Microcytic and Macrocytic anaemia Flashcards
What is the MCH in a blood test?
Average haemoglobin content of RBC
What is the MCHC in a blood test?
Calculated measure of haemoglobin concentration in given red blood cells.
What is the RDW in a blood test?
The rage of deviation around RBC size.
What does Microcytic mean?
Small RBC, reduced MCV
What conditions are associated with a microcytic appearance?
- Iron deficiency (heme deficiency)
- Thalassamia (globin deficiency)
- Anaemia of chronic disease
What conditions are associated with normocytic appearance?
- Anaemia of chronic disease
- Aplasia
- Chronic renal failure
What conditions are associated with microcytic appearance?
- B12 deficiency and folate deficiency
- Myelodysplasia
- Reticulocytosis
- Drug induced
- Liver disease
- Myxoedema
What is iron important for?
Iron is an essential component of cytochromes, oxygen-binding molecules (i.e., haemoglobin and myoglobin), and many enzymes.
Where is dietary iron absorbed?
Iron is absorbed from duodenum via enterocytes into plasma and binds to transferrin and then transported to bone marrow to make red blood cells.
How does Fe3+ circulate in the plasma?
Bound to plasma transferrin and accumulate within cells in the form or ferritin
Which cells in the body act as storage deposits of iron?
Hepatocytes and reticuloendothelial macrophages
What is the role of reticuloendothelial macrophages?
They ingest senescent red cells, catabolise haemoglobin to scavenge iron, and load the iron onto transferrin for reuse.
How much iron do men and non-menstruating women lose a day?
1mg of iron per day
What are the storage and transport proteins?
Storage and transport proteins, ferrin and haemosiderin. Found in cells of liver, spleen and bone marrow
What happens to excess iron?
Excess absorption of iron is stored as ferritin.
What is the role of hepcidin?
“The iron-regulatory hormone hepcidin and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution or 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 form iron-storing hepatocytes.
Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoitic demand for iron.
What different iron studies exist?
- Serum Fe
- Ferritin
- Transferrin saturation
- Total iron binding capacity
What would you expect to see in iron deficiency anaemia on iron studies?
- Serum Fe = low/normal
- Ferritin = low (unless inflammation)
- Transferrin saturation = low
- Total iron binding capacity = high
What are the key facts about ferritin?
Primary storage protein & providing reserve, water soluble.
What does transferrin saturation show?
Ratio of serum iron and total iron binding capacity - revealing %age of transferrin binding sites that have been occupied by iron
What does iron binding capacity show?
Measurement of the capacity of transferrin to bind iron. It is an indirect measurement of transferrin - a transport protein that carries iron.
serum Fe is variable during the day - T/F?
True
What are the causes of iron deficiency?
Not enough in:
• Poor diet
• Malabsorption
• Increased physiological needs
Losing too much:
• Blood loss
• Menstruation, GI tract loss, parasites
What are the causes of macrocytosis?
Megaloblastic: Low reticulocyte count:
• Vitamin B12/Folic acid deficiency
• Drug-related
- Interference with B12/FA metabolism
Nonmegaloblastic • Alcoholism ++ • Hypothyroidism • Liver disease • Myelodysplastic syndromes • Reticulocytosis (haemolysis)
When are megaloblastic changes of blood cells seen?
Megaloblastic changes of blood cells are seen in B12 and folic acid deficiency. They are characterised on the peripheral smear by macroovalocytes and hypersegmented neutrophils..
What is the function of folate?
Folate necessary for DNA synthesis:
Adenosine, guanine and thymidine synthesis
What are the causes of folate deficiency?
- Increased demand:
- pregnancy/breastfeeding
- infancy and growth spurts
- Haemolysis & rapid ccell turnovers 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
What is the function of vitamin B12?
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.
What foods contain vitamin B12?
Animal sources: Fish, meat, dairy
What are the causes of B12 deficiency?
- Increased absorption
- pernicious anaemia
- gastrectomy or ileal rsection
- Zollinger-Ellison syndrome
- Parasites - Decreased intake
- Malnutrition
- Vegan diet - Congestinal 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 is pernicious anaemia?
- Autoimmune disorder
- Lack of IF
- Lack of B12 absorption
- Gastric parietal cell antibodies
- IF antibodies
What would the blood film of a patient with iron deficiency anaemia look like?
• The blood film of a patient with iron deficiency anaemia shows anisocytosis, poikilocytosis (including elipo)
• Hypochromic cells
Microcytosis