiency lead to megaloblastic anemia
reduces the rate of conversion of dUMP to dTMP which is the rate limiting step in DNA synthesis. dTMP is converted into dTTP and a failure of this conversion leads to the inclusion of dUTP which can lead to DNA fragmenting and premature death of cell
what are causes of vitamin B12 deficiency
pernicious anemia-the failure of gastric parietal cells to synthesise intrinsic factor
total or partial gastrectomy- removes the source of IF production
some drugs impair b12 absorption
what are causes of folic acid deficiency
dietary
demand-folic acid deficiency is common in pregnancy as there is an increased demand
drugs- some drugs affect the absorption eg methotrexate as well as alcohol
what is haemolytic anemia
anemias that result from an increase in the rate of red cell destruction
why is it difficult to notice HA (haemolytic anemia)
normal adult bone marrow can produce red cells at 6-8 times the normal rate during a HA episode and so unless the lifespan reaches below 30 days it may not be noticeable
what is immune haemolytic anemia
caused by the presence of auto-antibodies or complement on the surface of the RBC leading to cell death
what is drug induced haemolytic anemia
antibody directed against drug-red cell membrane complex eg penicillin
deposition of complement by drug protein antibody complex
what is haemostasis
is the stopping of excessive bleeding from a cut or severed vessel to prevent excessive blood loss
what are the three phases of haemostasis
- formation of a temporary platelet aggregate
- formation of a fibrin mesh
- dissolution of the haemostatic plug
what happens after a vascular injury
reflex vasoconstriction as well as the endothelium cells releasing endothelin which causes vasoconstriction
what happens in primary haemostasis
-platelets bind to collagen via von willebrand factor (vWF) and are activated then undergo a shape change and release granules. the released granules then induce additional platelet aggregation and through binding fibrinogen form the primary haemostatic plug
what happens in secondary haemostasis
local activation of the coagulation cascade (involving exposed tissue factorand platelet phospholipids) results in fibrin polymerisation due to the action of thrombonin. this solidifies the platelets into a definitive secondary haemostatic plug
what is a coagulation cascade
the coagulation cascade by clotting factors lead to a proteolytic conversion of prothrombin to thrombin. thrombin catalyses fibrinogen to to initiate fibrin clot formation
what are inactive proteins involved in coagulation cascade called
zymogens
how are zymogens activated
by cleavage into the same number but with a so zymogen 11 to 11a
how does the intrinsic pathway work (use roman numerals)
zymogen 12 is activated to by a negatively charged surface eg phospholipids into 12a which activates 11 into 11a which activates 9 to 9a. 9a and 8a convert 10 into 10a which combined with 5a converts prothrombin into thrombin
which activated zymogen is involved in both the intrinsic and extrinsic process
10a
how does the extrinsic pathway work
it is activated by tissue factor which activates 7 into 7a which combined with another tissue factor converts 10 into 10a which then combines with 5a to convert prothrombin into thrombin
how does coagulation cascade happen in vivo(real time)
the same pathways occur and there is an amplification loop so the same thing is happening multiple times due to the activity of thrombin.
what stabilizes the fibrin clot
the thrombin converts the 13 into 13a which stabilizes the fibrin clot
what is the fibrinolytic system
the fibrin clot is broken down to restore normal function to a vessel
what happens during the fibrinolytic process
the zymogen plasminogen is converted into plasmin which degrades fibrin to form fibrin degradation products including D dimers
how is plasminogen activated
by tissue and urinary plasminogen activator (tPA) produced by endothelial cells
how do we prevent the formation of primary haemostatic plug
intact endothelium releases factors, prostacyclin, NO that inhibit platelet aggregation
how do we confine clotting to site of injury
control mechanisms mediated by tissue plasminogen activator (tPA) and thrombomodulin confine the haemostatic process to the site of injury
how do we limit the coagulation cascade ( name the three proteins that stop it )
thrombomodulin binds to thrombin and this complex leads to the degradation of factors 5a and 8a via activation of protein C.
- anithrombin inhibits 10a.
- tissue factor pathway inhibitor (TFPI) inhibits 10a via interaction with TF-7a complex
how do we regulate the fibrinolytic system
plasminogen activator inhibtors (PAI) that inhibit tPA
alpha-antiplasmin binds to and inhibits plasmin
how can we access the haemostasis process in patients
- full blood count (platelet numbers)
- quantify fibrinogen. deficiency due to liver disease or DIC ( when proteins responsible for clotting become overactivated)
- D-dimers increased due to DIC
what is involved in the coagulation test prothrombin time (PT)
measures extrinsic pathway and measures the time for clot formation after adding phospholipids and tissue factor. we use a international normalized ratio (INR) to compare times
what is involved in the coagulation test activated partial thromboplastin time (APTT)
measures intrinsic pathway aclcium and contact surface activator
what is involved in the coagulation test thrombin clotting time
measures common pathway. calcium and thrombin added
what are examples of genetic disorders of haemostasis
haemphilia A
haemophilia B
von willebrand disease
these are X linked so affect mostly males
what is affected in haemophilia A and haemophilia b
factor 8 and factor 9
how does von willebrand disease affect haemostasis
it affects the primary haemostatic plug as its responsible for binding the platelets to the collagen but it also affects factor 8
what are examples of acquired haemostasis disorders ( more common)
- liver disease
- thromboctytopenia due to : impaired production of platelets, immune mediated destruction of platelets and excessive coagulation in DIC
how does liver disease affect haemostasis
may increase prothrombin time due to deficiency in coagulation factors as the liver synthesizes bile salts which absorb the vitamin K from the blood which synthesizes clotting factors
what can happen in severe liver disease
-if severe we see decrease in fibrinogen levels and may also cause thrombocytopenia
what happens in thrombosis
it is the formation of a blood clot inside a blood vessel obstructing the flow of blood through the circulatory system
what are the three factors in virchows triad
stasis (reduced blood flow ), vessel wall injury and hypercoagubility
what is disseminated intravascular coagulation (DIC)
a life threatening disorder of haemostasis. it occurs when there is a sytemic activation of coagulation and can be triggered by a variety of conditions eg bacterial sepsis and metabolic stress
what is leukodepletion
when the white blood cells are removed before transferring blood components to reduce an immune reaction and infection
how are specific blood components seperated
anticoagulated blood undergoes centrifugation and the dense RBCs go to the bottom and the white blood cells and platelets form a buffy coat and the free cell plasma collects at the top
when would you use RBCs thats been seperated
- hypovolaemia due to blood loss
- severe anemia
- anemia that cant be corrected by bone marrow function
when would the fresh frozen plasma be used ( rich in coagulation proteins and inhibitors)
- massive transfusion and dilutioal coagulapathy
- liver disease
- DIC
when would the cryoprecipitate be used (rich in fibrinogen)
- in DIC
- hypofibrinogenaemia
when would platelets be used
-lack of production or peripheral consumption
what are the most important antigens on a RBC
- ABO blood group antigen
- rhesus D antigen
what are ABO antigens
they are carbohydrates
what antigen do all blood groups have and what is it
H antigen and its fucose
what antigen is present in group O
only H
what antigen is present in group A
N-acetylgalactosamine and H
what antigen is present in group B
D-galactose and H
what antigen is present in group AB
both N-acetygalactosamine and D-galactose as well as H
what enzyme do A and B alleles encode for
glycosyltrasferase which then adds the respective antigens
why can we not add any more sugars to the O group
the O allele doesnt code for a functional protein so nothing is added to the H
what is landsteiners rule
individuals will form immune antibodies to ABO blood group antigens they dont possess
why are antibodies to A and B blood group called natural anitbodies
you do not need prior exposure to either the A or B antigen to have anti-A or anti-B and are naturally produced
what happens when incompatible blood is transfused and whats it called
the antibodies wil bind to the RBC and will lyse it through the use of complement. its called intravascular hemolysis
what are the five major Rh antigens
D,C,c,E,e
which is the most common rh antigen
D
what does the D gene produce
a single protein the D antigen
what does the CE gene produce
two proteins generation one of four combinations CE,Ce,cE,ce
what gene do rh negative individuals have
lack the D gene but have a CE gene
whats the difference between C and c and E and e
C and c differ by 4 amino acids
E and e differ by 1 amino acid
whats the difference between the CE and D
differ by 400 amino acids
whats the name of the antibodies created for the ABO antigen and the Rh antigen
ABO-IgM
Rh-IgG
what process does IgG lead to
extravascular remval via spleen
how does blood group typing work
mix sample of the patients blood with anti A, anti B and anti AB. if the anti -antigen stick together is is present
what is a hemolytic transfusion reaction
inflammatory cascade which may cause disseminate intravascular coagulation
what is a febrile non haemolytic transfusion reaction
antibody mediated recognition of leukocytes transfused as part of RBC/platelet units
what is an allergic transfusion reaction
may be present with hives
what is a transfusion related acute lung injury
sudden acute respiratory distress due to transfused antibodies and leads to granulocyte activation in the lungs
What’s the function of tPA
Breakdown of the clot
