Megaloblastic Anaemia Flashcards
What is macrocytic anaemia?
Anaemia in which red blood cells have a larger-than-normal volume
What characterises megaloblastic anaemia?
Presence of erythroblasts with delayed nuclear maturation due to defective DNA synthesis in the bone marrow
What is the result of DNA defects in megaloblastic anaemia?
Reduced cell division and increased apoptosis
List causes of Vitamin B12 deficiency
Low dietary intake (e.g., veganism)
Pernicious anaemia (autoimmune destruction of gastric parietal cells)
Gastrectomy
Congenital deficiency of intrinsic factor
List causes of folate deficiency
Inadequate intake (e.g., low leafy green vegetable consumption)
Malabsorption
Excess utilization (e.g., haemolysis, pregnancy, malignancy)
Drugs (e.g., anticonvulsants)
What is a megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus
What happens in maturing megaloblasts in the bone marrow?
Division is reduced, apoptosis increases, and cytoplasmic development proceeds normally, resulting in larger cells (macrocytes)
Why are Vitamin B12 and folate important?
They are essential co-factors for DNA synthesis, nuclear maturation, DNA modification, and gene activity
Describe Vitamin B12 metabolism
(1) Released from food protein by gastric enzymes.
(2) Binds to an R-binder protein, then an intrinsic factor.
(3) Absorbed in the ileum and transported by transcobalamin II to tissues.
Describe folate absorption
Dietary folates are converted to monoglutamate and absorbed in the jejunum. Folate stores are lower than those of B12
What are the clinical features of B12 and folate deficiency?
(1) Anaemia symptoms
(2) Weight loss, diarrhoea, infertility
(3) Sore tongue, jaundice
(4) Neurological symptoms in B12 deficiency (neuropathy, dementia)
What does a blood film show in macrocytic anaemia?
Macroovalocytes and hypersegmented neutrophils
What investigations are done for megaloblastic anaemia?
FBC: Increased MCV, possible pancytopenia
Blood film: Macroovalocytes, hypersegmented neutrophils
Serum B12 and folate levels
Auto-antibodies: Anti-parietal cell and anti-intrinsic factor
How is pernicious anaemia diagnosed?
By detecting autoantibodies against intrinsic factor
What is the management of B12 deficiency?
Intramuscular Vitamin B12 (hydroxycobalamin) injections for life.
Higher doses if neurological features are present
What is the management of folate deficiency?
Folic acid tablets (5 mg/day PO)
Supplement B12 before folate to prevent neurological complications
Why should B12 be corrected before folate?
To prevent subacute combined degeneration of the spinal cord
What biochemical cycles involve B12 and folate?
(1) Folate Cycle
= DNA/nucleoside synthesis.
(2) Methionine Cycle
= DNA modification and gene activity.
What is the role of ineffective erythropoiesis in megaloblastic anaemia?
It causes intramedullary (inside bone marrow) haemolysis, leading to fewer but larger red blood cells
What neurological symptoms are associated with B12 deficiency?
Posterior/dorsal column abnormalities
Neuropathy
Dementia
Psychiatric manifestations
What signs might be present in a patient with macrocytic anaemia?
Mild jaundice → due to ineffective erythropoiesis and intramedullary haemolysis
What drugs are associated with folate deficiency?
(1) Anticonvulsants → prevent/ control seizures
(2) + others
What findings on FBC suggest macrocytic anaemia?
Elevated MCV, macrocytes, and possible pancytopenia
What are macroovalocytes?
Abnormally large, oval-shaped red blood cells seen in macrocytic anaemia
Why might a patient with macrocytic anaemia have a sore tongue?
Due to epithelial cell changes caused by B12 or folate deficiency
What is the difference between the terms ‘megaloblastic’ and ‘macrocytic’? In which compartment would you usually expect to find megaloblasts – blood or bone marrow?
Macrocytic refers to enlarged red blood cells (MCV > 100 fL) in the blood.
Megaloblastic refers to abnormal, immature red cell precursors due to impaired DNA synthesis, seen in thebone marrow.
Megaloblasts are typically found in thebone marrow, not the blood.
Name two organ systems that can be affected by B12 deficiency, in addition to the haemopoietic system
Nervous + GI system
Why do the cells become macrocytic in B12/folate deficiency, yet there is an anaemia?
In B12/folate deficiency, impaired DNA synthesis delays cell division, leading to larger, immature red cells (macrocytosis). However, ineffective erythropoiesis and increased destruction of abnormal precursors cause anaemia
If the blood film shows polychromasia, why might the blood count analyser report a high MCV? Name two situations when this could happen
Polychromasia indicates young, larger red cells, which can cause the analyser to report a high MCV. This can occur inreticulocytosis (e.g., haemolysis) or recent blood losswith regeneration
What are common non-megaloblastoid causes of macrocytosis?
(1) Alcohol → may not associated with anaemia
(2) Liver disease → may not associated with anaemia
(3) Hypothyroidism → may not associated with anaemia
(4) Marrow failure → associated with anemia
How is the blood film useful in the diagnostic work-up of macrocytosis?
(1) Anisocytosis (size variation)
(2) polychromasia (young cells)
(3) Abnormal shapes (e.g., megaloblasts)
Aiding in diagnosing conditions likeB12/folate deficiencyor alcoholism
In pernicous anaemia how is Vitiamin B12 prescribed?
IM Hydroxycobalamin = intramuscularly
What types of anaemia can alcoholism cause?
macrocytic anaemia
fatigue, weight gain, cold intolerance, and changes in skin and hair describe what type of anaemia?
megaloblastic anaemia secondary to hypothyroidism
autoimmune conditions such as autoimmune thyroid disease, type 1 diabetes, and autoimmune gastritis describe what type of anaemia?
Megaloblastic anemia
= pernicious anaemia
A 30-year-old woman presents with a history of shortness of breath, fatigue and pale skin. She has a past medical history of Hashimoto’s hypothyroidism and type 1 diabetes. She has also noticed that her tongue is thicker than usual and she occasionally gets pins and needles in her feet. Initial blood tests reveal low haemoglobin, and low vitamin B12 and blood film reveals abnormally large and oval-shaped RBCs.
What test would confirm the diagnosis of the above condition?
Autoantibodies against intrinsic factor (IF)
= suggests pernicious anemia
A 58-year-old woman presents to her GP complaining of feeling tired and cold all the time. On further questioning, no red flag features of malignancy are reported and a PHQ-9 depression screen is negative. Clinical examination is normal.
Her full blood count returns showing a Hb of 88g/L (normal range 120 -165g/L) and MCV of 115fL (normal range 80 - 100 fL). Her liver and renal function are normal, as are her haematinics (B12 and folate). Her TSH level is raised.
What is the single most underlying cause of these blood test results? and why?
Hypothyroidism
= The raised TSH level confirms hypothyroidism
The blood film of a patient with megaloblastic anaemia typically shows what?
Hypersegmented neutrophils (neutrophils with more than 5 lobes)
A 21-year-old male presents to his general practice with a 4-week history of ‘tingling’ in his hands and fatigue. In addition, he complains of falling over at night when walking in the dark. He has no other relevant past medical history however he does admit to regular consumption of alcohol and using nitrous oxide at parties.
On general examination, conjunctival pallor and areas of hyperpigmentation are noted on the oral mucosa and hands. On neurological examination of the upper limbs, there is abnormal light touch, vibration sensation and loss of proprioception. The lower limb neurological examination shows absent reflexes and upgoing plantars.
What is the most likely cause of his symptoms? and why?
B12 deficiency
= The patient has a history of fatigue suggesting he is anaemic. The falling over at night refers to his sensory ataxia (a- loss, -taxia control). Recreational use of nitrous oxide (laughing gas) is known to deplete B12 reserves
What are the Neurological Symptoms of Macrocytic Anaemia?
(1) Paresthesias (tingling and numbness)
(2) Ataxia (impaired coordination)
(3) cognitive impairment
What are the 3 potential causes anaemia with raised MCV?
B12/folate def
Alcohol/ liver disease
Hypothyroid
What is the most common cause of hypothyroidism in the UK?
Hashimoto’s disease
A 67-year-old woman presents with fatigue, shortness of breath and paraesthesias in her hands and feet. Her physical examination reveals pallor and her neurological examination is notable for decreased vibratory sensation and proprioception.
Her lab tests show low haemoglobin, elevated mean corpuscular volume (MCV), and low serum vitamin B12 levels.
What is the underlying mechanism for the most likely diagnosis?
Autoimmune destruction of parietal cells
Define Erythroblasts
Erythroblasts are immature red blood cell precursors found in the bone marrow. They develop into mature red blood cells through a process called erythropoiesis
A 30-year-old woman presents to the clinic with worsening fatigue and breathlessness on exertion. Her husband also notes that she has become more forgetful recently. Her past medical history includes vitiligo and her sister has type 1 diabetes. On examination, she has a lemon tinge to her skin and her tongue has no papillae. Blood tests reveal a Hb of 96g/L.
What autoantibodies have the highest specificity for her underlying diagnosis?
Anti-intrinsic factor antibodies
What are the main symptoms of hypothyroidism?
Fatigue
Weight gain
Cold intolerance
Dry skin & brittle hair
Bradycardia
Constipation
Depression & slow thinking
