Nutritional Anaemias Flashcards
What is anaemia?
A condition where the number of red blood cells (or oxygen carrying capacity) is insufficient to meet the body’s physiologic needs
What is haemoglobin?
Haemoglobin structure?
iron containing oxygen transport metalloprotein within RBCs.
4 iron-containing haem groups
4 globin chains able to bind 4 O2
reduction in Hb = anaemia
Where are the blood cells made?
Bone marrow
Normal Erythropoiesis
- Erythropoiesis begins in the bone marrow
- the cells go through multiple processes of maturation
- lose their nucleus and then are transferred into the peripheral blood where they are considered circulating RBCs.
What does maturation of red blood cells require?
- Vitamin B12 & folic acid
- DNA synthesis
- Iron
- Haemoglobin synthesis
- Vitamins
- Cytokines (erythropoietin)
- Healthy bone marrow environment
Causes of anaemia
Failure of production :
hypoproliferation or reticulocytopenic
Ineffective Erythropoiesis
Decreased Survival:
Blood loss, haemolysis , reticulolysis
How to investigate the underlying CAUSE of anaemia?
Investigate the SIZE of RBC
Reticulocyte count then adds further clue as to failure of production or increased loss.
Function of iron
essential for O2 transport
The daily requirement for iron for erythropoiesis varies depending on gender and physiological needs
Nutritional anaemia
Nutritional anaemia is anaemia that is caused by a lack of essential ingredients that the body acquires from food sources:
- iron deficiency
- vitamin B12 deficiency
- folate deficiency
Which gender needs more daily iron?
Women need more daily iron than men (e.g. due to menstruation).
When pregnant, a lot more iron is needed.
Women reach male iron levels post-menopause
Where is dietary iron absorbed?
predominantly in the duodenum and the proximal jejunum via ferroportin receptors on enterocytes
Types of iron in food
Haem (meat, chicken, fish)
-easily absorbed
Non-haem (plant foods)
-not as easily absorbed
Recommended intake assumes 75% of iron is from haem iron sources
Non-haem iron absorption is lower for those consuming vegetarian diets, for whom iron requirement is approximately 2-fold greater.
Amount of iron absorbed depends on…
TYPE of iron ingested
-more haem iron and ferrous iron (e.g. red meat) is absorbed than non-haem and ferric forms
What is iron absorption regulated by?
What happens after iron is absorbed?
How is iron lost?
GI mucosal cells and hepcidin
iron is transferred into plasma and binds to transferrin
through sloughed mucosal cells and Desquamination/menstruation. You can’t excrete it or lose it by urination
How does Fe3+ circulate?
bound to plasma transferrin and accumulates within the cells as ferritin (stored)
-stored iron can be mobilised for reuse
Hepcidin
Stable iron forms
a hormone which regulates the absorption of iron in circulation
Ferric state- Fe3+
Ferrous state- Fe2+
Iron stores in men and women
Adult men normally have 35 to 45mg of iron per kg of body weight. Premenopausal women have lower iron stores as a result of their recurrent blood loss through menstruation.
Distribution of iron in the body
More than two thirds of the body’s iron content is incorporated into haemoglobin in developing erythroid precursors and mature red cells.
Most of the remaining body iron is found in storage and transport proteins found in hepatocytes and reticuloendothelial macrophages in liver, spleen and bone marrow:
- Ferritin
- Haemosiderin
Function of reticuloendothelial macrophages
Ingest senescent red cells, catabolise haemoglobin to scavenge iron, and load the iron onto transferrin for reuse
Iron metabolism
Controlled by absorption rather than excretion, as we don’t have a natural excreting method for iron.
If you take in an excess of iron, the body doesn’t have a natural way of losing it. Some is lost through:
- Blood loss/Menstruation
- Mucosal cells desquamation
How does hepcidin function in iron homeostasis?
Hepcidin causes ferroportin internalisation and degradation, thereby decreasing iron transfer into blood plasma from:
- duodenum
- macrophages involved in recycling senescent erythrocytes
- iron-storing hepatocytes.
Regulation of hepcidin
Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron.
Excess iron is stored as…
State of iron store…
Ferritin (protein)
reduce Ferritin stores and increase transferrin
What happens to iron when absorbed in plasma?
Iron attaches to transferrin and transported to bone marrow, binding to receptors on RBC precursors
Laboratory Iron studies
Serum Fe Haemoglobin levels Ferritin Transferrin Saturation Total Iron Binding Capacity
Laboratory investigations of iron deficiency anaemia
Ferritin - low
TF saturation - low
TIBC - high
Serum iron - low/normal
Iron deficiency causes
Not enough in:
- poor diet
- Malabsorption (celiac disease)
- increased physiological needs (e.g. pregnancy)
Losing too much:
- blood loss (menstruation, GI tract loss, parasites)
Stages in the development of iron deficiency anaemia
Before anaemia develops, iron deficiency occurs in several stages:
The percentage saturation of transferrin with iron and free erythrocyte protoporphyrin values do not become abnormal until tissue stores are depleted of iron.
A decrease in the haemoglobin concentration occurs when iron is unavailable for haem synthesis.
MCV (mean corpuscular volume) and MCH (mean corpuscular haemoglobin) do not become abnormal for several months after tissue stores are depleted of iron.
What is the most sensitive laboratory indicator of mild iron deficiency?
Serum Ferritin
Signs and symptoms of iron deficiency anaemia
Symptoms:
- fatigue
- lethargy
- dizziness
Signs:
- smooth tongue
- systolic flow murmurs
- pallor of mucous membranes
- bounding pulse
- koilonychias (thin,concave nails)
Vitamin B12 and Folate Deficiency
· Both have very similar laboratory finding and clinical symptoms.
· Can be found together or as isolate pathologies
What causes B12 and folate deficiency?
Macrocytic Anaemia
Laboratory findings of B12 and folate deficiency
[Hb] = low [MCV] = high [MCHC] = normal
Macrocytic Anaemia
Macrocytic anaemia can be subdivided into megaloblastic and non-megaloblastic anaemia depending on their cause.
Macrocytic anaemia: Megaloblastic
Megaloblastic: low reticulocyte count
>Vitamin B12/Folic acid deficiency
>Drug-related (interference with B12/Folic acid metabolism)
Characteristics of megaloblastic anaemia on peripheral smear
- macroovalocytes
- hypersegmented neutrophils
Macrocytic anaemia: Non-megaloblastic
Non-megaloblastic: if patient has macrocytic anaemia but not B12/Folic acid deficient >Alcoholism >Hypothyroidism >Liver disease >Myelodysplastic syndromes >Reticulocytosis (haemolysis)
Where do we get vitamin B12 from?
Where is vitamin B12 absorbed?
Where do we get Folate from?
Where is folate absorbed?
animal and dairy produce
Ileum via intrinsic factor
Vegetables, Liver
duodenum and jejunum
Role of vitamin B12 and folate
Final maturation of RBC and synthesis of DNA
Both are need for thymidine triphosphate synthesis
function of folate
DNA synthesis:
-adenosine, guanine, and thymidine synthesis
Causes of folate deficiency
Increased Demand
- pregnancy/breast feeding
- infancy and growth spurts
- haemolysis & rapid cell turnover (e.g. SCD)
- disseminated cancer
- urinary losses (e.g. heart failure)
Decreased Intake
- poor diet
- elderly
- chronic alcohol intake
Decreased Absorption
- medication (folate antagonists)
- coeliac
- jejunal resection
- tropical sprue
Folate stores
usually has enough stores for 3-5 months
Role of vitamin B12
co-factor for methylation in DNA and cell metabolism
intracellular conversion of vitamin B12 to 2 active coenzymes is necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine
What does vitamin B12 require for absorption?
Presence of intrinsic factor for absorption in terminal ileum
Where is the intrinsic factor found?
How is vitamin B12 transported to tissues?
parietal cells in stomach
Transcobalamin II and Transcobalamin I transport vit B12 to tissues
Causes of vitamin B12 deficiency
see picture
Clinical consequences of Vitamin B12/Folate Deficiency
· Brain: Cognition, Depression, Psychosis
· Neurology: Myelopathy, Sensory changes, Ataxia, Spasticity (SACDC)
· Infertility
· Cardiac cardiomyopathy
· Tongue: glossitis, taste impairment
· Blood: Pancytopenia
Pernicious anemia
an autoimmune disorder which causes vitamin B12 deficiency.
> antibodies are made against the cells which make the intrinsic factor (gastric parietal cells), or against the intrinsic factor itself
> lack of intrinsic factor therefore causes lack of B12 absorption
Treatment of pernicious anaemia
If oral B12 given to patient, they still won’t be able to absorb it. To treat, patients are given injections of vitamin B12.
Treatment of iron deficiency
Diet, oral, parenteral iron supplementation, stopping the bleeding
treatment of folate deficiency
Oral supplements
Treatment of vitamin B12 deficiency
oral vs intramuscular treatment
