Introduction Blood –composition -function -volume -physical properties plasma Plasma proteins Hematopoiesis Erythrocytes Blood indices Variations in RBC count, shape, size

1. Blood Physiology
BY,
DR ASHWITHA BELLUDI
ASST PROFESSOR
DEPT OF PEDODONTICS

2. contents
• Introduction
• Blood –composition
-function
-volume
-physical properties
• plasma
• Plasma proteins
• Hematopoiesis
• Erythrocytes
• Blood indices
• Variations in RBC count, shape, size

3. The average adult has
about five litres of blood
living inside of their body,
coursing through their
vessels, delivering
essential elements, and
removing harmful wastes.

4. Bloodisconsideredas
FLUID of LIFE
HEALTH
GROWTH

5. Blood is the only fluid tissue.
 Blood is a complex connective tissue in which
living cells, the formed elements, are
suspended in the nonliving fluid called plasma.
Blood

6. Functions of blood`
• RESPIRATORY FUNCTION: Transport oxygen to
the tissues and co2 to the lungs. Thus helps in
respiration.
• NUTRIENT FUNCTION: Distributes various nutrients to
all parts of the body.
• EXCRETORY FUNCTION: Helps the process of
excretion by transporting waste materials to the
organs of excretion.

7. • REGULATION OF ACID BASE BALANCE: Helps to
maintain acid-base balance
• REGULATION OF BODY TEMPERATURE:
The volume of blood is large and the specific heat of
blood is high. Therefore, a good deal amount of heat
(calories) can be absorbed or lost by the blood
without a great rise or loss in the temperature
• STORAGE FUNCTION: Acts as storage medium for
various essential elements, water, electrolytes and drugs

8. Defensive action : Blood acts as a great defensive
mechanism in two ways
1. The white cells due to their phagocyte properties
engulf bacteria and foreign particles.
2. It develops antibodies which combat toxic agents.
By the property of coagulation it guards against
hemorrhage

9. Blood volume
• The total amount of blood present in the
body.
• The average volume in males- 5 ltr
females- 4.5 ltr
newborn- 450ml
• Blood volume= plasma volume+ cell
volume

10. Variation of blood volume
• In children the volume is comparatively more
than adults.
• The males have higher volumes than
females.
• It increases in pregnancy by 20 – 30%
• In high altitude increases due to rise in RBC
count.
• Decreases in prolonged standing.
• Pathologic rise is seen in congestive cardiac
failure, hyperthyroidism, polycythaemia .

11. Blood composition
• Blood consists of
liquid plasma
(volume-55-60%)
formed elements (cells)
(volume-40-45%)

12. Blood
• Formed elements include
Erythrocytes (red blood cells);
Leukocytes (white blood cells);
Thrombocytes (platelets)

14. Hematocrit

15. Hematocrit
• If a portion of blood is centrifuged or allowed to stand
for a sufficient long time, it will be found that the
blood cells will settle towards the bottom of the test
tube while the plasma remains on top.
• By this means the percentage of blood cells in whole
blood can be determined.

16. Hematocrit
The hematocrit , also
known as packed cell
volume (PCV)
or erythrocyte volume
fraction (EVF), is the
volume percentage (%)
of red blood cells in the
blood. It is normally about
40-48% for men and
36-42% for women

17. Overview: Composition of Blood
• Hematocrit – measure of % RBC
– Males: 47% ± 5%
– Females: 42% ± 5%
Figure 17.1

18. Figure 19.1b
Composition of Whole Blood

19. Figure 19.1c
Composition of Whole Blood

20. Blood composition
55% Plasma (fluid matrix of water, salts, proteins, etc.)
45% Cellular elements:
 Red Blood Cells (RBCs): 5-6 million RBCs/ml of blood. Contain
hemoglobin which transport oxygen and CO2.
 White Blood Cells (WBCs): 5,000-10,000 WBCs/ml of blood.
Play an essential role in immunity and defense. Include:
 Lymphocytes: T cells and B cells
 Macrophages: (phagocytes)
 Granulocytes: Neutrophils, basophils, and eosinophils.
 Platelets: Cellular fragments, 250,000- 400,000/ml of blood.
Important in blood clotting.

21. • Staining of blood cells
– Acidic dye – eosin – stains pink
– Basic dye – methylene blue – stains blue and purple

22. Wright’s Stain
Figure 17.2b

23. Human blood smear

24. Physical Characteristics and Volume
Sticky and metallic tasting…
Color: Scarlet = O2 rich; Dull red = O2 poor
Heavier than H2O; 5X thicker
pH = 7.35 - 7.45
Temp = 38ºC or 100.4ºF (higher than normal)
8% body weight; 5 - 6 liters

25. PLASMA

26. Blood plasma
 The main (inorganic) mineral components :
(0.9-1.5 %):
Cations : Anions :
 Sodium (Na+), Chlorides(Cl⁻)
 Potassium (K+), Phosphates (PO4⁻)
 Calcium (Ca++), Bicarbonates(HCO3⁻)
 Magnesium (Mg++)

27. Blood plasma
 A solution with the same salt concentration 0.9% is
named isotonic solution.
 If salt concentration more than 0.9% such solution is
called hypertonic.
 If salt concentration is less than 0.9% – hypotonic
solution.

28. Blood plasma
 The organic components of plasma include :
proteins
lipids
carbohydrates

29. PLASMA PROTEINS
NORMAL VALUES
TOTAL PROTEINS - 7.3 gm% (6.4 to 8.3gm%)
Serum albumin - 4.7 gm%
Serum globulin - 2.3 gm%
Fibrinogen - 0.3 gm%
Prothrombin – 0.1gm%
A-G Ratio: 1.5:1

30. Plasma proteins and their role
 Plasma proteins include :
 Albumin - mol. Wt 69,000 .HALF LIFE OF 19days
(65-85 g/l) Regulation of oncotic pressure
Regulation of pH
 Recent studies show that serum albumin is not a single
pure entity. It is a mixture of several albumins.
 Isoelectric pH is 4.7.
 The albumin molecule is an ellipsoid made up of a single
polypeptide chain. It is smaller and more compact than
other plasma proteins.
 It is heat – coagulable

31.  Globulin - α
(28 g/l) β - Transportation
γ - Defense
Are elongated in shape having a molecular weight, varying from
90, 000 to 156,000.
It is insoluble in distilled water, but soluble in salt solutions.
It is coagulated at about 70C.
Globulin, like albumin, is also a mixture of several globulins.
It is formed partly by liver but mainly by reticulo endothelial
system

32.  By means of Electrophoresis serum globulin has been
separated into three fractions.
 1 and 2 globulin’s molecular weigh ranges from 41,000 to
200,000 , Isoelectric pH 5.1
 1 globulin’s consists of two fractions.
1.one fraction combines with bilirubin
2.Another fraction helps in the carriage of lipids, steroids
and glycoproteins.
 2 globulin’s consists of 2-macroglobulins,
mucoproteins, ceruloplasmin , hepatoglobulins – the latter
combine with free hemoglobin in the plasma.

33.   - Globulin molecular weigh ranging from
90,000 to 13,00,000 isoelectric pH 5.6 .
  - Lipoprotein helps in the carriage of lipid,
steroid, carotene & also helps in the transport of
iron e.g, transferin (siderophilin)
 Prothrombin is a  - globulin.
  globulin – molecular weight ranging from
150,000 to 190,000 isoelectric pH 6.0 . Antibodies
belong to this class

34.  Fibrinogen - Blood clotting (haemostasis)
(3 g/l)
 It is globulin in nature, molecular weight 341,000
isoelectric pH 5.8 .
 It is coagulated at about 56C and precipitated by one –
fifth saturation with ammonium sulphate and half
saturation with NaCl .
 It is insoluble in distilled water.
 It is distinguished from other plasma proteins by its
property of clotting during which fibrinogen is
converted into fibrin.

35. Lipids and carbohydrates in plasma
 The major plasma carbohydrate is glucose
(3.3-5.5 mmol/L) .
 Plasma normally contains varying amounts of
hormones, enzymes, pigments, and vitamins.
 The composition of plasma varies with the
body’s activity and different physiological
states.

36. Functions of plasma proteins
 Essential for blood clotting. Fibrinogen and prothrombin are essential
for coagulation of blood
 Maintain colloidal osmotic pressure of blood and aid in
regulating the distribution of fluid between blood and tissues.
Albumin having the smallest and the most symmetrical molecule
exerts the maximum osmotic pressure. Osmotic pressure depends
upon a number of molecules in the solution. Albumin has a
considerably smaller molecular weight than globulin and comprises 52
% of plasma protein. The total colloidal O.P varies from 25 to 30 mm of
Hg and albumin is responsible for 80% of it.
 Maintain viscosity and blood pressure. The proteins of plasma
mainly globulin’s due to larger molecules and asymmetry of their
structure are responsible to some extent for the viscosity. it is an
important factor in maintaining blood pressure.

37.  Concerned with erythrocyte sedimentation rate (ESR).
The plasma proteins exert a great influence upon the
suspension stability of blood. This is chiefly dependent on
fibrinogen. An increase in fibrinogen speeds rouleaux
formation.
 Act as buffers. They act as buffers in maintaining acid –
base balance
 Act as a protein reserve. serve as a store house of
proteins from which the tissue can draw during starvation
or in inadequate protein diet.
 Help CO2 carriage by forming carbamino proteins

38.  Form trephones. The leucocytes prepare substance from
the plasma proteins called trephones, which are necessary
for the nourishment of the tissue cells grown in culture.
 Antibodies. The antibodies being  - globulin in nature,
defense body against infection.
 Help transport of certain substance in blood. Plasma
proteins combine with certain substance and help to carry
them in blood stream.
 Some hormones, enzyme are part of globulin fraction of
plasma proteins
 Iron (transferrin) and copper (ceruloplasmin) are bound to
globulin fractions.

39. ORIGIN OF PLASMA PROTEINS
• In the embryo, the primitive plasma and the plasma proteins
are produced by secretion of the mesenchymal cells.
• The albumin fraction is first to be formed. The other varieties
appear later.
• In the adults all the four fractions are produced by the liver.
• For globulin, several other sources have been suggested,
such as
From the disintegrated blood cells
From the reticulo – endothelial system (specially the 
globulin)
From the tissue cells in general
From lymphoid nodules

40. • The plasma proteins are not static entities.
• Isotopic experiments indicate that they
are completely used up and replaced
every fourteen days.
• Albumin synthesis is stimulated by osmotic
pressure changes and by
hypoproteinemia;
• Globulin synthesis is stimulated by a
depressed blood pressure pool .
• fibrinogen by systemic inflammation.

41. VARIATION IN PLASMA PROTEIN LEVELS
Decreased- hypoproteinemia
 Hemorrhage, extensive burns, pregnancy, malnutrition,
prolonged starvation , cirrhosis of liver, chronic infection like
chronic hepatitis or chronic nephritis
Increased – hyperproteinemia
 Dehydration , acute infection like acute hepatitis or acute
nephritis

42. Rate of regeneration of plasma proteins
• After depletion of plasma proteins, such as by
severe hemorrhage or after blood donation,
the plasma proteins come to the normal level
in about fourteen days. Fibrinogen is
regenerated first, then comes globulin and
last of a serum albumin.
• The regeneration rate is studied by
plasmapheresis.
• Plasmapheresis is used to remove harmful
autoantibodies from the plasma as in
Myasthenia gravis, paraprotienemic
peripheral neuropathy

44. HEMATOPOIESIS
HEMATOPOIESIS is the Process of production of
blood cells.

45. ERYTHROPOIESIS
Erythropoiesis is the process which involves the origin,
development and maturation of erythrocytes
 Theories of origin . There are two theories: intravascular and
extravascular.
 Formerly, it was believed that the red cells were formed only
intravascularly from the capillary endothelium.
 Turnbell and Gilour (1941) have shown that they are undoubtedly
produced from the extravascular sources. They have shown that the
parent cell is an extravascular cell, known as haemocytoblast, which by
active amoeboid movement burrows into the blood sinuses, multiply
there and mature into normal erythrocytes.
 The general trend of opinion seems to be in favour of the extravascular
theory now.

46. Stages of blood formation in the embryo
and foetus
 There are three successive stages of blood
formation in the embryo and foetus
 Mesoblastic haemopoiesis is demonstrable in
the first two months of embryonic life. Through
out this period , no blood forming organ is present and most of the cells
are formed outside the embryo.
 Hepatic haemopoiesis constitutes the second stage and include the
splenic and thymic blood formation. This stage occurs from the second
to the fifth month.
 The final or myeloid period of haemopoiesis begins approximately at
the fifth month, with the establishment of the placental circulation. At
first, the liver is chiefly occupied with erythropoiesis and the bone
marrow leucopoiesis, but the bone marrow soon takes overall
haemopoietic activity.

47. Sites of erythropoiesis
3rd week of IU- yolk sac
3rd month IU- liver &
spleen
From 5th month-bone
marrow

48. IN NEW BORN BABIES AND ADULTS
 Upto 5-6yrs- from red bone marrow of all bones
 From the age of 6 yrs upto 20yrs- from red bone
marrow of long bones and all membrnous bones
 After 20 yrs- from membranous bones

49. PROCESS OF ERYHROPOIESIS
STEM CELL: defined as a cell which is capable of
both self renewal and differentiation
PLURIPOTENT HEMATOPOIETIC STEM CELL:
defined as a cell that gives rise to cells of all
groups of hematopoietic cells like myeloid cells
and lymphoid
Unipotent stem cells
Uncommitted committed

51. Cell renewal
Stem cells give rise to all blood cells. But if all the stem cells convert to
mature blood cells, then stem cells will be exhausted. To prevent this,
some stem cells remain as stem cell while others form blood cells. This is
called cell renewal.

53. STAGES OF ERYTHROPOIESIS
CELL DIAMETER NUCLEUS CYTOPLASM
15-20 μm Big & strongly Very scanty & basophilic
basophilic No Hb.
11-16 μm Smaller Scanty & basophilic.
No Hb.
10-12 μm Smaller & Hb starts to appear,
Denser cytoplasm polychromatic
8-10 μm Ink spot Plentiful, eosinophilic.
nucleus increase in Hb.
8-10 μm Absent Some RNA still present.
7.5 μm Absent Hb++.
CELL TYPE
Proerythroblast
Early erythroblast
Late erythroblast
Normoblast
Reticulocyte
Erythrocyte

54. 7days
5days 2days

55. FACTORS NECESSARY FOR
ERYTHROPOIESIS:
 GENERAL FACTORS
1. ERYTHROPOIETIN
2. THYROXINE
3. HEMOPOIETIC
GROWTH FACTOR
4. VITAMINS
 MATURATION FACTORS
1. VITAMIN B12
2. INTRINSIC FACTOR OF
CASTLE
3. FOLIC ACID

56.  Erythropoietin also known as erythropoietin factor or EPO,
is a humoral peptide hormone that is synthesized by cells
of the kidney and is involved in regulating erythropoiesis,
or red blood cell production (Silverthorn, 2009).
 Erythropoietin is a glycoprotein molecule, contains:
 165 amino acids and
 40% carbohydrate, sialic acid and other sugars (Hadley &
Levine, 2007).
 The sialic acid residues in the molecule acts as a
protectant, and is necessary for biological activity in vivo,
as the absence of these residues (asialo form of EPO)
causes the hormone to be cleared too rapidly by the liver,
preventing it from exerting its hematopoietic effects
(Hadley & Levine, 2007).
Erythropoietin

57. Regulation of red blood cell
production
Regulation of red blood cell production

58.  Presently, erythropoietin is manufactured artificially using recombinant
DNA technology because of its potential as a therapeutic agent and has
already been used in treatment of anemia and certain cancers (Fisher,
2010)

59. 2. THYROXIN : accelerates erythropoiesis
3. HEMOPOIETIC GROWTH FACTOR:
interleukins: IL-3 , IL-6, IL-11
stem cell factor

60. Components of Blood:
Formed Elements
Erythrocytes or RBCs
Normal structure:
Non -nucleated- they lack a
nucleus
ENUCLEATION

61. Why do mammalian red blood cells lack a nucleus?
According to one research (Ji, et al., 2008), occurs in mice is
that a ring of actin filaments surrounds the cell, and then
contracts. This cuts off a segment of the cell containing the
nucleus, which is then swallowed by a macrophage.
Enucleation in humans most likely follows a very similar
mechanism.
Shown to be in mice & rats (and sick humans), the cell-cell
interaction between a macrophage (this is a big engulfing cell
required for immunity) and young red blood cells (RBC), is
known as the erythroblastic island (commonly known as EBI).
-a scientific review in 2008.

62. In addition to engulfing the RBC nuclei, it is believed that the
macrophage acts as a "nurse" cell as proposed in the 50s. In
other words, possibly providing iron, and possibly providing
some proteins required for young RBC to mature.
In early 2013, for the first time, it was showed that these
macrophages are important in animal models

63. The absence of a nucleus is an adaptation of the red blood cell
for its role.
• It allows the red blood cell to contain more hemoglobin.
• It also allows the cell to have its distinctive bi-concave
shape which aids diffusion.
Because of the advantages it gives, it is easy to see why
evolution would cause this to occur. However, since little is
known about the genes the control enucleation, it is still not a
fully understood process.
Advantage of absence of nucleus:

64. A normal healthy adult individual would produce about
2 million RBC per second

65. Red blood cells specialisations:
normal shape
1) biconcave shape

66. Normal size:
• Diameter
• Thickness
• Surface area: 120sq m
• Volume:85-90cu m

67. 1) ROULEAUX
FORMATION
Properties of RBC’S

68. 2) specific gravity of RBC: 1.092- 1.101
3)suspension stability: during circulation…
- uniform RBC suspension

70. Structure and metabolism
• RBC membrane is made up of proteins
and lipids. Protiens on the outer surface
form receptors or antigens. The proteins
on the inner surface of the membrane form
part of the cytoskeleton.
• These are ankyrin ,spectrin, actin, band 3
& band 4 protiens.
Ankyrin and spectrin are responsible for
biconcave shape of red cells.
2 types of proteins: Integral protein
peripheral protein: spectrin, actin,
tropomysin
This strengthens the membrane and gives it its elastic properties

71. Haemoglobin
gives red blood cells their
colour
Is a chromoprotein 95% of
dry weight of RBC and 30-
34% of wet wt.
can carry up to 4 molecules
of O2
associates and dissociates
with O2
contains iron

73. Components of Blood: Formed
Elements
Erythrocytes or RBCs
The more hemoglobin molecules the RBCs
contain, the more oxygen they can carry.
1RBC - 250 million molecules of
hemoglobin, each binding 4 molecules of
oxygen.

74. Structure of
hemoglobin

76. When there is a high concentration of oxygen e.g
in the alveoli haemoglobin combines with oxygen to
form oxyhaemoglobin. When the blood reaches the
tissue which have a low concentration of oxygen
the haemoglobin dissociates with the oxygen and
the oxygen is released into body tissues
Function of Haemoglobin

77. • Heme portion- acetic acid and glycine
• - mitochondria
• Acetic acid- krebs cycle- succinyl coa
2
succinyl
coA+2
glycine
pyrrole
4
pyrrole
compo
und
Proto
Porphy
rin IX
HEME
Fe
Synthesis of haemoglobin

78. NORMAL VALUES
Average hemoglobin (Hb) -- 14 to 16 gm%.
– At birth : 25 gm%
– After 3rd month : 20 gm%
– After 1 year : 17 gm%
– In adult males : 15 gm%
– In adult females : 14.5 gm%

79. Variations of Hb under different
physiological conditions
• Age : In the fetus the concentration is
highest.
• Sex : In females the amount of haemoglobin
is slightly lower than in males.
• Diurnal variation ; Variation of at least 10%
occurs throughout the day. In the morning it
is lowest; in the evening highest.
• Altitude : At higher altitude haemoglobin
percentage rises.
• Exercise , excitement, adrenaline injection,
etc., increase the amount of haemoglobin.

80. RBC life span and circulation
• Replaced at a rate of approximately 3 million
new blood cells entering the circulation per
second
• Damaged or dead RBCs are recycled by
phagocytes
• Components of hemoglobin individually
recycled
– Heme stripped of iron and converted to
biliverdin, then bilirubin
• Iron is recycled by being stored in
phagocytes, or transported throughout the
blood stream bound to transferrin

83. Figure 19.5
Red Blood Cell Turnover 10% destroyed/day

84. Iron metabolism
• Needed for synthesis of haemoglobin, myoglobin,
cytochromes.
• Total body iron is 3- 4 gm, 2/3 rd present in Hb.
• Source- meat, fish, eggs, milk and vegetables. Iron in the
body is also recycled and major source is dead RBCs.

85. • Absorption and Transport. Iron is absorbed from the the
gastro-intestinal tract , a large amount is absorbed from the
upper part of the small intestine particularly the duodenum.
• Dietary iron is absorbed through the mucosal cells as ferrous
(Fe++) form.
• Iron in diet is mostly present as ferric (Fe+++) state which is
reduced to ferrous form during absorption
• After entering the mucosal cell as ferrous form, the iron
molecules are rapidly reconverted into ferric state.
• The ferric iron as ferric-hydroxide phosphate combines with a
protein, apoferritin of the mucosal cells with the formation of
iron-phosphorus protein complex, ferritin. This ferritin is one
of the storage forms of iron in the tissue.

87. • Excess iron is stored as ferritin in RE cells,
which mostly comes from dead RBC.
• Excess ferritin in the body forms
hemosiderin, which is useless to the body
and damages the cells.
• Excess storage in tissues results in a
disease called Haemochromatosis

88. • Iron in blood Whole blood contains about
45-50 mgm of iron per 100 ml. The total
quantity present in all the red cells is about
3gm. Another 1-3gm is present in the rest
of the body. .
• As haemoglobin—This accounts for
about 92-98% of the total blood iron. It
corresponds to about 50 mgm of inorganic
iron per 100ml of blood.

89. Types of haemoglobin
HbA – consists of two α and two β chains.
HbF- seen in foetus and new borns. β chain is
replaced by γ chain.
Abnormal haemoglobin
HbS- in adult Hb in β chain at 6 th
position glutamic acid is replaced by
valine. This leads to change in RBC
shape which looks sickle and destroyed
quickly resulting in sickle cell anaemia

90. Derivatives of Haemoglobin
• Oxyhaemoglobin : It is a compound of haemoglobin
with oxygen. Iron remains in the ferrous (Fe++) state in
oxyhaemoglobin. It is not a stable compound. Oxygen
may be removed when the blood is exposed to a
vacuum.
• Methaemoglobin : It is also a compound of
haemoglobin with oxygen. It can be produced after
treating the blood with potassium ferricyanide. It is
chocolate brown in colour. It is stable compound.
Oxygen cannot be removed by exposing the blood to a
vacuum. Iron remains in the ferric (Fe+++) state. This
can be reduced by the enzyme
methaemoglobin reductase.

91. • Carbohaemoglobin : It is a compound haemoglobin
with CO2. The compound is formed by union of CO2 with
globin portion
• Carboxyhaemoglobin or Carbonmonoxy-haemoglobin.
Haemoglobin combined with CO instead of oxygen. It is
present in blood in coal gas poisoning. The affinity of
human haemoglobin at 380C for CO is 210 times greater
than O2. The extremely poisonous nature of the gas can
easily be understood from the above statement.

92. • Sulphaemoglobin : It is formed by the
combination of haemoglobin with H2S. The
compound is very stable and is sometimes found
in the blood after certain drug poisoning.
• Nitric oxide haemoglobin : Haemoglobin
combined with NO instead of oxygen, seen in
nitric oxide, poisoning.

93. FETAL
HAEMOGLOBIN
 Fetal hemoglobin (HbF) is the main oxygen transport protein in
the fetus
 Functionally, fetal hemoglobin is able to bind oxygen with
greater affinity than the adult form, giving the developing fetus
better access to oxygen from the mother's bloodstream
 Fetal hemoglobin's affinity for oxygen is substantially greater than
that of adult hemoglobin. Notably, the P50 value for fetal
hemoglobin is roughly 19 mmHg, whereas adult hemoglobin has
a value of approximately 26.8 mmHg. As a result, the so-called
"oxygen saturation curve", which plots percent saturation vs.
pO2, is left-shifted for fetal hemoglobin in comparison to the
same curve in adult hemoglobin

94. This greater affinity for oxygen is explained by the lack of fetal
hemoglobin's interaction with 2,3-bisphosphoglycerate (2,3-BPG
or 2,3-DPG).
In adult red blood cells, this substance decreases the affinity of
hemoglobin for oxygen. 2,3 BPG is also present in fetal red blood
cells, but interacts less efficiently with fetal hemoglobin than adult
hemoglobin, due to a change in a single amino acid found in the
2,3 BPG 'binding pocket': from lysine to serine

95. ERYTHROCYTE SEDIMENTATION RATE
Definition:
The rate at which the erythrocytes settle
down is called ESR .
Determination
– Westergren’s Method
– Wintrobe’s Method
Normal Values of ESR
– Westergren's Method
• Males 3-7mm in 1 hr
• Females 5-9 mm in 1 hr
• Infants 0 – 2mm in 1 hr
300mm long tube
1.6 ml of blood+ 0.4ml of 3.8%sodium citrate
110mm long tube
1ml blood+ EDTA

96. FACTORS AFFECTING ESR
1. Specific gravity of RBC’s :
2. Rouleaux formation
3. size of RBC’s
4. Viscosity of blood.
5. Number of RBC’s

97. VARIATIONS OF ESR
–PHYSIOLOGICAL
•Age: Less in children & infants
•Menstruation: Increased
•Pregnancy: Increased
–PATHOLOGICAL
•Increases
TB, Anemia, Malignant tumors and Liver diseases.
•Decreases
Allergic conditions, Sickle cell Anemia, Peptone
shock, Polycythemia and Extreme Leukocytosis

98. MEAN CORPUSCULAR VOLUME (MCV)
Average volume of a single red blood cell
Normal MCV = 90 cu µ (78to 90 cu µ).
Increased- macrocyte
• pernicious anemia
• megaloblastic anemia
Decreased-microcyte
• microcytic anemia
MCV = Volume of packed cells in 100ml of blood
number of Red blood cells in 100ml of blood
BLOOD INDICES

99. MEAN CORPUSCULAR HEMOGLOBIN(MCH)
QUANTITY OR AMOUNT OF HB PRESENT IN ONE RBC
Normal value of MCH is 30 pg (27 to32pg)
increases or remains normal
Pernicious anemia
Megaloblastic anemia
Decreases in hypochromic anemia.
MCH = Hemoglobin in grams per 100 ml of blood
RBC count in 100ml

100. MEAN CORPUSCULAR HEMOGLOBIN
CONCENTRATION (MCHC)
Means the conc. of Hb present in one of RBC
VERY IMPORTANT AND ABSOLETE IN THE
DIAGNOSIS of IRON DEFICIENCY ANEMIA
Relates to the color of the cells.
MCHC = Hemoglobin in grams/ 100 ml of blood x 100
PCV in 100 ml of blood
Normal value of MCHC is 30 % (30 to38%)

101. COLOUR INDEX (CI)
Ratio between % of Hb and % of RBC’s in blood.
Avg Hb content in 1 cell of a patient compared to avg
Hb content in 1 cell of a normal person.
– Normal colour index is 1.0 (0.8to 1.2).
– Useful in determining type of anemia.
– Raised in pernicious anemia and megaloblastic
anemia.
– Reduced in iron deficiency anemia.
– Normal in normocytic normochromic anemia.

102. COLOUR INDEX
Colour Index = Hemoglobin%
RBC%
Hemoglobin % = Hemoglobin content in the subjectx100
Normal hemoglobin content
RBC % = RBC count in the subject x 100
Normal RBC count

103. VARIATIONS IN RBC COUNT
• INCREASE IN COUNT--Physiological Polycythemia
– High altitude
– Muscular exercise
– Emotional conditions
– Increased environmental temperature
– After meals
– Diurinal variation
• DECREASE IN COUNT
– High barometric pressure
– After sleep
– Pregnancy

104. PATHOLOGICAL VARIATIONS

105. Excessive RBCs (erythrocytes)
Polycythemia - abnormal increase in erythrocytes,
caused by:
Bone marrow cancer
High altitudes
Thickens and slows blood, impairs
circulation

106. POLYCYTHEMIA
Polycythemia is defined as an abnormal
increase in the number of red blood cells in
the peripheral blood, usually with an increased
hemoglobin level
Three forms of the disease are recognized
(1)Relative polycythemia
(2) Primary polycythemia or erythremia
(polycythemia rubra vera) of unknown etiology
(3) Secondary polycythemia or erythrocytosis,
due to some known stimulus.

107. Relative polycythemia
• Is an apparent increase in the number of
circulating red blood cells
• Occurs as a result of loss of blood fluid with
hemoconcentration of cells
• Seen in cases of excessive loss of body fluids
such as chronic vomiting, diarrhea, or loss of
electrolytes with accompanying loss of water.
• This increase in the number of red blood cells is
only relative

108. Primary polycythemia
• Also called polycythemia rubra vera
• Is characterized by a true idiopathic increase in the
number of circulating red blood cells and of the
hemoglobin level.
Secondary polycythemia
Is similar to primary polycythemia except that the
etiology is known.
In general, the stimulus responsible for producing a
secondary polycythemia is either
(1) Bone marrow anoxia
(2) Production of an erythropoietic stimulator factor

109. Clinical Features
• Polycythemia vera often manifests itself primarily by
headache or dizziness, weakness ,lassitude, tinnitus,
visual disturbances, mental confusion, slurring of the
speech and inability to concentrate.
• The skin is flushed or diffusely reddened,
• This condition is most obvious on the head, neck and
extremities, although the digits may be cyanotic.
Polycythemia Vera

110. Oral Manifestations
• The oral mucous membranes appear deep
purplish red, the gingiva and tongue being
most prominently affected.
• The cyanosis is due to the presence of
reduced hemoglobin in amounts exceeding 5
gm./dl.
• The gingivae are often engorged and swollen
and bleed upon the slightest provocation.
• Submucosal petechiae are also common, as
well as ecchymoses and hematomas.

111. Laboratory Findings
• The red blood cell count is elevated and may
even exceed 10,000,000 cells per cubic
millimeter.
• The hemoglobin content of the blood is also
increased, often as high as 20 gm./dl.
• Because of the great number of cells present,
both the specific gravity and the viscosity of
the blood are increased

112. POLY

113. • Dental management
• Blood profile that include
hemoglobin,differential WBC count, and
platelet count should be obtained before dental
treatment.
• Intraoral bleeding can be controlled by local
measures such as primary closure, pressure
and adjunctive topical hemostatics
• Bleeding tendencies, anaemia, and
delayed drug metabolism can be
expected when the patient enters the
later phase of the disease.

114. • Chemotherapeutically induced oral ulcers may require
topical anaesthesia and antibacterial rinses.
• Two contraindications during dental care are:
• Epsilon amino caproic acid should not be used
because of the increased risk of thrombosis.
• Surgery in uncontrolled polycythemic patients is
contraindicated as it is associated with significant
postoperative bleeding.
• In emergency conditions patients with polycythemia
should be treated conservatively
• Non antiplatelet analgesics such as acetaminophen
and codiene should be prescribed.

115. Anemia: a decrease in the
oxygen-carrying capacity of the
blood
Anemia results from:
Lower # RBCs
Deficient hemoglobin

116. Anemias from lower RBCs:
Hemorrhagic anemia: sudden hemorrhage
Hemolytic anemia: lysis of RBCs from bact. infection
Pernicious anemia: lack of B12
Aplastic anemia: depression/destruction of bone
marrow by cancer, radiation, meds.

117. Anemia: abnormal hemoglobin
Sickle Cell Anemia:
Deficient hemoglobin - a point mutation changes a
single amino acid.

118. anaemia
Anaemia is defined as an abnormal
reduction in the number of circulating
RBC, the quantity of hemoglobin & the
volume of packed red cells in a given unit
of blood

119. etiology
• Blood loss
• Excessive destruction- malaria, splenic
sequestration, chemicals, erthropoietic
porphyria, lead poisoning
• Impaired blood production resulting from
deficiency of substance essential for
erthropoiesis- iron, B12 & folic acid, pyridoxine &
niacine, riboflavin, pantothenic acid, thiamine,
ascorbic acid
• Inadequate production- atrophy of bone marow,
infiltration of bone marrow
• Chronic renal disease
• Cirrhosis of liver

120. Morphologic classification of
anaemia
type Description Common causes
Macrocytic Increased
MCV,MCH
Normal MCHC
Lack of erthrocyte
maturing factors
Normocytic Reduction only in
RBC number
Hemorrhage,
hemolysis
Microcytic Reduced MCV,
MCH
Normal MCHC
Associated with
infections &
inflammatory
disease
Hypochromic
microcytic
Reduced
MCV,MCH,MCHC
Iron deficiency

121. PERNICIOUS ANEMIA
• Pernicious anemia, a form of megaloblastic
anemia, is a chronic disease of late adult life
resulting from a deficiency of vitamin B 12 due to
atrophy of the gastric mucosa and subsequent
loss of intrinsic factor
• It develops most frequently in patients above the
age of 60 years and occurs equally among the
sexes.
• It is often associated with addisons disease

122. Clinical Features
• Age of 30 years and increases in frequency
with advancing age.
• A sore, painful tongue, numbness or tingling
of the extremities.
• Diarrhea, loss of appetite, shortness of
breath, loss of weight, pallor and abdominal
pain.
• Patients with severe anemia exhibit a
yellowish tinge of the skin and the sclerae.
• The skin is usually smooth and dry

123. Oral Manifestations
• Glossitis, tongue is .generally inflamed, often
described as "beefy red" in color, either in entirety or in
patches scattered over the dorsum and lateral borders
• shallow ulcers resembling aphthous ulcers occur on
the tongue
• Glossitis, Glossodynia and Glossopyrosis is seen
• There is gradual atrophy of the papillae that
eventuates in a smooth or "bald" tongue which is often
referred to as Hunter's glossitis or Moeller's glossitis
and is similar to the "bald tongue of Sandwith" seen in
pellagra.
• Loss or distortion of taste is sometimes reported
accompanying these changes.

124. • Farrant, Boen and Boddington have reported
that cells from buccal scrapings of patients
with pernicious anemia presented nuclear
abnormalities consisting of enlargement,
irregularity in shape and asymmetry.
• These were postulated to be due to a reduced
rate of nucleic acid synthesis with a reduced
rate of cell division.

125. Laboratory Findings
• This chronic disease often exhibits periods
of remission and exacerbation
• The red blood cell count is seriously
decreased, often to 1,000,000 or less per
cubic millimeter.
• Many of the cells exhibit macrocytosis; this,
in fact is one of the chief characteristics of
the blood in this disease.

126. Diphenhydramine elixir is given to patients with
painful oral conditions to provide symptomatic relief
Oral health is restored on administration of vitamin
B12
Surgical procedures must be deferred until the anemia
and the thrombocytopenia are controlled , otherwise
bleeding could become a problem.
DENTAL MANAGEMENT

127. FOLIC ACID DEFICIENCY ANEMIA
• this is most often seen in patients who
have poor dietary intake often coupled
with alcoholism.
• This is because alcoholics eat poorly and
also alcohol interferes with the
metabolism and absorption of folic acid.
• Folic acid is essential for the maturation
of the erythrocytes, therefore a deficient
state causes the RBC to remain large like
their precursor .

128. • Clinical findings:
• They include features typical of anaemia together with
a smooth bald tongue, angular chelitis,
hyperpigmentation, peripheral edema, and signs of
malnutrition.
• Peripheral neuropathy if present is the consequence of
the concurrent vitamin B complex deficiency and not
folic acid deficiency.
• Liver dysfunction and hepatomegaly are common
findings.

129. • Oral manifestations:
– Glossitis and angular cheilitis is seen in patients
with folic acid deficiency.
– In severe cases ulcerative stomatitis and pharyngitis
is seen.
– Administration of folate tablets causes the oral
features to regress within 2 weeks.
– Palliation of oral discomfort may be provided by
diphenhydramine elixir.
• Dental management:
– Folate deficiency leads to bleeding problems
because of inhibition of liver coagulant precursors.
– Therefore blood report should be obtained before
dental procedures that are likely to induce
haemorrhage.
– Oral surgical procedures should be deferred if the
blood values or bleeding time is abnormal.

130. Aplastic anemia
• Aplastic anemia is a disease characterized
by a general lack of bone marrow activity.
• It may affect not only the red blood cells
but also the white cells and platelets,
resulting in a pancytopenia.

131. It is common to recognize two chief forms of aplastic
anemia;
• primary
• secondary.
• Primary aplastic anemia is a disease of unknown
etiology which occurs most frequently in young
adults, develops rapidly and usually terminates
fatally
Fanconi's syndrome
• Consists of aplastic anemia associated with a variety
of other congenital defects including bone
abnormalities, microcephaly, hypogenitalism and a
generalized olive-brown pigmentation of the skin

132. • Secondary aplastic anemia, is of known
etiology, occurs at any age and presents a
better prognosis
• The etiology of secondary anemia is the
exposure of the patient to various drugs ,
chemical substances or to radiant energy
in the form of x-rays, radium or radioactive
isotopes.

133. Oral Manifestations
• Petechiae, purpuric spots or frank
hematomas of the oral mucosa may occur
at any site
• while hemorrhage in the oral cavity,
especially spontaneous gingival
hemorrhage, is present in some cases
• As a result of the neutropenia there is a
generalized lack of resistance to infection,
and this is manifested by the development
of ulcerative lesions of the oral mucosa or

134. Dental considerations:
Gingival bleeding can be reduced by using systemic
antifibrinolytic agents such as aminocaproic acid or
transsexamic acid and local hemostatic measures.
Transexamic acid is given in the dose of 20 mg/kg body
weight four times a day starting 24 hours before oral
procedures and continued to 3-4 days afterward.
Oral rinses with chlorhexidine 0.2% in an aqueous solution
will reduce the amount of plaque and the number of
microorganisms in the oral cavity.
However intramuscular injections and nerve block
anaesthesia should be avoided because thrombocytopenia
and bleeding tendencies.

135. Thalassemia
• The disease's geographical association
with the Mediterranean sea was
responsible for its naming: Thalassa is
Greek for the sea, Haima is Greek for
blood
• Thalassemia is a recessive trait inherited
disease of the red blood cells.
• In thalassemia, the genetic defect results in
reduced rate of synthesis of normal globin
chains leading to instability or abnormal
oxygen transport

136. Classification
• The thalassemias are classified according to
which chain of the globin molecule is affected:
In α thalassemia, the production of α globin is
deficient, while in β thalassemia the production
of β globin is defective
Alpha (α) thalassemias
• The alpha thalassemias involve the genes
HBA1 and HBA2
• There are four genetic loci for α globin, two of
which are maternal in origin and two of which
are paternal in origin.

137. • Most such infants are dead at birth with
hydrops fetalis, and those who are born alive
die shortly after birth
• There is a microcytic hypochromic anemia
with target cells and Heinz bodies on the
smear

138. Beta (β) thalassemias
• In β thalassemia, a decrease in beta-globin
production occurs, causing a less than normal
amount of beta-globin chains to be made
• Any given individual has two β globin alleles, one
from their mother and one from their father:
• If both have thalassemia mutations, a severe
microcytic, hypochromic anemia called β
thalassemia major or Cooley's anemia results
• If only one β globin allele bears a mutation, β
thalassemia minor results
• This is a mild anemia with microcytosis

139. Roentgenographic Features.
• Described by Caffey, In the skull there is
extreme thickening of the diploe.
• The inner and outer plates become poorly
defined, and the trabeculae between the
plates become elongated, producing a bristle
like "crew-cut" or "hair-on-end" appearance of
the skull
• Both the skull and long bones exhibit some
degree of osteoporosis.

140. Intraoral roentgenograms
 some cases reveal a peculiar trabecular
pattern of the maxilla and mandible.
 characterized by an apparent coarsening of
some trabeculae and the blurring and
disappearance of others, resulting in a "salt
and pepper" effect

141. Dental Management:
• Prevention of dental disease
• Avoidance of general anaesthesia in the
presence of chronic, severe anaemia,
cardiomyopathy, endocrine problems
• Need for antibiotic prophylaxis

142. Sickle Cell Anemia
• The name is derived from the peculiar
microscopic appearance of sickle- or crescent-
shaped erythrocytes found in the circulating
blood.
• Hemoglobin (HbA) is genetically altered to
produce sickle hemoglobin (HbS) by the
substitution of valine for glutamine at the sixth
position of the l3-globin chain.

143. Clinical Features
• Sickle cell anemia is more common in females
and usually becomes clinically manifest before the
age of 30 years
• Sickle cell crises may occur under a variety of
situations, administration of a general anesthetic,
probably as a result of decreased oxygenation of
the blood.
• Other triggering causes of deoxygenation may
include exercise or exertion, infections, pregnancy
or even sleep.

144. Oral manifestations
• Dental x-rays show alterations from mild to
severe generalized osteoporosis
• loss of trabeculation of the jaw bones with the
appearance of large, irregular marrow spaces
"hair-on-end" pattern, identical to that seen in
thalassemia

145. Laboratory Findings
• The red blood cell count may reach a
level of 1,000,000 cells or less per
cubic millimeter with a decreased
hemoglobin level.
• On the blood smear typical sickle-
shaped red blood cells are commonly
seen

146. • Dental management:
• Patients with sickle cell trait and sickle cell disease in non crisis periods can
receive non hemorrhagic dental care.In noncrisis situations the patient with sickle
cell trait should receive antibiotics when active infections is present.
• Prophylactic antibiotics is given before and after tooth extraction and flap surgery
in patients with sickle cell disease to minimize the frequency of postoperative
osteomyelitis
• Respiratory distressing drugs must be avoided as hypoxemia is of prime concern
in patients with sickle cell anemia
• Nitrous oxide oxygen analgesia is permitted as long as the oxygen flow rate is
50% or greater
• General anesthesia can be performed as long as the Hb is above 10g/dl.

147. IRON DEFICIENCY ANEMIA
• It is the most common type of anaemia
• It is a microcytic, hypochromic type of
anaemia cause by blood loss.
• There are three major factors in the
pathogenesis of iron deficiency anaemia
• - an increased physiologic demand for
iron.
• - pathologic blood loss
• - inadequate iron intake.

148. Symptoms and sign
 Cracks or fissures at the corners of the mouth,
 Lemon-tinted pallor of the skin.
 Smooth, red, painful tongue with atrophy of the
filiform and later the fungiform papillae
 Dysphagia resulting from an esophageal stricture
or web
 The mucous membranes of the oral cavity and
esophagus are atrophic and show loss of normal
keratinization.
 Koilonychia (spoon-shaped fingernails) or nails
that are brittle and break easily have been
reported in many patients.

149. Laboratory Findings
• Blood examination reveals a hypochromic
microcytic anemia
• The red blood cell count is generally between
3,000,000 and 4,000,000 cells per cubic
millimeter
• The hemoglobin is invariably low
• Serum iron is low

150. Dental considerations:
In patients with significant anemia, surgical
procedures may result in bleeding problems or poor
wound healing.
Hemoglobin values below 10gm/100ml is unsafe for
elective dental care and general anesthesia.
Oral discomfort may be palliated with the use of
topical rinses consisting of viscous lignocaine .
Persistant oral ulcerations may signal plummer
Vinson syndrome or a developing oral carcinoma.
Biopsy is mandatory for unexplained oral
ulcerations

151. VARIATIONS IN RBC SIZE
• Microcytes
– Iron deficiency anemia
– Prolonged forced breathing
– Increased osmotic pressure in blood
• Macrocytes
– Megaloblastic anemia
– Muscular exercise
– Decreased osmotic pressure in blood
• Anisocytes
– Pernicious anemia

152. VARIATIONS IN RBC SHAPE
Crenation : Shrinkage -- hypertonic solution
Spherocytosis : Globular -- hypotonic solution
Sickle cell : Crescent -- sickle cell anemia

153. references
• Textbook of Medical Physiology, Guyton, 7th Edition
• Shafer’s textbook of Oral Pathology, 5th Edition
• Burket’s Oral Medicine, 11th Edition
• Textbook of physiology, Anil Baran singh Mahapatra
• The physiological basis of Medical Practice,7th
edition
• Medical phrmacology KD TRIPATHI- 4th edition
• National hemophilia foundation, Educational Tools

154. THANK
YOU