Revision Flashcards
what is serum
clotted plasma
what is the liquid in blood
plasma
what is haematopoiesis
production of blood cells
where does haematpoiesis occur
embryo- yolk sac then liver then marrow
birth- bone marrow, liver and spleen when needed
adult- bones in axial skeleton: skull, ribs, sternum, pelvis, proximal ends of femur
what are the steps in the haematopoietic tree
stem cells multipotent progenitors (ones that proliferate the most) oligolineage progenitors (becomes the different types of these depending on the bodys needs) mature cells (RBC, platelets, granulocytes, macrophages, dendritic, T cells, B cells, NK cells)
what is erythopoiesis
formation of mature red blood cells
what are the stages in erythropoiesis
pronormoblast
(lots of others, all in bone marrow, cell and its nucleus gets smaller each differentiation)
reticulocyte (enters circulation)
mature red cell/ erythrocyte
what is a reticulocyte
immediate precursor of red blood cell, has no nucleus but some RNA which makes it appear darker in colour
is in the circulation not bone marrow
what do platelets originate from
bud off megakaryocytes (cytoplasm doesnt divide)
what is the role of platelets
stop bleeding
what are the types of granulocytes
eosinophils
basophils
neutrophils
what are granulocytes
most common type of WBC, contains granule
what are neutrophils
type of granulocyte
first white cell to respond in an infection (Q specific to bacterial infections)
what are polymorphs
different name for neutrophils (called this because segmented lobular nucleus)
what is the main phagocytosing cell
macrophage
what are the roles of neutrophils
short life in circulation- goes to tissues where it:
phagocytoses invaders
kills with granule contents (dies in process)
attracts other cells
what can increase neutrophils
body stress - infection, trauma, infarction
steroids (makes them unable to leave blood stream and get into tissues)
what are eosinophils
type of granulocyte
are bilobed, granules makes them look red-orange
what are the roles of eosinophils
fight parasitic infections
involved in hypersensitivity reactions/ allergic conditions
what are basophils
type of granulocyte w/ purple- black granules
what are the roles of basophils
mediates hypersensitivity reactions
granules contain histamine
FcReceptors bind IgE
what are monocytes
largest type of white blood cell, pale, single nucleus
what is the role of monocytes
circulate for a week then enter tissues to become macrophages
-phagocytose invaders (endocytosis, present antigen to lymphocytes)
-attract other cells
more long lived than neutrophils
what is the structure of lymphocytes
mature- small
activated (aka atypical)- large open structure
what is the function of lymphocytes
lots of diff types: B, T, NK
adaptive immune system
where are common sites for bone marrow aspiration/ biopsy
posterior iliac crests
what are target cells
In liver disease the red cell membrane is disrupted which causes change in shape of the red cell from pale bit in the middle (concave) –> dark part in the middle = target cells
what is the most common cause of macrocytic anaemia
liver disease (due to alcohol most commonly, then NAFLD)
what are the Hb levels below which probs means anaemia
children 6mnth-6yrs = 110 6-14 120 men 130 females 120 pregnant females 110
what are haematinics
MCV
MCH (cell Hb content)
what does anaemia with increased reticulocyte mean
caused by haemolysis or blood loss
what does anaemia with reduced reticulocyte mean
maturation abornmalty or hypoproliferative
what will MCV be like in hypoproliferative anaemias
normocytic (and normochromic)
what can distinguish haemolysis from blood loss causing anaemia
(obvs Hx and clinical picture, blood film)
if bleeding then rbcs gone, nothing to breakdown
if haemolysing:
-increased unconjugated serum bilirubin
-increased urinary urobilinogen
-work hypertrophy (splenomegaly)
what causes hypochromic microcytic anaemia
problems with haemoglobin formation:
- iron deficiency
- haem defects (rare, lead poisoning, congenital sideroblastic anaemia)
- globin defects (thalassaemias)
what causes macrocytic anaemias
nuclear maturation defects (failure of cell division)
- diet: B12, folate (megaloblastic)
- myelodysplasia
- drugs e.g. chemo
what can cause macrocytosis without significant anaemia
hypothyroidism
alcohol
liver disease
what can cause normochromic normocytic anaemia
hypoproliferative:
-marrow failure :drug induced, aplastic anaemia (can be mactocytic)
hypometabolic (can be macro)
marrow infiltration (mets, fibrosis)
renal impairment
chronic disease (infective. inflammatory, malignant= anaemia of chronic disease) (can be micro)
what is renal anaemia
an anaemia of chronic disease due to failure of erythropoietin production
what is the second most common cause of anaemia after iron deficiency
anaemia of chronic disease
what causes anaemia of chronic disease
inflammatory stimulus activates monocytes and T cells which releases inflammatory cytokines:
- inhibits erythropoietin release
- inhibits erythroid proliferation
- augments haemophagocytosis = reduced red cell survival
- increases hepatic syntheses of hepcidin (negative regulator of iron absorption, decreasing iron)
why might anaemia of chronic disease by microcytic
If the predominant mechanism is through hepcidin stimulation
reduced release of iron from macrophages ie failure of haemoglobin synthesis
Explains low transferrin saturation despite normal/raised ferritin
Explains why it may respond to IV iron
are iron def anaemias always microcytic
no- relative measure so many normocytic (in normal range just not normal for the individual)
how do you differentiate anaemia of chronic
serum iron:
- ID: reduced
- ACD: reduced
transferrin:
- ID: normal/ increased
- ACD: normal/ reduced
% transferrin sat:
- ID: reduced
- ACD: reduced
Ferritin:
- ID: reduced
- ACD: normal/ increased
MCV:
- ID: reduced (can be normal)
- ACD: normal (can be reduced)
what are the implications of the biconcave shape of ebcs
needed for increased gas exchange
need more room for Hb so why nucleus removed
what is needed to make the rbc flexible
lipid bi layer membrane with protein spars and anchors
what is enucleation
when the nucleus is budded off with other organelles and functional fibrous proteins (absorbed by the macrophage)
In what circumstances might nucleated red cells appear in the blood?
bone marrow damage or severe stress
- severe anaemia
- thalassaemia
- hypoxia
- myelomas
- leukemias
- lymphomas
- myelofibrosis
removal of spleen can make immature cells more apparent in the blood
is Fe2+ or Fe3+ oxygenated- which one is blue or red
Fe2+ deoxygenated- blue
Fe3+ oxygenated- red
what does free iron cause
is toxic- causes inflammation
what can free Hb cause in the blood
can be life threatening
can cause DIC and other dysfunctional responses
what different mechanisms can cause red cell membrane damage
Mutations in cytoskeletal proteins resulting in the cell membrane not working well:
- Hereditary spherocytosis (this is usually autosomal dominant)
- RARE! Zieve’s syndrome: haemolysis related to alcoholic liver disease. Abnormalities of lipid metabolism results in red cell membrane damage
Autoimmune haemolytic anaemia: autoantibodies against red cells damage the red cell membrane
Infection
- DIC(disseminating intravascular coagulopathy)
- Sepsis
Mechanical damage
- Severe burns: capillaries are damaged and as blood vessels squeeze through these they get sheared resulting in microspherocytes
- Heart valve
- Haemolytic Uraemic Syndrome (E.Coli)
- Thrombotic Thrombocytopenic Purpura (TTP)
what virus might cause a decompensation in HS
parovirus
virus enters bone marrow and stops erythroid precursors from dividing
What are the sources of energy and reducing powers which protect the red blood cell against oxidative damage?
(Anaerobic) NADH and NADPH are important molecules generated by the cycle (direct or hexose monophosphate shunt)
G6PD contributes to formation of glutathione which is required for NADPH formation
what does a G6PD deficiency result in
reduced protection from oxidative damage
what is dapsone
antibiotic previously used in the treatment of leprosy
can induce oxidative stress
what drugs induce oxidative stress
dapsone, quinines, anti-malarials, fava beans
can lead to splenomegaly
what are the clinical manifestations of increased oxidative damage
tiredness, lethargy, pale gums, pallor, jaundice
what are heinz bodies
Red cells with haemoglobin exposed to oxidative stress–>Hb has been oxidised + damaged–>clumped together in a ball (Heinz body)–>red cells are contracted–>heinz body anaemia
this seen in G6PD deficiency causing haemolytic anaemia
what can cause a problem with Hb synthesis
Haem production
- Iron deficiency
- Porphyrin synthesis
Globin production
-Thalassaemia
what are the symptoms and signs of microcytic hypochromic anaemia
Signs: Tachycardia, tachypnoea, rising pulse or even extra heart sound, pallor
Symptoms: Palpitations, lethargic, fatigue, TATT, tinnitus, somnolence
how does the red cell try and improve oxygen delivery in microcytic anaemia
increase 2,3-DPG to increase oxygen dissociation
what codes for beta chains
1 gene on each chromo 11
what are the affects of beta thalassaemia major
Failure to thrive
General Sx of anaemia
Splenomegaly
Chronically - permanent bone marrow changes. Frontal bossing, skeletal deformities, spinal cord compression
what is B12 important for the production of
thiamine
what are agranulocytes
leukocytes and monocytes
what are the symptoms of megaloblastic anaemia
Pallor, mild jaundice (lemony tinged), red beefy tongue, reduced vibration and proprioception sense (dorsal columns): rely on proprioception in the dark (falling over in the night), lemony tinged/mild jaundice
what causes sickle cell anaemia
substitution of valine for glutamic acid at codon 6 of beta glogin gene
homozygotes produce only haemoglobin S and variable amount of haemoglobin F
sickled red cells produces microvascular obstruction and ischaemia
Pale patient Mildly jaundiced No obvious bleeding Dark urine suspect what?
haemolysis
what tests to confirm haemolysis
Blood film: polychromasia, spherocytes
Reticulocytosis
Unconjugated hyperbilirubinaemia
if intravascular : haemoglobinuria haemosiderinuria methaemalbuminaemia
what are the acuired immune causes of haemolysis
Autoimmune: spherocytic
Alloimmune: haemolytic disease
of the newborn (non-spherocytic)
ABO mismatch transfusion
what are the non immune acquired causes of haemolysis
Mechanical: prosthetic heart valve,
disseminated intravascular coagulation
Infection: malaria, Clostridium welchii
Chemical/ physical: oxidative stress
(aspirin, dapsone, anti-malarials), burns
Membrane: liver disease
what are the inherited causes of haemolysis
red cell enzyme defects: G6PD def
red cell membrane defects: HS, hereditary elliptocytosis
what diagnostic tests for haemolysis
Direct Coombs test: detects antibody coated red cells using antisera to immunoglobulins; end point is red cell agglutination
Osmotic fragility test: incubate red cells in increasingly hypotonic solutions and measure release of haemoglobin from lysed cells. Increased fragility in hereditary spherocytosis.
G-6-PD enzyme activity screening test: quantitate fluorescence of NADPH generation by G-6-PD. Detects enzyme activity <20%
what are causes of macrocytosis not related to B12 or folate deficiency
Drugs: methotrexate/ AZT/ metformin
Alcohol abuse/ liver disease/ myelodysplasia (stem cell dysfunction) /myeloma/anaplastic anaemia/ hypothyroidism
pregnancy, neonatal, reticulocytosis
why would hypothyroidism be relevant in a Hx of macrocytic anaemia
as can cause macrocytosis but also is associated with pernicious anaemia
what is pernicious anaemia
autoimmune condition that results from atrophic gastritis and destruction of the gastric parietal cells ultimately leading to a reduction in intrinsic factor.
IF is required to bind to vitamin B12 to allow absorption in the terminal ileum.
Pernicious anaemia is also linked with other autoimmune conditions such as hypothyroidism, vitiligo and addison’s disease.
is macrocytosis always associated with anaemia
no
what is the most common cause of macrocytosis
alcohol consumption
what does a MCV >120 mean
macrocytosis usually caused by def of B12 or folate