L5- blood cells and disorders 2 Flashcards
what does thrombopoietin cause?
causes heamopoietic stem cells to differentiate into megakaryoblasts
what do megakaryoblasts produce?
megakaryocytes
what are megakaryocytes responsible for?
production of platelets
what are platelets
small nucleate cells required for haemostasis
volume of platelets
150,000-400,000/ml
life span of platelets
life span 5-9 days
what 3 things occur upon injury
platelet plug formation
blood clotting
vascular spasm
what happens in vascular plasm
arteries/arterioles constrict to reduce blood flow
what does platelet plug formation require?
exposure of extracellular matrix proteins
requires several steps
example of extracellular matrix proteins needed for platelet plug formation
vWF
fibrogen
collagen
5 steps of platelet plug formation
adhesion outside-in signalling-integrin activation secretion aggregation thrombin production
what is the platelet disorder Bernard-soulier caused by
abnormality in the genes for glycoprotein lb/V/IX
what is the platelet disorder Glanzmann thromasthenia caused by?
abnormaily in the genes for glycoproteins llb/llla
symptoms of Glanzmann thrombasthenia and Bernard-soulier
- easy bruising
- nose bleeds
- bleeding from gums
- heavy or prolongued menstrual bleeding (menorrhagia) or bleeding after childbirth
- abnormal bleeding after surgery or dental work
- rarely, vomiting blood or passing blood in stool due to bleeding from the gut (gastrointestinal haemorrhage)
what are some storage pool deficiencies caused by?
a lack of granules
what are most storage pool deficiencies caused by?
most common ones are caused by a failure of the platelets to empty the granules
what causes delta storage pool deficiency
a lack of dense granules
what can delta storage pool deficiency be a feature of
other inherited conditions (such as hermansky-pudlak syndrome and chediak-higashi syndrome)
what is grey platelet syndrome, how is it caused
a very rare platelet disorder caused by lack of alpha granules and the chemicals normally stored inside them
what happens if there is a deficiency in alpha granules
without these proteins, platelets cannot stick to the blood vessel wall, clump together the way they should or repair the injured blood vessel
characteristics of extrinsic pathway of blood clotting
fewer steps and rapid
how is extrinsic pathway of blood clotting initiated
is initiated by TF leaking into the blood from cells outside the bloodstream
characteristics of intrinsic pathway of blood clotting
more complex and is slower
outside tissue damage is not needed e.g caused by endothelial cell damage
in the intrinsic pathway of blood clotting, what activates FXII
Surface contact
in the intrinsic pathway of blood clotting, what activates FXI?
FXlla
in the intrinsic pathway of blood clotting, what releases bradykinin
FXlla
what is bradykinin
a vasodilator from HMWK
in the intrinsic pathway of blood clotting, what activates FIX
Ca2+ and FXla
what is FIX
a serine protease
in the intrinsic pathway of blood clotting, what hydrolyses FX
FXla
in the intrinsic pathway of blood clotting, what hydrolyses Ca2+ and phosphatidylserine
FXla
in the intrinsic pathway of blood clotting where are Ca2+ and phosphatidylserine found
on activated platelets, and FVllla - the tenase complex
in the intrinsic pathway of blood clotting, what is FVIII
a cofactor
in the intrinsic pathway of blood clotting, what is FVIII activated by?
thrombin from platelets
in the intrinsic pathway of blood clotting, FX is activated leading to what
the common pathway
in the intrinsic pathway of blood clotting, what is FVII activated by?
by thrombin and FXa
in the intrinsic pathway of blood clotting, what is FX activated by?
FVIIa and its cofactor TF (FIII)
In the common pathway of blood clotting, what cleaves prothrombin (FII)
FXa
in the common pathway of blood clotting, where is prothrombin (FII) cleaved
on the surface of activated platelets
in the common pathway of blood clotting, what does the cleavage of prothrombin (FII) create
a prothrombinase complex with Ca2+, phospholipids, prothrombin, FXa and FV
in the common pathway of blood clotting, what is FV activated by
small amounts of thrombin
in the common pathway of blood clotting, what is fibrogen converted to and by what
converted to fibrin by thrombin
in the common pathway of blood clotting, what activates FXIII and what does this do
thrombin which cross links the fibrin clot
what plugs the ruptured area
the clot
what is clot retraction
the tightening of the fibrin clot
what contracts when platelets pull on them
fibrin threads attached to the damaged surfaces of the blood vessel
what does fibrin threads attached to the damaged surfaces of the blood vessel do
pulls the edges of the wound together
what does fibrinolysis dissolve
small inappropriate clots and dissolved clots at sites of repair
what is incorporated into the clot
inactive plasminogen
what is inactive plasminogen activated to?
plasmin
how is inactive plasminogen activated
by substances in the body tissue (thrombin and t-PA)
what does plasmin digest
fibrin threads
what does plasmin inactivate
fibrinogen, prothrombin, FV and FXII
What type of genetic disease is haemophilia A
X linked
what does haemophilia A lead to
leads to FVIII deficiency
how is extrinsic pathway assessed by in haemophilia A
assessed by prothrombin time (PT) by addition of TF to plasma
in haemophilia A which pathway works
extrinsic pathway
how is the intrinsic pathway assessed by in haemophilia A
assessed by activated partial thrombosplastin time- APTT
in haemophilia A why are phospholipids added in the intrinsic pathway
added to mimic contact factor
how many males affected by haemophilia A
affects 1:5,000 males
what is haemophilia B?
Christmas disease, X linked disorder leading to FIX deficiency
what is normal in haemophilia B
normal PT time
what is abnormal in haemophilia B
abnormal APTT time
how many males affected by haemophilia B
affects 1:30,000 males
what is warfarin
vitamin K antagonist to prevent clotting factor activation
what is EDTA
compound used in medicine settings to chelate calcium in donated blood
define chelate
a compound containing a ligand (typically organic) bonded to a central metal atom at 2 or more points
what does aspirin inhibit
inhibits TxA2 synthesis
what does streptokinase do
activates t-PA
what does the surface of RBCs contain which act as antigens
range of glycoproteins and glycolipids
if a RBC has antigen A what antibody does it have
anti-B antibody
if a RBC has antigen B what antibody does it have
anti-A antibody
if a RBC has antigen A+B what antibody does it have
neither
if a RBC has neither antigen A or B what antibody does it have
both antibodies
what is missing if a person is rhesus negative
the D antigen
don’t normally have Rh antibodies
when can rhesus negative develop
after blood transfusion, causes problem for later transfusions
what problem can rhesus negative cause in pregnancy
in the next Rh positive pregnancy, maternal antibodies attack fatal RBCs
symptoms of severe anaemia
fainting
chest pain
angina
heart attack
causes of anaemia
reduced oxygen carrying capacity
what can reduced oxygen carrying capacity cause
iron- deficiency megaloblastic (large RBC) pernicious haemorrhagic haemolytic thalassemias
what is thalassemias
haemoglobin problems
what is pernicious
lack of haemopoiesis
what can kill malaria
low potassium levels
in haemophilia what happens if the father has the disease and the mother is healthy
1/4 chance son will have haemophilia
1/4 chance the daughter is a carrier
what is leukaemia
production of malignant WBC cells, supress production of all normal cells in RBM
what can oncogenes cause
cause malignancy when mutated leading to their activation (growth factors, receptors, DNA binding proteins)
what can tumour suppressor genes cause
cause malignancy when mutated leading to their supressed growth)
characteristics of acute lymphoblastic leukaemia
short onset, derived from lymphoid stem cells
where is acute lymphoblastic leukaemia more common
most common in children
what ages do acute myelogenous leukaemia affect
affects all ages
where is chronic lymphoblastic leukaemia more common
most common in adults (55+)
characteristics of chronic myelogenous leukaemia
prolonged onset, derived from myeloid stem cells
where is chronic myelogenous leukaemia more common
mostly in adults
causes of leukaemia
unknown but can be radiation or chemotherapy, genetics (down syndrome), environmental factors,viral .g Epstein-barr virus
what does bone marrow transplant involve
replacement of cancerous or abnormal red bone marrow with healthy RBM
how is patient RBM destroyed
by chemotherapy and whole body radiation
where can healthy RBM be from
a donor or patient if in remission
where does marrow migrate to and then what does it do
to red bone marrow cavities and multiplies
what can bone marrow transplant create
graft vs. host disease
what does the patient need to stay on when going through a bone marrow transplant
need to stay on immunosuppresants
