Scribd
Upload
223 views74 pages

Megaloblastic Aneamia

The document discusses anemia, specifically megaloblastic anemia caused by vitamin B12 or folic acid deficiency. It provides details on the pathogenesis, signs and symptoms, diagnostic evaluation and comparison of vitamin B12 versus folic acid deficiency. Key points include: 1) Megaloblastic anemia is characterized by large, immature red blood cells and can be caused by deficiencies in vitamin B12 or folic acid. 2) These deficiencies impair DNA synthesis, leading to abnormal and delayed cell maturation in the bone marrow. 3) Distinguishing the two deficiencies can be done by measuring serum methylmalonic acid and homocysteine levels, which are elevated in vitamin B12 but

Uploaded by

Physiology by Dr Raghuveer
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF or read online on Scribd
223 views74 pages

Megaloblastic Aneamia

The document discusses anemia, specifically megaloblastic anemia caused by vitamin B12 or folic acid deficiency. It provides details on the pathogenesis, signs and symptoms, diagnostic evaluation and comparison of vitamin B12 versus folic acid deficiency. Key points include: 1) Megaloblastic anemia is characterized by large, immature red blood cells and can be caused by deficiencies in vitamin B12 or folic acid. 2) These deficiencies impair DNA synthesis, leading to abnormal and delayed cell maturation in the bone marrow. 3) Distinguishing the two deficiencies can be done by measuring serum methylmalonic acid and homocysteine levels, which are elevated in vitamin B12 but

Uploaded by

Physiology by Dr Raghuveer
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PPTX, PDF or read online on Scribd

Anemia

Blood
HEMATOLOGY

Anemia
Dr. Raghuveer Choudhary
Assistant Professor of
Physiology
Dr [Link] College Jodhpur
RBC disorders (Anemias) :
“Anemia is decreased red
cell mass affecting tissue
oxygenation”
Practical - Low Hb* or Low Hematocrit*
Anemia
Anemia means a decrease in hemoglobin content,
or RBCs count,
or both of them below the normal range.
Anemia leads to a decrease in blood ability to
transport oxygen to tissue cells.
Low RBC count(<4million/cmm)
Anaemia is labelled
when Hb Conc is less Gradings of Aneamia
13 gm/dl in adult males Mild Aneamia- Hb 8-10
11.5 gm/dl in adult Gm%
females Moderate Aneamia- 6-8
15 gm/dl in newborns Gm%
9.5 gm/dl at 3 month of Severe Aneamia –Hb <6
age Gm%
Anemia
Types & causes of anemia:

I-Blood loss anemia:


A-Acute blood loss anemia:
 Due to severe hemorrhage.
 Plasma volume is replaced rapidly by the fluids
present in tissue spaces.
 This leads to marked dilution of the blood.
 RBCs are replaced within 2-3 weeks.
 Sufficient iron gives normocytic cells but
insufficient iron will produce microcytic RBCs.
Anemia
Types & causes of anemia:
I-Blood loss anemia:
B-Chronic blood loss anemia:
 Due to repeated loss of small amounts of blood
over a long period e.g.:
-Gastrointestinal bleeding (peptic ulcer)
-Excessive menstruation.
-Hemorrhagic diseases.
 Due to depletion in iron stores the newly formed
RBCS are microcytic.
Anemia
Types & causes of anemia:
II-Aplastic anemia:
It results from destructione of bone marrow.
 It may result from:
1-Excessive exposure to x-rays or gamma rays.
2-Chemical toxins e.g. cancer therapy & prolonged exposure
to insecticides or benzene.
3-Invasion of bone marrow by cancer cells.
4-Following infection by hepatitis.
 Damaged bone marrow don’t produce any RBCs, so in
aplastic anemia RBCS are normocytic.
 It is associated with decrease in WBCs & platelets.
Aplastic Anemia
Fanconi anemia – congenital
Direct stem cell destruction – external radiation
Drugs - chloramphenicol, gold, sulfonamides, felbamate
Other Toxins - Solvents, degreasing agents, pesticides
Viral infection - parvovirus B19, HIV, other
Idiopathic
Anemia
Types & causes of anemia:
III-Hemolytic anemia:
It results from increased rate of destruction of RBCs inside
the cardiovascular system.
 Causes of hemolytic anemia:
A-Hereditary:
1-Membrane abnormalities.
2-Enzyme deficiency e.g. G-6-P Dehydrogenase.
3-Hemoglobin abnormalities.
B-Acquired:
1-Incompatible blood transfusion.
2-Parasitic infection e.g. malaria.
3-Toxic agents e.g. snake venom & insect poisons.
4-Thermal e.g. several burns.
Anemia
Types & causes of anemia:
IV-Dyshemopoietic anemia: Which may be due to:
1-Iron deficiency anemia.
2-Maturation failure (megaloblastic) anemia:-
a-Vitamin B12 deficiency.
b-Folic acid deficiency.
3-Anemia of endocrine disorders.
4-Nutritional anemia.
5-Anemia of renal failure.
PATHOLOGY, SYMPTOMS, AND SIGNS OF
ANEMIA
1. Morphological Approach
Red blood cell size
Microcytic (Cells Smaller than normal size
i.e. MCV< 80 fl)
Normocytic (Cells Normal sized i.e. MCV =
80-00 fl)
Macrocytic (Cells bigger than normal size
i.e. > 100 fl)
Concentration of Hb
Hyperchromic (Increased Hb
Concentration)
Normochromic (Normal Hb Concentration)
Hypochromic (Decreased Hb
Concentration- cells paler than normal)
MORPHOLOGICAL
CLASSIFICATION OF ANEMIA
Megaloblastic anemia:
Vitamin B12/Folic acid deficiency
Second most common type of anemia.
Multi System disease – All organs with increased
cell division.
Macrocytic anemia, pancytopenia.
Pernicious anaemia –
 autoimmune, Gastric atrophy, VitB12 def.
Megaloblastic anemia - Etiology
Malnutrition
Intrinsic factor Ab - Pernicious anemia
Gastrectomy, Ileal resection
Inflammatory bowel disease
Malabsorption syndromes - Sprue
Blind loop syndrome
Megalobl - Pathogenesis:
Decreased Vit B12 / Folate
Decreased DNA Synthesis
Delayed maturation of erythroblasts (Nucleus)
Increased cell size (macrocytes)
Normal hb content (Normochromia)
Decreased RBC number
Decreased WBC number (pancytopenia)
Anemia & Pancytopenia.
Macrocytic Anemia (Meg.):
[Link]
Megaloblastic Anemia :
Maturation factors
Vitamin B12 and Folic acid:
Essential for DNA synthesis (Thymidine triphosphate)
Abnormal and diminished DNA
Failure of division and maturation
Macrocytic / Megaloblastic anemia
Megaloblastic Aneamia
The presence of macro-
ovalocytes
having an MCV >115 fl,
anisocytosis, poikilocytosis
and
hypersegmented neutrophils
suggests a megaloblastic
disorder
associated with a nutritional
deficiency, i.e., vitamin B12
or
folate deficiency.
Megaloblastic Anemia
Smear
 Macro-ovalocytic
 Polychromasia
 Hypersegmented neutrophil
Other Labs
 Homocysteine – Folate def.
 Methylmalonic acid – B12 def.
 Intrinsic Factor Ab test – very
specific for pernicious anemia but
only 50% sensitive
 Parietal cell AB test – quite
sensitive (90%) but not specific
 Schilling test
The bone marrow is hypercellular,
showing evidence of abnormal
proliferation and maturation of multiple
myeloid cell lines.
These abnormalities are most evident in
the erythroid precursors with large
megaloblastic erythroblasts present in
increased numbers throughout the
marrow.
Bone Marrow Cellularity:

Normal Hypercellular Hypocellular


Similar morphologic abnormalities can be
seen in the other myeloid elements, e.g.,
large or giant metamyelocytes and other
granulocytic precursors.
This ineffective erythropoiesis is
accompanied by intramedullary
hemolysis causing an elevated
lactate dehydrogenase and indirect
bilirubin in the serum.
However, the reticulocyte count is low due
to the abnormal maturation process.
CAUSES OF MEGALOBASTIC ANEMIA
COMPARISON OF FEATURES OF VITAMIN B12 AND FOLIC ACID
DEFICIENCY STATES
Methylmalonic Acid (MMA) and
Homocysteine Serum Concentrations
Cobalamin and folate are cofactors in several
important metabolic pathways in the cell.
The hydroxylated form of cobalamin plays an
important role in the metabolism of
homocysteine and MMA. The conversion of
homocysteine to methionine requires both
vitamin B12 and folate as cofactors.
However, the metabolism of L-
methylmalonyl CoA to
succinyl CoA, an enzymatic
pathway involved in oxidative
phosphorylation reactions within
the cell, only requires
vitamin B12.
Differentiating cobalamin
deficiency from folate
deficiency by measuring
serum MMA and
homocysteine levels.
Both of these metabolites
are elevated in cobalamin
deficiency,
In folate deficiency patients, serum
homocysteine levels are markedly
increased, while serum MMA
levels are not elevated
Vitamin B12 Absorption

B12

B12 Parietal cells -


Stomach produce IF
IF

BIF
12+IF
Ileum -
IF receptors
B12
IF
B12
COMPARISON OF FEATURES OF VITAMIN B12 AND
FOLIC ACID
DEFICIENCY STATES
Thank you

You might also like