Haem important Flashcards
what cells are affected in Multiple myeloma? what is the effect?
Abnormal plasma cells (antibody-producing B lymphocytes) accumulate in the bone marrow and replicate in an uncontrolled way –> leads to one specific type of immunoglobulin being massively overproduced.
presentation of multiple myeloma
- CRABBI: hyperCalcaemia, Renal failure, Anaemia, Bone lesions (and bone pain), Bleeding, Infection
multiple myeloma investigations
- Bloods: FBC- anaemia and thrombocytopoenia, U&Es- raised urea and creatinine + raised calcium
- raised conc of IgA/IgG on serum/urine electrophoresis
- Bone marrow aspiration/trephine biopsy CONFIRMS DIAGNOSIS
- whole body MRI done to survey skeleton for bone lesions
- Rouleaux formation on blood film
3 criteria for diagnosing multiple myeloma
1- monoclonal plasma cells in bone marrow >10%
2- monoclonal protein within serum or urine
- evidence of end-organ damage (hypercalcaemia, elevated creatinine, anaemia, lytic bone lesions/fractures)
treatment of myeloma
- under 65: stem cell transplant + Bortezomib (chemo) + dexamethasone
- Over 65: just chemo
hodgkin’s lymphoma- causes
mononucleosis infections from EBV or CMV
What cells are affected in Hodgkin’s kymphoma and what is the effect?
B lymphocytes stop expressing antibodies due to mutations but do not die due to mutations in the Fas gene –> they develop own self regulatory growth mechanism + become large cells (REED STERNBERG CELLS)
appearance of Reed-Sternberg cells on histology
“owl-like” (because multi-nuclei)
lunar histiocytes
giant malignant cells
management for Hodgkin’s
ABVD chemo: Adriamycin Bleomycin Vinblastine Dacarbazine
is Hodgkin’s contiguous
yes- only spreads to ADJACENT lymph nodes/structures due to flow of lymph- doesn’t arise in several unlinked structures
investigations hodgkin’s
- bloods: normocytic anaemia (low number RBCs), oesinophilia (abnormally high eosinophils)
- Raised LDH (serum lactate dehydrogenase)
- lymph node biopsy- reed sternberg cells
non-hodgkins’ lymphoma symptoms
- Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
- Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
- Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
differentiating between Hodgkin’s and Non-hodgkin’s lymphoma
- Biopsy- Hodgkin’s contains Reed-sternberg cells
- Hodgkin’s lymphadenopathy triggered by alcohol
- B symptoms typically occur earlier in Hodgkin’s lymphoma and later in non-Hodgkin’s lymphoma
- Extra-nodal disease is much more common in non-Hodgkin’s lymphoma than in Hodgkin’s lymphoma
2 examples of non-hodgkin’s lymphoma
MALT (mucosa associated lymphoid tissue)- occurs normally in stomach, often associated with H pylori infection
Burkitt’s lymphoma; associated with west africa, childhood disease, jaw lymphadenopathy - often associated with malaria infection
Investigations for non-hodgkin’s
- excisional node biopsy= diagnostic
- CT chest/abdo/pelvis for staging
- HIV test (HIV= risk factor for NHL)
staging system for lymphoma
Ann-Arbor: •I: single lymph node •II: 2 or more lymph nodes/regions on same side of diaphragm •III: nodes on both sides of diaphragm •IV: spread beyond lymph nodes
Treatment for high-grade non-hodgkin’s
RCHOP
- Rituximab
- Cyclophosphamide
- Hydroxyduanomycin
- Oncovin
- Prednisolone
treatment for low grade non-hodgkin’s
chlorambucil for chemo, a-interferon/rituximab to maintain remission
what type of cells does leukaemia affect?
Blast cells- white blood cells which are not developed
what are the two types of acute leukaemia?
1- ALL- acute lymphoblastic leukaemia- too many lymphoblasts in the blood and bone marrow. Most common malignancy in childhood
2- AML- acute myeloid leukaemia- too many myeloblasts in blood and bone marrow (immature WBCs which become neutophils/eosinophils/basophils)
what % of bone marrow is blast cells in acute leukaemia? what is the effect?
more than 20% (normally should be 1-2%)
large proportion of blast cells means other cells cant differentiate or be produced in bone marrow properly –> leads to anaemia (fatigue), thrombocytopoenia (bleeding), neutropoenia (infection)
symptoms of acute leukaemia
- bone marrow failure- anaemia (tiredness, SOB, weakness), thrombocytopenia (bleeding + bruising), Leukopenia (infection), bone marrow infiltration (bone pain)
systemic signs- fever, pallor, petechiae
ALL: lymphadenopathy, hepatosplenomegaly, testicular enlargement
AML: violaceous skin lesions
investigations acute leukaemia
- FBC- low Hb, high WBC, low platelets
- blood film shows blast cells, in ALL large blast cells, in AML there are AUER RODS
- CXR shows mediastinal widening in T-cell ALL
treatment in acute leukaemia
1 - remission induction- chemo destroys majority of tumour
2- remission consolidation- involves bone marrow transplant
3- maintainign remission + supportive care
distinguishing between chronic and acute leukaemia
in chronic, blast cells mature partially whereas in acute, they don’t mature at all
philadelphia chromosome
chromosome abnormality seen in CHRONIC MYELOID LEUKAEMIA
most common of all leukaemias
chronic lymphoid leukaemia
treatment of CML
- biological therapy- tyrosine kinase inhibitor (e.g. Imantinib), prevents action of Philadephia chromosome
- chemo
- stem cell transplant
- bone marrow transplant
risk factors for CLL
low immunity due to HIV/AIDS
which cancer is also known as lymphocytic lymphoma
mature CLL (because leads to formation of masses in lymph nodes)
smudge cells are seen on the blood film in
chronic lymphocytic leukaemia
which cells are affected in CML v CLL
CML- affects basophils, neutrophils and eosinophils (granulocytes)
CLL- affects B lymphocytes
treatment of CLL
1st line: fludarabine, cyclophosphamide or rituximab
2nd line: chlorambucil with prednisolone
what is microcytic anaemia? what are the causes?
Small RBCs in peripheral blood smear, usually characterised by low MCV
Causes= TAILS:
- Thalassaemia
- Anaemia of chronic disease (can occur with illnesses like TB, Crohns, RA, lupus, polymyalgia etc)
- Iron deficiency
- Lead poisoning
- Sideroblastic anaemia (bone marrow produces ringed sideroblasts instead of healthy RBCs)
Normocytic anaemia- what is it? what are the causes?
normal MCV and normal haem levels, but insufficient numbers of RBCs
caused by
- Haematological disorders such as aplastic anaemia and some haemolytic anaemias
- Anaemia of chronic disease
- Acute blood loss
- Endocrine disorders
- Combined haematinic deficiency (iron, B12 AND folate deficiency)
Macrocytic anaemia- what is it and what are the causes
RBCs are larger than their normal volume (high MCV)
causes:
- B12/folate deficiency
- Alcohol excess/liver disease
- Hypothyroid disease
- Haematological causes; antimetabolite therapy, haemolysis, bone marrow failure and bone marrow infiltration
What is Polycythaemia rubra vera? what mutation is present in over 90% of cases?
-a myeloproliferative disorder where too many
RBCs are produced by the bone marrow. Primary cause of polycythaemia (high concentration of RBCs in the blood)
- JAK2 mutation in haemopoietic myeloid stem cells–> no apoptosis –> proliferation of RBCs, WBCs and platelets
- can lead to hyper-viscosity and thrombosis
presentation of polycythaemia rubra vera
Characteristic signs : itch after hot bath &
erythromelalgia (burning sensation in fingers +
toes)
• Hyper viscosity can cause headaches, dizziness,
tinnitus, visual disturbance
• Facial plethora + splenomegaly on examination
• Gout (due to high urate from RBC turnover)
• Features of arterial or venous thrombosis may be
present
Investigations for polycythaemia rubra vera
- RAISED RED CELL MASS ON CHROMIUM STUDIES AND SPLENOMEGALY
- FBC: high red cell count, high Hb, high haematocrit, high packed cell volume and sometimes high WBC count and platelets
- increased B12
- Marrow shows hypercellularity with erythoid hyperplasia
treatment for polycythaemia rubra vera
- aim to keep haematocrit below 0.45 to reduce risk of thrombosis
- venesection (young low risk pts)
- hydroxycarbamide (hydroxyurea) if old or previous thrombosis
- a-interferon for women of childbearing age
sickle cell anaemia pathology
mutation in the HBB gene causes the Beta globin chains in Haemoglobin A to be misshapen (mutation causes amino acid substitution in gene coding the Beta globin chain, causing production of HbS instead of HbA)
- HbS polymerises when deoxygenated, causing RBCs to deform, producing sickle cells- these are fragile, haemolyse and block small blood vessels
- Sickling happens a lot when theres acidosis
because Hb’s affinity for oxygen decreases & in
low flow blood vessels because Hb has lots of time
to dump O2 = the Hb is deoxygenated so the RBC
sickles
- Repeated sickling of RBCs damages the RBCs cell
membrane which leads to premature destruction
- called intravascular hemolysis. This causes
anaemia + spillage of Hb into vessels that joins
with haptoglobin to be recycled (hence low
haptoglobin)
inheritance pattern sickle cell
autosomal recessive
investigations- sickle cell
- protein electrophoresis of Hb to find HbS
- blood smear shows sickled cells
- can be diagnosed at birth using newborn blood spot screen using cord blood
symptoms sickle cell
- anaemia , enlarged cheeks, hair on end appearance on skull
- hepatomegaly
- jaundice, bilirubin gallstones
- pain and avascular necrosis (due to vaso-occlusion through sickled cells getting stuck)
treatment of sickle cell
1- long term management
2- crisis management
1- hydroxycarbamide
2- analgesia (opiates), rehydration, oxygen, antibiotics if evidence of infection, blood transfusion
Von Willebrand disease signs, investigations, treatment
signs- bruising, epistaxis, menorrhagia, increased bleeding post tooth extraction
- Investigations: increased activated partial thromboplastin time, increased bleeding time
Treatment: desmopressin used in
mild bleeding, WVF-containing factor VIII
concentrate for surgery/major bleeds, avoid NSAIDs
Thrombocytic thrombocytopenic purpura (TTP) - signs and treatment
TPP pentad: Microangiopathic haemolytic anaemia, Thrombocytopenic purpura, neurological abnormalities, fever, renal disease
treatment: emergency- urgent plasma exchange, steroids, eculizumab (mab)
4 organisms which cause malaria + which is most deadly?
plasmodium falciparum/vivax/ovale/malariae, plasmodium falciparum is most deadly , vivax is most likely non-deadly cause
treatment for malaria
Artesunate (severe or uncomplicated) - quinine is second line if artesunate is unavailable
Chloroquine
Sepsis 6
- give high flow oxygen
- Blood cultures
- Antibiotics within first hour
- give fluid challenge
- measure lactate
- measure urine output
