4: Macrocytosis and macrocytic anaemia Flashcards
What is macrocytic anaemia?
Reduction in red blood cell number in which the red blood cells are larger than normal
In macrocytic anaemia, haemoglobin is (high / low) and MCV is (high / low).
Hb low
MCV high (> 100 fL)
What is macrocytosis?
Increase in red blood cell size
NOT the same as macrocytic anaemia (Hb and red cell count normal)
Normal ranges for MCV vary from hospital to hospital.
On a blood film, what can red blood cells be compared with to say whether or not they are macrocytic?
Nucleus of a lymphocyte
because they tend to be larger than an RBC should be
What values of MCV are
a) normal
b) indicative of macrocytosis?
a) 80 - 100 fL
b) > 100 fL
Where are red blood cell precursors found?
Bone marrow
Before reticulocytes, what are precursor red blood cells called?
Do they have a nucleus?
Erythroblast
Yes
What do precursors to red blood cells accumulate as they divide?
Hb
Red blood cell precursors get (bigger / smaller) as they divide.
smaller
Where are reticulocytes found?
Circulation
What do reticulocytes lose before becoming mature RBCs?
RNA
What is a megaloblast?
Big erythroblast (precursor RBC) with abnormal nucleus
What happens to
a) Hb synthesis
b) DNA synthesis and nuclear maturation
c) RNA synthesis
in a megaloblast?
a) Normal
b) Abnormal
c) Normal
i.e this is a problem with the DNA / nucleus, which remember causes a macrocytic anaemia
What does a megaloblast turn into when it differentiates?
Macrocyte
Due to nuclear problem, most of the cells have undergone apoptosis, so cell count is reduced (macrocytic anaemia)
What is the main causes of megaloblastic (a type of macrocytic) anaemia?
Vit B12 / Folic acid deficiency
Why do Vit B12 and folic acid deficiencies cause megaloblastic anaemia?
Both involved in DNA synthesis and nuclear maturation
What genetic process are Vit B12 and folic acid involved in?
Gene silencing
Which vitamin is carried to the distal ileum by intrinsic factor?
Vit B12
Which protein carries Vitamin B12 to the duodenum before it is bound to intrinsic factor?
R protein
In which foods is Vitamin B12 found?
Animal products
Red & white meat, fish, eggs, cow’s milk
Who is prone to Vitamin B12 deficiency?
People who don’t eat animal products
People on PPIs (inadequate stomach acid to liberate Vit B12 from food)
People at risk of malabsorption (overgrowth, surgical resection)
Alcoholics (indaequate nutrition)
Which stomach cells produce intrinsic factor?
Parietal cells
In which autoimmune disease are gastric parietal cells destroyed?
Pernicious anaemia
Causes Vit B12 deficiency
Who is prone to folate deficiency?
Alcoholics (inadequate nutrition)
What are the general symptoms of anaemia?
Pallor
Fatigue
Difficulty concentrating
Dizziness
Shortness of breath
What are specific symptoms of Vit B12 / folic acid deficiency?
GI problems - weight loss, diarrhoea, jaundice etc. - suggest a primary GI cause
Glossitis (sore tongue)
Delayed development
What irreversible neurological changes are caused by Vit B12 deficiency?
Delayed degeneration of dorsal columns (spinothalamic tract)
Dementia
NOT the same as the B1 encephalopathy
What are blood film findings specific to macrocytic anaemia caused by Vit B12 / folate deficiency?
Macrovalocytes
Hypersegmented neutrophils
How is megaloblastic anaemia treated?
Treat underlying cause e.g diet, malabsorption
Vit B12 injections in pernicious anaemia
Folic acid supplements
What are some causes of isolated macrocytosis?
Alcohol
Liver disease
Hypothyroidism
What bone marrow response to blood loss can cause a false macrocytosis?
Reticulocytosis
because reticulocytosis are immature RBCs and naturally bigger
What are cold agglutinins?
What false reading do they cause?
Proteins which stick RBCs together in clumps
False macrocytosis
Why do patients with pernicious anaemia appear jaundiced?
Vit B12 / Folate deficient
MCV increases (macrocytosis)
RBCs can’t pass into the circulation and die in the bone marrow (ineffective erythropoiesis)
Hb broken down into bilirubin > jaundice
What does MCV mean?
What unit is it measured in?
Mean cell volume
Femtolitres
What is the normal range of MCV in femtolitres?
80 - 100 fL
ranges vary slightly
Which value and above of MCV is abnormal?
> 100 fL ish
compare the red blood cell size to the nucleus of a lymphocyte - bigger is abnormal
From which dietary sources is
a) vitamin B12
b) folate
obtained?
a) Animal products
b) Leafy veg, liver, fortified cereals
How long do folate stores last?
4 months
How long do vitamin B12 stores last?
2 - 4 years
What is a hypersegmented neutrophil?
Neutrophil with nucleus containing 6+ lobes
