blood Flashcards
describe 5 differences between veins and arteries
large diameter v small diameter
thin wall v thick wall
thin tunica media v thick tunica media
low pressure v high pressure
valves v no valves
give 6 functions of the blood
hydration of tissues and organs
delivery of oxygen and nutrients to tissues and organs
distribution of endocrine hormones
fight infections - innate and adaptive immune response
regulation of body temperature (hypothalamus) and pH
to prevent its own loss
what white blood cells are involved in allergic reactions?
eosinophils and basophils
how is the blood involved in hormone distribution
endocrin hormones (paracrine) are secreted by specific endocrine glands into the blood to be circulated to remote target tissues
how are different blood cells produced?
all blood cells come from the common progentior cell in the bone marrow. multipotential haematopoietic stem cell
there are 2 lineages - myeloid and lymphoid
these produce 11 different types of blood cell
which blood cells come from common myeloid progenitor?
platelets, erythrocyte, mast cells, basophil, neutrophil, eosinophil, macrophages
what blood cells come frm common lymphoid progenitor cells?
natural killer cell, T lymphocyte, B lymphocytes, plasma cells
which blood cells are found in bone marrow?
haemocytoblast, common lymphoid progenitor, common myeloid progenitor, myeloblast, megakaryocyte
what is the difference between blood plasma and serum?
blood plasma contains serum and clotting factors
blood serum contains plasma but no clotting factors
what is the haematocrit?
relative colume of blood taken up by cellsa nd plasma - normally around 0.4
blood plasma has 55% volume of the blood
what are the major blood group systems?
ABO and Rh
which blood group is universal donor?
O
what blood group is a universal recipient?
AB
describe why in first pregnancy the newborn will not get haemolytic syndrome but may do in second pregnancy?
the rhesus blood group - postive = has Rh agglutinogens
negative = no Rh agglutinogens
during first pregnancy, the baby is protected by placenta-blood barrier and the mother is not exposed to Rh agglutinogens until the time of childbirth due to placental tearing
this causes the generation of anti-Rh agglutinins by the mother.
this means in a second pregnancy, antibodies cross the placental barrier and the baby is born with severe anaemia. need to treat with anti-Rh globulin to mask Rh agglutinogens
what are the main causes of bleeding?
trauma, surgery, infection, sepsis, aneurysm rupture, drugs, vitamin K deficiency, inherited
what are the main causes of thrombosis?
arterial = damage to arterial wall
ventral = blood pooling
what is haemotological malignancy?
cancer of the blood cells
how can haemotological maligancies be classified?
classified according to blood lineage - myeloid neoplasm or lymphoid neoplasm.
location - leukaemia=blood, lymphoma=lymph nodes
duration - acute=blasts, chronic=mature cells
what are the main causes of acquired anaemia?
erythrocyte loss
decreased response to erythroprotein - iron deficiency, B12 deficiency, folate deficiency,
how can iron deficiency be shown on a blood smaple?
small RBC increased central zone of pallor anisocytosis - variation in size poikilocytosis - variation in shape elongated RBC
how can B12 or folate deficiency been seen in a blood sample?
larger RBC
formation of macroovalocytes
hypersegmented neutrophils
what are the main differences between iron deficiency and B12 deficiency
iron is involved in haemaglobin whereas B12 is involved in DNA replication
iron leads to decreased haemaglobin production whereas B12 leads to problems with mitosis of proerythroblast
iron leads to microcytic anaemica whereas B12 leads to megaloblastic or macrocytic anaemia
what is the difference between haemolytic anaemia and anaemia affecting the production of RBCs
haemolytic anaemia is due to increased RBC destruction, reducing lifespan of RBC and bone marrow is unable to replace suffiecntly
whereas anaemias affecting the production of RBCs
what is the role of erythropoietin in stem cell differentiation
erythropoietin is a glycoprotein hormones that stimulates the formation and differentiation of erythroid precursor cells in the bone marrow via the EPO receptor
what are the causes f acquired haemolytic anaemia
immune - haemolytic syndorme in newborn who is Rh positive whereas mum is Rh neg. - autantibodies
non immune - durg-induced, snake venom, mechanical (heart valves), infections (malaria and septicaemia)
what are the causes of inherited haemolytic anaemia?
RBC cytoskeletal defects cuased by mutations in alpha or beta spectrin = hereditary spherocytosis
RBC enzyme defects - causesd by G6PD deficienct involved in NADPH metabolism
haemoglobin defects - sickle cell disease, thalassaemia
what causes sickle cell anaemia
mutation of the HbB globin gene Glu6 to Val
leads to polymerisation of Hb, distorting the RBC and causing sickling of the RBC (particularly homozygous)
haemolytic crisis is due to blockage of microvasculature
what is the cause of a sickle cell crisis?
blockage of microvasculature by sickled red blood cells
what is the cause of thalassaemia?
microcytic anaemia caused by defects in either alpha or beta chains of ahemoglobin, leading to ineffective erythropoiesis and haemolysis
alpha thallasaemia and beta thallasaemia
why are thallasaemia and sickle cell anaemia releatively common in africa and asia?
when heterosygous they provide protection against malaria so due to natural selection they are mpre abundant here
what is primary haemostasis?
refers to platelet aggregation and platelet plug formation (platelet adhesion, platelet activation, platelet plug formation)
describe primary haemostasis
platelet adhesion and spreading, the first platelet send out chemical messages so other platelets come and bind close to the area
dense granules - ADP, ATP seratonin and Ca2+ help platelet activation (positive feedback)
alpha granules - platelet factor 4, plasminogen activator inhbitor (pAI-1), chemokines = help coagulation and aid wound healing
what is the secondary haemostatic response?
deposition of insoluble fibrin generated by the proteolytic coagulation cascade = insoluble fibrin mesh that is incorporated around the platelet plug
what is the trigger for primary haemostasis?
dormant platelets in the blood undergo explosive activation when they encounter vascualr injury
when come into contact with collagen and von willebrand factors
what stimulates adhesion?
collagen and von willebrand factor
what stimulates platelet activation?
collagen
thrombin
ADP
what stimulates platelet agrregation?
fibrinogen
what are the main structural characteristics of platelets?
reegular shaped cells
flat
non-nucleated
basophillic granules in its centre
formed from megakaryocytes
describe platelet activation
when endothelial damage occurs platelets come into contact with exposed collagen and von willebrand factor, activating them - also activated by thrombin and negatively charged surfaces such as glass
describe platelet adhesion and aggregation
von willebrand mediates the linking of platelets to collagen via a specific receptor in the platelet membrane - cuasing platelets to become dentritic = indicates activation and releases prothrombic ADP
by binding of receptors ADP causes adhesion of platelets and induces aggregation, recruiting more platelets
thromboxane binds to platelets and causes cross linkage
activated latelets trigger coagulation
thrombin stimulates further platelet activation = positive feedback
fibrin forms to stabilise clot
what is proteolysis?
when protein is incubated with relativelt low cxoncentrations of different proteases, which cut at recognition sites throughout the protein - normally exposed regions such as loops.
in coagulation proteolysis activates the clotting factors
describe the 4 main reactions and factors in intation of coagulation
- after injury FVII binds to TF expressed on membrane of cells surrounding blood vessel
- FVII is a peculiar clotting factor as it shows auto activation. activated FVIII proteolytically cleaves and activates FX
- FXa converts prothrombin to thrombin
- thrombin coverts fibrinogen into fibrin
describe the reactions and factors involved in consolidation phase of the coagulation response
intial pathway is not enoguh for normal haemostatic response so:
activation of FIX by TF/FVIIa which can convert FX to FIXa
activation of FXI, FVII and FV by thrombin which act as cofactors for FIXa and FXa
discuss the intrinsic coaulation pathway
triggered by glass, clay particles , platelets
FXII is activated by negatively charged surfaces, FXIIa then activates FXI and so on.
FXII deficiency does not lead to bleeding
discuss the extrinsic coagulation pathway
the extrinsic pathway is triggered by TF on the cell membrane of perivascular cells
TF/FVIIa, FIXa/FVIIIa and FXa/FVa enzyme complexes are vitamin K-dependent
vitamin K dependent carboxylation of factors VII, IX and X is required for calium binding and formation of active enzyme complexes on the activatied platelet membrane
what is the difference between major and minor bleeds?
major bleeds require intervention whereas minor bleeds do not (bruises, menorrhagia -menstrual periods, epistaxis (nose bleeds etc)
what are the common cuases of major bleeding?
trauma surgery sepsis intravscular TF exposure systematic coagulation activation leading to microvascular clots/ cnsumption of clotting factors and platelets leads to bleeding mulitorgan failure
how can vitamin K deficiency lead to bleeding?
vitamin k is a cofactor for an enzyme used to form completed forms of clotting factors , vitamin is found in diet and is a fat soluble cofactor
what are the causes of vitamin K deficiency?
malnutrition
fat malabsorption
liver disease (alcoholic cirrhosis)
may occur in newborns (vitamin K injections/tablets for newborns)
due to vitamin K antagonists (VKA = warfarin, acenocoumarol) overdose
how does oral anticoagulation with warfarin work?
warfarin is a type of anticoagulant medication that helps prevent clots forming in the blood. warfarin inhibits vitamin K dependent synthesis of clotting factors II, VII, IX and X as well as the regulatory factors protein C, S and Z
what is the difference between haemophilia A and B
haemophilia is an X kinked recessive disease expressed by males and carried by females
it is due to the insufficient thrombin generation
heamophilia A= FVIII
haemophilia B = FIX
what are the 3 main types of von willebrand disease?
type 1 - mildest, have reduced level of von willebrand in the blood
type2 von willebrand factor does not work properly - heavier bleeding than type 1
type 3 - most severe and rarest , very low levels of von willbrand factor or non at all
what is thrombocytopenia
loss or dysfunction of platelets
what are the primary causes of thrombocytopenia?
leukaemia blood loss DIC drug induced immune thrmbocytopenia purpura (ITP)
Which types of thrombosis are classfied as venous?
deep vein thrombosis
pulmonary embolism
what types of thrombosis are classified as arterial?
myocardial infarction
atrial fibrillation
peripheral vascular disease
stroke
how does deep vein thrombosis occur?
DVT is a blood clot that forms in a vein deep in the body, usually in legs below the knee
venous thrombus is fibrin and erythrocyte rich
occurs in areas of low blood flow
involves platelets but driven by excess thrombin inareas around valves
the clot can break free a= embolism and become lodged in blood vessel of the lung = pulmonary embolism
what are the main risk factors of venous thrombosis?
immobilisation surgery cancer - tumour cells release TF pregnancy oral contraceptives genetic risk factors
how does fibrinolysis work?
when fibrin clot is broken down. plasmin cuts the fibrin mesh at various places leading to the production of cirulating fragments that are cleared by proteases or by the kidney and liver
how does arterial thrombosis develop?
caused by atherosclerosis lipids accumulate in the blood vessel wall and oxidise, with time the plawues rupture and induces thrombotic events
- platelets bind to collagen and exposed to oxidised lipids form plaques
- activation
- release of proaggreotry substances - ADP and TxA2
- autocatalytic expansion of thrombus
- reduced bioavailability of endothelial NO and production of PGI2
- occlusive thrombi
what are the main risk factors of arterial thrombosis
advanced age smoking diabetes hypertension cholesterol poor diet lack of excersize ethnicity
give 3 different types of drugs that target venous thrombosis
immediate onset of anticoagulant effects
- unfractionated heparin (intraveous - helps antithrombin to inhibit thrombin and FXa)
- low molecular weight heparin subcutaneous
slow onset
-VKA monitored by INR such as warfarin
direct thrombin inhibitors (diagatran ) promising in clinal trials
give 2 types of drugs used to target arterial thrombosis
antiplatelets - aspirin (inhibition of COX-1 and thromboxane production)
anti aIIbb3 , anti P2Y
fibrinolytics
tPA/uPA derivatives
what hormone is essentiasl for stimulating the production of platelets?
thrombopoeitin
what does prasugre block in order to inhibit plateet aggregation?
ADP binding to P2Y receptors
what happens at high altitude that affects binding of oxygen to haemaglobin?
at high altitude, BPG in red blood cells increases, decreasing affinity of Hb for oxygen
abciximab (reppro) inhbits platelet…..?
aggregation
