Nutritional Anaemias Flashcards
What is an anaemia?
- Anaemia is the defiency of red blood cells and/ or haemoglobin concentration within the blood meaning the oxygen-carrying capacity is insufficient to meet the body’s physiological needs
- Anaemia = ‹ RBC or ‹ Hb conc. in blood -> insufficient 02 carrying capacity
What is the role of haemoglobin (Hb) in RBCs?
- Hb = Iron containing oxygen transport metalloprotein within RBCs
- Therefore Reduction of haemoglobin in blood = (reduction in oxygen carrying capacity) = anaemia
State the main components of blood?
- RBCs
- Platelets
- WBCs: Monocyte, lymphocytes, eosinophil, basophil and nuetrophil
What are the main factors used for the diagnosis of anaemia?
- Hb levels
- Age
- Gender
- Side note: Anaemia is found more likely in pregnant women or during menstruation
Define erythropoesis
Erythropoeisis - Maturation of RBCs (RBCs are formed + matured in the bone marrow)
State the factors required for normal erythropoeisis? (5)
- Factors required:
- Vitamin B12 & folic acid: DNA synthesis
- Iron: Haemoglobin synthesis
- Vitamins
- Cytokines (erythropoeitin): Erythropoitein = a hormone secreted by the kidneys that increases the rate of production of red blood cells in response to falling levels of oxygen in the tissues
- Healthy bone marrow environment
State the 3 major mechanisms of action which can lead to anaemia?
- Failure of Production: hypoproliferation Reticulocytopenic
- a. Bone marrow prodcues reticulocytes (developing RBCs)
- b. Hypo. -> BM doesn’t have sufficient factors -> decreased production of reticulocytes (sign of anaemia)
- Ineffective Erythropoiesis
- Decreased Survival: Blood loss, Haemolysis, reticulocytosis
Define haemolysis and reticulocytosis
- Haemolysis: Destruction of red blood cells
- Reticulocytosis: Increase in reticulocyte production due to BM using up factors for Blood cell production to compensate for anaemia
State the 3 types of classification of anaemia and state the additional factor which may indicate the potential mechanism for cause?
- Based on MCV (mean cell volume) - average size of RBC
- Microcytic (smaller than average range)
- Normocytic (within normal range)
- Macrocytic (larger than average range)
- Reticulocyte count then adds further clue as to failure of production or increased losses
State 3 causes of microcytic anaemia?
- Iron deficiency (heme deficiency)
- Thalassamia (globin deficiency)
- Anaemia of Chronic Disease
State 5 causes of normocytic anaemia?
- Anaemia chronic disease
- Aplastic anaemia
- Chronic renal failure
- Bone marrow infiltration
- Sickle cell disease
State 5 causes of macrocytic anaemia?
- B12/folate deficency
- Myelodysplasia
- Alcohol induced
- Drug induced
- Liver disease
- Myxoedema
What is nutritional anemia and state 3 deficiencies which lead to this?
- Anaemia caused by lack of essential ingredients that the body acquires from food sources
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
What is the role of iron in the body and state the factors which determine the daily requirement of iron for erythropoiesis?
- Iron role = Essential for 02 transport (part of Hb)
- Iron required for erythropoiesis factors = gender + physiological needs (greater for pregnant and during menstruation)
How does iron intake differ between vegan and meat diets?
- Recommended intake assumes 75% of iron is from heme iron sources (meats, seafood) - as it contains blood.
- Non-heme iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater
Describe the sites of iron distribution including site of iron absorption, sites sent to and areas of iron loss? VD
Iron cannot be excreted
Describe the 2 forms of iron and how they can be found within the body?
- Stable forms of iron: Ferric states (3+) and Ferrous states (2+)
- Sites of Fe in body: Most iron is in the body as circulating Hb
- A. Hb: 4 haem groups, 4 globin chains able to bind 4 02
- (2). Remainder as storage and transport proteins
- A. ferritin (major one) and haemosiderin
- B. Found in cells of liver, spleen and bone marrow
State how iron absorption occurs describing the regulation and site?
- Regulated by Gl mucosal cells and hepcidin in duodenum & proximal jejunum: Hepcidin = Hepcidin is an iron-regulating peptide hormone made in the liver.
- Via ferroportin receptors on enterocytes (cells of the intestine)
- Transferred into plasma and binds to transferrin (transport protein)
State the factors which affect the rate of iron absorption?
- Type of iron ingested: Heme, ferrous (red meat, > than non-heme). Ferric forms Heme iron makes up 10-20% of dietary iron
- Other foods
- GI acidity
- State of iron storage levels
- Bone marrow activity
State the role of hepcidin in iron regulation?
- The iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron…
- Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes.
- Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron.”
Describe what occurs once iron transported from the enterocytes and how these will differ during iron deficiency?
- Either into plasma or if excess iron stored as ferritin
- In plasma: attaches to transferrin and then transported to bone marrow binds to transferrin receptors on BC precursors
- Iron deficency: Decreased ferritin stores + increased transferrin
State 5 factors and describe them as used to investigate iron levels in labs?
- Serum Fe: Hugely variable during the day
- Ferritin: Primary storage protein & providing reserve, water soluble
- Transferrin Saturation: Ratio of serum iron and total iron binding capacity - Revealing %age of transferrin binding sites that have been occupied by iron
- Transferrin: Made by liver, Production inversely proportional to Fe stores. Vital for Fe transport
- Total iron binding capacity: Measurements of the capacity of transferrin to bind iron. It is an indirect measurement of transferrin
State how ferritin, TF saturation, Total Iron Binding Capacity and serum iron levels (low, normal or high) will be during iron deficiency anaemia?
- Ferritin = Low
- TF saturation = Low
- TIBC = high
- Serum iron = Low/normal
State causes of iron defiency (5)?
- Not enough iron in: Poor diet, Malabsorption (difficulty in digestion of nutrients), Increased physiological needs
- Losing too much iron: Blood loss, Menstruation, GI tract loss, Paraistes (parasites)
State the 4 investigations that should be performed to help diagnose iron deficiency?
- FBC (full blood count): Hb, MCV, MCH (mean cell haemoglobin), Reticulocyte count
- Iron Studies: Ferritin, Transferrin Saturation
- Blood film: Examination of blood cells using microscope
- ?BMAT and Iron stores: BMAT = bone marrow biopsies - not really done as too invasive
How does IDA normally start with and generally how does the stages of IDA go?
- IDA is initally normocytic (cytic = size) and normochromic (chromic = conc. of Hb in RBCs
- Produces dark layer depending on Hb count)
- VD
What is the most common cause of Iron Deficiency Anaemia in men and women?
- Blood loss from the Gl tract: Men + postmenopausal women
- Excessive menstrual losses: Premenopausal women
State 3 symptoms of Iron Deficiency Anaemia?
- Fatigue
- Lethargy
- Dizziness
State 5 signs of Iron Deficiency Anaemia?
- Pallor of mucous membranes,
- Bounding pulse
- Systolic flow murmurs
- Smooth tongue
- Koilonychias (spoon nails)
Why are B12 and folate defiency commonly referred to each other and what type of anamia does it result in?
- Both have very similar laboratory finding and clinical symptoms
- Can be found together or as isolated pathologies
- Results in Macrocytic Anaemia: Low Hb and high MCV with normal MCHC
State the 2 types of macrocytic anaemia and state examples that cause them?
- Megaloblastic: Low reticulocyte count. Vitamin B12/Folic acid deficiency, Drug-related (interference with B12/FA metabolism)
- Non-megaloblastic: Alcoholism ++, Hypothyroidism, Liver disease, Myelodysplastic syndromes, Reticulocytosis (haemolysis)
What is it called when anaemia occurs in the presence of macrocytosis and hyper segmented neutrophils?
- Anemia occurring in the presence of macrocytosis and hypersegmented neutrophils is known as megaloblastic anaemia
- The absence of hypersegmented neutrophils characterizes non-megaloblastic anemia.
State the source, effect of cooking, absorption site and average body store of vitamin B12 and folate?
- Basically B12 required less as its stored for much longer
- VD
State another term for vitamin B12 and state the uses of vitamin B12 and folate (3)
- Vitamin B12 = cobalamin
- Both important for the final maturation of BC, synthesis of DNA and thymidine triphosphate synthesis
State the megaloblastic characteristics of blood cell film seen in Vit. B12 and folic acid deficiency?
Characterised on peripheral smear via macroovalocytes and hypersegmented neutrophils VD
What is folate necessary for?
DNA synthesis: Adenosine, guanine and thymidine synthesis
State the 3 major reasons why folate defiency occurs?
- Increased demand
- Decreased intake
- Decreased absorption
State 5 causes of increased demand leading to folate defiency?
- Pregnancy/breast feeding
- Infancy and growth spurt
- Haemolysis and rapid cell turnover e.g. SCD
- Disseminated cancer -> cancer that has spread throughout the body
- Urinary losses e.g. heart failure
State 3 causes of decreased intake leading to folate defiency?
- Poor diet
- Elderly
- Chronic alcohol intake
State 4 causes of decreased absorption leading to folate
defiency?
- Medication (folate antagonists)
- Coeliac
- Jejunal resection
- Tropical sprue (small intestine can’t absorb properly)
What is the role of vitamin B12 and state the conversion required?
- Role: Essential co-factor for methylation in DNA and cell metabolism
- Intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
- Defiency of B12 = 1 MMA
- DNA methylation is essential for silencing retroviral elements, regulating tissue-specific gene expression, genomic imprinting, and X chromosome inactivation
- Importantly, DNA methylation in different genomic regions may exert different influences on gene activities based on the underlying genetic sequence.
State 3 animal sources of B12?
- Fish
- Meat
- Dairy
How is B12 absorped into the terminal ileum?
- Requires the presence of Intrinsic Factor for absoprtion in terminal ileum
- IF made in Parietal Cells in stomach
- Transcobalamin II and Transcobalamin I transport vitB12 to tissues for absorption to occur
State major causes of B12 defiency?
- Impaired absorption = pernicious anemia, zollinger-ellison syndrome. Pernicious anaemia is an autoimmune condition that affects your stomach
- Decreased intake
- Congenital causes - IF receptor defiency, Cb mutation
- Increased requirements
- Medications -> metoformin
State the level or what can be seen in MCV, Hb, reticulocyte count, LDH, Blood film, BMAT and MMA in B12 deficiency?
VD
State clinical consequences of B12 defiency in terms of the brain, tongue and blood, neurology
- Brain: cognition, depression, psychosis
- Neurology: myelopathy, sensory changes, ataxia, spasticity (SACDC)
- Infertility
- Cardiac cardiomyopathy
- Tongue: glossitis, taste impairment: Glossitis is a problem in which the tongue is swollen and inflamed, This often makes the surface of the tongue appear smooth.
- Blood: Pancytopenia - deficiency of all three cellular components of the blood (red cells, white cells, and platelets).
What is pernicious anaemia?
- Autoimmune disorder
- Lack of Intrinsic factor
- Lack of B12 absorption
- Gastric Parietal cell antibodies
- IF antibodies
State the treatment for iron, folic acid and B12?
- Iron: diet, oral, parenteral iron supplementation, stopping the bleeding
- Folic Acid: oral supplements
- B12: oral vs intramuscular treatment
