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Year 2 - 2nd Semester > Megaloblastic Anaemia > Flashcards

Megaloblastic Anaemia Flashcards

1
Q

What is macrocytic anaemia?

A

Anaemia in which red blood cells have a larger-than-normal volume

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2
Q

What characterises megaloblastic anaemia?

A

Presence of erythroblasts with delayed nuclear maturation due to defective DNA synthesis in the bone marrow

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3
Q

What is the result of DNA defects in megaloblastic anaemia?

A

Reduced cell division and increased apoptosis

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4
Q

List causes of Vitamin B12 deficiency

A

Low dietary intake (e.g., veganism)

Pernicious anaemia (autoimmune destruction of gastric parietal cells)

Gastrectomy

Congenital deficiency of intrinsic factor

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5
Q

List causes of folate deficiency

A

Inadequate intake (e.g., low leafy green vegetable consumption)

Malabsorption

Excess utilization (e.g., haemolysis, pregnancy, malignancy)

Drugs (e.g., anticonvulsants)

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6
Q

What is a megaloblast?

A

An abnormally large nucleated red cell precursor with an immature nucleus

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7
Q

What happens in maturing megaloblasts in the bone marrow?

A

Division is reduced, apoptosis increases, and cytoplasmic development proceeds normally, resulting in larger cells (macrocytes)

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8
Q

Why are Vitamin B12 and folate important?

A

They are essential co-factors for DNA synthesis, nuclear maturation, DNA modification, and gene activity

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9
Q

Describe Vitamin B12 metabolism

A

(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.

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10
Q

Describe folate absorption

A

Dietary folates are converted to monoglutamate and absorbed in the jejunum. Folate stores are lower than those of B12

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11
Q

What are the clinical features of B12 and folate deficiency?

A

(1) Anaemia symptoms

(2) Weight loss, diarrhoea, infertility

(3) Sore tongue, jaundice

(4) Neurological symptoms in B12 deficiency (neuropathy, dementia)

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12
Q

What does a blood film show in macrocytic anaemia?

A

Macroovalocytes and hypersegmented neutrophils

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13
Q

What investigations are done for megaloblastic anaemia?

A

FBC: Increased MCV, possible pancytopenia

Blood film: Macroovalocytes, hypersegmented neutrophils

Serum B12 and folate levels

Auto-antibodies: Anti-parietal cell and anti-intrinsic factor

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14
Q

How is pernicious anaemia diagnosed?

A

By detecting autoantibodies against intrinsic factor

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15
Q

What is the management of B12 deficiency?

A

Intramuscular Vitamin B12 (hydroxycobalamin) injections for life.

Higher doses if neurological features are present

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16
Q

What is the management of folate deficiency?

A

Folic acid tablets (5 mg/day PO)

Supplement B12 before folate to prevent neurological complications

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17
Q

Why should B12 be corrected before folate?

A

To prevent subacute combined degeneration of the spinal cord

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18
Q

What biochemical cycles involve B12 and folate?

A

(1) Folate Cycle
= DNA/nucleoside synthesis.

(2) Methionine Cycle
= DNA modification and gene activity.

19
Q

What is the role of ineffective erythropoiesis in megaloblastic anaemia?

A

It causes intramedullary (inside bone marrow) haemolysis, leading to fewer but larger red blood cells

20
Q

What neurological symptoms are associated with B12 deficiency?

A

Posterior/dorsal column abnormalities

Neuropathy

Dementia

Psychiatric manifestations

21
Q

What signs might be present in a patient with macrocytic anaemia?

A

Mild jaundice → due to ineffective erythropoiesis and intramedullary haemolysis

22
Q

What drugs are associated with folate deficiency?

A

(1) Anticonvulsants → prevent/ control seizures
(2) Certain other medications affecting folate metabolism

23
Q

What findings on FBC suggest macrocytic anaemia?

A

Elevated MCV, macrocytes, and possible pancytopenia

24
Q

What are macroovalocytes?

A

Abnormally large, oval-shaped red blood cells seen in macrocytic anaemia

25
Q

Why might a patient with macrocytic anaemia have a sore tongue?

A

Due to epithelial cell changes caused by B12 or folate deficiency

26
Q

What is the difference between the terms ‘megaloblastic’ and ‘macrocytic’? In which compartment would you usually expect to find megaloblasts – blood or bone marrow?

A

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.

27
Q

Name two organ systems that can be affected by B12 deficiency, in addition to the haemopoietic system

A

Nervous + GI system

28
Q

Why do the cells become macrocytic in B12/folate deficiency, yet there is an anaemia?

A

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

29
Q

If the blood film shows polychromasia, why might the blood count analyser report a high MCV? Name two situations when this could happen

A

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

30
Q

What are common non-megaloblastoid causes of macrocytosis?

A

(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

31
Q

How is the blood film useful in the diagnostic work-up of macrocytosis?

A

(1) Anisocytosis (size variation)

(2) polychromasia (young cells)

(3) Abnormal shapes (e.g., megaloblasts)

Aiding in diagnosing conditions likeB12/folate deficiencyor alcoholism

32
Q

In pernicous anaemia how is Vitiamin B12 prescribed?

A

IM Hydroxycobalamin = intramuscularly

33
Q

What types of anaemia can alcoholism cause?

A

macrocytic anaemia

34
Q

fatigue, weight gain, cold intolerance, and changes in skin and hair describe what type of anaemia?

A

megaloblastic anaemia secondary to hypothyroidism

35
Q

autoimmune conditions such as autoimmune thyroid disease, type 1 diabetes, and autoimmune gastritis describe what type of anaemia?

A

Megaloblastic anemia

= pernicious anaemia

36
Q

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?

A

Autoantibodies against intrinsic factor (IF)

= suggests pernicious anemia

37
Q

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?

A

Hypothyroidism

= The raised TSH level confirms hypothyroidism

38
Q

The blood film of a patient with megaloblastic anaemia typically shows what?

A

Hypersegmented neutrophils (neutrophils with more than 5 lobes)

39
Q

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?

A

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

40
Q

What are the Neurological Symptoms of Macrocytic Anaemia?

A

(1) Paresthesias (tingling and numbness)
(2) Ataxia (impaired coordination)
(3) cognitive impairment

41
Q

What are the 3 potential causes anaemia with raised MCV?

A

B12/folate def
Alcohol/ liver disease
Hypothyroid

42
Q

What is the most common cause of hypothyroidism in the UK?

A

Hashimoto’s disease

43
Q

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?

A

Autoimmune destruction of parietal cells

44
Q

Define Erythroblasts

A

Erythroblasts are immature red blood cell precursors found in the bone marrow. They develop into mature red blood cells through a process called erythropoiesis

Year 2 - 2nd Semester (24 decks)

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