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99 Cards in this Set
- Front
- Back
What is the most common form of anaemia?
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Microcytic hypochromic
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What is microcytic hypochromic anaemia most commonly caused by?
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iron deficiency
thal and other Hb pathologies |
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Why does impaired Hb synthesis lead to microcytic cells?
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Normally, once we reach optimum Hb conc in the developing RBC, signal feeds back to the cell to stop developing and not divide further
If there's problem with Hb synthesis, we won't reach this optimum conc -> do another division -> smaller cells |
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Why is blood film analysis not the best way to look for microcytosis?
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The diameter of teh cells is usually only slightly reduced - they're much flatter than normal - may not pick this up with the naked eye
MCV is better |
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What is the white pulp in the spleen?
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The arteries supplying the blood to spleen are surrounded by sleeve of lymphocytes (mostly T-cells + there are some follicles with B-cells)
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What is the red pulp in the spleen?
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Once the arteries are in the spleen, they open out into splenic cords = meshwork of fibroblasts and macrophages
This is the red pulp |
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What does the average spleen weigh?
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135g
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where does blood from the spleen drain into?
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Portal circulation
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What four main groups of things could cause splenomegaly?
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- congestion (ie increased portal pressure)
- increased phagocytic activity - eating up all the dodgy RBCs - infiltration by abnormal cells (eg leukemia,lymphoma) - sometimes seen in autoimmune diseases |
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What are the two functions of the spleen?
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immune function
filters out the defective RBCs |
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What is the commonest cause of fever of recent onset in adults and children?
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infection
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How do we best diagnose malaria?
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Microscopic examination
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Is antimalarial prophylaxis 100% effective?
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no
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what happens to your partial immunity if you move away from a malaria endemic area?
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It declines with time
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what happens if you live in an area endemic with malaria?
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you develop partial immunity
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Which mosquito genus transmits malaria?
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anopheles
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What does the mosquito inject into the human when they take a blood meal?
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Sporozoites
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Once sporozoites have been injected into the human blood, where do they go?
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To hepatocytes
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What do the malaria parasites do in the hepatocytes?
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Grow into stages called trophozoites
Then they divide by schizogony --> we get a schizont that contains lots of merozoites |
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What is a schizont?
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Thing that's developed in the hepatocyte - contains lots of merozoites (up to 40,000)
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What are the two cycles of schizigony in the human host?
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ex-RBC phase (ie hepatic)
erythrocytic phase |
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When an malaria infected hepatocyte ruptures, what is the name of the things it releases into blood stream?
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Merozoites
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What do merozoites do after leaving the hepatocyte
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they infect red blood cells and replicated
then infected cell ruptures -> more merozoites are released into blood to infect more RBCs |
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How does P.falciparum cause damage?
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Sequestration
ie the RBCs adhere to the microvasculature of organs eg brain and kidneys |
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What is special about P.vivax and P.ovale?
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They don't develop into schizonts immediately after infecting hepatocytes - they become hypnozoites ie sleeping animals
-> get reactivation months or even years later |
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Why does sickle cell trait protect against malaria?
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There's a structural change in Hb -> RBCs don't survive as long -> disrupt P falciparum's life cycle
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How long does it take to develop the erythrocytic schizont in P falciparum vivax and ovale?
P malariae? |
48 hours
Malariae -> 72 hours |
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Where does the parasite hang out in the RBC?
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Vacuole
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How does parasite get food in the RBC?
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Lives in the vacuole. Here, it digests Hb -> gets aas that it uses for energy and to produce new proteins
The haem that's left over is potentially toxic to the parasite -> the parasite polymerises the haem into non-toxic, insoluble molecule |
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What is the normal lifespan of a RBC?
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120 days
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How do quinolones work?
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they prevent the parasite frombeing able to polymerise haem -> can't protect themselves from the toxic haem -> die
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On a blood film, what are the unique characteristics of P.falciparum?
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- infected RBCs are normal size
- The parasite is in ring form (very thin rings) and there are multiple in one cell (only one that has multiple rings) - Gametocyte = bana shaped |
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On a blood film, what are the unique characteristics of P vivax?
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- The infected RBCs are enlarged.
- Only one parasite p/RBC - Schuffner's stippling ie little granules in the RBC |
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On a blood film, what are the unique characteristics of P ovale?
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- RBC is enlarged + OVAL shaped and there's often fimbirated ends
Schuffners granules like vivax |
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On a blood film, what are the unique characteristics of P malariae?
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Often see band form of parasite in the RBC
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Which are the two malaria species which cause the infected RBCs to be enlarged?
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vivax and ovale
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Which are the two malaria species which go dormant?
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vivax and ovale
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What type of mosquito can transmit malaria?
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Female anopheles
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Which sorts of RBCs are most infected with ovale and vivax?
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Reticulocytes
(There's obviously a limited number of these) |
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Which sorts of RBCs are most infected with malariae?
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Very old RBCs (there aren't heaps of these)
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Which sorts of RBCs do falciparum infect?
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unlike the others, falciparum doesn't show specificity for types of RBCs -> infects them all!
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How long do the parasites spend in the hepatocytes before rupturing out?
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6-16 days (won't have symptoms during this stage)
someone infected with falciparum will get sick very quickly though |
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Why do we get paroxysmal fever?
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occurs if the development of schizonts and their subsequent release from RBCs is synchronised
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What happens if you get cerebral malaria? which species is this associated with?
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falciparum
you get seizures, convulsions, coma |
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What's the difference between thick and thin blood films?
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thick - have lots of layers of RBCs -> good for looking for presence of parasites, but not good for morphological info
Thin film - single layer of cells -> morphological information |
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What are the three diagnostic methods we can use for diagnosing malaria?
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1. microscopy
2. immuno testing (have monoclonal antibodies directed against malarial antigen - if you get a reaction, coloured line will show up) molecular tests (very sensitive- looking for malarial DNA) |
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How do the prophylactic malarial drugs work?
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They target the parasites when they're breaking out of the hepatocytes
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What's the problem with chloroquine?
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Resistance is increasing
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What is the definition of haemolytic anaemia?
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We have accelerated RBC destruction for which the BM can't compensate
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What's intravascular haemolysis?
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Happening in the BVs themselves due to trauma or complement
This is very severe, mostly haemolysis isn't this severe |
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What's extravascular haemolysis?
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It's happening outside BVs ie they're being destroyed by cells in the RES (mostly in the spleen)
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What happens to LDH and bilirubin with haemolysis? How do we test them?
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They'll both be increased. Tests:
- serum unconjugated bilirubin - raised urinary urobilinogen - raised serum LDH |
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What happens to haptoglobin levels with haemolysis?
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Decreased
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What haemoglobin do we have in fetuses?
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alpha2gamma2
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What's the difference between the R and T forms of Hb?
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R = relaxed = oxygenated
T = tense = deoxygenated |
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what is the concentration of Hb in RBCs?
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334mg/mL = 20mM
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What is the solubility of O2 in plasma (no RBCs)?
What's solubility in whole blood (with RBCs)? |
Plasma => 0.1mM
Whole blood => 10mM |
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Which has higher O2 aff: fetal or adult Hb?
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Feta (facilitates transfer of O2 into the fetal circulation from the mother's blood)
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What are the four thigns that affect Hb's O2 affinity?
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- H+ ions
- CO2 - 2,3BPG - temp |
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What happens to malaria susceptibility in kids with homozygous alpha+ thal?
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When they're young, they are more susceptible to mild infections with vivax and falciparum
This early immunisation then provides them with protection later in life |
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How do the malaria that are resistant to the quinolone drugs achieve this resistance?
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They reduce the accumulation of the drug in the acidic vacuole
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Are a) thal and b) sickle cell due to quantitative or qualitative problems with Hb?
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Thal = quantitative
Sickle cell = qualitative ie producing defective Hb chains |
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How many genes encode alpha chain of haemoglobin?
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2 genes (and 2 copies on each chrom -> 4 in total)
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Where are the genes encoding alpha Hb chains located?
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chromosome 16
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Is alpha thal usually due to deletions or point mutations?
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deletions
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What happens if you have one, two three or four alpha genes affected?
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one and two = trait. one is silent. two might have low MCV and MCHC but asymptomatic
three = HbH disease - they have clinically significant anaemia four = Hb Barts / hydrops fetalis - die in utero or just after birth |
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How many genes encode beta Hb chain?
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just one (two copies)
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Where is beta Hb chain located?
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on chromosome 11
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is beta thal usually due to deletions or point mutations?
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point mutations
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What's the difference between beta thal major and minor?
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Major -> you're homo ie both genes are affected -> severe anaemia
Minor -> you're just a carrier, might have mild anaemia. Only one gene is affected |
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What is HbA?
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adult Hb - alpha2beta2
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What is HbF?
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fetal Hb - alpha2gamma2
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What is HbA2?
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2nd adult Hb - alpha2delta2
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Which chromosome is the alpha Hb chain on? Beta? Gamma? Delta?
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Alpha is on 16 (with zeta = the first alpha-like chain produced)
all the others are on 11 - they're arranged in the order they're usually expressed ie beta is teh last one, gamma is further up |
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What are the TWO effects of beta thal on RBCs ? and which is the major effect?
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Get ineffective erythropoiesis
and will get alpha chains (= main one) precipitating out -> haemolysis of the RBCs |
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What other Hb chains do we start expressing in a) beta thal major and b) beta thal trait?
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Major -> icnreased gamma -> HbF
Trait -> increased delta -> HbA2 |
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What other Hb chain do we start producing in beta thal major?
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gamma chain
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What other Hb chain do we start producing in beta thal minor?
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delta
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What is the inheritance pattern of beta thal?
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autosomal recessive
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What characteristic things do we see in kids with untreated beta thal?
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Severe anaemia. And because of ineffective erythropoeisis, we get increased EPO -> marrow expansion --> bossed forehead (big frontal bone) and on x-ray, bones have unique appearance 'like hairs standing up on end'
Will be severely anaemic too |
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What organs does iron overload damage?
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The heart (cardiomyopathy)
Liver (cirrhosis and carcinoma) Endocrine glands |
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What do we see on blood film of someone with beta thal major?
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hypochromic microcytic anaemia
anisopoikilocytosis target cells, basophilic stippling, nucleated red cells and tear drops |
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How much HbA2 does a normal person have? How much does someone with beta thal minor have?
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Less than 1% is normal
Beta trait - over 4.5% |
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What is HbH?
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four beta chains (we get it in alpha thal)
High O2 affinity -> won't release O2 at the tissues |
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What do HbH bodies look like on blood film?
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Golf balls
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Are people with HbH disease transfusion dependent?
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No
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What's the main problem in HbH disease? And in beta major?
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HbH - main problem is haemolysis
Beta major - ineffective erythropoiesis |
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What do we give as iron chelation therapy?
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Desferrioxamine
Exjade (deferasirox) Ferripox |
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About what time in pregnancy can we do chorion villus sampling (CVS)
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week 11 ie first trimester
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About what time in pregnancy do we do amniocentesis?
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2nd trimester
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How do we diagnose beta thal?
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microcytic hypochromic anaemia
increased HbA2 in carriers (do this with electrophoresis gel) DNA analysis |
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What is a pyrogen?
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A substance that produces fever
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When person's temp > 41, are pyrogenic cytokines likely to be involved?
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No because they don't usually get your temperature up to such dangerous levels
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What is PUO
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Pyrexia of unknown origin
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What is a noscomial fever?
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One that's acquired in hospital
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What happens to HbA2 levels in beta trait and beta major?
How do we measure these levels? |
Trait - they're increased
Major - they're usually about normal Test using electrophoresis gel |
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What upregulates hepcidin during infection?
When is hepcidin decreased? |
IL-6 increases
Decreased when we have lots of erythropoeisis |
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What does hepcidin act on?
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It binds to ferroportin and prevents release of Fe from the enterocytes and macrophages
ie it's a negative regulator of iron levels |
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What sort of mutation usually causes a) alpha thal and b) beta thal?
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alpha - > deletion
beta - > single base mutation |