Anaemia Flashcards
What is the defintion of anaemia
Reduction in haemoglobin (Hb) or red blood cell function
There are different rages for different groups of people. Can you name them?
Like men and women etc
Men-> Higher HB level (<130)
Pregnancy
Age
Labs dependent
Altitude
For men androgens stimulate EPO (erthyproptein)
women have a lower haemoglobin when pregnant you expand your plasma so there’s lower haemoglobin
babies have about a few months supply of haemglobin
What can we find in blood
Cells, etc
- plasma proteins
- electrolytes
- hormones
- nutrients
- Platelets (buffy coat)
- White cells (buffy coat)
- red cells (because they are heavier account for 45%)
Describe the structure of erthrocytes and how it affects functions
- Biconcave structure → allows them to squeeze through caparlieis
- No nucleus → so that they can have as much haemoglobin in it
- Colour comes from an iron-containing oxygen transport metalloprotein called haemoglobin in the cytoplasm
What is the function of red blood cells
they carry o2 and co2
How many days do RBCs live
120 days
Describe erthyropoiesis
Pronormobolast: large immature cells found in bone marrow (have blue cytoplasm)
Reticulocyte has extruded nucleus but still has RNA so can still make haemoglobin (not possible in erythrocyte)
Describe Haemoglobin
- Iron containing, oxygen-transport protein
- Hb made up of 4 polypeptide chains
- (tetramer)
- 1 x heme molecule per chain
- 4 binding sites for O2
- adult haemoglobin has two alpha and two beta,
- we make a little HbA2
What is the difference between fetal haemoglobin and adult haemoglobin
Fetal haemoglobin has two alpha two gamma, whereas adult haemglobin has an alpha and beta haemoglobin
after first 6 months of life fetal gets replaced by adult
What condition to we use fetal haemoglobin for
Sickle cell anameia
Can you describe the oxygen dissociation
If it shifts right you will readily release
- why? if you work really hard in the gym, the muscle produces lactic acid,
- the temperature will rise, and you will produce more CO2
- so all of that will shift the curve to the right,
- which means more oxygen will be released into the cells →
- and haemoglobin is less attracted to the oxygen
What are the symptoms of anaemia
Symptoms
- fatigue
- breathlessness on exertion
- because of o2 carrying capacity has decreased
- palpitations
- because your heart is working harder to pump more oxygen around your body
- angina
- coronary heart, the heart has to go work harder
What are the signs of anaemia
- pallor
- patients can look a bit green
- achycardia
- because the heart is beating faster
- bounding pulse
- flow murmur
- signs of heart failure
- if it gets worse
- Kolionchyia
- when thumb , tips of nail will curve up
- Angular stomatitis
- cuts or sore lips
What are the causes reduced production
like the causes of anaemia
- Iron defiency
- B12 and folate defiency
- bone marrow pathology (aplastic anaemia, myelodysplasia)
- Displacement in bone marrow (leukaemia, other cancer, myleofibrosis
- Chronic disease (renal failure, myeloma, chronic inflammatory conditions
How do people get iron defiencies
causes of iron defiency
- Dietary
- Malabsorption (celiacs, and chrons)
- Chronic blood loss (don’t release you’re losing blood over a long period of time
What can cause anaemia due to a lack of b12 and folate
- Pernicious anaemia
- Alcohol / diet
- Increased cell turn over
What bone marrow pathologies can cause anaemia
Aplastic anaemia
Myleodysplasia
AA: when stem cells get replaced by fat cells, in bone marrow and then you cant make as many red blood cells
M: youre making red blood cells, but they don’t function that well
How does displacement in the bone marrow occur
Leukaemia (when you have loads of WBCs you don’t have time of space to make other cells)
Other cancer (go to the bone, they cant make as many blood cells)
Myelofibrosis
Myeloma
Chrnonic inflammatory conditions
Chronic inflammatory conditions
raised inflammatiatoy agents : IL-6 stimulates hepcidin → blocks abosption of iron in the small intestine, and stops iron from escaping the macrophages
Myeloma: malgiancy of plasma cells
Where is iron absorbed in the body
Absorbed in duodenum & proximal jejunum in ferrous (Fe2+) state.
In what form do we prescribe iron
often prescribe ferrrous sulfate because its in fe2+ form,
Can take tablet with a glass orange juice so it can turn it fe2+
How is iron stored in the body
like what is stored iron called
Stored as ferritin
Where in the body is iron formed
majority in bone marrow, liver and spleen
Why do we need folate
- Folate is needed to turn uracil into thymidine, an essential building block of DNA
B12 is involved in this process
Where is 95% of the folate in the body stored
More than 95 % of folate in the body is in the red blood cells. (we have a short store of folate)
What happens to folate when the body is under stress
folate store gets depleted
Where in the body do we store B12
Liver
How long can we store B12
3-5 years
How long can we store folate
about 4 months
What can proudcing excess RBCs do to folate
in haemolysis
can cause folate defiency
becasue the rbcs are dying
Explain how problems in the GI tract can cause anameia
Any inflammation or dysfunction of stomach , duodenum, liver, small or large bowel can cause malabsorption
Eg: Gastritis / colitis Pernicious anaemia / Coeliac disease Gastrectomy / colectomy
What is haemolysis
breakdown of red blood cells
What are the immune reasosn for haemolysis
you make antibodies against RBCs,
they stick to RBCs,
and then the macrophage eats it,
What are the non immune causes of haemolysis
– Splenomegaly (steal RBCs)
– Bleeding
What is Hereditary spherocytosis
It is when there is a defect in the red blood cell cytoskeleton (spectrin helps keep integrity)
usually there is genetic inherited mutations in spectrin (sometimes other proteins) that makes it go from a biconcave structure to a sphere
Why is that a problem?
it’s the least flexible configuration – gets damaged easily
What happens to red blood cells during Hereditary spherocytosis
Macrophage is like hey you don’t look like an RBCs,
so the damaged cells get removed by macrophages in the spleen
What are the symptoms of Hereditary spherocytosis
Symptoms presnet during childhood
Paleness
jaundice
Stomach pai
Shortness of breath
Lack of energy
Lack of appetite
Irritability
but a virus can make symptoms worse
What is the treatment of Hereditary spherocytosis
- Folic acid
- splenectomy
- complication in terms of infections
- VERY RARE but can do a transfusion
How do we diagnose Hereditary spherocytosis
through genetic tests
Is Hereditary spherocytosis autsomal or sex linked
and is it dominant or reccessive
Autosomal dominant
What is thalassaemia and what is the effect in haemoglobin
Defect in alpha or beta globin gene
Results in an abnormal form of haemoglobin which presents with anaemia
What populations does thalassaemia affect
Usually South Mediterranean, north Africa, middle east and SE asia distribution
What are the presentations of someone with Thalassaemia
dark urine, jaundice, and splenomegaly
Find out what haemoglobinopathy ….
Haemoglobinopathies are inherited disorders of globin
Is Thalassaemia, autosmoal or sex linked
and is it dominant or reccessive
autosomal recessive
What is beta thalassemia
caused by absent or reduced synthesis of beta globulin
Happens in children
How can a child inherit beta thalassemia
it’s autosomal recessive
you can have asymptomatic carriers, two parents carriers can have a 25% chance of producing a child with beta-thalassemia major
If a child has beta thalassemia what treatment options are avaliable
the child from a young age will be transfusion-dependent
(gene therapy is being trialed)
How can we diagnose HB problems
electrophoresis
Is sickle autsomal or sex linked
and is it reccessive and dominant
Autosomal recessive
How can you have sickle cell anaeima and be asymptomatic
if you have one beta chain, you are usually asymptomatic
In what countries is there a high level of sickle cell anaemia
(and why)
High prevalence West / North Africa
(Why: due to protection of malaria)
How does having sickle cell anaemia affect RBC
- Defect of Hb beta-globin gene
- What happens is there is a single amino acid change from Glutamic acid → valine
- this then Changes the shape of Hb
- No biconcave shape, so it can obstruct capillaries → They can get stuck and cause painful crises & end organ damage
- What happens is there is a single amino acid change from Glutamic acid → valine
What can be a side effect of sickle cell anaemia
- Hyposplenism
- they can get a small spleen
- which can put them at risk of capsule bacteria infections,
To prevent this you can put them on penicillin
What is the treatment of sickle cell anaemia
- oxygen, fluids
- warm them up
- give them pain killers
- Exchange transfusion (if hypoxic or have other features like severe crisis)
- take a pint of their blood and replace it with normal blood
- Hydroxycarbamide
- suppresses bone marrow production
- for sickle cell anaemia, it increases HBf production
Hydroxycarbamide: which is helpful as sickle cells readily gives oxygen, and HBf does the opposite
Is G6PD deficiency autosomal or sex linked
X linked
So affects men more
What will a lack glucose-6-phosphate dehydrogenase (G6PD)
- Important enzyme in pentose phosphate shunt
- Maintains reduced NADPH = only source of glutathione in RBC
- glutathione mops up free radicals
- If you are in a stress-oxidative state then you produce too many free radicals which will cause RBC to haemolyse (break down)
At what age do people with G6PD deficiency present?
and what do they present with
Present as neonates with neonatal haemolytic anaemia
What food do people with G6PD defiency have to avoid and why?
AVOID: Fava beans
Why: they produce more free radicals so patients must avoid them. → ‘Favism’
What can G6PD cause
Acute non spherocytic haemolytic anaemia
causes destruction of RBCs
How would you investigate anaemia
- Full history + exam
- full blood count and film
- measure ferritin, b12, and folate
- look at liver (TPO) and kidney function (EPO)
- Haemolysis screen (is the bilirubin up, are the reticulocytes up, is the LDH up)
Full blood count terms
Haemoglobin
Concentration of Hb in blood
Full blood count terms
Haematocrit
or Packed cell volume (centrifugation)
Ratio of volume of red blood cells to the total volume of blood
useful in patients that make too many red blood cells, (too much RBCs, puts them at risk at stroke)
Full blood count terms
Red blood count
How many red blood cells you have
Full blood count terms
Mean cell volume
Average red blood cell size
How to calculate = (=PCV/RBC)
Haemrocrit / red blood cell count
Full blood count terms
Mean corpuscular hemoglobin (MCH)
Amount of haemoglobin per red blood cell
How to calculate= (=Hb/RBC)
Full blood count terms
Mean corpuscular hemoglobin concentration (MCHC)
The amount of haemoglobin relative to the size of the cell
How to calculate: (=Hb/PCV)
How we use HB and MCV to diagnose anaemia
Someone’s FBC shows low HB and Low MCV
What are the potential causes
Low mcv: microcytsois (small red blood cells)
Iron defiency
Thalassemia
Sickle cell
How we use HB and MCV to diagnose anaemia
Someone’s FBC shows low HB and Normal MCV
What are the potential causes
Chronic disease
Acute blood loss
Bone marrow failure
How we use HB and MCV to diagnose anaemia
Someone’s FBC shows low HB and high MCV
What are the potential causes
high mcv (macrocytosis) large red blood cells
B12 + Folate
Alcohol and drugs
Haemolytic anaemia
In summary what the two common causes of anaemia
blood loss
- iron deficiency
