Nutritional Anaemia Flashcards
What is the definition of Anaemia?
- Reduced O2 carrying capacity
- Conditions where the number of red blood cells is insufficient to meet the bodies physiological needs
What are the formed elements in the blood?
- Red blood cells
- Platelets
- Monocyte
- Lymphocyte
- Eosinophil
- Basophil
- Neutrophil
Describe normal erythropoesis
- Starts in the bone marrow
- Stimulated by cytokine EPO released from the kidney
- Undergoes multiple round of maturation from Megakaryocyte Erythroid Progenitor (MEP) to Late Erythroblast
- Nucleus is extruded and forms a reticulocyte
- Which then forms a mature RBC
- Requires vitamin B12 = co factor for methylation in DNA + cell metabolism
- Intracellular conversion of 2 active enzymes necessary for homeostasis methylmalonic acid + homocysteine
- Requires folate = necessary for DNA synthesis -> adenosine, thymine and guanine synthesis
- Requires iron = necessary for Hb synthesis
- Requires vitamin B12 = co factor for methylation in DNA + cell metabolism
What are the three main mechanisms of action which cause anaemia?
- Failure of Production - not producing enough RBCs - hypoproliferation, reticulocytopenic (low reticulocyte count) = shows the bone marrow isnt able to catch up - hence failed production
- Decreased survival - can be due to stabbing leading to blood loss, haemolysis, reticulocytosis - increased reticulocyte cound due to bone marrow stimulating further erythropoesis
- Ineffective Erythropoesis - main cause of microcytic (iron deficiency ) and macrocytic (B12 and folate)
- What is used to assess anaemia clinically in the UK?
- What is used to assess the underlying CAUSE of anaemia?
- Haemoglobin concentration
- Red blood cell SIZE
- Reticulocyte count will then add further clue to increased loss (reticulocytosis) or failure of production (reticulocytopenia)
What are causes of microcytic anaemia?
- Iron deficiency
- Thalassaemia
- Anaemia of chronic disease
What are causes of normocytic anaemia?
- Anaemia of chronic disease
- Sickle cell disease
- Chronic renal failure
- Aplastic Anaemia
What are causes of macrocytic anaemia?
(Macrocytic can further be split into megaloblastic and non-megaloblastic)
- Vitamin B12 and Folate deficiency
- Myelodysplasia (cancer where immature blood cells in bone marrow do not mature and become healthy blood cells)
- Alcohol induced
- Drug induced
- Liver disease
- Myoxedema
What can a mixture of iron deficiency and vitamin B12 and Folate deficiency lead to?
Normocytic Anaemia
Because macrocytic anaemia (due to Folate and vitamin B12) and microcytic anaemia (due to iron deficiency)
Aswell as looking at MCV (size = normocytic, macrocytic and microcytic) what else can you look for to discover the type of anaemia?
Reticulocyte count adds further clue as to failure of production (reticulocytopenia) or increased losses (reticulocytosis)
Briefly describe the structure of haemoglobin
- Iron containing oxygen transport metalloprotein
- Composed of 2 alpha and 2 beta globin chains
-
4 iron containing haem groups
- Reduced HB leads to anaemia as it reduces the O2 carrying capacity
Define nutritional anaemia and list the main ones
Nutritional anaemia = Anaemia due to lack of essential ingredients that the body acquires from food sources
3 Types
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
Why is iron important for the body?
-
Essential for O2 transport
- Most abundant trace element in the body
- We cant keep a big store of iron therefore we need our daily requirement needed for EPO
- We cant naturally excrete iron from the body its uptake is regulated by hepcidin
Which gender needs more iron?
- Women need more daily iron than men (due to menstruation)
- When pregnant, a lot more iron is needed
- Women reach male iron levels post-menopause
Where do we get our iron from?
Which form of iron is easily absorbed?
We get our iron from our food
- Haem (meat, chicken and fish) - easily absorbed
- Non-haem iron absorption is lower for those consuming vegetarian diets, for whom the iron requirement is 2 fold greater
Where is dietary iron predominantly absorbed?
Predominantly in the duodenum and proximal jejunum via ferroportin transporters on enterocytes
What are the two forms of iron?
- More than one stable form of iron
- Ferric state (3+) and Ferrous state (2+)
Describe iron absorption
- Regulated by GI mucosal cells and hepcidin
- Occurs in the duodenum and the proximal jejunum via ferroportin transporters on the enterocytes
- Transferred into plasma and bound to transferrin
The amount absorbed depends on the type ingested!!
- Haem iron (ferrous) sources (from meats and seafood) higher absorption
- Non haem (ferric) (from vegetarian diets) - need to eat more to acquire the same level of iron
What factors can affect iron absorption in our body?
- Haem iron (ferrous) absorbed more than non haem iron (ferric)
- GI acidity
- State of iron storage levels
- Bone marrow activity
How are iron levels regulated?
Via HEPICIDIN (iron regulatory hormone) and FERROPORTIN (iron channel)
- Hepicidin causes ferroportin internalisation and degradation decreasing iron transfer into blood plasma from
- Duodenum
- Macrophages (recycle senescent erthyrocytes)
- Iron-storing hepatocytes
- Feedback is regulated by iron concentrations in plasma adn liver and by erythropoeitic demand for iron
From what areas does hepcidin cause degradation and internalisation of ferroportin channels?
- Duodenum
- Macrophages involved in recycling senescent erthythrocytes
- Iron-storing hepatocytes
This will decrease iron transfer from these into blood
What happens after iron is absorbed?
- Iron will be transferred into plasma and binds to transferrin (iron transporting circulating plasma protein)
- This will then be transported to bone marrow and binds to transferrin receptors on RBC precursors
What will the transferrin levels and ferritin stores look like in iron deficiency?
IRON DEFICIENCY - will see reduced ferritin stores and increased transferrin
What are the ways in which iron can be lost from the body?
- Desquamation of sloughed mucosal cells
- Menstruation/ blood loss
The iron metabolism is controlled by absorption rather than excretion as we do not have a method of excreting iron
What is the main distribution of iron in the body?
- Mostly incorporated into haemoglobin in developing erythroid precursors and mature red blood cells
- Remaining iron is found in storage and transport proteins found in hepatocytes, reticuloendothelial macrophages in liver, spleen and bone marrow
What are the two storage proteins of iron?
Haemosiderin and ferritin
What is the role of reticuloendothelial macrophages?
Ingest senescent red blood cells, catabolise haemoglobin to scavenge iron and load the iron onto transferrin for reuse
This process will be regulated by hepcidin which can downregulate ferroportin transporters preventing iron recycling
What are the laboratory studies which determine someone’s blood iron levels?
- Serum Fe (not used as much)
- Ferritin - most commonly used
- Transferrin saturation - ratio of serum iron and total iron binding capacity - reveals percentage of binding sites that have been occupied by iron
- Transferrin
- Total iron binding capacity = measure of capacity of transferrin to bind iron, indirect measurement of transferrin
What are the lab results in iron deficiency anaemia?
- Ferritin = LOW
- Transferrin Saturation = LOW
- Total Iron binding capacity = HIGH
- Serum Iron = LOW/ NORMAL
- Reticulocyte = low
- This is low because although bone marrow is capable of making RBC it cant because it doesnt have enough iron, therefore when patients are given iron it rises drastically
What are the causes of iron deficiency?
- Either you dont get enough due to
- Poor diet, malabsorption or increased physiological needs
- Or you’re losing too much due to
- Blood loss (menstruation), GI tract loss, parasites
Excessive menstrual loss = first cause of iron deficiency in premenopausal women
Blood loss from GI = second cause of iron deficiency in postmenopausal women and men
Describe the stages of iron deficiency anaemia
- Serum ferritin is most sensitive indicator of mild iron deficiency - first to drop during iron depletion
- Percentage saturation of transferrin with iron and free erythrocyte protoporphyrin do not become abnormal until tissue stores are depleted of iron
- Decrease in Hb concentration occurs when iron is unavailable for haem synthesis
- MCV and MCH do not become abnormal for several months after tissue stores are depleted of iron
What are some investigations carried out to investigate iron deficiency?
- FBC (full blood count): Hb, MCV (mean cell volume), MCH (mean corpuscular haemoglobin), Reticulocyte count (likely to be low as it won’t have enough iron, this will increase when you take iron)
- Iron Studies: Ferritin, Transferrin Saturation
- Blood film
- Bone Marrow Aspirate Trephine Biopsy and Iron stores
What are signs and symptoms of iron defiency anaemia?
Symptoms
- Gradual fatigue
- Lethargy
- Dizziness
Signs
- Pallor of mucous membranes
- Bounding pulse
- Systolic flow murmurs
- Smooth tongue
- Koilonychias (spoon nails)
What are the main causes of iron deficiency ?
- Excessive menstrual loss in premenopausal women
- Second cause is blood loss from GI tract in adults and post-menopausal women
What does the lab investigations of folate and vitamin B12 deficiency look like?
- Low Hb
- High MCV
- Normal MCHC (average Hb concentration)
What are the two divisions of macrocytic anaemia
Megaloblastic and Non-megaloblastic anaemia
What is macrocytic anaemia (megaloblastic anaemia, low reticulocyte count) caused by?
- Vitamin B12 and folic acid deficiency
- Drug-related (interferance with b12 and folic acid metabolism)
What are the cause of non-megaloblastic anaemia?
This is when the patient has macrocytic anaemia but is not vitaminB12/ folate deficient
- Alcoholism
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (haemolysis)
What is the difference in the appearance of the blood film in megaloblastic and non-megaloblastic?
- Megaloblastic macricytic anaemia contains RBCs that are large and oval shaped (macroovalocytes) and hypersegmented neutrophils
Where do we get vitamin B12 and folate from?
Where is vitamin B12 and folate absorbed?
Folate = Vegetables and Liver (stored here)
Absorbed by duodenum and jejunum
Vitamin B12 = Animal and dairy produce
Absorbed by terminal ileum
What is the function of folate?
DNA synthesis required for synthesis of thymidine, adenosine and guanine
What are some of the causes of folate deficiency?
Increased Demand
- Pregnancy/ Breast Feeding, Infancy and Growth spurt, Haemolysis and rapid cell turnover
- Disseminated Cancer
- Urinary losses
Decreased Intake
- Poor diet
- Elderly
- Chronic alcohol intake
Decreased absorption
- Medication
- Coeliac
- Jejunal resection
- Tropical Sprue
What is the role of vitamin B12?
Essential co-factor for methylation in DNA and cell metabolism
Undergoes intracellular conversion to 2 active co-enzymes necessary for homeostasis of methylmalonic acid (MMA) and homocysteine
What is special about Vitamin B12 absorption?
- Requires presence of IF instrinsic factor for absorption in terminal ileum
- IF is made in parietal cells of stomach
- Transcobalamin II and transcobalamin I transport Vitamin B12 to tissues
What are some causes of vitamin B12 deficiency?
What is pernicious anaemia?
- Autoimmune disorder
- Produce antibodies against parietal cells or antibodies against intrinsic factor itself
- Lack of IF
- Lack of B12 absorption
- Oral vitamin B12 as treatment is ineffective due to inability of absorption due to lack of intrinsic factor
- Requires injections of vitamin B12!!!
- Oral vitamin B12 as treatment is ineffective due to inability of absorption due to lack of intrinsic factor
What are haematological consequences of vitamin B12 and folate defiency?
What are clinical consequences of vitamin B12 deficiency?
- Brain: Cognition, depression, psychosis
- Neurology: Myelopathy (compression of spinal cord), sensory changes, ataxia, spasticity (Sub acute combined degeneration of the chord)
- Infertility
- Cardiac cardiomyopathy
- Tongue: Glottis, taste impairment
- Blood: Pancytopenia
How do you treat nutritional anaemia?
Treat underlying cause
- Iron – diet, oral, parenteral iron supplementation, stopping the bleeding
- Folic Acid – oral supplements
- Vitamin B12 – oral vs intramuscular treatment
- Remember pernicous anaemia you cant give oral B12!!
What is the function of folate in RBC synthesis?
Folate is required for DNA synthesis
- Adenosne, guanine and thymidine synthesis
What is the role of vitamin B12
Co-factor for methylation of DNA and cell metabolism
Intracellular conversion of vitamin B12 to 2 active enzymes is necessary for homestasis of methylmalonic acid and homocysteine
How is vitamin B12 transported to tissues?
Trancobalamin I and II
