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128 Cards in this Set
- Front
- Back
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At what size do we consider a LN to be abnormally enlarged?
What are the exceptions? |
If they are greater than 1cm in diameter
Exceptions: it's 0.5cm for epitrochlear nodes and 1.5cm for inguinal nodes |
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Three things that would raise particular alarm in someone with lympadenopathy / that would make you consider doing other tests
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- Progressive enlargement over 2-3 weeks
- No change in size over 6 week period - Supraclavicular lymphadenopathy |
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When would we think of doing a LN biopsy?
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It keeps getting bigger and there's no sign of underlying infection
Greater than 2.5cm in diameter Supraclavicular location Systemic symptoms are present |
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What is the difference between lympadenopathy in kids and in adults?
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Kids -> rarely due to an underlying malignancy (only about 20% of the time)
Adults -> more likely to be due to a malignant change |
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Normal numbers of neutrophils in the blood
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2-7.5 x109 /L
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Normal numbers of eosinophils in the blood
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0.04-0.4 x109/L
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Normal numbers of basophils in the blood
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0.01-0.1 x 109 / L
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Normal numbers of monocytes in the blood
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0.2-0.8 x 109 / L
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Normal numbers of lymphocytes in the blood
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1.5-4 x 109 / L
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What are neutrophils aka'ed?
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polymorphonuclear lymphocytes
'polymorphs' granulocytes |
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How long does it take to produce a neutrophil in the bone marrow?
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6-10 days
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What is the half life of a neutrophil?
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6-7 hours
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How do we get increased number of neutros in the circulation in response to infection?
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- Release of stored cells from the BM
- Increased production of neutros by the precursor cells |
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What do neutros protect us from?
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Bacteria
They're ineffective against viruses and fungi |
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WHat is the 'respiratory burst' that neutros can undergo?
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Increased O2 uptake and then release of superoxide and hydrogen peroxide
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How long do monocytes usually circulate in teh blood before going into tissues?
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3 days
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CLL: what do we see in the peripheral blood?
SPecifically, what do we see on a blood film? |
Lot of mature lymphocytes in the blood
Blood film: - increased numbers of small, round lymphocytes with scant cytoplasm - smudge cells (because they're really fragile) - might see spherocytes (if they develop autoimmune haemolytic anaemia) - also might see immature RBCs (ie nucleated) because of either serious anaemia and/or BM infiltration |
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CLL: how do we diagnose?
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Based on proving monoclonality (all have either kappa or lambda light chain)
And that the B-cells express CD5 (usually on T-cells only) ie they're CD5+ CD19+ Lymphocyte count > 5x109 |
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CLL: how do patients present?
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Usually an incidental finding
They could have painless LN enlargement |
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CLL: what's peak age incidence
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Occurs in over 50s. peak is between 60-80
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CLL: what's the gender ratio?
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More common in males, 2:1
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CLL: what haematological complications often occur?
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Anaemia (autoimmune haemolytic) and thrombocytopenia
Both due to production of a paraprotein by the CLL B-cells and/or marrow infiltration |
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CLL: treatment?
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At diagnosis we do NOT give the patient chemo - studies have shown that this does not improve their prognosis
just observe them until there's evidence of disease progression: - rising lymphocyte count - progressive lymphadenopathy or splenomegaly - development of anaemia or thrombocytopenia |
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CLL: what are indicators of disease progression? might raise some alarm bells
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- rising lymphocyte count
- progressive lymphadenopathy or splenomegaly - development of anaemia or thrombocytopenia |
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CLL: if we chose to give them chemo / had to do so, what would we give them?
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Older patients -> chlorambucil = oral alkylating agent. well tolerated
Younger - might use combo approach, more aggressive approach eg R-FC = rituximab, fludarabine an cyclophosphamide |
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CML: what are the characteristics?
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Philadelphia chromosome! Can usually see the karyotype changes (9 gets bigger and 22 smaller)
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What is the philadelphia chromosome
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Occurs when we have translocation involving the BCR gene on chromosome 22 and ABL on chromosome 9
ABL gene comes over very close to BCR gene -> get a fusion protein of the two --> rapid replication of myeloid stem cells |
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CML: what do we see in the peripheral blood?
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There are both mature and immature lymphocytes
Danny said that the film looks a lot like a BM film |
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CML: treatment?
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We have developed drugs that target the BCR-ABL fusion protein = oral tyrosine kinase inhibitors
the drug is IMATINIB They work because the fusion protein has high tyrosine kinase activity get complete haematological response in most patients |
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What is imatinib?
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oral tyrosine kinase inhibitor used in CML
Results in complete haematological response in almost all patients. ?complete cure - different studies suggest different things re what happens when you stop the drug. Recent studies suggest you might get complete cure |
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CML: what happens to the BM?
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It's usually 50% fat, 50% cells
In CML (and i think other leukemias as well), we get decrease in the amount of fat - BM becomes almost 100% cellular |
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What do we see in the peripheral blood in the acute leukemias?
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See very immature cells (=blasts)
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What is ALL ? who does it affect?
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This is the one that mostly gets kids
85% of the time it's due to B-cell that proliferates out of control we have immature lymphocytes in the periphery - these are known at lymphoblasts |
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ALL: treatment?
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Very good in kids - 90% are cured
About 2/3 of adults are cured |
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How do you tell AML and ALL apart on a blood film?
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AML - there are granules in the cytoplasm
ALL there aren't granules (Danny taught this!) |
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Which leukemias are curable?
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CML (oral tyrosine kinase inhibitors)
ALL (90% cure rate in kids, 2/3 in adults) AML - though it's harder to cure than ALL |
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Which leukemias are not curable?
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CLL
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Which lymphomas are curable?
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Large cell non Hodgkin's
Hodgkins |
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Which lymphomas are not curable?
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Indolent non-H lymphoma
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How do we define bone marrow failure?
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It's when the precursor cells in the BM stop replicating -> we won't get continued production of mature blood cells
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What happens if we don't have proper production of RBCs? What's it called and what happens to the patient?
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Anaemia
They have reduced O2 carrying capacity -> pallor, fatigue, SOB |
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What happens if we don't have proper production of myeloid cells? What's it called and what happens to the patient?
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Myeloid -> neutrophils
ie if production isn't good, we have neutropenia This means they will have impaired phagocytosis -> increased fevers, infections and mouth ulcers |
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What happens if we don't have proper replication of megakaryocytes? What's it called and what happens to the patient?
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Won't have enough platelets = thrombocytopenia
They won't clot properly Increased bleeding, bruising and they get petechiae |
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What happens if we don't have proper replication of lymphoid SCs? What's it called and what happens to the patient?
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Won't have enough lymphocytes = lymphopenia
They are immune deficient --> increased infections |
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What sorts of things can cause BM failure? (8!)
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1. Haematological malignancy eg leukemia, lymphoma, myeloma, myeloproliferative disorders, myelodysplasia
2. Solid tumours 3. Fibrosis eg from radiation damage or following infection - particularly TB 4. Storage disorders eg Gaucher's 5. Nutritional problems (eg B12, folate) 6. Virus infections eg parovirus, hep viruses 7. Drugs - particularly anticancer drugs 8. Stem cell defects / damage eg in aplastic anaemia |
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What do we call it when we have antibodies against coagulation proteins?
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Coagulation inhibitors
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What is it when we have antibodies against phospholipids involved in coagulation?
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Lupus anti-coagulant, anti-cardiolipin antibodies
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In autoimmune haemolysis, what do the antibodies bind to?
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Proteins on the RBC - these are from the Rh blood group
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What is lupus anticoagulant ?
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It's an antibody that binds to phospholipids involved in coagulation and actually INCREASES the chance of a thrombus (ie it's a misnomer!)
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What is the difference between a primary and a secondary immunodeficiency?
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Primary - it's from spontaneous or inherited gene mutations (or could occur without known cause)
Secondary - it's acquired eg due to HIV or chemo |
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What happens if you are deficient in B-cells in particular? ie immunodeficiency that's involving predominately the B-cells
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Typically get infected with polysaccharide encapsulated bacteria --> sinusitis, otitis media, bacterial pneumonia, infections of the skin
the common bugs are strep pneumoniae, h influenzae B, strep pyogenes, staph aureus, giardia lamblia and camplybacter jujeni |
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What happens if you are deficient in T-cells in particular? ie immunodeficiency that's involving predominately theT-cells
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T-cells required for getting rid of intracellular pathogens: viruses, fungi, protozoa, listeria
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What happens if you are deficient in macros in particular? ie immunodeficiency that's involving predominately the macros
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Rare
you would get high grade bacterial infections |
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What happens if you are deficient in the complement system in particular? ie immunodeficiency that's involving predominately complement
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If it's C5-9, susceptible to neisseria meningitidis and gonorrhoeae
If it's problems with the earlier components (particularly C3), they are susceptible to gram neg bacteria and pyogenic organisms |
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What are the common opportunistic infections?
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PCP = pneumocystis carinii pneumonia
Cryptococcal miningitis Candidiasis CMV |
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What cell type do all the haematopoietic cells come from?
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the haemoatopoietic stem cell
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In developing babies (in utero), how do we get the first haematopoietic SC?
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It is not the first blood cell to be produced! Contrary to what you might think
In fact, we get blood cells further down from the HSCs produced first and then we get consecutive waves of blood cells and we eventually get HSCs made |
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What is the yolk sac?
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A bilayered membrane that surrounds the embryo and supplies it with nutrients from the mother's side
It is the first site of haematopoiesis in embryos |
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Where do we first get red cells produced in the embryo? and When ?
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7.5 dpc (= days post coitus ie after intercourse) in the yolk sac
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When are transplantable HSCs first present?
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9.5 dpc (days post coitus) - but the first blood cells were produced on day 7.5 ie we're producing the later cells first then we get the first cell (HSC)
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Where is the second place we get blood cells produced in the embryo?
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AGM = aorta-gonadal-mesonephros ie one the wall of the dorsal aorta, in a special area - known as the AGM
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As the embryo develops, what are the different places where red blood cells are produced?
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1. yolk sac (day 7.5-11.5)
2. AGM (day 11.5) 3. placenta and umbilical vessels (day 12.5) |
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What is the third place in the embryo where haematopoiesis occurs?
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The placenta and umbilical vessels
This is 12.5 dpc |
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What happens in the fetal liver in terms of haematopoiesis
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It doesn't generate the HSCs themselves
But it's important because it's where we get expansion of the HSCs |
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What are haemogenic endothelial cells?
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They are believed to be the origin of HSCs during embryogenesis
IT's a group of endothelial cells that on about 8.5-12.5 dpc break off from the endothelial wall, shut down their expression of endothelial genes and up-regulate their haematopoietic genes -> they produced HSCs |
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What is the Runx1 gene?
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It plays crucial role in the transition of teh haemogenic endo cells from endothelial cells to haematopoietic cells
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What factors affect embryonic haematopoiesis? (3)
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- Presence of circulation itself (mice with no heart beat -> won't have good production of red cells)
- physical shear force of teh blood flow - transcription factors : Scl and Lmo2 |
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What location of lymphadenopathy worries doctors the most?
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Supraclavicular
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In CLL, what markers are on the surface of the B-cells?
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CD5 - normally only on T-cells
CD19 and CD23 |
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In CLL, do you have increased, normal or decreased levels of Igs in the blood?
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Decreased - this happens later in disease
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What is chlorambucil?
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An oral alkylating agent used in older people with CLL. It's quite gentle and well tolerated
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What leukemia do we have smudge cells on the blood film?
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CLL
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Are leukemias more common in men or women?
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MEN
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T/F: incidence of leukemia has been decreasing recently
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False. incidence INCREASING. we don't know why
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How do we diagnose acute leukemia?
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More than 20% of blast cells in BM or peripheral blood
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What would the BM trephine show in leukemia?
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It would normally be 50/50 with fat and cells
Leukemia -> it's hypercellular --> almost 100% cells now |
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Which leukemia will have karyotypic changes?
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CML
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How do we treat CML?
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Imatinib = oral tyrosine kinase
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Side effects of imatinib?
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Rash, fluid retention, muscle cramps, nausea
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Following an allogenic SC transplant, what is graft vs host disease?
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The donor's imm cells start attacking the hosts cells
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3 months after an allogenic BM transplant, what percentage of people will be dead?
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10-20%
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What infection are people with CLL most susceptible to?
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Reactivation of herpes zoster = shingles. we don't really know why this is
Probably due to generalised immune dysregulation |
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How does herpes zoster usually present?
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first 1-2 days = prodromal period. Headache, flu-like symptoms etc
Then you get the characteristic RASH which follows DERMATOME REGIONS The rash evolves into vesicles / small blisters which are filled with serous fluid |
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N-H lymphoma - what cell type does it mostly commonly originate from?
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in 85% cases, originates from B-cells
The other 15% are from T-cell or NK cells |
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What's the difference (in terms of cell types) between H and NH lymphomas?
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H => characteristic Reed-Sternberg cells (they're multi-nucleated cells present in the swollen LN)
HS => don't have these RS cells |
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What percentage of patients with H lymphoma are cured?
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85%
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How do NH lymphomas normally present?
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Lymphadenopathy - usually asymmetrical and painless
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How do we look for monoclonality in CLL?
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Flow cytometry - looking at kappa and lambda chains on surface of the B-cells
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What cell type does ALL originate from?
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Lymphoid stem cells
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What cell type does CLL originate from?
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Mature B-cell
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What cell type do B-cell lymphomas originate from?
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Maturing B-cells
Different lymphomas come from different stages of B-cell development |
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What's the difference between indolent and aggressive NH lymphomas in terms of speed of growth?
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Indolent grow slowly
Agressive grow rapidly |
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What's the difference between indolent and aggressive NH lymphomas in terms of lymph node pattern?
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Indolent -> nodular or follicular pattern
Aggressive -> more diffuse LN pattern |
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What's the difference between indolent and aggressive NH lymphomas in terms of treatment and prognosis?
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Indolent - grows slowly --> doesn't respond well to treatment ie they're incurable
Aggressive - they're growing rapidly --> we give them aggressive treatments |
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What is the median survival of someone with indolent NH lymphoma?
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8 years. It's slow growing -> will never cure it. But it takes a long time to get bad enough that it will kill you
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What is your prognosis if you have aggressive NH lymphoma?
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It's growing rapidly -> can be targeted by drugs. About 40-50% are cured. The others will die pretty quickly
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Which lymphomas will kill you and which can be cured?
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Curable lymphomas = hodgkin's lymphoma and aggressive NH lymphoma
Incurable = indolent NH lymphomas |
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How do you diagnose NH lymphoma?
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Biopsy of the lymph node:
- Indolent (small cell) --> you see nodes / follicles in the LN. Cells are small - Aggressive (large cell) --> cells are diffuse all throughout the node |
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What are the four stages of lymphoma?
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1. Single group of LNs
2. 2 groups of LNs, same side of diaphragm 3. LNs on both sides of the diaphragm 4. Extra lymphatic disease |
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In terms of staging lymphoma spread, what does stage 2 represent?
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2 -> 2 groups of nodes on the SAME side of the diaphragm
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What is the IPI? and what is it?
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International Prognostic Index. It looks at a number of factors that affect your prognosis with lymphoma, scores them and gives you a number between 0-3 which is predictive of your life expectancy
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What factors does the IPI take into account?
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- age (the older you are, the worse your outlook)
- stage (more developed, the worse your outlook) - serum LDH levels (bad if they're raised) - ECOG performance - measures your independence - number of extranodal sites |
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What does IPI stand for and what are the scores you can get in it?
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International Prognostic Index
Given number between 0-3 0=> 80% 5 year survival rate 3 => 20% 5 year survival rate |
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How do we treat indolent NH lymphoma?
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It grows slowly --> treat it slowly
Not curable! Might use local radiation if it's in one area. Or some chemo. But can't cure it |
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How do we treat aggressive NH lymphoma?
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They grow fast -> treat fast
We use multi-agent chemo + radiation in young healthy people. R-CHOP In elderly people, might just use the better tolerated drug chlorambucil = oral alkylating agent |
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What are the five main groups of chemo drugs?
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1. Alkylating agents
2. Anti-metabolites 3. Cytotoxic antibiotics 4. Vinca alkaloids 5. Taxanes |
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Which haematological malignancies are incurable?
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CLL
And indolent NH lymphoma (because they're both so slow growing) |
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How do the alkylating agents work? Main eg
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They add alkyl group to DNA --> the strands cross-link -> don't get DNA synthesis
Chlorambucil is an eg |
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How do the anti-metabolite chemo drugs work?
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They are structual analogues of natural enxymes / molecules involved in DNA synthesis -> the drugs competitively inhibit DNA synthesis
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What are egs of anti-metabolites that we should know (2)
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Methotrexate - interferes with folate pathway
5-FU is a pyrimidine analogue |
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What is the timing of administration of the anti-metabolite drugs?
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Since they work during S phase (DNA synthesis), they will only work on a few cells at each administration (because cells aren't in S phase for long)
-> we like to give them continuously -> ideally, liquid or tablet form they can take at home |
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What are two egs of cytotoxic antibiotic drugs used in chemo?
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Bleomycin
Doxorubicin |
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What is doxorubicin? What's its SE?
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A cytotoxic antibiotic used in chemo
It is cardiotoxic |
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How do the vinca alkaloid drugs (chemo) work?
Egs |
They act on micro-tubules in M-phase of the cell cycle -> the chromosomes don't get separated
Eg vincristine, vinblastine, vinorelbine |
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How do the taxanes (chemo drugs) work?
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They act on micro-tubules in M-phase of the cell cycle -> the chromosomes don't get separated
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What SE do we get specifically with the vinca alkaloids?
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Neurotoxicity because of their effect on micro-tubules in nerves
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What SEs do we get specifically with the taxane chemo drugs? (3)
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- Neurotoxicity (because they act on the micro-tubules in nerves)
- Myalgia and neuralgia - Lots of people get allergic reactions to the solvents used (they aren't H20 soluble -> need to give with prednisone) |
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What's a complication of taxane use? How do we overcome this?
(remember: taxanes are very taxing for the body) |
Taxanes are NOT H20 soluble -> need to dissolve them in solvent (castor oil or detergent) Lots of people get bad allergic responses to the solvent
Overcome by giving large doses of prednisone |
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What are the platinums used for (chemo) and what are two egs?
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They're particularly effective in testicular cancer
Eg cisplatin and carboplatin |
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What is cisplatin and what is it's major SE?
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Cisplatin is from the platinum group of chemo drugs
Because it's a heavy metal, it's quite nephrotoxic |
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What happens to the gamma globulin levels in CLL?
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They fall ie we get hypogammaglobulinaemia
This is due to the abnormal lymphocyte population -> we get generalised deficiency in the gamma globulins |
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What are the two main groups of non-hodgkin's lymphoma?
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1. Indolent / follicular / small cell = slow growing - can't cure but takes a while to kill you
2. Aggressive / diffuse / large cell = rapidly growing -> will either kill you quickly or you'll get cure |
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What type of malignancy originates from the lymphoid SC?
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ALL
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What type of malignancy originates from the mature B-cell
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CLL
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What type of malignancy originates from the plasma cell?
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Multiple myeloma
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What type of cell do B-cell lymphomas originate from?
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THye come from teh maturing B-cells - different types come from different stages of the maturation
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What are the four stages of lymphoma?
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1. Single gorup of nodes
2. Same side of teh diaphragm 3. diff sides of diaphragm 4. Extra lymphatic disease |
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What does the IPI consider? (5)
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- Age
Stage Serum LDH levels ECOG performance (indepence) Number of extranodal sites |
