Anaemia Flashcards
What type of deficiency are pencil cells associated with
iron
Reticulocytes
- new RBCs (1 day old)
- indicates the rate of production of
RBCs by the marrow *** - can be used to monitor progress of
treatment; demonstrates that more
RBCs are being produced in
response to replacement
Anaemia is like money (4 reasons):
not making enough = synthesis problem
spending too much = consumption
been lost = bleeding
hidden away = sequestered (but will
come back)
anaemia definition
condition that arises when there is a deficiency in the number of red blood cells and or the haemoglobin in circulation
not a diagnosis
WHO def = Hb<130g/L men and <120 female
Anaemia Symtpoms:
- lethargy
- shortness of breath
- palpitations
- headache
- non-specifically unwell
Anaemia Signs:
- pallor
- pale conjunctivae
- tachypnoea
- tachycardia
- changes to hair and nails: brittle, Koilonychia (spoon shaped nails)
20% of all maternal deaths are due to
anaemia either during or after pregnancy
B12 and folate important for —– which starts eryhtropoeisis
dna replication
Reticulocytes causes “—–” on blood film
polychromasia
large bluish red cells
Reticulocytes are measured by
flow cytometry (counts the cells with RNA)
usually around 1%
If reticulocyte count is low
- precursor deficiency or bone
marrow failure
If reticulocyte count is high
in chronic bleeding or haemolysis
RBC normal shape? Relies on (3)?
- biconcave
- specific cytoskeletal proteins
- normal enzymes (pyruvate kinase)
- normal type and amount of Hb
RBC life span?
- relatively short
- 120 days
RBCs carry millions of Hb molecules. Each Hb molecule has
4 goblin proteins
2 alpha and 2 beta
Haematocrit
- volume percentage of RBC in blood
- RBC make up the major component
of blood - gives an idea of the proportion of
the mass of RBCs that make up the
whole blood pool - dervied result (not measured
directly)
MCH
mean cell haemoglobin
average amount (mass) of Hb in the average cell (derived)
MCV
mean corpuscular volume
volume of the average RBC
measured using a red cell distribution width RDW
the greater the RDW
the greater the variation in the size of the cells
Investigations in Anaemia:
- full blood count: haemoglobin,
platelet, haematocrit, MCV, MCH,
neutrophils - blood film = direct inspection of
size and shape
Sequestration definition (anaemia)
iron is trapped in macrophages as a result of chronic inflammation meaning supply of iron to RBC becomes limited
Why do we get anaemic? Problem with synthesis:
- deficiency of a building block of
RBC/Hb eg: iron/B12/folate - bone marrow failure: leukaemia,
aplastic anaemia
Why do we get anaemic? Consumption problem:
- premature destruction of RBCs
(haemolysis) because the body
knows they are damaged due to:
- inherited problems with Hb eg
sickle cell, thalassemia
- acquired haemolysis eg
autoimmune (mechanical heart
valve)
Why do we get anaemic? Sequestration/ bleeding anaemic problems?
- bleeding from somewhere in the
body: bowel perforation, heavy
periods
Establishing the cause of anaemia 4 steps:
- MCV: microcytic, normo, macro?
- causes for micro, normo, macro
- clues in history and rest of FBC
- what further tests would help?
Establishing the cause of anaemia: Step One:
Establishing the cause of anaemia: Step 2:
Establishing the cause of anaemia: Step 3:
Establishing the cause of anaemia: Step 4:
Problems with Synthesis: Iron Deficiency:
- is
- population
- broad categories of causes (3)
- not enough iron = small, pale cells:
MICROCYTIC & hypochromic - most common
- causes: bleeding, nutritino
deficiency, increased requirements
Diagnostic Tests for Iron deficiency (problems with synthesis):
- Serum Iron:
- labile, so reflects recent intake
of iron - Serum Ferratin:
- storage form of iron
- low = iron deficient
- high = overload/chronic dis - Serum Transferrin:
- carrier molecule for iron in the
blood
- homeostatically UP if iron
deficient
- similar to total iron binding
capacity - % Transferrin saturation:
- sensitive measure of iron
status
- low = iron deficient
- high = iron overload
Depth into 3 broad causes of iron deficiency:
- Blood loss: menstrual, OCCULT GI
MALIGNANCY, stomach wall
ulceration - Dietary: malabsorption, poor diet,
vegan/veg - increased requirements: pregnancy
what does this blood film show
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Problems with synthesis: B12 deficiency: how is B12 absorbed?
- B12 (cobalmin) in food
- binds to intrinsic factor (IF)*** from
gastric parietal cells - transported to terminal ileum for
absorption
Problems with synthesis: B12 deficiency: causes (6):
- genetic abnormalities (rare)
- meds: protein pump inhibitors
(omneprazole), metformin - infections: fish tapeworm, H pylori
- dietary: strict vegans, pregnancy
increases requirements - malabsorption
- autoimmune
Problems with synthesis: B12 deficiency: malabsorption as a cause:
- post grastric or ileal surgery y
- removal of parietal cells decreases
intrinsic factor production - Crohn’s disease (inflammatory
bowel disease due to decreased
B12/IF absorption
Problems with synthesis: B12 deficiency: autoimmune causes:
- Pernicious anaemia
- check for auto-antibodies to IF
- routine testing not recommended
- leads to deficiency of IF
- can not absorb B12 in terminal
ileum
Problems with synthesis: B12 deficiency: treatment:
- oral replacement may be sufficient
in dietary or med related - for pernicious anaemia or
absorptive problem: B12 injections
(load and then every 3 months) - both B12 and folate deficient, B12 must be replaced first because sudden replacement of folate in someone who is also B12 deficient, can drop B12 even lower and hasten subacute GI combined degeneration of the cord
Megaloblastic anaemia:
- B12/folate deficiency most
common cause - bone marrow produces large RBC
- often low WBC and platelets
- sufficient iron for Hb
- sufficient precursors for cell growth
- INSUFFICIENT PRECURSORS FOR
CELL DIVISION
clinical manifestations of B12 deficiency
insert table
sub-acute combined degeneration of the cord
- very rare
- progressive demyelination of dorsal and lateral columns of the spinal cord
- due to severe B12 deficiency
- presents:
- altered sensation: vibration
- numbness/tingling
- weakness
- ataxia and gait disturbance
Red cells are microcytic, hypochromic and show anisopoikilocytosis
- small pale different shapes and size and some long thin like pencils
- iron deficiency
Problems with synthesis: Folate Deficiency: causes:
- dietary
- malabsorption: Coeliac, Crohns
- excessive utilisation: chronic haemolysis, pregnancy
- alcohol
- drugs: phenytoin, methotrexate
Management of sub-acute combined degeneration of the cord:
replace B12
What is the most common anaemia in hospitalised patients?
anaemia of chronic disease
Common causes of chronic disease anaemia:
- chronic inflammation
- auto-immune: rheumatoid arthiritis
- chronic infection; TB
- cancer
- chronic kidney disease
- advancing age
Iron deficient anaemia vs anaemic of chronic disease
insert table
Anaemia of chronic disease: poor utilisation of iron:
-*** iron is stuck in the macrophages of the RE system, can not be mobilised into erythroblasts
- decreased transferrin
Anaemia of chronic disease: impaired proliferation of erythrooid progenitors:
- blunted response to erythropoietin
- IRON UNAVAILBLE
Anaemia of chronic disease is a cause of which type of anaemia
normocytic
Problems in synthesis: Bone marrow failure:
- not making enough haematopoeitic cells
- RETICULOCYTES LOW
- haematinics are normal
3 causes of bone marrow failure as a problem in synthesis for anaemmia
- marrow not working myelodysplasia
- marrow is full of other things (infiltration eg leukeamia)
- marrow is empty (aplastic anaemia)
Diagnosis of bone marrow failure as a problem of synthesis (anaemia)
- myelodysplastic syndrome
- not effectively working maymore, weary
- low blood counts lead to fatigue, infections, bleeding
Management of bone marrow failure as a problem of synthesis (anaemia)
- supportive
- chemotherapy in some cases
- bone marrow transplant if young
Anaemia: Excess consumption of RBCs: causes
- haemolysis = red cell breakdown
- inherited: membrane, Hb, metabolic problems
- acquired: immune 9antibodies, non-immune (direct damage)
Symtpoms and signs of haemolysis
insert
Inherited red cell problems are what type of mutation
recessive
Qualitative inherited red cell problem
wrong type of haemoglobin produced
Quantitative inherited red cell problem
not enough haemoglobin produced
Combine inherited red cell problem
mix of quant and qaul (HbS Beta Thal)
Sickle Cell Disease:
- type of mutation
- life expectancy
- RBC turnover
- reticulocyte count
- triggers
- diagnosis
- management
- autosomal recessive
- shortened life expectancy
- point mutation in beta gobulin gene
- increased RBC turnover (20 days) because body tries to compensate for removing damaged RBCs from circulation
- reticulocytes raised 10%
- many triggers, vaso-occlusive: ischaemia, pain, chest crisis, organ failure
- HIGH PERFORMANCE LIQUID CHROMOTAGROPHY
management: analgesics, hydration, transfusion, red cell exchange
Sickle Cell Disease vs Trait:
- mutated sickle haemoglobin HbS:
- forms long filamentous strands
- insoluble at low O2 tension
- RBC inflexible and sticky = CRISIS - sickel cell trait:
- heterozygous for HbS and HbA
- much lower risk of crisis
- RESISTANCE TO MALARIA INFECTION
Haemolysis screen results
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Sickle cell trait diagram
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sickle cell diagram
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sickle cell disease chromatography
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Thalassaemia:
- 4 alpha genes and 2 beta genes and can inherit mutations in the alpha genes or beta genes or both
- alpha thalessemia, beta thalassaemia
- leads to less or no HbA production
- most mutations are deletions
- affects people of mediterranean, south asian, south east asiam, middle eastern
Iron deficient anaemai vs thalassemia
Alpha Thalassemia
- problems arise due to genertic mutations that lead to ABSENT alpha chains
Alpha Thalassemia
- problems arise due to genertic mutations that lead to ABSENT alpha chains
hydrops fetalis
alpha thalessamia
no alpha chains
fatal
Iron deficient anaemia vs thalassemia:
- insert side
- thalassemia is very microcytic and hypochromic
- if not anaemic at all then thalassemia
- life long family history?
- high iron number in thalassemia
- thalassemia: no pencil cells, RDW
Thalassemia can have associated anaemia, but also not be associated
True or False
True
Inherited Red cell problems: enzymopathies:
- G6PD
- pyruvate kinase
- if these enzymes are deficient then under the influence or certain triggers or insults in food, medicine, oxidative haemolysis can occurr causing Hb to precipitate out, then cells rejoin forming blister cells
G6PD deficiency
x linked recessive (males)
- due to fava beans causing oxidative crisis
- drugs like aspirin, anti malarials
- management = support, avoid oxidative stress
To differentiate between acquired disorders using haemolysis
- immune will have DAT positive
- non-immune DAT negative
