95 - Megaloblastic Anemias Flashcards
698-708
What are the causes for ineffective erythropoiesis in Megaloblastic anemia? 3
- B12/ folate deficiency
- Idiopathic (methotrexate, cytosine arabinoside, AZT)
- AML / myelodysplasia
What is the daily requirement of B12 and how much do we store in our body?
1-3 ug per day, we store 2-3 Mg which is sufficient for 3-4 years.
Where can B12 be absorbed?
Passive- buccal, duodenal, ileal mucosa
Active- ileum, mediated by gastric intrinsic factor
What are the two cobalamin transport protein found in human serum?
TC (transcobalamin) 1- from specific granules n neutrophils
TC 2- from the liver, macrophages, ileu, vascular endothelium
What is the adult daily requirement for folic acid? how much do we store?
Daily requirement of 100 ug, store 10 mg, last 3-4 months
Where does folate get absorbed?
Upper small intestine.
How does folate travel in the serum?
1/3 bound to albumin, 2/3 unbound.
What is the biochemical function of folate?
Purine and pyrimidine synthesis necessary for DNA and RNA replication.
What is the biochemical basis of Megaloblastic anemia?
A defect in DNA synthesis that affect rapidly dividing cells in the bone marrow.
What does B12 deficiency may cause to the CNS? 2
- Bilateral peripheral neuropathy
or - Degeneration (demyelination) of the cervicle and thoracic posterior and lareral tracts of the spinal cord.
Name the neurological manifestation of cobalamin deficiency (8)
- Paresthesia
- Muscle weakness
- Difficulty walking
- Dementia
- Psychotic disturbances
- Visual impairment
- Loss of proprioception/ vibration
- Positive Romberg.
What are the ANS manifestation of cobalamin deficiency? 3
- Postural hypotension
- Impotence
- Incontinence.
What are the neurological manifestation of cobalamin deficiency in infants? (4)
- Poor brain development
- Feeding difficulty
- Lethargy
- Coma.
What is the second most likely tissue to be affected by cobalamin/folate deficiency?
Epithelial surfaces (mouth-glossitis, GI, UG, respiratory)-we will see increased number of multinucleate and dying cells.
How does folate and cobalamin deficiency affect pregnancy? (4)
- Reduce fertility in both men and women
- NTD
- Prematurity
- Recurrent fetal loss.
What are the main features of peripheral RBC in megaloblastic anemia? (3)
- Oval macrocytes with poikilocytosis
- High MCV (>100)
- Hypersegmented neutrophils
What are the main features of cells in bone marrow with megaloblastic anemia?
Marrow is hyper cellular with accumulation of primitive cells.
Cells are larger than normoblastswith eccentric lobulated nuclei or nuclear fragments
Giant and abnormally shaped metamyelocytes and enlarged hyperpolypoid megakryocytes.
In megaloblastic anemia, what is the reason for accumulation of unconjugated bilirubin in the plasma?
Death of nucleated RBC in the marrow (ineffective erythropoiesis).
Define pernicious anemia (PA)?
Severe lack of intrinsic factor (IF) due to gastric atrophy
Who is more likely to suffer from pernicious anemia? 5
- Familial history of PA
- AI disease (vitiligo, hypoparathyroidism, DM1)
- Hypogammaglobulinemia.
- older age
- women
In PA a single gastric endoscopy and biopsy are recommended. What will we see? (5)
Atrophy of all layers of the body and fundus Loss of glandular elements Absence of parietal and chief cells Replacement by mucous cells Intestinal metaplasia
Hw does gastrectomy affect B12?
Leads to cobalamin deficiency. Prophylactic therapy should be commenced after surgery.
Name the Intestinal lesions leading to malabsorption of cobalamin 7
Jejunal diverticulosis Enteroanastomosis Intestinal stricture/fistula Anatomic blind loop due to Crohn's Tuberculosis Operative procedure Ileal resection of >1.2 m of terminal ileum
What is Imerslund’s syndrome?
Autosomal recessive disease most common cause of megaloblastic anemia due to cobalamin deficiency in infancy in Western countries. 90% of patients present nonspecific proteinuria with preserved renal function.
Name a parasite leading to megaloblastic anemia
Fish tapeworm.
Why do we get megaloblastic anemia in severe chronic pancreatitis?
Lack of trypsin causing the dietary cobalamin attached to gastric non IF biners to be unavailable for absorption.
Where do we see nutritional folate deficiency?
Kwashiorkor (a form of severe protein malnutrition)
Scurvy
Infants with repeated infactions
Infants feeding of solely goat milk
What are the major causes for folate deficiency?
Tropical sprue
Gluten induced enteropathy
Association with dermatitis herptiformis
Intestinal megablastosis
What is the folate requirement increase during pregnancy?
200-400 ug daily
Name hemato logic disorders leading to folate deficiency
Chronic and AI hemolytic anemia
Sickle cell
Congenital spherocytosis
Why do we give prophylactic folate to patients on long term dialysis?
Folate is losley bound and is easily removed from plasma during dialysis
Name Antifolate drugs
Epileptic therapy (phenytoin, primidone)
Alcohol
Methotrexate
What is the normal serum level of cobalamin and folate?
118-738 pmol/L (megaloblastic anemia will start < 74 pmol/L)
11-82 nmol/L
What does high level of cobalamin suggest?
Liver/renal/myeloproliferativ disease
Breast/colon/liver cancer
How will we diagnose PA?
Raised serum gastrin
Decreased pepsinogen
Gastric endoscopy
