Nutritional anaemias Flashcards
what is anaemia?
Anaemia is a condition in which the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body’s physiological needs. / also low levels of haemoglobin
what are the ingredients for making RBCs
Vitamin B12 folic acid and iron (also cytokines and healthy bone marrow niche)
What are the 3 causes for anaemia
Failure of production of haemoglobin
Ineffective erythropoiesis (rbc production)
Decreased survival (blood loss, haemolysis, reticulocytosis)
What is reticulocytopenia?
a reticulocyte is an immature red blood cell, reticulocytopenia is a condition where there is an abnormal level of reticulocytes in the body
What does failure of production of haemoglobin/rbcs mean
it means there might not be enough ingredients resulting in hypo proliferation (not enough rbcs produced)
or it could be due to reticulocytopenia (not enough baby rbcs in the body)
what does ineffective erythropoiesis mean
decreased output of rbcs basically ineffective rbc production
how do we investigate anaemia
based on whether blood test results show rbcs are microcytic (smaller than normal) or macrocytic (bigger than normal)
why are macrocytic rbcs bad
they dont have enough nutrients
what causes rbcs to be macro and microcytic
microcytic- Iron deficiency
macrocytic- B12, folate deficiency
what role does iron have in blood
O2 transport
why do daily requirement for women after 51 years become the same as men
menopause they no longer have periods and no longer need more iron to make up for blood loss.
(pregnant women have the highest iron requirement)
where does most of our iron go and how
most of it goes to bone marrow to be carried by blood via transferrin a transport protein (some goes to muscles and liver)
where is iron stored
in the liver and can be transferred back out via transferrin
how many states of iron are there in the body and what form are they mostly found as in the body
Fe+3 (ferric state) Fe+2 (ferrous state), most of it is found as Hb (haemoglobin)
what are the transport and storage proteins of iron
ferritin
haemosiderin
found in bone marrow spleen and liver
how is iron absorption regulated
GI mucosal cells and hepcidin
How does hepcidin regulate iron absorption?
Causes ferroportin internalization and degradation decreasing the iron transfer into the blood plasma from the duodenum.
what are the duodenum and the jejunum
Duodenum- First part of the small intestine
Jejunum- middle part of the small intestine
how does the duodenum and jejunum regulate iron absorption
They contain ferroportin receptors on cells which transfer iron into the plasma where the iron binds to transferrin and is taken wherever needed
what cells have ferroportin receptors
enterocyte cells (a cell of the intestinal lining)
found in the Duodenum and Jejunum
What affects the amount of iron the body absorbs
Type of iron ingested (Heme, Ferrous, non heme)
GI acidity
Iron storage levels
Bone marrow activity
how does hepcidin regulate iron absorption
it gets rid of ferroportin receptors available (by degradation and internalisation) which means iron can no longer be transferred to the plasma and cant bind to transferrin.
how is hepcidin regulated
via iron conc and rbcs production demand for iron
what happens to excess iron
stored as ferritin (a storage protein)
What happens to the levels of transferrin and ferritin in iron deficiency?
Transferrin- increased
Ferritin- decreased
How can we test for iron deficiency?
Iron binding studies
what does low ferritin levels show and how can it be artificially increased
low ferritin levels mean low iron levels (i.e iron deficient)
Ferritin is part of the immune system so if you’re unwell it can be raised
what are causes of iron deficiency
Blood loss (mensturation, undiagnosed GI tract blood loss, parasites)
Poor diet (can also be because of malabsorption or ^inc physiological needs)
how is iron deficiency investigated
full blood count: checks Hb conc, mean cell volume, mean cell haemoglobin and reticulocyte count (baby rbc count)
blood film
BMAT (bone marrow biopsy)- very outdated
How does Iron deficient anaemia (IDA) present under a microscope?
Microcytic (smaller than WBC)
Hypochromic (pale)
what are the symptoms of IDA (iron deficiency anaemia)
Symptoms:
fatigue, lethargy, dizziness
Signs:
pallor of mucous membrane, bounding pulse, systolic flow murmurs, smooth tongue, koilonychias (spoon nail, the centre of the nail is depressed and starts looking like a spoon)
Why are B12 & folate grouped together?
Both have similar clinical findings and are normally found together but can be isolated from one another in diagnosis
what happens with B12 and/or folate deficiency
macrocytic anaemia
They have low Hb and high MCV (mean corpuscular volume, meaning bigger cell with more volume), as well as normal MCHC (mean corpuscular haemoglobin concentration).
How do the previous symptoms (macrocytic anaemia blood results) cause anaemia?
Because the cells are bigger and have more volume this means they can hold more Hb in ONE cell, this gives the illusion of a healthy cell in a patient if you’re only looking at MCHC (Hb conc in a cell) since the cell is larger and has a higher capacity for Hb, however overall there is low Hb since there aren’t enough cells in the body to keep up with Hb demand meaning theres less cells overall resulting in less Hb overall causing anaemia.
macrocytic anaemia has 2 descriptions
Megaloblastic- Vitamin B12 or folate deficiency, or drug related
Non-megaloblastic- every other cause
B12 and folate sources
fish, meat, dairy vegetables (oil), liver
B12 folate
What are some differences between Megaloblastic and non-megaloblastic anaemias?
Megaloblastic- Hyper segmented neutrophil (too many nucleus nodes in a neutrophil, normally has 3-4 where you can see up to 7 in a B12/Folate deficient patient), oval RBCs
Non-megaloblastic- has many macrocytic rbcs present but there is no uniformity to rbc size, theres just a bunch of different rbcs with no pattern in size.
what is folate used for
A, T, G synthesis
what are causes of folate deficiency
increased demand- breast feeding, growth spurts, cancer, rapid cell turnover, heart failure
decreased intake- diet, elderly, alcohol
decreased absorption- medicine, coeliac, jejunal resection, tropical sprue
what is vitamin b12 essential for
methylation in DNA and cell metabolism
necessary for homeostasis of MMA and homocysteine
what are some lab studies they carry out for iron
Fe serum- hugely variable in the day
Ferritin
Transferrin (inversely proportional to Fe stores)
Transferrin saturation- amount of transferrin that is bound to iron
Total Iron binding capacity- measurement of the capacity of transferrin to bind to iron (indirectly measures transferrin)
Difficult to carry out and is unreliable, ferritin is the most reliable measure of iron levels of a patient
How is ferritin measurement sometimes unreliable?
It is also part of the immune system meaning if there is an infection or any activity of the immune system ferritin levels can be artificially boosted by such causes
Why is transferrin inversely proportional to Fe stores
because the less fe available the more the body wants to transfer from the stores so they increase transferrin production to try make up for the lack of iron in the body. basically supply and demand if you think about it there was more supply so less demand now theres less supply so more demand
How is B12 absorbed
In the terminal Ileum (last section of the small intestine) via intrinsic factor (a glycoprotein made in stomach parietal cells found in the stomach same cell make acid)
what is pernicious anaemia
an autoimmune disease where antibodies attack either intrinsic factor or parietal cells destroying them so there is lack of B12 absorption resulting in anaemia no amount of B12 supplementation will rectify this as it wont be absorbed, you need B12 injections straight into the blood to treat this.
What are some causes of B12 deficiency?
Impaired absorption- pernicious, gastrectomy/ ileal resection, parasites, zollinger-ellison syndrome
decreased intake- malnutrition, vegan diet
Congenital causes- IF receptor deficiency, folate mutation CG1 gene
inc req- Haemolysis, HIV, pregnancy, growth spurts
Medication- Alcohol, NO, metformin, PPI/H2 antagonists
What is the difference between Iron deficient anaemia and B12 and/or folate anaemia?
Iron- Microcytic (smaller rbc)
Folate &/or B12- Macrocytic (enlarged rbc)
Why are B12 & folate grouped together?
Both have similar clinical findings and are normally found together but can be isolated from one another in diagnosis
What are the haematological consequences of B12 deficiency?
MCV- Normal or raised
Hb- Normal or low
Reticulocyte count- Low
LDH- Raised
Blood film- Macrocytes, ovalocytes, hyper segmented neutrophils
BMAT- Giant metamyelocytes, hypercellular, megaloblastic (Large immature WBCs, very unusual to need this test)
MMA- Increased
What are some clinical consequences of B12?
Brain: low cognition, depression, psychosis
Neurology- sensory changes, ataxia (disorder of balance and speech), spasticity (abnormal muscle stiffness), myelopathy (compressed spine)
Infertility
cardiomyopathy
Tongue: taste impairment, glossitis
Blood: Pancytopenia (deficiency of rbc wbc and platelets)
