Macrocytic anaemia Flashcards
Macrocytic anaemia : Pathophysiology
1 .“macrocytic” : larger size of red blood cells
2 . “megaloblastic” : presence of abnormal megaloblasts in the bone marrow.
Megaloblastic anemia is a subtype of macrocytic anemia with a distinctive morphological pattern associated with vitamin B12 or folate deficiency.
Folate deficiency -definition
- clinical condition that occurs due to levels of folic acid (vitamin B9) being too low in the body
* Sources : leafy green vegetable and citrus fruits
Folate deficiency -pathophysiology
1 . Folate (Vit B9)
* synthesis DNA precursors for DNA replication and cell division
* via amino acid called homocysteine
2 . DNA synthesis impaired
* Folate deficiency impairs DNA synthesis and replication
* excess of homocysteine in the body.
3 . Bone marrow dysfunction
* Impaired DNA synthesis results in larger, less mature red blood cell precursors (megaloblasts) produced the bone marrow.
4 . Megaloblasts
* Less oxygen carrying capacity - Anaemia
* Increased breakdown in the spleen
Can also impact WCC and platelet cell production leading to excess precursor cells being produced
Folate deficiency - Clinical features;
- Anaemia - fatigue, pallor, palpitations
- Tongue glossitis - impaired repair and replacement of epithelial cells
- High levels of Homocysteine - homocystinuria, binds to the endothelial cells which can lead to atherosclerosis, bind to platelets making them hypercoagulable thus increasing the risk of clots
Folate deficiency - Causes;
- Increased demand : pregnancy
- Impaired absorption of Vitamin B9 - coeliac’s disease, excess alcohol
- Drugs : methotrexate, trimethoprim, phenytoin can interfere with folic acid absorption
Folate deficiency - Management
Folic acid supplementation, lifestyle advice
Vitamin B 12 deficiency - Definition
- clinical condition caused by low levels of vitamin B12/Colbamin in the blood
- Source : animal and diary products such as meat, eggs, milk
Vitamin B12 - Physiology
- Food is broken down in the stomach by enzyme pepsin to release vitamin B 12
- Parietal cells release intrinsic factor which binds to B12 to create a complex through which it passes through the intestines
- In the blood ; Transcolbamin II bind to Vitamin B12 and transfers in around the body to organs and bone marrow for RBC synthesis
- Stored : in the Liver.
Vitamin B12 anaemia - Pathophysiology
1 . DNA synthesis
* Vitamin B 12 is used to synthesis DNA
* conversion of methylmalonyl-CoA to succinyl-CoA, a critical step in the synthesis of DNA and RNA
2 .Megaloblastic changes
* Vitamin B12 deficiency impairs DNA synthesis, leading to ineffective erythropoiesis in the bone marrow.
Larger and structurally abnormal red blood cell precursors (megaloblasts).
Can also impact WCC and platelet cell production leading to excess precursor cells being produced
Vitamin B12 anaemia -Clinical features
- Anaemia - fatigue, pallor, palpitations
- Tongue glossitis - impaired repair and replacement of epithelial cells
-
High levels of methylmalonic acid -
builds up in the myelin sheath of the neurone leading to decline in neurological function
* Peripheral neuropathy
* with numbness or paraesthesia (pins and needles)
* Loss of vibration sense
* Loss of proprioception
Vitamin B12 anaemia -Causes
-
Pernicious anaemia -
* increased production of IgA antibodies against intrinsic factor/parietal cells - preventing Vitamin B12 from being absorbed
2 . Impaired absorption
* Crohn’s disease causes damage to the enterocytes in the terminal ileum preventing B12 from binding to the transcobalamin,
* Gastric bypass causes ingested food to bypass the stomach too quickly
3 . Lack of dietary intake
Vitamin B12 anaemia - Diagnosis
Lab results :
First-line investigation : Intrinsic factor antibodies
* low B12, high homocytiene/methylmalonic acid levels
* Blood smear : marcocytic erythrocytes
Vitamin B12 anaemia - Management
Intramuscular hydroxocobalamin is initially given to all patients with B12 deficiency, depending on symptoms:
* No neurological symptoms – 3 times weekly for two weeks
* Neurological symptoms – alternate days until there is no further improvement in symptom
B12/Folate deficiency : Blood smear
Megaloblastic anaemia is secondary to B12 and Folate deficiency
- Macrocytic, Megaloblastic anaemia
-
Hypersegmented neutrophils:
-Due to delayed maturation of nuclei in the bone marrow
B12 and Folate deficiency : Management
- B12 deficiency - Treated FIRST
* Neurological sx : secondary to accumulation of methlmalonic acid in the tissues due to B12 deficiency
* Giving patients folic acid when they have a B12 deficiency can lead to subacute combined degeneration of the cord, with demyelination in the spinal cord and severe neurological problems.
