Unit 9: Major Pernicious Anemia Flashcards
Why does anemia cause tiredness?
Low arterial O2
Less oxygen perfusion to tissue, reduced respiratory rate, leads to a lower metabolic rate.
Causing fatigue
Why does PA cause breathlessness?
Low arterial O2. - detected by peripheral chemoreceptors. (aortic arch and vagus nerve, carotid bodies and glassopharangeal nerve)
Severe anemia may cause elevated CO2 - detected by central chemoreceptors
Signals are transmitted along afferent neurons to the medulla oblongata
Acts on the respiratory control centre, result in activation of the SNS, signals sent along the phrenic nerves and intercostal nerves to increase rate of respiration.
What is the life cycle of a red blood cell?
- haemopoietic stem cell
- Common myeloid progenitor (CFU-GEMM)
- Erythroid progenitors BFU-E and CFU-E
- Early pro-erythroblast - ribosome manufacturing
- Late pro-erythroblast - Hb accumulation
- Normoblast
- Reticulocyte
- Erythrocyte
This process is guided by growth factors.
Process occurs in the red bone marrow. Stimulates by EPO production in the kidney due to hypoxemia.
How does VitB12 deficiency affect blood cell development?
VitB12 is required for proliferation of erythroblasts, as used in DNA production.
Without it can’t produce mature erythrocytes, results in megaloblastic anemia.
Also affects DNA production in wbc - resulting in hypersegmented nuclei in neutrophils
Why in a suspected anemia case would a doctor ask about medication?
Drugs associated with anemia:
- metformin
- cephlasporins, penicillin and levofloxacin - immune hemolyitic
- NSAIDs (bleeding in GI)
- acetaminophen
- methyldopa ( to treat high BP) in an immune hemolyitic
- levodopa (to treat parkinsons) causes microcytic due to a vitamin B6 deficiency.
Why do you check for signs of dehydration in differential diagnosis of PA?
Dehydration may be present due to rapid reduction in blood volume, such as GI bleeding which can also cause normocytic anemia.
Dehydration can also cause microcytic anemia with reduced Hb, do to waters role in Hb production
Dehydration - may be sign of diabetes - differential diagnosis for tiredness
Why do you check for jaundice in a differential diagnosis for PA?
Jaundice - accumulation of bilirubin
Can indicate a haemolytic anaemia
Why did the doctor check fingernails in differential diagnosis for PA?
Clubbing fingernails - indicate GI malabsorption - indicate atrophic gastritis - related to cause of B12 deficiency.
Iron deficiency anaemia would present with pale and spoon shaped nails (koilnychia)
Why did the doctor check her tongue in differential diagnosis of PA?
Look for signs of glossitis - indicates of vitamin B12 deficiency, PA - low oxygen flow to tongue, results in atrophic gastritis
Why did the doctor check for gait and recent falls in a differential diagnosis of PA?
Fatigue may indicate stroke, this can be assessed by watching for difficult in limb movement.
Anaemia is a risk factor for falls is assessing this risk.
Assessing for brain injury, mental activity takes more energy can result in rapid mental fatigue.
Describe how PA may present on a full blood count.
Increased MCV
Decreased or same serum Vitamin B12
Decreased wbcs and platelets
Decreased reticulocyte count
Haemoglobin decrease
Haematocrit decreased
MCH - decreased
LDH and bilirubin increase - as immature RBCs are destroyed
What additional blood test is normally done to confirm a PA diagnosis?
MMA and HC levels may be elevated
Intrinsic factor auto-antibodies or/and parietal cell auto-antibodies may be present.
If auto-antibodies against parietal cells are identified may run an addition Intrinsic Factor assay to identify the level still being produced.
How does the immune system produce antibodies against patients own parietal cells and intrinsic factor?
Autoimmune condition
Managed to evade central and peripheral tolerance
Apoptotic components of parietal cell cleared by a macrophage and presented as foreign on MHC2 to T cell in the lymph node.
Is a complex autoimmune disease, is influenced by both genetic and environmental factors.
Why does anti-parietal cell antibodies lead to a deficiency in VitB12?
Lack of intrinsic factor secretion from parietal cells
Why do anti-intrinsic factor antibodies lead to a deficiency in VitB12?
Lack of intrinsic factor - less binds to VitB12 - decreased ability of VitB12 to be absorbed in the ileum as unable to bind to IF receptor
Why is hydroxocabalamin given more frequently during the first two weeks of treatment, then reduced?
Higher doses first to increase deficiency to normal level
Dose can then be decreased as simply need to maintain level.
Why is hydroxocabalamin given IM rather than orally in treatment of autoimmune PA?
Most cases of PA are unable to absorb VitB12, and already have sufficient B12 in their diet - orally administered B12 would also not be absorbed
Must be given in a way that can be quickly absorbed into blood stream to bypass the absorption process in the ileum.
What health problems does VitB12 deficiency pause a risk factor for?
Anaemia
GIT symptoms - associated with chronic atrophic gastritis such as vomiting, diahorrea, abdominal pain, weight loss
Neurological symptoms - loss of memory, loss of cognitive reasoning and changes in behaviour.
What are some of the potential health problems for a menopausal woman?
Osteoporosis - lack of oesotrgen results in lack of bone mineral density.
UTIs - change in oesotrgen alters vaginal walls can affect normal microflora
Cardiovascular disease - increased risk of atherosclerosis.
Why does vitamin B12 deficiency affect the nervous system?
Deficiency results in eegernateion of myelin sheath and atrophy of neural tissue
Due to accumulation of methylmalonate (abnormal lipid in the neurons) and lack of myelin sheath synthesis .
Mainly affects sensory nerves resulting in peripheral neuropathy and cognitive changes.
VitB12 aids the conversion of methymalonyl coenzyme A to succinyl coenzyme A.
Deficiency leads to a build up methylmalonic acid.
This causes the development of abnormal fatty acids in neuronal lipids
Leads to degeneration of myelin sheath, hence spinal cord.