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SALMAN HARRISON'S > 95 - Megaloblastic Anemias > Flashcards

95 - Megaloblastic Anemias Flashcards

698-708

1
Q

What are the causes for ineffective erythropoiesis in Megaloblastic anemia? 3

A
  1. B12/ folate deficiency
  2. Idiopathic (methotrexate, cytosine arabinoside, AZT)
  3. AML / myelodysplasia
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2
Q

What is the daily requirement of B12 and how much do we store in our body?

A

1-3 ug per day, we store 2-3 Mg which is sufficient for 3-4 years.

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3
Q

Where can B12 be absorbed?

A

Passive- buccal, duodenal, ileal mucosa

Active- ileum, mediated by gastric intrinsic factor

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4
Q

What are the two cobalamin transport protein found in human serum?

A

TC (transcobalamin) 1- from specific granules n neutrophils

TC 2- from the liver, macrophages, ileu, vascular endothelium

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5
Q

What is the adult daily requirement for folic acid? how much do we store?

A

Daily requirement of 100 ug, store 10 mg, last 3-4 months

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6
Q

Where does folate get absorbed?

A

Upper small intestine.

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7
Q

How does folate travel in the serum?

A

1/3 bound to albumin, 2/3 unbound.

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8
Q

What is the biochemical function of folate?

A

Purine and pyrimidine synthesis necessary for DNA and RNA replication.

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9
Q

What is the biochemical basis of Megaloblastic anemia?

A

A defect in DNA synthesis that affect rapidly dividing cells in the bone marrow.

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10
Q

What does B12 deficiency may cause to the CNS? 2

A
  1. Bilateral peripheral neuropathy
    or
  2. Degeneration (demyelination) of the cervicle and thoracic posterior and lareral tracts of the spinal cord.
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11
Q

Name the neurological manifestation of cobalamin deficiency (8)

A
  1. Paresthesia
  2. Muscle weakness
  3. Difficulty walking
  4. Dementia
  5. Psychotic disturbances
  6. Visual impairment
  7. Loss of proprioception/ vibration
  8. Positive Romberg.
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12
Q

What are the ANS manifestation of cobalamin deficiency? 3

A
  1. Postural hypotension
  2. Impotence
  3. Incontinence.
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13
Q

What are the neurological manifestation of cobalamin deficiency in infants? (4)

A
  1. Poor brain development
  2. Feeding difficulty
  3. Lethargy
  4. Coma.
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14
Q

What is the second most likely tissue to be affected by cobalamin/folate deficiency?

A

Epithelial surfaces (mouth-glossitis, GI, UG, respiratory)-we will see increased number of multinucleate and dying cells.

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15
Q

How does folate and cobalamin deficiency affect pregnancy? (4)

A
  1. Reduce fertility in both men and women
  2. NTD
  3. Prematurity
  4. Recurrent fetal loss.
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16
Q

What are the main features of peripheral RBC in megaloblastic anemia? (3)

A
  1. Oval macrocytes with poikilocytosis
  2. High MCV (>100)
  3. Hypersegmented neutrophils
17
Q

What are the main features of cells in bone marrow with megaloblastic anemia?

A

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.

18
Q

In megaloblastic anemia, what is the reason for accumulation of unconjugated bilirubin in the plasma?

A

Death of nucleated RBC in the marrow (ineffective erythropoiesis).

19
Q

Define pernicious anemia (PA)?

A

Severe lack of intrinsic factor (IF) due to gastric atrophy

20
Q

Who is more likely to suffer from pernicious anemia? 5

A
  1. Familial history of PA
  2. AI disease (vitiligo, hypoparathyroidism, DM1)
  3. Hypogammaglobulinemia.
  4. older age
  5. women
21
Q

In PA a single gastric endoscopy and biopsy are recommended. What will we see? (5)

A 
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
22
Q

Hw does gastrectomy affect B12?

A

Leads to cobalamin deficiency. Prophylactic therapy should be commenced after surgery.

23
Q

Name the Intestinal lesions leading to malabsorption of cobalamin 7

A 
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
24
Q

What is Imerslund’s syndrome?

A

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.

25
Q

Name a parasite leading to megaloblastic anemia

A

Fish tapeworm.

26
Q

Why do we get megaloblastic anemia in severe chronic pancreatitis?

A

Lack of trypsin causing the dietary cobalamin attached to gastric non IF biners to be unavailable for absorption.

27
Q

Where do we see nutritional folate deficiency?

A

Kwashiorkor (a form of severe protein malnutrition)
Scurvy
Infants with repeated infactions
Infants feeding of solely goat milk

28
Q

What are the major causes for folate deficiency?

A

Tropical sprue
Gluten induced enteropathy
Association with dermatitis herptiformis
Intestinal megablastosis

29
Q

What is the folate requirement increase during pregnancy?

A

200-400 ug daily

30
Q

Name hemato logic disorders leading to folate deficiency

A

Chronic and AI hemolytic anemia
Sickle cell
Congenital spherocytosis

31
Q

Why do we give prophylactic folate to patients on long term dialysis?

A

Folate is losley bound and is easily removed from plasma during dialysis

32
Q

Name Antifolate drugs

A

Epileptic therapy (phenytoin, primidone)
Alcohol
Methotrexate

33
Q

What is the normal serum level of cobalamin and folate?

A

118-738 pmol/L (megaloblastic anemia will start < 74 pmol/L)

11-82 nmol/L

34
Q

What does high level of cobalamin suggest?

A

Liver/renal/myeloproliferativ disease

Breast/colon/liver cancer

35
Q

How will we diagnose PA?

A

Raised serum gastrin
Decreased pepsinogen
Gastric endoscopy

SALMAN HARRISON'S (163 decks)

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