chemical pathology: hemolysis, B12 & folate Flashcards
What is folate essential for
Cell division
What is folate used for
Methyl fragment is used for:
1. Synthesis of purine & pyrimidine base for DNA/RNA synthesis forming methylene THF
2. Methylation of homocysteine to form methionine & requires vitamin B12 forming methyl THF
What is the pathway of folate use
diagram
What is the two uses of folate in CNS reactions
- Synthesis of neurotransmitters like acetylcholine
- Synthesis of phospholipids used to make myelin
What happens when folate is low
Synthesis of SAM & methionine is prioritized to maintain stable levels & prevent neurological degradation
What happens with severe primary folate deficiency
Death as cells can’t replicate
Does B12 deficiency means that there is a folate deficiency
No, but get trapped as methyl THF causing megaloblastic anemia to prevent neurological degradation
What happens when a patient with a B12 deficiency receives only folate
DNA/RNA synthesis & cell division resume using the little available methionine & SAM to make proteins & diverted form neurological pathway resulting in worsening neurological damage
What 3 cells require folate
Rapidly dividing cells:
1. Blood cell precursors in bone marrow causing microcytic anemia
2. Mucosal cells of intestine causing malabsorption
3. Rapidly growing fetus leading to NTD
What 3 populations are at risk of developing folate deficiency
- Intestinal disease, malabsorption or poor folate diet
- Pregnancy w/ poor diet & no supplemental folate (1st trimester)
- Patient on anti-folate chemotherapeutic drugs (methotrexate)
What two pathways are vitamin B12 a cofacter
- Methionine synthase
- Methylmalonyl mutase: entry of some amino acids & fatty acid degradation products into Krebs cycle
What is six enzymes that are required for digestion & absorption of vitamin B12
- Haptocorrin: salivary glycoprotein that stabilize free B12 in acidic stomach environment
- Intact gastric mucosa: HCl & pepsin production to help with release of B12 from proteins
- Intrinsic factor: binds & stabilize free B12
- Pancreatic proteases: release more B12 from proteins
- Functional distal ileum: B12 absorbed via receptors
- Transcobalamin II: plasma protein that carries B12 around body
What is the two haematological diseases of vitamin B12 deficiency
Megaloblastic anemia
Pancytopenia with hypersegmented neutrophils
What is the two neurological signs of vitamin B12 deficiency
Paraesthesias
Demyelination of spinal tract causing combined system disease
What is the two psychiatric signs of vitamin B12 deficiency
Irritable, personality change, memory impairment, dementia, depression & psychosis
What is a sign linked with vitamin B12 deficiency
Babinski reflex
What diagnostic tests are used to detect folate deficiency
Red cell folate
What diagnostic tests are used to detect B12 deficiency
s-B12 & LDH1 isoenzyme (late sign)
First sign is elevated homocystein
Accurate history taking
Gastroscopy & biopsy (check integrity)
Anti-parietal cell & -intrinsic factor antibodies (pernicious anemia)
Investigation of distal ileum for TTG antibodies & HLA for celiac disease
Trial of non-absorbed antibiotics
What is the link between megaloblastic anemia & HIV
B12 deficiency due to leaky gut syndrome affecting absorption
Lymphoproliferation requires high amount of RNA & DNA
Folate & B12 supplement leads to increased CD4 counts & improved immune response to HIV
