Week 3 Flashcards
(47 cards)
1
Q
Haematopoiesis
A
- Haematopoiesis = production of new cells (2-3x10^6/sec)
- Primitive haematopoiesis = blood production in developing embry
-0-2 months > yolk sac
-2-7 months > liver, spleen
-5-9 months > bone marrow
2
Q
definitive/ adult haematopoiesis
A
= blood production in infants
3
Q
sites of adult/ definitive haemopoiesis - bone marrow
A
- blood production limited to red marrow
- liver and spleen can resume haematopoietic role
4
Q
bone marrow anatomy
A
- highly cellular, vascularized and innervated
- rich vasculature network interwoven amongst trabecular bone
- interface between bone and bone is endosteum
4
Q
HSC properties
A
- numbers decline with age
- extremely rare
- pluripotent
- expansive
- reside in special niches
- mostly quiescent
- capable of self renewal or differentiation
- Fate regulated by growth factors/ cytokines
- rarely present in peripheral circulation
- naturally home to bone marrow in response to SDF1
5
Q
HSC isolation - density gradient centrifugation
A
- separates peripheral blood, core blood or bone marrow into constituent parts
- diluted blood layered over sucrose containing solution
- blood cells fractionate according to density and sedimentation rate
6
Q
HSC niche
A
- HSC reside in endosteal (bone) and perivascular niches
- HSC believed to reside in a hypoxic environment
- anchored in a place with cell adhesion molecules
- surrounded by multiple different cell types contributing to HSC fate
7
Q
Cell types in HSC niche
A
- all cells contribute to HSC maintenance
- niche constituents change with age
- understanding incomplete
8
Q
CXCL12/CXCR4 in stem cell transplantation
A
- exploited for stem cell transplantation
- procedure for relapsed/ refactory bone marrow disease or poor prognosis maligancies
- highly toxic, risky and expensive procedure
9
Q
HSC maturation - dictated by physiological demand
A
HSPC > Blood loss > erythropoiesis
HSPC > infection > granulopoiesis / monopoiesis
HSPC > inflammation > thrombopoiesis
10
Q
haematopoietic growth factors/cytokines
features
A
- act hierarchically
- produced by cell types inc haematopoietic cells
- affect more than one lineage
- act on HSPC and differentiated cells in endocrine, paracrine and autocrine
- synergise with other growth factors
11
Q
current understanding of haematopoietic development
- although precise hematopoietic hierarhy is still to be determined, fundamental principles remain
A
HSC give rise to maturing progeny
-GF/CK act on cell (receptors) to direct lineage commitment
-signalling pathways and TF promote repress lineage specific genes
12
Q
main blood cell types, features and functions
A
erythrocytes,Thrombocytes ,Leukocytes , Granulocytes : neutrophils ,Granulocytes : eosinophils , Granuloytes : basophils ,lymphocytes , B cell lymphocytes , T cell lymphocytes , Normal NK cells
13
Q
erythrocytes
A
- lifespan - 90-120 days
- function - 02/c02 transport
- identification - CD235a+, anucleate , small pink hollow
14
Q
Thrombocytes
A
- lifespan - 7-10 days
- function - haemostasis
- identification - CD41/42/61+, anucleate, discoid, dark granular cytoplasm
15
Q
Leukocytes
A
- properties - heterogeneous class of cells, normal blood range: 4-11 x10^9/L
- Function - immune defence
- identification - CD45+
16
Q
Granulocytes : neutrophils
A
- function - innate immunity
- identification - hypersegmented nucleus
17
Q
Granulocytes : eosinophils
A
- function - innate immunity (parasites, viruses and fungi)
- identification - hyppersegmented nucleus, course red cytoplasmic granules
18
Q
lymphocytes
A
- function - adaptive (antibody mediated) immunity
- identification - CD45 bright , HSC like appearance
19
Q
B cell lymphocytes
A
- make up 20% of lymphocyte pool and have long life span
- give long term immunological memory by inducing immunoglobulin production following antigen exposure
20
Q
what type of genetic abnormalities lead to blood cancer
A
- types of genetic aberration
-cytogenic abnormalities ]
-gene mutations
-epigenetic lesions
20
Q
T cell lymphocytes
A
- make up 80% of lymphocyte pool and have variable life span
- multi functional :
-t helper cells
-t cytotoxic cells
-t regulatory
20
Q
Normal NK cells
A
- function major cell of innate immunity
- identification - CD8/56+ often large cytoplasm
20
Q
blood cancer symptoms
A
general symptoms
- rapid weight loss
- loss of appetite
- fatigue/ breathlessness
- fever / night sweats
- prolonged frequent infection
serious complications include
- anaemia
- thrombocytopenia
- persistent infection
20
Other mature blood cell types
plasma cells, macrophages, mast cells, dendritic cells
- derived from mature b cells
- reside in bone marrow
- produce antibody
- eccentirc round nucleus
Macrophages
- dervied from monocytes
- mainly tissue resident
- phagocytic
- round nucleus
mast cells
- derived from basophils
- tissue resident
- release histamine upon allergen
dentritic cells
- both myeloid/ lymphoid origin
- tissue resident
- phagocytic antigen presenting cells
21
what causes blood cancer
known risk factors include
- exposure to ionising radiation
- exposure to benzene
- exposure to chemotherapy
- presence of existing blood disorders
- infection - bacteria, viruses, protozoa
22
leukaemia diagnosis
primaru healthcare setting
- gp assessment
- accident and emergency
laboraroty based tests
- full blood count
- ESR
- biochemistry
- morphology
- immunophenotyping
- cytogenetic analysis
- molecular analysis
23
Haemostasis
- prevent loss of body fluids
- patient undergoes trauma > healing process
involved :
- blood vessels and platelets
- coagulation and inhibitor mechanisms
- fibrinolysis
24
physiological variation
- haemorrhagic tendency
- haemorrhagic tendency
- thrombotic tendency
25
trauma to blood vessels - vascular damage
Haemorrhage > Vascular smooth muscle contraction > vasoconstriction > reduced blood loss
Haemorrhage > platelet adhesion > platelet activation > platelet aggregation > platelet plug formation > reduced blood
Haemorrhage > coagulation activation > fibrin formation > platelet plug re-enforcement > reduced blood loss
26
Clinical investigation of disorders of haemostasis
- patient/ family history
- prolonged vs recent haemorrhage history
- type of - skin, bruises, haematoma
- trauma or spontaneous
- medication history
- sex - linked
27
Factors, tests and drugs - key points
- vitamin K dependant coagulation factors: 2,7,9,10
- formed in liver, require vit K for complete molecule
- without vit K they are inactive
- factors measured by prothrombin time, 2,5,7,10
- vitamin k antagonist - coumarin drugs e.g warfarin
- factors measured by aPT : 12,11,8,9
- Heparin - antithrombin, low molecular weight herapin- anti- Xa inhibitor
28
patterns of bleeding
-vascular / platelet defect
-skin - superficial bleed
-coagulation defects
28
laboratory blood tests
- bioassays
-measuring time for clot formation
-chromogenic assays - colour or fluorescence
- screening tests
-platelet count/bleeding time
-Activated partial thromboplastin time (aPTT)
-prothrombin time (PT)
-thrombin (TT)
29
Which blood sample is required
clotting tests :
- venous blood with sodium citrate anticoagulant, 9:1 ratio
- removed calcium ions essential for clotting mechanism
- centrifuge to separate plasma from red blood cells and platelets
- calcium is added plasma to begin clotting and time to clot is measured
30
platelet structure
- membrane receptors
-adhesion
-aggregation
-resting vs activated
- actin/ myosin
-shape change
-clot retraction
- internal vesicles
31
platelet activation
- surface receptors are expressed
-linked to production of intracellular messenger systems
-glycoprotein fibrinogen receptor is expressed
32
platelet disorders
- bleeding/small haemorrhage into skin/mucous membranes
- thrombocytopeni
33
bernard - soulier syndrome
-reduced adhesion
-defective aggregation, lack glycoprotein lb
-large platelets
34
thrombolysis in a blood vessel showing strands of fibrin
thrombosis : a balancing act
- blood coagulation and then resulting thrombus formation continually takes place physiologically
- blood clot breakdown - fibrinolysis/ thrombolysis
35
acquired defects of fibrinolysis associated with thrombosis
physiological changes :
- pregnancy
- ageing
- stress
- obesity
- temperature alterations
36
types of thrombi
- occlusive - obstruct blood vessels
- mural - adhere to one side of blood vessels
37
thrombus formation
- arteries
- veins
- capillaries
- cardiac chambers
38
arterial thrombosis
- common in aorta and arterial bifurcations
- rapid, pulsating blood flow
- thrombus consists of aggregated platelets, fibrin, leucocytes
- associated with lipid - rich fibrotic, inflammatory lesions of vessel wall
39
blood flow and thrombus/ plaque formation
- thrombus increases blood flow becomes distorted
- vessel/ heart chamber becomes blocked
- ischaemia occurs (tissue damage)
- results in tissue necrosis
40
how does laborartoy test for thrombotic events
- diagnosis is often based on clinical symptoms, calf pain post operatively
- vein thrombus
test for
- fibrinogen levels
- D- dimers/ FDPs
41
