The Nutritional Anaemias Flashcards
Define 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 physiologic needs.
Briefly describe haemoglobin.
- it’s an iron-containing oxygen transport metalloprotein
- it’s found within RBCs
- a reduction in haemoglobin leads to anaemia, as it reduces the oxygen-carrying capacity
What is erythropoiesis?
It is the process of maturation of red blood cells.
What does erythropoiesis require?
- Vitamin B12
- Folic acid
- DNA synthesis
- Haemoglobin synthesis
- Iron
- Vitamins
- Cytokines (erythropoeitin)
- Healthy bone marrow environment
What are anaemia’s three main mechanisms of action?
FAILURE OF PRODUCTION: hypoproliferation, reticulocytopenic (relative to absolute bone marrow failure)
INEFFECTIVE ERYTHROPOIESIS (bone marrow sort of works)
DECREASED SURVIVAL: blood loss haemolysis, reticulocytosis
Define nutritional anaemias, and list the three main ones.
It’s anaemia caused by the lack of essential ingredients that the body acquires from food sources.
The three nutritional anaemias are:
- iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
List the three nutritional anaemias based on their RBC size.
MICROCYTIC:
- iron (haem) deficiency
MACROCYTIC:
- folate deficiency
- B12 deficiency
Why is iron important for the body?
- it’s essential for O2 transport
- it’s the most abundant trace element in the body
- we cannot keep a big store of iron, so we NEED to get our daily requirement
- we can’t naturally excrete iron from the body, so it’s uptake is regulated by hepcidin
Briefly describe iron metabolism.
There is more than 1 stable form of iron: ferric states (3+) and ferrous states (2+).
Most iron is in the body as circulating Hb. Haemoglobin has 4 haem groups, so we have 4 globin chains that are able to bind to 4 O2.
The remainder of the iron is bound to storage and transport proteins (ferritin and haemosiderin). It is found in cells of the liver, spleen and bone marrow.
Briefly describe iron absorption.
- it’s regulated by GI mucosal cells and hepcidin
- it occurs mostly in the duodenum & proximal jejunum via ferroportin receptors on enterocytes
- it is then transferred into the plasma and bound to transferrin
The amount absorbed depends on type ingested.
More haem, ferrous (red meat) is absorbed than non-haem, ferric forms.
Haem iron makes up 10-20% of our dietary iron.
Other foods, GI acidity, the state of iron storage levels and bone marrow activity also affect absorption.
Describe iron regulation via hepcidin.
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 iron transport and storage after it’s been absorbed.
The iron is transported from enterocytes and then either into plasma or, if in excess, the iron is stored as ferritin.
In the plasma: it attaches to transferrin and is then transported to bone marrow, where it binds to transferrin receptors on RBC precursors.
A state of iron deficiency will see reduced ferritin stores. and then increased transferrin.
Describe the different laboratory tests we can do to study someone’s blood iron levels.
SERUM FE: not too reliable as has a hugely variable during the day
FERRITIN: it’s the primary storage protein & providing reserve; it’s water soluble
TRANSFERRIN SATURATION: the ratio of serum iron and total iron binding capacity – revealing the percentage of transferrin binding sites that have been occupied by iron
TRANSFERRIN: it’s made by the liver; its production is inversely proportional to Fe stores. as it is vital for Fe transport
TOTAL IRON BINDING CAPACITY: it’s the measurement of the capacity of transferrin to bind iron; it is an indirect measurement of transferrin
What would be the lab results if we did all the tests on someone with iron-deficiency anaemia?
FERRITIN: low
TF SATURATION: low
TIBC: high
SERUM IRON: low/normal
What are some causes of iron deficiency?
Either, you don’t get enough in, due to:
- poor diet
- malabsorption
- increased physiological needs
Or, you’re losing too much, due to:
- blood loss (menstruation, GI tract loss, parasites)
Describe the stages of iron deficiency anaemia.
Serum ferritin is the most sensitive laboratory indicators of mild iron deficiency; it is the first to drop during iron depletion.
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 and MCH do not become abnormal for several months after tissue stores are depleted of iron.
What are some symptoms and signs of iron deficiency anaemia?
SYMPTOMS:
- (gradual) fatigue
- lethargy
- dizziness
SIGNS:
- pallor of mucous membranes
- bounding pulse (because heart has to work harder to pump blood)
- systolic flow murmurs
- smooth tongue
- koilonychias (spoon nails)
How is macrocytic anaemia characterised in a blood test?
- low Hb
- high MCV
- normal MCHC
How are macrocytic anaemias split up (into two categories)?
MEGALOBLASTIC (LOW RETICULOCYTE COUNT):
- Vitamin B12/Folic acid deficiency
- Drug-related (interference with B12/FA metabolism)
NONMEGALOBLASTIC:
- Alcoholism ++
- Hypothyroidism
- Liver disease
- Myelodysplastic syndromes
- Reticulocytosis (due to haemolysis)
What is the importance of folate in the body?
Folate is necessary for DNA synthesis: adenosine, guanine and thymidine synthesis.
Both Vitamin B12 and folate are important for the final maturation of RBCs and for the synthesis of DNA. Both are also needed for thymidine triphosphate synthesis.
How are macrocytic anaemias characterised on a blood film?
They are characterized on the peripheral smear by macroovalocytes and hypersegmented neutrophils.
What are some causes of folate deficiency?
INCREASED DEMAND:
- pregnancy /breast feeding
- infancy and growth spurts
- haemolysis & rapid cell turnover: eg SCD
- disseminated cancer
- urinary losses: eg heart failure
DECREASED INTAKE:
- poor diet
- elderly
- chronic alcohol intake
DECREASED ABSORPTION:
- medication (folate antagonists)
- coeliac
- jejunal resection
- tropical sprue
What is the importance of Vitamin B12 in the body?
It is an essential co-factor for methylation in DNA and cell metabolism.
It undergoes intracellular conversion to 2 active coenzymes necessary for the homeostasis of methylmalonic acid (MMA) and homocysteine.
What is special about the absorption of Vitamin B12?
It requires the presence of Intrinsic Factor (IF) for absorption in the terminal ileum.
IF is made in the parietal cells in the stomach.
Transcobalamin II and Transcobalamin I transport Vitamin B12 to tissues.
What are some causes of Vitamin B12 deficiency?
IMPAIRED ABSORPTION:
- pernicious anaemia
- gastrectomy or ileal resection
- Zollinger-Ellison syndrome
- parasites
DECREASED INTAKE:
- malnutrition
- vegan diet
CONGENITAL CAUSES:
- intrinsic factor receptor deficiency
- cobalamin mutation
C-G-1 gene
INCREASED REQUIREMENTS:
- haemolysis
- HIV
- pregnancy
- growth spurts
MEDICATION:
- alcohol
- NO
- PPI, H2 antagonists
- Metformin
What are some haematological consequences of Vitamin B12 deficiency?
MCV: normal or raised
Hb: normal or low
Reticulocyte count: low
LDH: raised
blood film: macrocytes, ovalocytes, hypersegmented neutrophils
BMAT: hypercellular, megaloblastic, giant metamyelocytes
MMA: increased
What are some clinical consequences of Vitamin B12 deficiency?
- BRAIN: cognition, depression, psychosis
- NEUROLOGY: myelopathy, sensory changes, ataxia, spasticity (SACDC)
- Infertility
- Cardiac cardiomyopathy
- TONGUE: glossitis, taste impairment
BLOOD: Pancytopenia
What is pernicious anaemia?
In most cases of pernicious anaemia, the body’s immune system attacks and destroys the cells that produce IF in the stomach. If these cells are destroyed, the body can’t make IF and can’t absorb Vitamin B-12 found in foods such as those listed above.
How would you treat the nutritional anaemias?
You would have to treat the underlying cause:
IRON: diet, oral, parenteral iron supplementation, stopping the bleeding
FOLIC ACID: oral supplements
B12: oral vs intramuscular treatment
