Haematopoiesis and the White Cell Flashcards
what are the three types of granulocytes?
neutrophils
eosinophils
basophils
what granulocyte deals with parasites?
eosinophils
what is the function of natural killer cells?
anti viral
anti tumour
what is the lifespan of a RBC?
120 days
what is the lifespan of a neutrophil?
7-8 hours
what is the lifespan of a platelet?
7-10 days
what are the five stages of neutrophil maturation from a myeloblast?
myeloblast promyelocyte metamyelocyte myelocyte neutrophil
what is a ‘blast’?
a primitive nucleated cell precursor
what cell is a platelet precursor?
megakarocyte
are haemopoietic stem cells derived from the endo, ecto or mesoderm?
mesoderm
at what gestation does yolk sac haemopoiesis stop by?
week 10
at what gestation does liver haemopoiesis start at?
week 6
at what gestation does spleen haemopoiesis start at?
week 12
at what gestation does bone marrow haemopoiesis start at?
week 16
where do you take a bone marrow sample from in a child?
tibia
where do you take a bone marrow sample from an adult?
iliac crest
what is the name for the minute projections of bone that are found throughout the metaphysis so that bone marrow is close to the bone surface?
trabeculae
what is the name for the interface of bone and bone marrow?
endosteum
what cells line the endosteum?
osteoblasts, osteoclasts and others
what is the name of specialised venules within the bone that forms a reticular network of blood vessels?
sinusoids
compare red marrow to yellow marrow?
red marrow: active
yellow marrow: fatty and inactive
how do you calculate the marrow cellularity % of a person?
100- age
what happens to the ratio of red to yellow marrow as you age?
ratio decreases
increase in yellow marrow
what is the myeloid:erythroid ratio?
ratio between neutrophils and neutrophil precursors to nucleated red cell precurosors
what factor regulate neutrophil maturation?
G-CSF
granulocyte- colony stimulating factor
what hormone regulates growth and development of megakaryocytes?
thrombopoietin
what is the name for the study of antigen expression using specific antibodies?
immunophenotyping
what are the primary lymphoid tissues?
bone marrow
thymus
what are the 2 main secondary lymphoid tissues?
lymph nodes
spleen
arterial and venous vessels serving lymph nodes enter and exit where?
at the hilum
where is lymph returned to the venous system?
junction of L or R subclavian and jugular veins
what is chylous ascites?
accumulateion of lymphatic fluid in the peritoneal cavity
what are the 2 main functions of the lymphatic system?
- return lymph to circulation
2. filter lymph
what artery supplies the spleen?
splenic artery from the coeliac trunk
what vein supplies the spleen?
splenic vein
what are the 2 main functions of the spleen?
- detects and eliminates unwanted/damaged material
- facilitates immune response to blood bourne antigens
what are the features of hypersplenism?
- splenomegaly
- fall in one or more cellular components of blood
- correction of cytopenias by splenectomy
what are the 3 features of splenic enlargement?
- dragging sensation in LUQ
- discomfort with eating
- pain if infarction
what is the most cause of hyposplenism?
splenectomy
what is the name for the nuclear remnants that can remain with RBCs due to hyposplenism?
howell-jolly bodies
does reduced spleen red pulp or white pulp cause howel-jolly bodies?
red pulp
which malignancy has the tendency to involve the CNS- ALL or AML?
ALL
what are auer rods?
clumps of granulated material which form needles in acute myeloid leukaemic cells
what diagnostic tool is used to differentiate between AML and ALL?
immunophenotyping to look for CD proteins
what is the curative treatment of acute leukaemia?
multi-agent chemotherapy
what line is chemo usually given through?
hickman line
what is the name for a cancer which arises from the bone marrow?
leukaemia
what is the name for a cancer which arises from the lymph node?
lymphoma
what are the 4 main types of leukaemia?
- acute myeloid leukaemia
- acute lymphoblastic leukaemia
- chronic myeloid leukaemia
- chronic lymphocytic leukaemia
what happens to the proliferation and maturation of blood cell precursors in leukaemia?
proliferation increases
maturation failure
why can you get bone pain in ALL?
bone marrow has expanded
why can you get symptoms of anaemia, infections and increased bleeding in ALL?
bone marrow failure
less RBC, WBC and platelets
compare the age groups of those who typically get AML and ALL?
AML - over 60 years old
ALL - children
why can the WBC count be high in patients with acute leukaemia despite having low RBC, platlets and neutrophils?
increased abnormal WBCs
what particular bacterial infections are you concerned about in neutropenic patients?
gram negative bacteria
what are the 3 biggest problems of marrow suppression?
- anaemia
- neutropaenia –> infections
- thrombcytopaenia –> bleeding
what is tumour lysis syndrome?
a side effect of chemotherapy where the contents of the tumour are released into the bloodsteam causing metabolic disturbances
why is cardiomyopathy a late effect of anthracylcines?
they produce free radicals which damage the cardiac muscle
what is remission classed as?
<5% marrow blasts with recovery of normal haemopoiesis
what is the pathologenesis of fanconi’s syndrome?
unable to correct inter-strand cross links (DNA damage)
what are the 3 main acquired causes of primary bone marrow failure?
- aplastic anaemia
- myelodysplastic syndromes
- acute leukaemia
what is aplastic anaemia?
autoimmune attack against the haemopoietic stem cell
what is the main inherited cause of primary bone marrow failure?
fanconi’s syndrome
what malignancy is there a propensity for myelodysplastic syndrome to evolve into?
AML
how can acute leukaemia cause pancytopaenia?
compromises normal stem cell activity
why is there a hypercellular bone marrow in B12/flate deficiency?
increased EPO stimulates the primitive precursors
compare a normal spleen with hypersplenism in terms of splenic red cell mass, cell transit and platelet pool?
splenic red cell mass is increased in hyperplenism
red cell transit speed is decreased in hypersplenism
splenic platelet pool is increased in hypersplenism
what is the triad of Felty’s syndrome?
rheumatoid arthritis
splenomegaly
neutropaenia
what is fanconi’s anaemia?
inherited bone marrow failure causing pancytopaenia
what 3 cell types are reduced in pancytopaenia?
red blood cells (anaemia)
neutrophils (neutropenia)
platelets (thrombocytopenia)
how do you test for Fanconi’s syndrome?
chromosome fragility testing
does aplastic anaemia give you hypo or hypercellular bone marrow?
hypocellular
do myelodysplastic syndromes give you hypo or hypercellular bone marrow?
hypercellular
does B12/folate deficiency give you hypo or hypercellular bone marrow?
hypercellular
does hyperslenism give you hypocellular or hypercellular bone marrow?
hypercellular
what is the specific treatment for idiopathic aplastic anaemia?
immunosuppression
anti-lymphocyte globulin
what are the 2 main functions of B cells?
antibody production
antigen presenting cells
what cells make antibodies?
B cells
plasma cells
what are antibodies made of?
2 heavy chains and 2 light chains
describe the structure of IgM, IgA, IgG, IgD and IgE?
IgM- pentamer
IgA- dimer
IgG, IgD, IgE- monomer
what cells does myeloma arise from?
plasma cells
describe the appearance of a plasma cell?
looks like a fried egg- peripheral nucleus
what is a paraprotein?
monoclonal immnoglobulin
how do you detect paraproteins?
serum electrophoresis
during serum electrophoresis, what region do immunoglobulins or paraproteins occur in?
gamma region
‘gamma globulins’
what test allows you to classify/identify the abnormal paraprotein found on electrophoresis?
serum immunofixation
how do you detect bence jones proteins?
urine electrophoresis
what are bence jones proteins made of?
precipitates of immunoglobulin light chains
why are bence jones proteins found in myeloma?
large amounts of light chains being over-produced, this passes into the urines
why are light chains found in the urine of a patient with myeloma but immunoglobulins arent?
Ig is too big to pass into urine, light chains are small enough
also there is an overproduction of light chains
what is the commonest cause of paraproteins in the blood?
monoclonal gammopathy of undetermined significance (MGUS)
why can you get immune suppression in myeloma?
overproduction of useless clonal antibody leads to underproduction of useful antibodies (hypogammaglobulinaemia)
why can you get hyperviscosity in myeloma?
high levels of paraprotein in the blood
what causes renal failure in myeloma?
multifactorial
- tubular cell damage by light chains, cast nephropathy
- hypercalcaemia with dehydration
- risk of infections leading to sepsis
- use of NSAIDs for bone pain
- hyperuricaemia (high cell turn over)
what is the most common type of myeloma?
IgG myeloma
usually IgG or IgA
what is bence jones myeloma?
myeloma where the plasma cells can only produce light chains, not full antibodies
why does myeloma cause lytic bone disease?
plasma cells produce substances (Eg IL 6) which causes overactivity of osteoclasts and suppression of osteoblasts (net loss of bone)
what are the 6 main symptoms of hypercalcaemia?
symptoms of renal stones bone pain abdominal groans psych moans symptoms of dehydration symptoms of renal impairment
in myeloma, what type of injury happens to the PCT in the kidney?
toxic injury
in myeloma, what type of injury happens to the thick ascending limb in the kidney?
cast injury
what marker do you use to monitor response to treatment in myeloma?
paraprotein level or bence jones protein
what is monoclonal gammopathy of uncertain significance? (MGUS)
an isolated finding of paraprotein (less than 30g/l) in someone who is well
what is AL amyloidosis?
a form of amyloidosis in which faulty light chains are overproduced (these form aggregates)
how do you diagnose AL amyloidosis?
tissue biopsy (ie bone marrow biospy, fat from abdominal wall, rectal biopsy)
does AL amyloidosis cause nephrotic or nephritic syndrome?
nephrotic (proteinuria)
what is characteristically seen under polarised light of AL amyloidisis?
apple-green birefringence
what is waldenstroms macroglobulinaemia?
a neoplasia of cells inbetween a lymphocyte and a plasma cell
what paraprotein is produces in walderstroms macroglobulinaemia?
IgM paraprotein
what is the treatment of waldenstroms macroglobulinaemia?
chemotherapy plasmapheresis (to treat hyperviscosity syndrome(
what are the 2 subgroups of chemotherapy drugs?
- cell cycle specific agents
- non cell cycle specific agents
what are the 2 main classes of cell cycle specific chemo agents?
antimetabolites
mitotic spindle inhibitors
for cell cycle specific chemo agents what is more important- duration of treatment or cumulative dose?
duration of treatment
what phase in the cell cycle are antimetabolite chemo drugs particularly effective in?
S phase
what phase in the cell cycle are mitotic spindle inhibitors particularly effective in?
M phase
how does methotrexate work?
an antimetamolite
interferes with folate metabolism (which is important for DNA synthesis)
for non-cell cycle specific chemo agents, what is more important- duration of treatment or cumulative dose?
cumulative dose
which is more likely to damage normal stem cells- cell cycle specific or non-cell cycle specific chemo agents?
non cell cycle specific
cytotoxic drugs affect rapidly dividing organs, what are the 3 main side effects because of this?
bone marrow suppression
gut mucosal damage
hair loss
why do you give chemo in cycles?
to let the normal organs recover
what is a specific side effect of alkaloids? (cell cycle specific agents)
neuropathy
what is a specific side effect of anthracyclines? (non cell cycle specific agents)
cardiotoxicity
what is a specific side effect of cis-platinum? (non cell cycle specific agents)
nephrotoxicity
what are 2 specific side effects of alkylating agens? (non cell cycle specific agents)
infertility
secondary malignancy
what pathway needs to be functional for chemotherapy drugs to work?
p53 apoptosis pathway
what chromosome translocation causes chronic myeloid leukaemia?
translocation between 9 and 22 (creates philadelphia chromosome )
what are myeloproliferative disorders?
clonal haemopoietic stem cell disorders with an increased production on one or more haemopoietic cell type
what makes myeloproliferative disorders different from acute leukaemia?
maturation is preserved
what are the 2 broad classes of myeloproliferative disorders?
BCR-ABL 1 positive and BCR-ABL 1 negative
what is the 1 BCR-ABL 1 positive myeloproliferative disorder?
chronic myeloid leukaemia
what are the 3 BCR-ABL 1 negative myeloproliferative disorders?
polycythaemia rubra vera (PRV)
idiopathic myelofibrosis
essential thrombocythaemia (ET)
what are the 3 phases of chronic myeloid leukaemia?
- chronic phase
- accelerated phase
- blast phase
what causes the BCR-ABL 1 gene?
the philadelphia chromosome 22 (translocation between 9 and 22)
acquired mutation
what is the main treatment for the BCR-ABL 1 gene?
tyrosine kinase inhibitors (eg imatinib)
what is polycythaemia rubra vera characterised by?
excess RBCs
what is essential thrombocythaemia characterised by?
excess platelets
what are the 3 main causes of pseudopolycythaemia?
dehydration
diuretics
obesity
what specific itch do you get with polycythaemia rubra vera?
aquagenic pruritus
will people with primary or secondary polycythaemia have splenomegaly?
primary polycythaemia
why should you not correct iron deficiency in someone with polycythaemia?
will make it worse
what mutation is common in polycythaemia rubra vera?
JAK 2
what is the treatment for polycythaemia rubra vera?
- venesect to haematocrit less than 45%
- aspirin
- if resistant: hydroxycarbamide (PO chemotherapy)
in essential thrombocythaemia, the platelets are functionally abnormal- what 2 things can this cause?
- thrombosis
- bleeding
why can bleeding occur in essential thrombocythaemia?
acquired von willebrand disease
what mutations are common in essential thrombocythaemia?
JAK 2
CALR
MPL
what is the treatment of essential thrombothaemia?
- antiplatelet (eg aspirin)
- cytoreductive therapy (eh hydroxycarbamide)
what are the 2 main features seen on blood film of idiopathic myelofibrosis?
- leukoerythroblastic appearance
- tear drop RBCs
what mutations are sometimes seen in myelofibrosis?
JAK 2
CALR
what drugs are used in myelofibrosis?
JAK 2 inhibitors
what CD number is rituximab specific against?
CD 20 (on B cells)
how do proteosome inhibitors work?
inhibit the proteosomes (which are basically bins for old proteins) leading to accumulation of toxic protein in the cell and therefore apoptosis
how do Hodgkins lymphoma cancer cells prevent surrounding T cells from attacking them?
immune evasion
-produce chemicals which bind to the T cell PD1 receptor and causes the immune system to be switched off
what cells are infected in glandular fever?
epithelium of the throat
and B lymphocytes
is hodgkins lymphoma or NHL more associated with alcohol induced pain?
hodgkins
is hodgkins lymphoma or NHL more likely in a younger patient?
hodgkins
what cells are characteristic of hogkins lymphoma?
reed sternberg cells
what 3 specific infections should you vaccinate those with splenectomys from?
- meningococcus
- pneumococcus
- haemophilus influenzae b
