Megallo Flashcards
Megaloblastic anemia is characterized by RBCs that are (smaller or larger?) than normal.
Larger
In Megaloblastic anemia , There are enough of the megaloblasts.
T/F
F
also aren’t enough of them.
When RBCs aren’t produced properly, it results in megaloblastic anaemia.
Because the blood cells are too large, they may not be able to ___________________________
exit the bone marrow to enter the bloodstream and deliver oxygen.
An increase in MCV can be due to a number of reasons but careful review of the _________ and _______ can narrow the diagnostic possibilities.
patient’s history and blood smear
The differential can be divided into two broad categories based on RBC morphology.
____ macrocytosis
______ macrocytosis
Round
Oval
Round macrocytosis: as a result of abnomal ———— in the ________. Round macrocytosis
Common etiologies include:
1.________.
2. _____ Disease.
3. _____ Disease.
4. _________ (“_________ of the red cell”).
deposition of lipids
erythrocyte membrane
Alcoholism; liver; kidney; Hypothyroidism
myxedema
Oval macrocytosis (macroovalocytes) is a sign of problem with cell _________.
DNA replica tion.
Oval macrocytosis
The developing red cell has difficulty in undergoing _______ but RNA continues to be translated and transcribed into protein leading to _______ while the ______ lags behind.
Often _____________ are skipped leading to a larger than normal cell.
cell division
growth of the cytoplasm
nucleus; one or more cell division
macrocytic anaemia
MCV > _____fl
100
macrocytic anaemia
Impaired ____ formation due to lack of —— or _______ in ultimatly active form
Therefore the, _________ is delayed to that of the cytoplasm
DNA
vit.B12 or folate
maturation of nucleus
Causes of megaloblastic anaemia
The two most common causes of megaloblastic anemia are deficiencies of _________ and ______
vitamin B12 and folate.
Which is affected more by cooking?
Vitamin B12 or folate
Folate is destroyed by cooking
Little effect on vitb12
Usual therapeutic form of vitamin B12
Usual therapeutic form of folate
Hydroxycobalamin
Folic acid
Major intracellular physiological form of
Vitamin B12 and folic acid
Methy and deoxyadenosylcobalamin
Reduced polyglutamate derivatives
VITAMIN B12 AND FOLATE-
METABOLIC PATHWAYS
Both vitamin B12 and folate are key components in the synthesis of DNA due to their role in conversion of ______ and ________
uridine to thymidine.
VITAMIN B12 AND FOLATE-
METABOLIC PATHWAYS
vitamin B12 and folate role in conversion of uridine to thymidine.
When ________ loses a methyl group to form ________, vitamin B12 “_____” the methyl group to _____ converting it to _____.
Tetrahydrofolate is eventually converted to ________ which is required for thymidine synthase.
methyltetrahydrofolate
tetrahyrodrofolate; shuttles
homocysteine; methionine
methylenetetrahydrofolate
Vitamin B12 other role is a co-factor in the conversion of _________ to _______
methymalonyl-CoA to succinyl-CoA.
ABSORPTION AND METABOLISM OF
FOLATE
Folate:
The body stores very (little or large?) folate (for several _____) and maintenance of folate stores is dependent on adequate _______.
Folate is found in ____________, and ______
Folate is absorbed in the ______ and circulates in a ____ form or (loosely or tightly?) bond to ______.
Little ; weeks; dietary intake
green leafy vegetables, and liver.
small bowel ; free
Loosely ; albumin
ABSORPTION AND METABOLISM OF VITAMIN B12 AND
FOLATE
Vitamin B12:
In contrast to folate the body stores copious amounts of vitamin B12 (for ___-___).
Absorption of vitamin B12 is complex and can be interrupted by a variety of mechanisms.
Vitamin B12 is synthesized by ____ and the major dietary source is _____.
2-6 years
microbes
animal protein.
Vitamin B12
When animal protein is ingested, vitamin B12 is freed from the protein and binds to “________”.
This complex travels to the _______ where ______ destroy the _______.
This allows _______ to bind to vitamin B12.
This latest complex is absorbed only in the ___________ of ________.
Vitamin B12 binds to ____________ and is delivered to tissues
R proteins; duodenum
pancreatic enzymes; R protein
intrinsic factor (IF)
last 1-2 feet; terminal ileum
transcobalamin II
CONSEQUENCES OF VITAMIN B12 OR FOLATE
DEFICIENCY
When vitamin B12 or folate is deficient, ______ synthase function is impaired and ___ synthesis is interrupted leading to megaloblastic changes in ____________ cells.
thymidine; DNA
all rapidly dividing
CONSEQUENCES OF VITAMIN B12 OR FOLATE
DEFICIENCY
The inability to synthesized DNA leads to _________________.
There is often ________ in the marrow but most of these immature cells ____ before reaching maturity.
This process, ______________, leads to the classic biochemical picture of hemolysis-elevated ____ and indirect _____.
ineffectual erythropoiesis
erythroid hyperplasia; die
intramedullary hemolysis; LDH; bilirubinemia
The LDH level is often in the ________’s in patients with megaloblastic anemia.
1,000
In Megaloblastic Anaemia, The lack of DNA synthesis affects the neutrophils leading to nuclear ______________.
hypersegmentation
Megaloblastic Anaemia
The anemia is of (gradual or sudden?) onset and is often very (well or poorly?) tolerated despite (low or high?) hematocrits.
Often a mild _______ is seen but ________ can be severe.
Gradual; well ; low
pancytopenia; thrombocytopenia
Other rapidly dividing tissue are influenced by the megaloblastic process.
In the GI tract this can lead to ________ of the ________ and further ________.
This also leads to the classic sign of ______________.
atrophy of the luminal lining
malabsorption
tongue smoothing
AETIOLOGIES OF FOLATE
DEFICIENCY
Decreased intake- The average intake of folate in the diet is only ____-___ ug/day which is (more or less?) than the estimated daily requirement. Thus, for most people a ______ or ____ will lead to folate deficiency.
2-300; less
poor diet or decrease eating
AETIOLOGIES OF FOLATE
DEFICIENCY
Increased requirements-Patients who are _______, have _____ anemia, or ______ have increased needs for folate which can cause them to rapidly develop folate deficiency if intake is not kept up.
pregnant; hemolytic; psoriasis
AETIOLOGIES OF FOLATE
DEFICIENCY
Malabsorption
T/F
T
AETIOLOGIES OF FOLATE
DEFICIENCY
Drugs - Patient with underlying mild folate deficiency are more susceptible to trimethoprim/sulfa, ______ and _______toxicity.
_________ and ________ lead to increase consumption of folate.
pyrimethamine and methotrexate
Oral contraceptive and anticonvulsants
AETIOLOGIES OF FOLATE
DEFICIENCY
Alcohol- Alcohol affects several aspects of folate metabolism.
Alcoholics have __________. In addition, folate metabolism is interfered with leading to a functional folate deficiency. Alcoholics have an inability to ________ and can have _______ with normal ________
poor intake of folate
mobilize folate stores
depleted tissue stores
serum levels of folate
AETIOLOGIES OF VITAMIN B12 DEFICIENCY
Inadequate intake is (common or rare?) but seen in very strict _____.
Abnormal gastric events include being unable to _____________ due to lack of _______ or enzymes. This is a recently recognized group of patients which may compose a very large subset of patients with vitamin B12 deficiency. 10-30% percent of patients with ___________ will develop vitamin B12 deficiency.
Rare; vegans
dissociated vitamin B12 from food ; stomach acid
partial gastrectomy
AETIOLOGIES OF VITAMIN B12 DEFICIENCY
Deficient intrinsic factor most commonly occurs due to ___________ by ______ (_______ anemia).
Abnormal small bowel events include _____ insufficiency, ______ syndromes (bacterial absorbing vitamin B12-IF complexes) and patients infested with ___________.
destruction of parietal cells; autoantibodies
pernicious; pancreatic; blind loops ; Diphyllobothrium latum
AETIOLOGIES OF VITAMIN B12 DEFICIENCY
Abnormal mucosal events including ______ syndromes and surgical removal of the ________.
Drugs -________, ____s
malabsorption
terminal ileum.
Metformin, PPIs
Causes of B12 Deficiency
Pernicious Anaemia:
Auto antibodies to intrinsic factor in <___% cases
Blocks attachment of ____ to ___
Chronic gastritis
Autoantibodies against ______ cells
blocks attachment of ______ to _____
70
Cobalamin to IF
parietal
Cbl-IF to ileal receptors
B12 deficiency symptoms
_______(shinny tongue)
_______ gait
Anaemia and related symptoms
______ atrophy
Malabsorption _______
Atrophic glositis
Shuffling
Vaginal; Jaundice
Personality changes is a B12 deficiency symptom
T/F
T
Hypohomocysteinemia is a B12 deficiency symptom
T/F
F
Hyperhomocysteinemia
Neurologic symptoms is a _____ deficiency symptom
B12
General Morphological features of Megaloblastic anaemia
Peripheral blood finding
haemoglobin- ____eased
Haematocrit- ____eased
RBC count- ___eased
MVC - > ____fl
MCH – _____
MCHC –_______
decr
decr
decr; 100; increased; normal
General Morphological features of Megaloblastic anaemia
Peripheral blood finding
_______penia
Total WBC count –________
Platelet count –________
________penia, esp. if anaemia is severe
Recticulocyto
normal/low
normal/low
Pancyto
Peripheral smear
RBC:
______ ovalocyte
_____cytic ____chromic
in severe anaemia in addition to macrocytosis, marked ______cytosis, ____philic stipplind, _____ bodies, ______may be found.
___________erthyroblast with fine open nuclear chromatin (megaloblast) may be seen in peripheral blood in severe anaemia
Macro
macro; normo
anisiopoikilo; baso; howell jolly
cabot’s ring
Late or intermediate
________ is the earliest sign in vit. B12 def. and be detected even before the onset anaemia
Macrcytosis
Peripheral smear in Megaloblastic Anaemia
WBC:
___________ count
____________neutrophils – is one of the earliest signs of megaloblastic haemopoeisis and can be detected even in the absence of anaemia
PLATELET:
_____________ count (severe anaemia)
______ platelet may occur
Normal to reduced
Hypersegemented
Normal or decreased
Giant
Bone marrow
Markedly (hypo or hyper?) cellular marrow
Myeloid : erythroid ratio is _______ or _____
Megaloblastic erthyroid hyperplasia
Giant ___________
Hyper
decreased or reversed
metamyelocyte
MEGALOBLAST
Cell and nuclear size and amount of cytoplasm (deeply ________) are ____eased
Nuclear chromatin is _____ like or ____ (____)
Nuclear-cytoplasm ______/_____
Abnormal (small or large?) precusor (promegaloblast and earl megaloblast) are increased in bone marrow as a result of _______ arrest
Abnormal mitosis (____eased)
basophilic royal blue; incr
sieve; stippled; open
asynchrony; dissociation
Large; maturation; incr
Granulocytic series also display megaloblastic changes
Most prominent changes –___________ with ______ shaped nuclei and finer nuclear chromatin, and in band forms
Megakaryocytes are often (small or large?) with multiple nuclear ____ and ____ of cytoplasmic granules.
giant metamyelocyte; horseshoe
Large; lobes; paucity
Biochemical findings in Megaloblastic Anaemia
___ease in serum unconjugated bilirubin
____ease LDH
______ serum iron and ferritin
Incr
Incr
Normal
Diagnosing Vit. B12 & folate deficiency
measuring serum levels of B12 or folate is very adequate to diagnosis deficiency.
T/F
F
Inadequate
Diagnosing Vit. B12 & folate deficiency
It turns out that simply measuring serum levels of B12 or folate is very inadequate to diagnosis deficiency.
B12 deficiency.
- there would be elevated ______ level.
-also _______ acid accumulates.
homocysteine
methylmalonic
Both homocysteine and methylmalonic acid assays are widely available and should be the first line tests for B12 deficiency.
T/F
T
Serum folate levels are also very unreliable.
T/F
T
serum homocysteine will also accumulate in folate deficiency
T/F
T
Serum homocysteine is a more sensitive marker of tissue folate stores.
T/F
T
Management of B12 deficiency
When vit.B12 is suspected a trial of B12 is essential
Failure to respond can only be determined after careful follow-up over a period of _______, particularly if the patient is still _______
Standard therapy for all cases of vitb12 deficiency is _________ injection of B12
Usually in the form of ____
In patient with inadequate intake, may be given by ____.
Underlying conditions should be treated.
several months; non-anaemic
intramuscular; hydroxycobalamin
supplements; mouth
Vitamin B12 treatment
After initiation therapy, reticulocyte count begins to increase around ____ day –peak at ___ or ____ day gradually returns to normal by the end of ______
Hematocrit steadily rises and normalise in about ________
Blood transfusion is indicated in ______________ patients or in patients with CCF.
3rd; 6th or 7th
3rd week.
1-2month
severe anaemic symptomatic
__________________ are given to patients if B12 deficiency has not been excluded.
Why?
Both B12 and folate
This is to prevent neurological damage, e.g subacute combined degeneration of the spinal cord.
Elevated levels of homocysteine are associated with an decreased risk of atherosclerosis or venous thrombosis.
F
Increased
Increased levels of homocysteine (reflecting lack of folic acid) in pregnant women is a risk factor for _________
neural tubes defects.
Patients with alcoholism and folate deficiency can take up to _____ to respond to folate therapy.
three weeks
Which is better, IM Injection or oral B13 therapy?
Oral therapy with 1-2000 ug/day has been tested and has been found to be just as reliable as IM therapy and is becoming more widely used.
megaloblastic anemia often present with severe anemia, therefore transfusion therapy is often indicated.
T/F
With reason
F
Although patients with megaloblastic anemia often present with severe anemia, transfusion therapy is rarely indicated.
Since the anemia is rapidly reversible with therapy there is little justification for exposing the patient to the risk of transfusion except if the patient is having life- threatening symptoms such as severe ischemia.
Megaloblastic anemia maybe caused by all of the following, except:
a. Phenytoin
b. Methotrexate
c. Pyrimethamine
d. Amoxycilline
D
A 1 year old child presented with severe macrocytic anemia with sub-nephrotic range proteinuria. His vitamin B12 levels are low. The diagnosis:
a. Imerslund-Grasbeck disease
b. Thiamine deficiency
c. Roger syndrome
d. Pearson syndrome
A
The earliest specific indicator of folate deficiency is:
a. Serum folate level
b. Red cell folate level
c. Anemia
d. Elevated homocysteine level
A
Hypothyroidism causes pancytopenia
T/F
F
Hypothyroidism does not causes pancytopenia.
- The earliest neurological sign of megaloblastic anemia is:
a. Loss of position sense
b. Loss of vibration sense
c. Dysdiadochokinesia
d. Romberg’s sign positive
A
Cobalamin deficiency is characterized by all of the following, except:
a. Angular cheilitis
b. Glossitis
c. Cognitive impairment
d. Jaundice
A
That’s for iron deficiency
megaloblastic anemia May be caused by nitrous oxide inhalation
T/F
T
By causing vitamin B12 deficiency
