Intro to Haematology Flashcards
components of blood
plasma
buffy coat
RBC
components of plasma
clotting or coagulation factors
albumin
antibodies
components of buffy coat
platelets
white cells or leuocytes
functions of blood
transport
maintenance of vascular integrity
protection from pathogens
what do red cells transport?
gases - oxygen and CO2
what does plasma transport?
nutrients
waste
messages
what maintains vascular integrity?
platelets and clotting factors
anticoagulants and fibrinolytics
in the blood what protects from pathogens?
granulocytes/monocytes
lymphocyte
what are the fucntions of granulocytes?
phagocytosis and killing
what are the funcitons of lymphocytes?
antigen recognition
antibody formation
pathogenesis of haematological abnormalities: high levels
increased rate of production
decreased rate of loss
pathogenesis of haematological abnormalities: low levels
decreased rate of production
increased rate of loss
using a diagram show haematopoeisis
see notes
stem cells are capable of what type of differentiation?
totipotent
discuss stem cells
self-renewal
home to marrow niche
what is marrow niche?
CXCR4 - antagonist plerixafor
how do stem cells increase numbers?
binary fission and flux through differentiation pathways
how is stem cells flux regulated?
hormones/growth factors
what hormones are used therapeutically to regulate flux?
erythropoietin
G-CSF
thrombopoeitin agonists
at what age is most bone marrow found?
children
in the elderly where is marrow found?
axial bones
what does marrow consist of?
stroma
sinusoids
describe the erythroid differentiation pathway
erythroblast
reticulocyte
erythrocyte
where is erythropoietin made in why?
kidney in response to hypoxia
what is reticulocyte used for?
measure of red cell production
when may you get polycythaemia?
myeloid malignancies
consequences of anaemia?
poor gas transfer
dyspnoea
fatigue
anaemia results in decreased production of?
haematinics - iron, folate, vit B12
thalassaemia
anaemias causes increased loss through
bleeding
haemolysis
how many red cells are made per day?
10g/l/day
function of platelets
haemostasis and immune
how is platelet production regulated?
thrombopoietin
discuss thrombopoietin
produced in liver
regulation by platelet mass feedback
agonists of thrombopoietin
romiplostim
eltrobopag
life span of platelets
7 days
when may you get thrombocytosis?
myeloid malignancies
when may you get thrombocytopenia?
marrow failure
what causes thrombocytosis?
reactive
what causes thrombocytopenia?
immune distruction
what drugs alter platelet function?
aspirin
clopidogrel
abciximab
function of neutrophils
ingest and destroy pathogens esp bacteria and fungi
neutrophils carry>
interleukins CSFs (colony stimulating factors)
what is G-CSF?
granulocyte colony stimulating factor
what regulates neutrophils?
immune responses - macrophages, IL-17
life span of neutrophils
1-2 days
how quickly to neutrophils respond?
few hours
what may cause neutrophilia?
infection
inflammation
neutrophilia in infection
G-CSF used therapeutically
left shift
toxic granulation
causes of neutrophilia in inflammation
MI
Post op
RA
what causes neutropenia through decreased production?
drugs
marrow failure
what causes neutropenia through increased consumption
sepsis
autoimmune
what causes neutropenia through altered function
chronic granulomatous disease
what are monocytes involved in?
reticuloendothelial system
what do monocytes do?
ingest and destroy pathogens, esp bacteria and fungi
some monocytes migrate into tissues becoming what?
macrophages
lifespan of macrophages?
many months
dendritic cells lifespan?
weeks
causes of monocytosis
myocbacterial infection
what is monocytosis usually associated with
usually associated with neutrophilia (GM-CSF)
causes of monocytopenia
mycobacteria in hairy cell leukaemia
what are eosinophils involved in?
parasites
allergy
function of lymphocytes
immunological memory
surface antigens on lymphocytes
CD markers
causes of lymphocytosis
infectious mononucleosis
pertussis
causes of lymphopenia
usually post iral
lymphoma
subtypes of lymphocytes
B cells
T cells
NK cells
types of T-cells
helper
cytotoxic
regulatory
where are lymphocytes produced?
bone marrow
where do B cells mature?
bone marrow
where do T cells mature?
thymus
where do lymphocytes circulate?
blood
lymph
lymph nodes
where do lymphocytes differentiate into effector cells?
secondary lymphoid organs
antibodies are also know as?
immunoglobulins
what are antibodies involved in?
pathogen clearance
opsonisation
fix complement
block binding
how does combinatorial diversity occur?
within each chain
any V region combined with any J or D region then C region
how does junctional diversity occur?
at any join
additional nucleotides added by enzyme (terminal deoxynucleotydyl transferase (TdT)
how does combinational diversity occur?
between chains
each alpha chain pairs with a beta chain
each light chain pairs with a heavy chain
mistakes in the diversity process can cause lymphoid malignancies. name common ones
IgH heavy locus on chromosome 14
t(14,18), t(8,14), t(11,14)
it is theoretically possible to create how many B cell receptors?
5x10^13
it is theoretically possible to create how many T cell receptors?
1x10^18
what type of maturation do B cells have?
Affinity
what is positive selection?
if gene rearrangement results in a functional receptor the cell is selected to survive
what is negative selection?
if the receptor recognises self antigens the cell is triggered to die
B cells that survive the processes of selection are exported to where?
periphery
where in lymph nodes are B cells found?
follicles
where in lymph nodes are T cells found?
paracortex
where in lymph nodes are plasma cells found?
in the medulla
within the B cell areas there are different popultions. name these
cells undergoing expansion and selection in the GCs
naive cells in the mantle zone
what is HLA?
human leucocyte antigen
what does class I HLA display?
internal antigens on all nucleated cells
what does class II HLA display?
antigens eaten by professional antigen presenting cells
how does HLA vary?
constant within
varies between individuals
how does RA affect the blood?
- Anaemia of chronic disease
- Iron deficiency
- Folate deficiency
- Immune haemolysis
- Neutrophilia
- Immune thrombocytopenia
- Cytopenias secondary to medication
- Felty syndrome
how does hepatic disease affect the blood?
anaemia
deficient clotting factors
how does renal disease affect the blood?
anaemia
HUS
how does CV disease affect the blood?
anaemia
how does resp disease affect the blood?
polycythaemia
how does GI disease affect the blood?
anaemia
to much plasma results in
paraproteins
to little plasma causes
clotting factors: haemophilia
abnormal plasma
clotting factors
haemophillia
normal Hb male
135-170 g/g
normal Hb female
120-160 g/l
normal RBC
4-5 x 10^12/l
normal platelets
150-400 x 10^9/;
normal WBC
4-10 x10^9/l
normal neutrophils
1.5-7 x10^9/l
normal lymphocytes
1.5-4 x10^9/l
normal monocytes
0.2-0.8 x10^9/l
normal eosinophils
0.1-0.5 x10^9/l
what diagnostic tools can you use for blood disease?
FBC clotting times for clotting factors bleeding time for platelets (platelet and leucocyte function tests) chemical assays - iron (ferritin), B12, folate marrow aspirate and trephine biopsy lymph node biopsy imaging
haematological treatment
replacement
transplantation
drugs
haematological treatment: replacement
blood
haematinics
coagulation factors
plasma exchange
haematological treatment: drugs
cytotoxics
monoclonal antibodies
inhibitors of cellular pro
what does hypersplenism cause?
pancytopenia
what does hyposplenism cause?
infections with encapsulated bacteria
red cell changes
what can cause splenomegaly?
infectious haematological malignant portal hypertension Haemolytic disorders connective tissue disorders storage pool disorders sarcoid malignant amyloid
causes of splenomegaly: infectious
acute - EBV, CMV
chronic bacterial - TB, Brucella, SBE
chronic parasitic - malaria, leishmaniasis, schistosomiasis
causes of splenomegaly: haematological malignant
various leukaemias and lymphomas
myeloproliferative disroders
causes of splenomegaly: haemolytic disorders
hereditary spherocytosis thalassaemia haemoglobinopathies megaloblastic anaemia autoimmune
causes of splenomegaly: connective tissue disorders
SLE
Felty syndrome
causes of splenomegaly: storage pool disordeers
Gauchers
Niemann-Pick
