25- NA: Vitamin B12 deficiency

Question 1

importance of vitamin B12 (2)

Answer 1

essential co-factor for DNA methylation and cell metabolism

fatty acid metabolism

Question 2

how is vitamin B12 important for fatty acid metabolism?

Answer 2

important for the intracellular conversion of methylmalonyl-CoA to succinyl-CoA

for the two active co-enzymes involved in the conversion are derived from vitamin B12

Question 3

effect of vitamin B12 deficiency on fatty acid metabolism?

Answer 3

vitamin B12 deficiency impairs synthesis of the coenzymes

leads to accumulation of MMA (methylmalonic acid) and homocysteine

Question 4

list the two methods of vitamin B12 deficiency testing

Answer 4

MMA/ methylmalonic acid testing
homocysteine testing

Question 5

describe MMA testing and why it’s used

Answer 5

MMA is a metabolic by-product that accumulates when there’s a vitamin B12 deficiency

elevated MMA = indicates impaired vitamin B12 metabolism/ deficiency

more reliable than serum B12 in diagnosing deficiency

Question 6

describe homocysteine testing and why it’s used

Answer 6

homocysteine requires vitamins B12, B6 and folate in its conversion to methionine, an essential amino acid

elevated homocysteine indicates deficiencies in the vitamins, including B12

Question 7

recommended intake of B12?

Answer 7

approx 1.5mcg a day

Question 8

describe how vitamin B12 is absorbed

Answer 8

intrinsic factor is produced by gastric parietal cells, produces a complex with vitamin B12 in the stomach to protect it from degrading against stomach acidity

IF-B12 travels to the terminal ileum, where the complex is recognised by receptors that facilitate the absorption of B12 into intestinal enterocytes

B12 is absorbed and binds primary to transcobalamin II to be transported to various tissues, sometimes is transported to transcobalamin I

Question 9

main transport protein for B12?

Answer 9

transcobalamin II (TCII)

Question 10

what is intrinsic factor?

Answer 10

a glycoprotein produced by gastric parietal cells - forms a complex with B12 in the stomach and takes it to the small intestine for transportation into circulation

Question 11

list the medicines/ substances that can cause B12 deficiency

Answer 11

alcohol
nitric oxide - e.g. laughing gas
proton pump inhibitors/ H2 receptor agonists
metformin - treats type 2 diabetes

Question 12

list the conditions that can impair B12 absorption leading to deficiency

Answer 12

pernicious anaemia - autoimmune condition

gastrectomy or ileal resection - affects production of IF from gastric cells, or B12 absoprtion from ileum

zollinger-ellison syndrome

parasites

Question 13

what is Zollinger-Ellison syndrome?

Answer 13

gastrin-secreting tumour/ hyperplasia of islet cells in pancreas causes overproduction of gastric acid

Question 14

list the two potential congenital causes of B12 deficiency

Answer 14

intrinsic factor receptor deficiency

cobalamin mutation in CG1 gene

Question 15

list the two potential causes of vitamin B12 deficiency from decreased intake

Answer 15

malnutrition

vegan diet

Question 16

what is pernicious anaemia? what are the causes of pernicious anaemia?

Answer 16

pernicious anaemia = autoimmune disorder characterised by the lack of intrinsic factor

causes:
1. antibodies against gastric parietal cells - affects production of IF
2. antibodies against intrinsic factor - destroys IF

both affect IF absorbing B12 from the stomach, cause deficiency

Question 17

what is the treatment for pernicious anaemia?

Answer 17

changes in dietary intake and oral supplements are futile as it’s the body’s absorption via IF that’s affected

1. B12 injections
2. high-dose oral supplements if patient has maintained a degree/proportion of absorption

Question 18

expected haematological results of B12 deficiency - MCV, Hb, reticulocyte count, LDH, BMAT and MMA results?

Answer 18

MCV = normal or raised

Hb = normal or low

reticulocyte count = low

LDH = raised

MMA = high/increased

Question 19

describe the expected blood film results for B12 deficiency

Answer 19

B12 deficiency leads to megaloblastic anaemia

macrocytes
ovalocytes
hyper-segmented neutrophils - multi-lobed nucleus has more than 3-5 lobes

Question 20

describe the results of a BMAT test from B12 deficiency? what is a BMAT test?

Answer 20

BMAT = bone marrow adipose tissue; refers to the fat cells in bone marrow

results: hypercellular megaloblastic giant metamyelocytes

• bone marrow has an increased number of cells = hypercellular
• abnormalities in size/shape of megaloblasts, RBC precursors
• giant immature WBCs/ metamyelocytes

Question 21

how does intramedullary haemolysis relate to raised LDH in B12 deficiency?

Answer 21

intramedullary haemolysis = destruction of BCs within bone marrow

occurs due to conditions affecting bone marrow or abnormal erythropoiesis - B12 needed for DNA synthesis and maturation for RBCs

Question 22

what is megaloblastic anaemia?

Answer 22

production of large immature RBCs/ megaloblasts

leads to anaemia due to decreased oxygen carrying capacity of blood

Question 23

list the clinical consequences of B12 deficiency - neurological, cardiac, oral, haematological, other?

Answer 23

neurological = cognitive impairment, depression, psychosis, SACDC (sensory changes, ataxia and spasticity)

cardiac = cardiac myopathy affecting the structure and function of the heart

oral = inflammation of the tongue, taste impairment

infertility

haematological = pancytopenia, megablastomic anaemia, macrocytic and ovalocytes, hypersegmented neutrophils

Question 24

differentiate megaloblastic and non-megaloblastic anaemia

Answer 24

megaloblastic
- low reticulocyte count from errors in DNA synthesis and replication in precursor cells
- caused by vitamin B12 or folate deficiency, or anything interfering with their metabolism
- macrocytic, oval-shaped RBCs & hyper-segmented/lobed neutrophils with more than 3-5 lobes

non-megaloblastic:
- high reticulocyte count = reticulocytes bigger than mature RBCs, increases average cell size
- causes: alcoholism, hypothyroidism, liver disease, myelodysplasia, haemolysis leading to reticulocytosis