HAEMATOLOGY

RED BLOOD CELLS

DISORDERS

‫ميسم مؤيد علوش‬.‫د‬.‫م‬.‫أ‬

LEC.3
Assistant Professor Dr.Maysem Alwash/Hematopathologist
•OBJECTIVES:
•1-define anemia of chronic diseases and its causes.
•2-define sideroblastic anemia.
•3-1-define macrocytic anaemia and its causes.
•2-define megaloblastic anaemia and its causes
•3- know the dietary sources,daily requirement, site of
absorption and function of folate and B12 in the body.
•4-know the causes for B12 and for folate deficiency.
•5-know the clinical and laboratory features of megaloblastic
anaemia.
•6-Enumerate causes of macrocytosis other than
megaloblastic anaemia
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Anaemia of chronic disease :

One of the most common anaemias .

-It occurs patients with a variety of chronic
inflammatory and malignant diseases .

Causes include :
tuberculosis, osteomyelitis, rheumatoid
arthritis, systemic lupus erythematosus and
other connective tissue diseases ,
sarcoidosis, Crohn's disease) Carcinoma ,
lymphoma, sarcoma
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Pathogenesis:

In anemia of chronic inflammation, increased levels of

hepcidin, an acute phase reactant, decrease iron
absorption in the intestines and sequester iron in
macrophages and hepatocytes.
Bone marrow macrophages show abundant stainable
iron, whereas developing erythroblasts show
inadequate iron (iron-restricted erythropoiesis).
Inflammatory cellular products also impair the
production and action of erythropoietin. RBC life span is
shortened.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Initially Normochromic, normocytic the become
hypochromic microcytic . Total iron-binding capacit
- Both the serum iron and TIBC are reduced.
-Decreased or normal transferrin saturation
- The serum ferritin is normal or raised.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Sideroblastic anaemia
This is a refractory anaemia with hypochromic cells in the
peripheral blood and increased marrow iron.
Sideroblastic anemias develop when the synthesis of
protoporphyrin or the incorporation of iron into
protoporphyrin is blocked. The result is accumulation of iron
in the mitochondria of developing erythroblasts.
. Assistant Professor Dr.Maysem Alwash/Hematopathologist
When stained with Prussian blue, the iron
appears in deposits around the nucleus
of the developing erythroblasts in the
bone marrow. These cells are called ring
sideroblasts

Pathological ring sideroblasts

in the bone marrow.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Protoporphyrin synthesis and iron
incorporation into protoporphyrin can be
blocked when any of the enzymes of the
heme synthetic pathway are deficient or
impaired. Deficiencies of these enzymes may
be hereditary, or acquired, as in heavy metal
poisoning. The most common of the latter
conditions is lead poisoning

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Macrocytic anaemia

In macrocytic anaemia the red cells are

abnormally large.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Causes of macrocytic anaemia:

1-Megaloblastic : B12 or folate

deficiency
2- Non-megaloblastic :e.g.
alcohol, liver disease e.t.c.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

-
This is a group of anaemias in
which the erythroblasts in the bone
marrow show a characteristic
abnormality, maturation of the
nucleus being delayed relative to
that of the cytoplasm.
-
Assistant Professor Dr.Maysem Alwash/Hematopathologist
The underlying defect is defective DNA
synthesis and in clinical practice this is
usually caused by deficiency of vitamin
Bl2 or folate.

-Less commonly, due to abnormalities

of metabolism of these vitamins or other
lesions in DNA synthesis.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Vitamin B12 (B12 cobalamin)

This vitamin is derived from animal products in the

-
diet such as liver, meat, fish and dairy products
-The daily requirement is about( 2μg).
-The main loss of B12 from the body is in the bile.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

-Dietary vitamine B12 is released from
food
.- by the action of hydrolytic acid and
peptic enzymes.

Bl2 is combined with the

glycoprotein intrinsic factor (IF)
(which is synthesized by the gastric
parietal cells) to form the IF- Bl2
Assistant Professor Dr.Maysem Alwash/Hematopathologist
complex .
In the distal ileum Bl2 is absorbed and IF
destroyed.

In the plasma vitamine B12 is transported

and delivered to the cells by
transcobalamin.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Vitamine B12 is essential for two
metabolic pathways:
1. It is a coenzyme in the conversion of 5-
methyl-tetrahydrofolate to hydrofolate and the
simultaneous conversion of homocystine to
methionine ,this pathway is essential for
- synthesis of DNA and RNA.

2.It is a coenzyme for the synthesis of succinyl

coenzyme A, a necessary step in catabolism of
some fatty acids and amino acids.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Causes of vitamin B12 deficiency:

1-Nutritional
Especially vegans
2-Malabsorption
. Gastric causes
Pernicious anaemia
Congenital lack or abnormality of intrinsic factor
Total or partial gastrectomy
. Intestinal causes
Chronic tropical sprue
Ileal resection and Crohn's disease
Fish tapeworm
Assistant Professor Dr.Maysem Alwash/Hematopathologist
Pernicious anaemia:

An autoimmune attack (autoantibodies)

on the gastric mucosa leading to gastric
-
atrophy with loss of secretion of
pepsin,acid and intrinsic factor with
resultant vitamine B12 deficiency.
-Autoantibodies against gastric parietal
cells mainly or against intrinsic factor.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Pernicious
Female ,Blue eyes, Early greying anemia
-Northern European
-Familial
-
-Blood group A
-there may be associated
autoimmune disease like Vitiligo,
Myxoedema,
Hashimoto's disease and other s.
-There is also an increased
incidence of carcinoma of the
stomach

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 Folic acid is derived from
the diet. Rich dietary
-- sources include fruit and
vegetables (particularly
green vegetables) , liver
,kidney ,yeast .
-Daily requirement 100–200
μg
-Dietary folate is absorbed
Assistant Professor Dr.Maysem Alwash/Hematopathologist
maximally in the upper
jejunum.
  The folate in the body is mainly in
the form of polyglutamates .

 -The role of folate is the transfer of

single carbon groups. It is essential
for the synthesis of purines and
pyrimidines and for inteconversions
of various amino acids.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Causes of folate deficiency.

 Excess utilization
Pregnancy and lactation,
--Nutritional haemolytic anaemias ,
Especially old age, Malignant disease,
poverty, goat's milk Inflammatory diseases:
anaemia, etc. Cron's disease,
 -Malabsorption tuberculosis.
 -Drugs
Tropical sprue, gluten- Anticonvulsants,
induced enteropathy sulfasalazine
(adult or  - Liver disease,
child).
Assistant Professor Dr.Maysem Alwash/Hematopathologist alcoholism
The mechanism of megaloblastic anaemia in
vitamine B12 deficiency is actually a
functional folate deficiency .When B12 is
deficient there is reduced conversion of 5-
methyl-tetrahydrofolate to hydrofolate,the
form that can be polygutamated and can
participate in pathways leading to DNA and
RNA synthesis.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 Vitamin B12 and folate: nutritional aspects

Vitamin B12 Folate

Food sources Animal products only Many foods, especially liver,

greens and yeast

Effect of cooking Little effect Easily destroyed

Minimal adult daily requirement 2 μg 100–200 μg

Absorption Ileum Duodenum and jejunum

Site Bound to intrinsic factor, Conversion to
Mechanism absorbed by cubam methyltetrahydrofolate

Transport in plasma Most bound to haptocorrin; Weakly bound to albumin

TC essential for cell
uptake

Major intracellular Reduced polyglutamate

physiological Methyl- and derivatives
forms deoxyadenosylcobalamin
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 CLINICAL FEATURES OF
MEGALOBLASTIC ANAEMIA:

General symptoms and signs of anaemia.

-

-
Mild jaundice (lemon yellow tint) because of the excess
breakdown of haemoglobin resulting from increased
ineffective erythropoiesis in the bone marrow.

Glossitis , angular stomatitis.

-
Mild symptoms of malabsorption and loss of weight may be
Assistant Professor Dr.Maysem Alwash/Hematopathologist
present because of the epithelial abnormality.
 Megaloblastic anaemia: glossitis

-The tongue is
beefy- red and painful. -Angular cheilosis

Assistant Professor Dr.Maysem Alwash/Hematopathologist

In vitamine B12 deficiency ,
recognised neurological features
include peripheral neuropathy
,subacute combined degeneration of
the spinal cord ,dementia,psychiatric
manifestation and optic atrophy
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 A baby with neural tube
defect (spina bifida).
Folate or B12
deficiency
- in the
mother predisposes to
neural tube defect
(NTD) (anencephaly,
spina bifida or
encephalocoele) in the
fetus.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 OTHER TISSUE ABNORMALITIES

-Sterility is frequent in either sex with

severe B12 or folate deficiency.
-Macrocytosis and other morphological
abnormalities of cervical, buccal, bladder
and other epithelia occur.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 LABORATORY FINDINGS
-The anaemia is macrocytic (high MCV).
-the total white cell and platelet counts may
be moderately reduced, especially in
severely anaemic patients.
-

• The reticulocyte count is

low .
Assistant Professor Dr.Maysem Alwash/Hematopathologist
- Blood film
-The macrocytes are typically oval in shape (oval
macrocytes).
-A proportion of the neutrophils show
hypersegmented nuclei (with six or more lobes).

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 HYPERSEGMENTED NEUTROPHIL

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 The bone marrow is usually hypercellular
and the erythroblasts are large and show
failure of nuclear maturation maintaining
an open, fine, lacy primitive chromatin
pattern but normal haemoglobinization.

 Giant and abnormally shaped

metamyelocytes are characteristic.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
 BLOOD FILM

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Assistant Professor Dr.Maysem Alwash/Hematopathologist
 GIANT METAMYELOCYTES

Assistant Professor Dr.Maysem Alwash/Hematopathologist

 The serum unconjugated bilirubin and
lactate dehydrogenase (LDH) are raised.
-Assay serum B12 , and serum and red
•
cell folate to confirm diagnosis.
•
-Tests for cause of vitamin B12 or folate
deficiency.
.

Assistant Professor Dr.Maysem Alwash/Hematopathologist

Causes of macrocytosis other than
megaloblastic anaemia:

1.Alcohol 6.Aplastic anaemia

2.Liver disease 7.Pregnancy
3.Myxoedema 8.Smoking
4.Myelodysplastic 9.Reticulocytosis
syndromes 10.Myeloma .
5.Cytotoxic drugs 11.Neonatal.
Assistant Professor Dr.Maysem Alwash/Hematopathologist
• REFERENCES:
1-Rodak s hematology:
Clinical principles and Applications , 6 th edition
2-Hoffbrand s essential haematology 8th edition

Assistant Professor Dr.Maysem Alwash/Hematopathologist

• T

THANK YOU

Assistant Professor Dr.Maysem Alwash/Hematopathologist