ANEMIAS

Lecturer prof. Yu.R. Kovalev

1
 DEFINITION AND CLASSIFICATION
Anemia is defined as a reduction of hemoglobin
(hematocrit) levels below the normal values for the
different age and sex groups. Hemoglobin is less than
13.5 g/dL (hematocrit < 41%) in males or less than 12
g/dL (hematocrit < 37%) in females.
CLASSIFICATION BASED ON ERYTHROCYTE
MORPHOLOGY
1. Microcytic 1. Hypochromic
2. Normocytic 2. Normochromic
3. Macrocytic 3. Hyperchromic
2
 COMMON CAUSES
1. Nutritional anemia due to deficiency of
essential nutrients or this absorption
disturbances such as iron, proteins, folates, vit C
and B12
2. Hemorrhagic anemia due to excessive
menstrual blood losses, hemorroids,
gastrointestinal carcinoma, bleeding peptic ulcer,
parasites or other causes lead to iron deficiency.
3. Hemolytic anemia
4. Hypoplastic anemia
3
5. Myelophtisic anemia
 IRON DEFICIENCY
Iron deficiency is the most common cause of anemia
worldwide. Total body iron ranges between 2 g and 4
g: approximately 50 mg/kg in men and 35 mg/kg in
women. Most (70-95%) of iron is present in
hemoglobin in circulating red blood cells. Aside
from circulating red blood cells, the major location
of iron in the body is the storage pool, as ferritin or
as hemosiderin and in macrophages. The range for
storage iron is wide (0.5 g); approximately 25% of
women have none.

4
 IRON DEFICIENCY
The average diet contains 10-15 mg of iron per day.
About 10% of this amount is absorbed. Absorption
occurs in the stomach, duodenum, and upper
jejunum. Dietary iron present as heme is efficiently
absorbed (10-20%) but nonheme iron less so (1-5%),
largely because of interference by phosphates,
tannins, and other food constituents. Small amounts
of iron — approximately 1 mg/d — are normally lost
though exfoliation of skin and mucosal cells. There
is no physiologic mechanism for increasing normal
body iron losses. In general, iron metabolism is
balanced between absorption of 1 mg/d and loss of5 1
mg/d.
 IRON DEFICIENCY
Pregnancy may also upset the iron balance, since
requirements increase to 2-5 mg of iron per day
during pregnancy and lactation.
Decreased iron absorption can on very rare
occasions cause iron deficiency and usually occurs
after gastric surgery, though concomitant bleeding
is frequent.

6
 CLINICAL FEATURES
Symptoms of iron deficiency anemia are those of the
anemia itself (easy fatigability, tachycardia,
palpitations and tachypnea on exertion). Severe
deficiency causes skin and mucosal changes,
including a smooth tongue, brittle nails, and
cheilosis. Dysphagia because of the formation of
esophageal webs (Plummer-Vinson syndrome) also
occurs. Many iron-deficient patients develop pica,
craving for specific foods.

7
 CLINICAL FEATURES
Pallor with greenish shade.
Stomatitis angularis
Pica chlorotica: the
patient eats Inedible
substances as earth,
clay, lime
(geophagia), soap,
chalk, plaster a.o.
8
 CLINICAL FEATURES

Brittle spoon-shaped nails esophageal webs

(koilonychia). sideropenic disphagia
9
(Plummer-Vinson’s syndrom)
 LABORATORY INDICES
MCV: mean corpuscular volume gives the
average size of red cells

hematocrite
MCV = ------------------------------- (fl or 10-15 L)
RBC count

Normal values: 80 – 100 fl

< 80 microcytosis; > 100 macrocytosis 10
 LABORATORY INDICES
MCH: mean corpuscular hemoglobin

hemoglobin
MCH = ------------------------------- (pg or 10-12 g)
RBC count

Normal values: 24 – 34 pg
< 24 – hypochromia; > 34 hyperchromia
11
 LABORATORY INDICES
NORMAL VALUES
Iron 9 – 31 micromol/l
Iron-binding capacity 45 – 80 micromol/l
Ferritin male: 16 – 300 ng/l
female: 4 – 160 ng/l
Transferrin 1,9 – 3,75 g/l

12
 LABORATORY FINDINGS
In the early stages, the MCV and MCH remain
normal. Subsequently, they fall and the blood smear
shows hypochromic microcytic cells. With further
progression, anisocytosis (variations in red blood
cell size) and poikilocytosis (variation in shape of
red cells) develop.
The platelet count is commonly increased.
Bone marrow shows nonrmoblaslic hyperplasia with
absence of stainable iron. It is not necessary to do
bone marrow examination in all cases of iron
deficiency anaemia.
13
 LABORATORY FINDINGS

Hypochromic
microcytic cells Normal
14
 LABORATORY FINDINGS
Iron deficiency: the serum ferritin will become
abnormally low. A ferritin value less than 30 µ g/L is
a highly reliable indicator of iron deficiency. The
serum total iron-binding capacity (TIBC) rises.
Serum iron values decline.

15
 DIAGNOSIS
Important part of diagnosis is identification of
the cause — especially a source of occult
blood loss:
•Bleeding in anamnesis
•Endoscopy or barium-contrast X-ray
investigation of gastrointestinal tract
•Feces to occult blood
•Gynecologist consultation
16
 MANAGMENT

The better treatment is ferrous sulfate, 325 mg

three times daily, which provides 180 mg of
iron daily of which up to 10 mg is absorbed.
An appropriate response is a return of the
hematocrit level halfway toward normal within
3 weeks with full return to baseline after 2
months. Reticulocytosis will increase within
5-7 days.

17
 MANAGMENT
Iron therapy should continue for 3-6 months
after restoration of normal hematologic
values in order to replenish iron stores.
Because of the possibility of complications
(anaphylactic reactions, hemosiderosis) parenteral
iron therapy should be used only in cases of
persistent anemia after a reasonable course of oral
therapy. But newer iron complexes have lower rate
of adverse effects (iron gluconat).

18
 VITAMIN B12 DEFICIENCY
All vitamin B12 comes from the diet and is present in
all foods of animal origin. The daily absorption of
vitamin B12 is 5 mg.
After being ingested, vitamin B12 is bound to
intrinsic factor, a protein secreted by gastric parietal
cells. The vitamin B12-intrinsic factor complex
travels through the intestine and is absorbed in the
terminal ileum by cells with specific receptors for the
complex. It is then transported through plasma by
transport proteins and stored in the liver. The liver
contains 2-5 mg of stored vitamin B12. So vitamin
B12 deficiency develops more than 3 years after
vitamin B12 absorbtion ceases. 19
 VITAMIN B12 DEFICIENCY
Vitamin B12 belongs to the family of cobalamins and
serves as a cofactor for two important reactions in
humans. As methylcobalamin, it is a cofactor for
methionine synthetase in the conversion of
homocysteine to methionine and as
adenosylcobalamin for the conversion of
methylmalonyl-CoA to succinyl-CoA.

20
 VITAMIN B12 DEFICIENCY
The disturb of the first reaction leads to defect in DNA
synthesis (megaloblastic anemia, affection of mucosae)
and high level of plasma homocysteine (risk factor for
thrombosis). There are also deficiency of cholin and
phospholipids (nervous system damage).
If the second reaction impaired the metabolism of fatty
acids changes and toxic methylmalonyl and propionyl
CoA accumulate (neurologic complications).

21
CAUSES OF VITAMIN B12 DEFICIENCY
• Dietary deficiency (rare)
• Decreased production of intrinsic factor
Pernicious anemia
Gastrectomy
• Competition for vitamin B12 in gut
Blind loop syndrome
Fish tapeworm (Diphyllobothrium latum)
• Pancreatic insufficiency
• Decreased ileal absorbtion of vitamin B12
Resection of the ileum
Crohn’s disease
• Strict vegetarians
• Transcobalamin II deficiency (rare) 22
 PERNICIOUS ANEMIA
PA is the most common cause of cobalamine
deficiency from either atrophy of the gastric
mucosae or autoimmune destruction of
parietal cells.
There are antiparietal cells antibodies directed
ageinst H, K-ATPase and anti-IF antibodies.
The incindence of PA is increased in patients
with some deseases is thought of immune
origin: Grave’s deseae, myxedema, thyroiditis,
adrenocortical insufficiency a.o.
23
 CLINICAL FEATURES
PA is the desease of the elderly and rare under 30.
B12 deficiency produces changes in mucosal cells,
leading to glossitis, as well as other gastrointestinal
disturbances, such as anorexia and diarrhea. The
spleen is palpable in 20% of patients.
Neurologic syndrome. The posterior columns
impaired (demyelination): paresthesias, difficulty
with balance, decreased vibration sense, neurogenic
bladder. May be dementia and other
neuropsychiatric changes.
24
 CLINICAL FEATURES
Patients are usually pale
and may be mildly icteric,
because of anemia and
hemolysis of hemoglobin-
containing megaloblasts in
bone marrow.

Hunter’s glossitis; then

papillae are atrophied and
tongue becomes smooth
and glazed. 25
CLINICAL FEATURES

Posterior columns
impairing
26
 LABORATORY FINDINGS
The hallmark of vitamin B12 deficiency is
megaloblastic anemia. The anemia may be severe,
with hematocrits as low as 10-15%, and hemoglobine
2,0 – 4,0 g/dl. The MCV is usually strikingly elevated,
between 110 and 140 fL. There are anisocytosis and
poikilocytosis, nuclear material in erythrocytes:
Howel-Jolly bodies and Cabot's rings.

27
 LABORATORY FINDINGS
A characteristic finding is the macroovalocyte. The
neutrophils are hypersegmented. Typical features
include a mean lobe count greater than four or the
finding of six-lobed neutrophils. The reticulocyte
count is reduced. Because vitamin B12 deficiency
affects all hematopoietic cell lines, in severe cases
the white blood cell count and the platelet count are
reduced, and pancytopenia is present.

28
LABORATORY FINDINGS

normal

29
 LABORATORY FINDINGS
Bone marrow morphology is characteristically
abnormal. Megaloblastic changes (abnormally large
cell size and asynchronous maturation of the
nucleus and cytoplasm) is present. The marrow
cellularity is often increased, but production of red
blood cells is increased (ineffective erythropoesis).
The diagnosis of vitamin B12 deficiency is made by
finding an abnormally low vitamin B12 serum level.
Whereas the normal vitamin B12 level is 150-350
pg/mL, most patients with overt vitamin B12
deficiency will have serum levels less than 100 30
pg/mL.
 MANAGMENT

Patients with pernicious anemia are often treated

with parenteral therapy. Intramuscular injections of
200 – 400 µ g of vitamin B12 are adequate for each
dose. Replacement is usually given daily for the first
week, weekly for the first month, and then 100 µ g
monthly for life.
Patients respond to therapy with an immediate
improvement in their sense of well-being. A brisk
reticulocytosis occurs in 5-7 days, and the
hematologic picture normalizes in 2 months.
31