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74 Cards in this Set
- Front
- Back
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what is the normal Hb level and hematocrit for men |
130-180 40-52% |
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what is the normal Hb level and hematocrit for women, pregnant and not |
120-160 normal, less than 110 35-47% |
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what is a high percentage of HbA2 indicative of |
beta-thalassaemia |
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what is the average RBC size |
80-100 femtolitres |
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what are the causes of microcytic hypochronic anaemia (4) |
iron deficiency thalassaemia Sideroblastic anaemia lead poisoning |
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what are the main causes of normocytic normochromic anaemia (4) |
Haemorhage haemolysis aplasia chronic disease |
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what are the main causes of macrocytic anaemia (5) |
B12 and folate deficiency liver disease hypothyroidism Retiulocytosis Myelodysplasia |
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what are the general symptoms of anaemia |
fatigue malaise SOBOE palpitations exacerbated angina Intermittent claudication Conjuctiva pallor palmar creases pallor Tachycardia Confusion/lack of concentration dry skin, thin hair koilonychia |
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what can cause iron deficiency |
chronic blood loss poor diet increased demand (pregnancy) Poor absorption (coeliac, parasitic infection) |
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what are the symptoms/signs of iron deficiency anaemia |
angular cheilitis atrophic glossitis stomatitis brttiel nails and koilonychia Pencil/cigar cells and target cells splenomegaly PICA decreased reticulocytes low iron, low ferritin, increased transferrin |
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why does lead poisoning cause anaemia and what is its blood smear signs |
it impairs the synthesis of heme - fragile RBCs, with low Hb Basophilic strippling (small blue dots in RBC) |
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what is sideroblasic anaemia, who is it more common in and what is it characterised by |
where the body is unable to incorporate heme into globin men - x linked iron dots in RBCs |
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why is the reticulocyte important in normocytic anaemia and what does high and low mean |
reticulocytes are the immature RBCs, meaning there is increased demand for blood and therefore increased new blood cells coming out and maturing in the circulatory system
high = blood loss/haemolysis low = no new cells = chronic disease, aplasia, infiltration |
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what can cause haemolysis |
membrane defects (spherocytosis) enzyme defects (G6PD deficiency - bite cells) Sickle cell anaemia autoimmunity (cold agglutinins) Erythroblastosis fetalis transfusion reaction microangiopathic haemolytic anaemia |
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what are two characterisitics of macrocytic anaemia |
hypersegmented neutrophils Big erythroblasts |
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What is rouleaux myeloma, and why does it cause anaemia |
cancer of plasma cells - very high amount of polyclonal or monoclonal (multiple isotypes or single isotype), which target RBCs autoimmune haemolysis |
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what is aplastic anaemia, and what causes it |
where there is very little or no functional bone marrow producing cells chemotherapy is the most common cause, with radiation and chemicals such as chloramphenicol etc) it can also be caused by infection (hep B, HIV, EBV) or immune |
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what are the main causes of B12 deficient anaemia and how long does it take to come on and what are the symptoms |
takes years to develop due to reserve in liver
insufficient absorption --> lack of intrinsic factor (pernicious anaemia), gastrectomy, veganism, IBD neurological symptoms --> peripheral neuropathy, subacute combined degeneration, dementia |
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what is pernicious anaemia |
autoimmune conditioon where the body has Ab and cellular infiltrate agaisnt the gastric parietal cells --> lack of intrinsic factor secretion --> lower B2 absorption |
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what is glucose-6-phosphatase deficiency |
The G6PD / NADPH pathway is the only source of reduced glutathione in redblood cells. The role of red cells as oxygen carriers puts them at substantialrisk of damage from oxidizing free radicals except for the protective effect ofG6PD/NADPH/glutathione --> no protection, oxidisation --> fragile cells |
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what is cold agglutinin haemolytic anaemia and when does it occur/causes |
Isan autoimmune disease, caused by cold-reacting antibodies (higher activity at coldtemperature relative to the body). The Ab are targeted at RBCs, thus when bloodfilm made at room temp, almost all RBCscoagulate, put back at room temp, should be much lesser extent Can be caused by leukaemia (early indicator) Commonly caused byinfection: Infectiousmononucleosis (60% of cases of IM) Mycoplasma pneumoniae |
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what is infectious mononucleosis |
EBV infection - infect B cells in oropharyngeal epithelium), then B cells spread infection through reticulo-endothelial system via migrating through the lymphatic system |
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what is hereditary sphereocytosis, what happens and its complications and how is it inherited |
RBC membrane abnormality Abnormalities in one or more of the cytoskeletal proteins inthe membrane of the RBC = disrupted cytoskeleton and turn from concave disk tosphere Turns into sphere as it is then most surface tensionefficient and least configuration Small, spherical RBCs which cannot withstand compressionforces and are easily ruptured in transit through spleen → extravascular haemolysis(in spleen/liver) Essentiallyhaemolytic anaemia Can result in iron deficiency anaemia due to Hb use Can cause haemolytic jaundice ↑spherocytes (recall, ↑schistocytes in intravascular). Transmitted as autosomal dom/recessive trait. |
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what is plasmodium falciparum and how does it show on a blood smear |
malaria With 'rings' in the cells |
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what is sickle cell anaemia characterised by |
a missence mutation in the beta chain gene --> less solubility of Hb and increased polymerisation with deoxygenation |
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what effect does anaemia have on the circulatory system |
Viscosity of blood drops with fewer RBCs, thus decreasingperipheral resistance → greatly increasingcardiac return Moreover, chronic hypoxemia causes peripheralvasodilatation, further increasing cardiac return to 1-4 times normal Thus, an effect of anaemia is increasedpumping workload on heart This partiallyoffsets peripheral hypoxia (i.e. delivering more blood), but the heart cannotmeet exceptional demands → predisposes patient to high output cardiacfailure when strain is place on heart. |
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what are the treatments of iron deficiency anaemia and their complications |
oral iron with vitamin C - stomach upset/darkening of faeces --> nausea, abdo cramps, constipation common Parenteral iron - IM injection (fever, arthralgia, abdo cramps, nausea, vomiting), can be given IV but usually not due to anaphylaxis risk Blood transfusion (if Hb less than 60), or between 60-100 if symptomatic EPO (with injected iron) --> maintain Hb at lowest levels that will both minimise transfusions and suit patient needs |
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what are the symptoms of iron toxicity |
shock, coma death intial symptoms are abdo pain from stomach ulceration and lateral potential necrotising gastroenteritis |
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how is B12 deficiency anaemia treated |
IM hydroxocobalamin --> 1mg every second day until levels normalise, then 1mg every 2 months for life (life long in pernicious anaemia) B12 must be given first, as folate will fix the anaemia, but not the B12 deficiency --> neurological deterioration |
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what is important to consider before given supplemental folate |
check B12 levels - as giving folate will correct the anaemia, but not the B12 deficiency --> eventual neurological deterioration |
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what is idiopathic myelofibrosis and what is it characterised by |
a rare bone cancer - high amounts of platelets andmegakaryocytes cause over-stimulation of fibroblasts via excess Platlet Derived Growth Factor-alpha or beta --> excess fibrosis of the bone marrow --> cannotproduce cells tear drop cells, reticulum fibrosis and megkaryocyte hyperplasia |
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what is the most common cause of thrombocytosis |
a JAK-2 mutation |
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what is the JAK-2 receptor responsible for |
When it binds to ligand,induces phosphorylation, causes the STAT complex to dimerise and move tonucleus and causes transcription of EPO Mutation causesauto-activation of the pathway, as pseudokinase is mutated and can no longerinhibit the pathway |
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what is the most common cause of leukocytosis and its appearance on blood smears |
infection neutrophils will have: toxic granulation vacuolation Dohle bodies |
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what are the histological signs of lymphocyte activation |
increased size and scallop (blue cytoplasmic edges to cells invaginate around RBCs) Large amount of cytoplasm Nucleoli visible |
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which pathway does the partial thrombin time measure and what specific factors |
extrinsic pathway Mostly factor 7, also F10/5, 2 (prothrombin) and fibrinogen (1) |
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what causes prolonged prothrombin time |
vitamin K deficiency (F10, 7, 2) DIC - used up clotting factors Liver disease - lack of clotting factor Warfarin use |
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how is prothrombin time performed |
tissue factor and calcium mixed into plasma |
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what is factor 2 in the clotting cascade |
prothrombin |
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what does the activated partial thromboplastin time measure and which factors |
the intrinsic pathway F12, 11, 9, 8 Also 10/5, 2 (prothrombin) and 1(fibrinogen) like other pathway |
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how is the aPTT performed |
citrated plasma incubated with phospholipid and F12/11 activator, then given time for for F11a to be formed and calcium then added |
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what would aPTT be elevated |
von willebrand deficiency (factor 8 dies) DIC - all used haemophilia lupus liver disease |
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what is the likely cause if both aPTT and PTT are raised |
common pathway problem i.e. DIC, F10/5 deficiency etc |
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what is a mixing blood test and why is it used |
patients serum mixed with normal serum 50-50, and then tests done If still raised = there is inhibitors in patient's plasma, if not, then there is a deficiency in the patient's factors which was corrected by adding normal serum |
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what are the 3 types of haemophilia and their prevalence |
type A: F8 deficiency - 1:5000 males Type B: F9 deficiency - 1:30,000 males Type C: F11: 1:100,000, but 8% of Ashkenazi Jews |
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why is haemophilia almost only seen in males |
it is x-linked recessive |
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why would a raised aPTT not indicate a factor 12 deficiency |
as F12 can be inactive and clotting will still occur due to F7a activating F9, which combines with F8 cofactor to form tenase complex and activate F10 |
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what are the symptoms of haemophilia |
IM haematomas Hemarthroses (bleeding into joints) Long bleeding after wounds |
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what is the most likely hematological cause of mucosal bleeding (epistaxis, gum bleeding etc), petechiae and bleeding from cuts |
platelet deficiency and von-willebrands (needed for platelets to adhere) |
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what is the most likely cause of deep haematomas, and bleeding in males |
factor deficiencies (80% of time occurs in males) |
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what is von-willebrands disease and what does it cause |
an autosomal dominant deficiency of vWF Low F8 levels (intrinsic pathway) Mucocutneous bleeds --> epistaxis, gum bleeds, menorrhagia, wounds etc, petechiae |
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where should bruises be investigated |
unexplained on tummy/trunk |
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will a platelet disease or factor disease cause spontaneously bleeding |
factors |
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what are the vitamin K dependant parts of the clotting cascade |
1972 --> factors 10, 9, 7, 2 and proteins C and therefore S |
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what are the main causes of vit K deficiency |
GIT disease --> less absorption of the fat soluable vitamin Liver disease - less bile |
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why are neonates given vitamin K |
as they have not yet developed normal gutflora and are particularly susceptible to haemorrhagic disease ofnewborn – especially intracranial haemorrhages |
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what is the most common megakaryocyte toxin |
alcohol - a serious session can knock levels --> bleed a lot more when drinking (and thinner blood) |
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what is bernard soulier disease |
congenital condition characterised by large RBC size platelets and mild thrombocytopenia, due to abnormal glycoprotein 1b96a, which interacts with vWF, causing adhesion and platelet plug formation |
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how long does it take platelet levels to return to normal after taking aspirin |
5-7 |
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what causes a normal aPTT and PT, but longer total clotting time, and why is this different from DIC |
thrombocytopenia everything longer in DIC due to everything being used |
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what are the common hallmarks of leukaemia |
recurrent infections, anaemia, bleeding from mucus membranes, fatigue (leukaemia takes up a lot of energy), muscle wasting/weight loss due to protein degradation, loss of appetite (due to splenomegaly pressing onto stomach = feel full = even more weight loss) |
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what is the difference between acute and chronic leukaemia |
where the mutations occur in the cell lineage --> early mutation = acute as unlikely to have many functional cells. Chronic = later in lineage, may have some function still |
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what lymphocyte are cancers most likely to be in and why |
B-cells - due to hypermutation, isotype switching, massive proliferation --> multiple chances for mutations to occur |
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what is the cause, signs and symptoms, diagnosis and prognosis of acute lymphoblastic leukaemia |
20% of patients = Philadelphia chromosome · (BCR:ABL9:22 translocation i.e. short 22 chromosome ABL = tyrosine kinase, the BCR gene causes constantactivation Tyrosinekinase fusion protein over expression → constitutiveactivation of myeloid cell proliferation Fever, lethargy, bleeding (mucus membranes), hepat/splenomegaly Lymphadenopathy, circulating blast cells, pancytopenia flow cytometry Prognosis: As mostly occurs in children good --> 98% go into remission, 90% disease free in 10 years untreated = dead in months from pneumonia etc |
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what is the cause, signs and symptoms, diagnosis and prognosis of chronic lymphocytic leukaemia |
20% of patients = Philadelphia chromosome · (BCR:ABL 9:22 translocation i.e. short 22 chromosome ABL = tyrosine kinase, the BCR gene causes constant activation Tyrosine kinase fusion protein over expression → constitutive activation of myeloid cell proliferation, but later down line than ALL recurrent infections, fatigue, similar to ALL Often asymptomatic and found to have leukocytosis in coincidental blood test high levels of partially matured B cells immunophenotyping 5 year survival rate of 60%, 10 year 34% |
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what is an important consideration when lymphocytosis is found in children |
pertussis infection |
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what is the cause, signs and symptoms, progression, diagnosis and treatment of chronic myelogenous leukaemia |
Philadelphia chromosome (BCR:ABL 9:22 translocation i.e. short 22 chromosome) ABL = tyrosine kinase, the BCR gene causes constant activation Tyrosine kinase fusion protein over expression → constitutive activation of myeloid cell proliferation Fatigue Bodyache Pallor Gout Splenomegaly Hepatomegaly“not quite right”· Thrombocytosis Anorexia 1. Chronic phase: 3-5years Easycontrol with therapy 2. Accelerated phase: Anothermutation superimposed upon 9:22 Moreblasts present (10-19% of FBE) 6-12months and difficult to control 3. Blast phase (BLAST CRISIS): Inevitableacute leukemic phase >20%blasts in bone marrow) Splenomegaly 3-6months then death Poorlyresponds to treatment a. Blastphase can be in form of ALL or AML –HSC proliferation can descend down either line. Needs 9:22 for diagnosis Treatment: imatinib(STI-571) MAB binds to, and inhibits, intracellular ATP activesite of cytoplasmic tyrosine kinase Prevents further phosphorylation (ie the phosphatefor cascade kinase activity is taken from the ATP → no ATP = no phosphate).Selective suppression→ CML cells undergo apoptotic death. |
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what is the cause, signs and symptomsand treatment of acute myelogenous leukaemia |
FLT3 tyrosine kinase in 30% of patients Membrane tyrosine kinase over expressed due to pointmutation Negatively predictive for long term survival vspatients with AML without FLT-3 Use of FLT-3 MABs have shown great promise. Splenomegaly Recurrent infection Swollengums/swollen tissue – dueto leucocyte infiltration in the highly vascular gums Very high percentage of blasts in marrow and blood Stem cell transplant: however not every patient canhave this - not required or not possible - decreasing chance with age due to risk with lack ofreward Chemo backbone: Cytarabine (cytosine arabinoside) - nucleoside analogue, targets rapidly proliferating cellsas interrupts DNA synthesis Doxorubicin: anthracycline antibiotic - is incorporate into DNA and branches across bothstrands = synthesis cannot continue Come in and out for consolidation |
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what is, what are the cause, signs and symptoms and treatment of acute promyelocytic leukaemia |
In APML, promyelocytesaccumulate in the bone marrow = decreased number of normal white blood cells inthe blood = reduces production of other types of myeloid cells Defined by the presenceof a reciprocal translocation between chromosome 15 and 17, creating a fusiongene PML/RAR-alpha RAR-alpha = retinoic acid receptor-alpha This fusion mutation = impairment of terminaldifferentiation and subsequent apoptosis of promyelocytes I.e. do notget any mature cells Symptoms/signs: Anorexia Fever Ecchymoses Mucosal bleeding Anaemia Coagulopathy – DIC Fatigue Weakness Auer rods Treatment: As the blockage to differentiation is due to theRAR-alpha portion of the fusion gene, thus give pharmacological doses ofvitamin A This activates the RAR portion of the fusion gene,allowing transcription = the cell can differentiate Givewith arsenic trioxide |
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what is multiple myeloma, what it's causes, signs and symptoms |
Cancer of plasma cells → rapid productionof antibodies that are monoclonal (arises from a single plasma cell C – hypercalcaemia R – renal failure A - anaemia B – bone lesions Bone pain: Diffuseosteoporosis or discrete osteolytic lesions develop, usually inthe pelvis, spine, ribs, and skull Lesionsare caused by bone replacement by expanding plasmacytomas or bycytokines that are secreted by malignant plasma cells that activate osteoclastsand suppress osteoblasts. Hypercalcaemia as a result. Renal failure: Light chain nephropathy Endogenoustoxic ATN Signs: Hypercalcaemia(bone mets) Hyperkalaemia Highgamma globulin Anaemia – marrow infiltration/renal failure Bence-Jonesproteins in urine Weight loss |
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what ist he difference between hodgkins and non-hodgins lymphoma |
the presence of Reed-Sternberg giant cells (multi-nucleated B cells) - recruits many many normal myelocytes into nodes found in hodgkins Waldeyer's ring is found in non-hodgkins (often not all time) |
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what causes follicular lymphoma, how percentage of lymphomas does it represent |
BCL-2 gene of ch18 translocates to antibody control region(↑Ig heavy chain) of ch14 –thus resulting in ↑↑production as this area is heavily expressed Mistakein VDJ recombination Bcl-2 is an apoptosisinhibitor – it is now overexpressed – cells immortalized (no apoptosis) 40% |
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what causes Burkits lymphoma and where does it usually effect |
B-cell neoplasm: Caused by translocationof B-cell receptor gene on chromosome 14 combing with the c-myc gene on chromosome8 c:MYCgene expression is increased2-10X · Expression enhanced by translocated B-cell receptorregion which is a gene promoter for Ig heavy chains and thus very active --> thus cells are upregulated are c:MYC acivates genes for cell division→ activation of proto-oncogene. the jaw |
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why is G-CSF and GM-CSF often given with chemo |
it up-regulates the differentiation and maturation of neutrophils --> immune system replenished quicker --> can give more chemo/higher doses |
