Sickle cell Anemia: A worldwide popular blood disorder, basically a inheritable disease. This document provides you with basic introduction to blood, Anemia its general considerations, signs and symptoms and lastly about Sickle cell Anemia in detail.

4. Blood &Its Constituents
■ Blood is a specialized fluid connective
tissue comprising of 55% fluid plasma
and 45% formed elements.
■ Plasma (55%) is a straw colored clear
liquid part of blood. It contains 91-92%
of water and 8-9% of solids. Plasma
contains ions, water, proteins,
nutrients, wastes and gases.
■ The 45% formed elements comprises of
Erythrocytes (RBC’s) , Leukocytes
(WBC’s) and Thrombocytes (Platelets).

6. Erythrocytes: Its Normal Shape & Size
■ Red Blood Cells are non-nucleated formed elements in
the blood. Red blood cells are also knows as
Erythrocytes; erythros = red.
■ Normal Shape: Disk Shaped and Biconcave (dumbbell
shaped). Central portion is thinner and Periphery is
thicker. The biconcave shape helps in equal and rapid
diffusion of oxygen and other substances inside the cell.
Also, the biconcave shape provides a larger surface
area for absorption or removal of different substances.
■ Normal Size:
Diameter: 7.2 μ (6.9 – 7.5 μ)
Thickness: 2.2-2.5 μ (periphery) and 1 μ (center)
Surface Area: 120 μ
Volume: 85 – 90 cu μ

7. Erythrocytes: Its Normal Value , Lifespan & Major
Component
■ Normal Value:- 5.5 ± 1.0 x 10²/L in
men and 4.8 ± 1.0 x 10²/L in
women.
■ Lifespan:- 120 days.
■ Major Component: Hemoglobin.
Hemoglobin consists of a basic
protein, globin and the iron-
poryphyrin complex, haem. The
Molecular weight of Hb is 68,000.
Hb Content in Man: 14.0 ± 2.5 g/dl.
Hb Content in Women: 11.5 – 16.5
g/dl.

8. Disorders Of Erythroid Series
■ The section of disorders of the
hematopoietic system is concerned with
diseases of the blood and the bone
marrow.
■ It comprises of discussion on diseases of
red blood cells, white blood cells,
platelets and bleeding disorders.
■ In this Presentation we will be dealing
with Anaemias and specifically Sickle
Cell Anaemia which forms an integral
part of Disorders of Erythroid Series.

9. Objectives:
■ Anemias- General Consideration, Pathophysiology, Clinical
Features and Classification of Anaemia.
■ Sickle Cell Anaemia: Type, Cause and Result.
■ Process Of Sickling.
■ Genetics Of Sickle Cell Anaemia.
■ Clinical Features.
■ Maxillofacial Manifestations.
■ Radiographic Features.
■ Laboratory Findings.
■ Histopathology and Treatment.

10. ANAEMIA-GENERAL CONSIDERATIONS
■ Definition: Anaemia is defined as reduced
haemoglobin concentration in blood
below the lower limit of the normal range
for the age and sex of the individual.
■ As per WHO, the lower extreme of the
normal Hb is taken as 13g/dl for adult
males and 12g/dl for adult females (11g/dl
in pregnant females). At birth, lower limit
of normal Hb level is 13g/dl whereas at 0-6
months the normal lower level is 10.5g/dl.
■ Parameter’s for determining person is
Anaemic or Not-
1. Haemoglobin value. (Major)
2. RBC count.
3. Haematocrit value- PCV
4. Absolute values- MCV, MCH and MCHC.

11. Pathophysiology Of Anaemia :-
■ Subnormal level of Haemoglobin causes lowered oxygen carrying
capacity of the blood. This in turn, initiates compensatory physiologic
adaptations such as follows:
1. Increased release of Oxygen from Haemoglobin.
2. Increased blood flow to the tissues.
3. Maintenance of the blood volume.
4. Redistribution of blood flow to maintain the cerebral blood supply.
Eventually, tissue hypoxia develops causing impaired function of the affected
tissues. Tissues with high oxygen requirement such as the heart, CNS and the
skeletal muscle during exercise, bear the brunt of clinical effects of anaemia.

12. General Clinical Features Of Anaemia:
■Symptoms: Tiredness, easy fatiguability, generalized muscular weakness,
lethargy and headache. In older patients, there may be symptoms of
cardiac failure, angina pectoris, confusion and visual disturbances.
■Signs: A few general signs common to all types of Anaemias are as under:
1. CVS- Tachycardia, collapsing pulse, congestive heart failure.
2. CNS- Faintness, Giddiness, Headache, drowsiness, numbness.
3. Reproductive Systems- Amenorrhoea, loss of libido.
4. Renal System- Mild Proteinuria, impaired concentrating capacity of the
kidney.
5. GIT- Constipation, weight loss, Nausea.

14. Classification Of Anaemia
A] PATHO-PHYSIOLOGIC CLASSIFICATION:
I. Anaemia due to increased blood loss-
a) Acute post-haemorrhagic Anaemia
b) Chronic Blood Loss
II. Anaemia’s due to impaired red blood cell production-
a) Cytoplasmic Maturation Defects- Iron deficiency anaemia and Thalassemic anaemia.
b) Nuclear Maturation Defects- Megaloblastic Anaemia (Vit. B12/folic acid deficiency.)
c) Anaemia of Chronic Disorders.
d) Bone marrow infiltration.
e) Congenital Anaemia.
III. Anaemia’s due to increased red blood cell production/ Haemolytic Anaemia’s-
a) Extrinsic red cell abnormalities.
b) Intrinsic red cell abnormalities.
B] MORPHOLOGIC CLASSIFICATION:
a) Microcytic, Hypochromic.
b) Normocytic, Hypochromic.
c) Macrocytic, Hypochromic.

15. Most common hereditary disease
of blood world wide, transmitted
through autosomal dominant trait.
Cause: A single Point mutation in
the beta globin gene alters the
structure of the haemoglobin
produced.
Result: The abnormal or sickle
haemoglobin (HbS), replaces the
normal adult haemoglobin (HbA).
Sickle Cell Anaemia

17. Process Of Sickling:
On Deoxygenation or low oxygen tension, HbS molecules begin to aggregate
and cause conversion of free flowing red blood cell cytosol to a viscous gel.
As deoxygenation continues, the aggregation increases and forms long needle
like fibres within the cell, producing the stiff, distorted sickle shaped erythrocytes.
The cumulative damage caused by repeated sickling eventually leads to
irreversible sickling of the cells.
The majority of these cells are destroyed rapidly by mononuclear phagocytes
(Extravascular Haemolysis) and remaining destroyed by intravascular haemolysis.
This haemolysis leads to sickle cell anaemia, and these cells cannot pass through
the microvasculature easily. They obstruct the microvasculature and cause tissue
hypoxia that promotes further sickling.

19. Genetics Of Sickle Cell Anaemia:
Heterozygotes/Carriers: Individuals who inherit only one copy of
the HbS allele from one parent and a copy of HbA from the other
parent. This is also known as sickle cell trait.
Genotype- HbAHbS
Feature:
Haemoglobin in these individuals contain 40% HbS and 60% HbA.
They do not show sickling, unless they are experiencing severe
hypoxia.
Homozygotes/Sufferers: Sickle cell Anaemia is seen in individuals
who inherit HbS allele from both the parents.
Genotype- HbSS
Feature:
Haemoglobin in these individuals contain 100% HbS.
They show sickling of cells and severe hypoxia.

20. Clinical Features:-
■ Fatigue, exercise intolerance, and jaundice.
■ Pain in bones, joints, abdomen and neuropathic pain.
■ A lifetime of poor oxygen delivery and microvascular
occlusion can lead to damage in a number of organs
including spleen, brains, eyes, lungs, heart, liver,
kidneys, joints, bones, penis and skin.
■ Reduced growth, increased susceptibility to infections,
Stroke, Chronic renal failure, convulsions accompany
the damaged organs.
■ Most common crisis= Vasculo-occlusive crisis including
Pain crisis, Acute Chest Syndrome involving the lungs
and typically presents a combination of fever, cough
and chest pain and pulmonary infiltrates in affected
children. This condition is an medical emergency and
requires immediate treatment.
■ Sequestration Crisis: Medical emergency associated
with SCA. Most frequently seen in children below five
years of age. It leads to sudden spleen enlargement &
shock.

21. Low Power View Of Blood Smear. High Power View Of Blood Smear.

22. Vasculo-Occlusion Of Blood Vessels

23. Maxillofacial Manifestations
■ Growth and development are often affected in individuals
with SCA.
■ Skeletal manifestations in maxillofacial region include:
1. Prominent cheekbones
2. Maxillary overgrowth
■ Occlusal manifestations include:
1. Increased overjet, overbite.
2. Increased Diastemata.
3. Delay in tooth eruption.
■ Chronic pain has been reported in TMJ.
■ Fibrous gingival enlargement.
■ No effect on dental caries.
■ Osteomyelitis is up to 200 times more common to individuals
with SCA than the ret of the population.

24. Radiographic Features
■ Osteoporosis between the apices of the posterior teeth and inferior
border of the mandible.
■ Mandible presents with a “step ladder” image on radiograph due to
increased intertrabecular spacing.
■ The vasculo-occlusive phenomenon causes a “bone within a bone”
image that represents an area of decalcification surrounded by
reactive sclerosis, demarcated from the remaining bone by a
radiolucent area.
■ Radiograph’s of Skull-
1. “Hair on end” pattern formed by perpendicular radiations
radiating outward from the inner table.
2. Diploe thickened.

26. Laboratory Findings
Laboratory Values Of Blood Indices-
■ Haemoglobin Level- 5-9g/dl
■ Haematocrit values- below 17-29%
■ Reduced ESR, elevated total leukocyte count to 12,000-20,000 cells/mm³, with a
predominant neutrophil component, increased platelet and reticulocyte count.
■ RBC count- 1,00,000 cells or less per mm³ with a decreased haemoglobin level.
Diagnostic Test:- Haemoglobin analysis by protein electrophoresis or liquid
chromatography.
A diagnosis od SCA is seen when the tests show absence of HbA in adults and a less
than 30% component of HbF in infants.
Electrophoresis can also differentiate between Sickle Cell Anaemia and Sickle Cell
Trait.
Blood Smear- Variable number of irreversibly sickled RBC, Target cells and Howell-
Jolly bodies.

27. Facts Of Life:
■ Howell-Jolly Bodies: Basophilic
nuclear remanants in circulating
erythrocytes. During maturation,
late erythroblasts normally expel
their nuclei; but, in some cases a
small portion of DNA remains.
■ Sickle Cell Trait provides a
survival advantage, against
malaria fatality, over people with
normal Hb in regions where
malaria is endemic. The Trait is
known to cause fewer deaths
due to malaria especially when P.
falciparum is the causative
organism.

29. Histo-Pathology
■ Nuclear enlargement, binucleation and an abnormal chromatin
distribution.
Treatment
• Check up every 3-12 months depending on their age.
• Adults, treated with hydroxyurea and if possible bone marrow
transplantation, which is the only curative option.

30. Reference's:-
■ Robbins Pathology- Sixth Edition
■ Medical Sembulingam-Physiology
■ Harsh Mohan – Pathology
■ Shafer’s Textbook Of Oral Pathology
■ Google