BLOOD

Dr. Hoe See Ziau

Department of Physiology
Faculty of Medicine
University of Malaya

160709 Biomed/Pharm 09/10 Blood Lecture 1

BLOOD
 A transport “vehicle” for
the organs of the
cardiovascular (CVD)
system

 Blood and the CVD

system constitute the
circulatory system

 Blood circulation:
 Heart→arteries
→capillaries →veins
→heart →lungs →heart
BLOOD

 A complex connective tissue

 Blood cells (formed elements) are

suspended in a fluid matrix (plasma)
COMPONENTS OF BLOOD
Blood

Cellular Component Fluid Component

(Formed Elements) (Plasma)

Erythrocytes Leukocytes
Thrombocytes
(red blood (white blood
(platelets)
cells, RBC) cells, WBC)
CHARACTERISTICS OF BLOOD
Properties

Bright red (oxygenated)

Colour Dark red/purplish red (deoxygenated)
Cherry red (CO poisoning)
pH 7.35 – 7.45 (Average 7.40)

Specific gravity 1.045

Plasma osmolarity 285 – 300 mOsm/L

BLOOD VOLUME

 About 8% of body weight

5 – 6 L in a young adult male of 70 kg
 Plasma volume
 About 5% body weight (3 L)
FUNCTIONS OF BLOOD

 Distribution & transport

 Regulation
(maintenance of
homeostasis)

 Protection
FUNCTIONS OF BLOOD
Distribution & transport
 Respiration
 O2from lung to tissues
 CO2 from tissues to lung

 Nutrition
 Nutrientsfrom intestine to tissues for use in
metabolism
 Excretion
 Waste products from metabolism, e.g. urea & uric
acid from cells to organs for excretion
 Hormones & enzymes
FUNCTIONS OF BLOOD
Regulation (maintenance of homeostasis)
 body temperature
 Absorbs and distributes heat throughout the
body and to the skin surface to encourage
heat loss
 normal body pH, fluid & electrolyte balance
 Through continuous exchange of its
constituents with those of interstitial fluid
FUNCTIONS OF BLOOD
Protection
 Defense against infection by foreign
organisms
 Prevents loss of blood by the mechanisms
of coagulation (haemostasis)
HAEMATOCRIT
HAEMATOCRIT
 Percentage of total blood volume occupied by
RBCs (packed cell volume)
 Average: 45 %
 Males: 42 – 48 %
 Females: 36 – 42 %
 HAEMATOCRIT
Significance of haematocrit (Hct)
 Index of circulating red cells mass
 Lower red cell mass (anaemia) → lower Hct
 Higher red cell mass (polycythaemia) → higher Hct

 Index of the amount of plasma in relation to RBCs

  plasma volume in dehydration (haemoconcentration) →  Hct
  plasma volume in overhydration (haemodilution) →  Hct

 Index of blood viscosity

 Hct is directly proportionate to blood viscosity
HAEMATOCRIT
 Plasma Albumins
~60 %
(Percentage by weight)
Globulins
Proteins 7 % ~34 %
Percentage by
Fibrinogen
volume ~4%
Water 91 %
Ions

Nutrients
Other solutes 2 %
Waste products
Formed elements
Gases
(number per mm3)
Plasma
55 % Regulatory
Platelets Substances
150 – 400 thousand
Neutrophils
Formed Leukocytes 60 – 70 %
Elements 5 - 9 thousand
45 % Lymphocytes
20 – 40 %
Monocytes
Erythrocytes 2–6%
4.2 – 6.5 million Eosinophils
1–4%
Basophils
0.25 – 0.5 %
PLASMA
 Straw / pale yellow colour, slightly opalescent
liquid
 Contributes 55 % of total blood volume
 Composed of 92 % water and 8 % solids
 Osmolarity: 285 – 300 mOsm/L
 Solids:
 Gases – O2 & CO2
 Electrolytes – Na+, K+, Ca2+, Mg2+, Cl-, HCO3-,
phosphate, etc
 hormones, nutrients, trace elements, waste products
 plasma proteins
PLASMA PROTEINS

 Intravascular osmotic effect

 Plasma proteins establish an osmotic gradient
between the blood and interstitial fluid

 This colloid osmotic pressure or oncotic pressure is

responsible for preventing excessive loss of plasma
from the capillaries into the interstitial fluid, thus help
maintaining plasma volume

 Partiallyresponsible for plasma’s capacity to buffer

changes in pH
PLASMA PROTEINS
 Albumins
 Most abundant (60 – 80%) of plasma proteins
 bind many substances (e.g. bilirubin, bile salt) for transport
through plasma
 Most important in maintenance of osmotic balance
 Globulins
 Alpha (α) & beta (β) globulins
 Important for transport of materials through the blood (e.g., thyroid
hormone, cholesterol & iron)
 Factors involved in blood-clotting process
 α -globulins – inactive precursor protein molecules
 Gamma (γ) globulins
 Immunoglobulins (antibodies)
 Crucial to the body’s defense mechanism
 Fibrinogen Plasma proteins are synthesised by
liver, except -globulins, which are
 Inactive precursor for the fibrin
produced by lymphocytes
meshwork of a clot
HYPOPROTEINAEMIA
  plasma protein (< 5 g/dL) [normal: 7- 8 g/dL]
  plasma colloid osmotic pressure →
excessive fluid accumulation in interstitial
space → oedema
 Causes:
 Malnutrition -  protein in diet
 Small intestinal disease -  absorption of protein
 Liver disease -  synthesis of plasma protein
 Kidney disease – protein lost in urine
FORMED ELEMENTS OF BLOOD

 Comprise ~ 45% of blood volume

 Three major types

 Erythrocytes(red blood cells; RBCs)
 Leucocytes (white blood cells; WBCs)
 Thrombocytes (platelets)
PRODUCTION OF BLOOD CELLS
 Haemopoises

 Haemopoietic sites
 In foetus: liver, spleen & thymus
 After birth until 13 – 15 years: marrow of all
bones
 After 18 years: bone marrow of vertebrae,
ribs, sternum, cranium, pelvis, proximal femur
& proximal humerus
HAEMOPOIESIS
 The maturation, development & formation
of blood cells
 Pluripotent haemotopoietic stem cells: the
mitotic precursors to blood cells before
differentiation
 Differentiation: maturing cell becomes
“committed” to being certain type of blood
cell
HAEMOPOIESIS
HAEMOPOIESIS
ERYTHROCYTES

 Red blood cells (RBCs)

 Non-nucleated & contain very few organelles
 Major factor contributes to blood viscosity
 Average: 5 x 106 / µl blood
 Males : 4.6 – 6.5 x 106 / µl blood
 Females: 3.9 – 5.6 x 106 / µl blood

 Contain haemoglobin – a red pigment containing

iron
ERYTHROCYTES
 Have a shape of biconcave disk & small size
FUNCTIONS OF ERYTHROCYTES

 Transport O2 from lungs to tissues

 Transport CO2 from tissues to lungs

 Regulate the pH of blood

FUNCTIONS OF ERYTHROCYTES
HAEMOGLOBIN (Hb)
 Red-coloured protein pigment found within
RBCs
 Made up of 4 units, each unit consists of:
 Haem group: red pigment that contains iron in the
ferrous form (Fe2+)
+
Globin: polypeptide chain
 Each haem (Fe2+) can bind easily & reversibly
with one O2 molecule
 Each haemoglobin molecule – 4 molecules of O2
HAEMOGLOBIN
HAEMOGLOBIN

O2
2+

Iron-containing haem group

HAEMOGLOBIN CONCENTRATION

 Average: 15 g/dL
 New-born (2 – 5 months): 17 – 23 g/dL
 Toddler (3 – 10 years): 11 – 15 g/dL
 Males: 14 – 18 g/dL
 Females: 12 – 16 g/dL

 1 g Hb can carry 1.34 ml O2

 A single RBC contains ~250 x106 Hb (i.e.: each

RBC has the capacity to carry > a billion O2!)
HAEMOGLOBIN

 Hb also contributes significantly to CO2

transport & the pH-buffering capacity of
blood
HAEMOGLOBIN TYPES
 Four types of globin molecule: α, β, δ & γ
 Three important, normal human Hb:
 Major adult haemoglobin (HbA)
 2 α chains & 2 β chains (α2 β2)

 Minor adult haemoglobin (HbA2)

 2 α chains & 2 δ chains (α2 δ2)

 Foetal haemoglobin (HbF)

 2 α chains & 2 γ chains (α2 γ2)

 has a higher affinity for O2 than HbA

 At birth, ⅔ of the Hb content is HbF & ⅓ is HbA

 By 5 years of age, HbA >95%, HbA2<3.5%,
HbF<1.5%
HAEMOGLOBIN DISORDER

 When Hb is abnormal (abnormal globin

chain) – it cannot carry O2
 Thalassemia
 Sickle cell anaemia
 If ferrous (fe2+) in haem is converted to
ferric (fe3+) (methaemoglobin) – Hb cannot
carry O2
ERYTHROPOIESIS
 The maturation, development, & formation of
RBCs

3 – 5 days 2 days
(in bone marrow) (enter circulation)
FACTORS NECESSARY FOR
ERYTHROPOIESIS
 Hormone erythropoietin (EPO)
 Glycoprotein hormone
 Synthesised in the kidney (85%) & liver (15%)
 Released into the blood stream in response to
hypoxia (decreased tissue oxygenation)
 ↓ O2 levels can be resulted from:
 ↓RBCs due to haemorrhage or excess RBC destruction
 ↓Availability of O2, e.g., at high altitudes or during pneumonia
 ↑tissue demands for O2 (in aerobic exercise)
 Stimulates production of proerythroblast
 ↑↑ rate of new RBC production
CONTROL OF ERYTHROPOIESIS
1 The kidneys detect reduced O2-
carrying capacity of the blood
2
2 When ↓ O2 is delivered to the
kidneys, they secrete EPO into
the blood

1 3 3 EPO stimulates erythropoiesis

by the bone marrow

5 4 The additional erythrocytes

increase the O2-carrying
4 capacity of the blood

5 The increased O2-carrying

capacity relieves the initial
stimulus that triggered EPO
secretion
FACTORS NECESSARY FOR
ERYTHROPOIESIS
 Iron in the diet
 Iron deficiency leads to inadequate Hb production
 Vitamin B12 (cobalamin) & folic acid
 Maturation factors
 Necessary for synthesis of DNA & RNA
 Vit B12 & folic acid deficiency causes maturation
failure in the process of erythropoiesis
 Intrinsic factor (IF) in gastric juice
 necessary for absorption of Vit B12 from the terminal
ileum
DESTRUCTION OF RBCs
 Life span of RBCs: 120 days

 With aging, the metabolic systems of the RBCs become

less active, the cells degenerate

 Old and damaged RBCs are removed from the circulation

by the phagocytic activities of macrophages in the liver,
spleen and bone marrow

 The chemical components of the RBC are broken down

within vacuoles of the macrophages due to the action of
lysosomal enzymes
DESTRUCTION OF RBCs
 The hemoglobin of these cells is degraded into:
 Globin
 which is further digested down to amino acids, which can then
be utilized by the phagocytes for protein synthesis or released
into the blood.
 Heme
 which is converted by macrophages into biliverdin and then
bilirubin.
 Iron
 which is removed from heme molecules in the phagocytes.
The macrophages can store iron or release it to the blood.
 In the plasma, it binds to the protein transferrin and is carried
to the bone marrow where the iron can be used to synthesize
new hemoglobin.
LIFE CYCLE OF RBCs
ERYTHROCYTE DISORDERS
 Anaemias or polycythaemias

 Anaemia
 Reduction in the Hb concentration below the
lower limit of normal range with respect to age,
gender and race of an individual
 Always associated with pallor (pale)
CAUSES OF ANAEMIA
 Insufficient number of RBCs
 RBC number < 5 X 106/ µl blood
 Haemorrhagic anaemia
 Results from blood loss
 Haemolytic anaemia
 Results from RBC rupture, or lyse, prematurely
 Aplastic anaemia
 ↓↓ production of RBCs in the bone marrow
 Tumors, drugs & chemicals, x-rays
CAUSES OF ANAEMIA
 Low haemoglobin content
 Hb concentration < 11 – 12 g/dL blood
 Hb molecules are normal, but RBC content <
normal
 Megaloblastic anaemia
 Microcytic anaemia
CAUSES OF ANAEMIA
 Low haemoglobin content
 Megaloblastic anaemia
 Results from deficiency of vitamin B12 &/or folic
acid
 Pernicious anaemia

 impaired absorption of vitamin B12 due to the

absence of intrinsic factor that caused by
atrophic gastritis and parietal cell loss
 It is characterised by many large immature,
fragile, and dysfunctional RBCs (megaloblasts)
CAUSES OF ANAEMIA
 Low haemoglobin content
 Iron-deficiency anaemia
 Results from inadequate intake of iron-containing
food & impaired iron absorption
 Most common cause of microcytic anaemia

 The RBCs are smaller and paler (hypochromic)

than normal
CAUSES OF ANAEMIA

Normal Blood Film Megaloblastic Anaemia Microcytic Anaemia

• large immature and • RBCs are smaller and
dysfunctional RBCs paler
• hypersegmented or
multisegmented
neutrophils
CAUSES OF ANAEMIA
 Abnormal haemoglobin
 Due to a genetic mutation that alters the Hb
chain
 Thalassaemia
 One of the globin chains is absent or faulty
 Sickle-cell anaemia
 Caused by the abnormal HbS formed – results
from a change in one of the amino acids in a β-
chain of the globin molecule
 In low O2 concentration condition, HbS molecules
interact with each other to form fiberlike structure &
cause RBCs to become sickle shape
ANAEMIA
Sickle cell anaemia
Sickle-shaped RBC

Normal RBC
POLYCYTHAEMIA
 Hb concentration > 16 – 18 g/dL or RBC number
> 8 x 106 /µL blood
 Cancer of the bone marrow causing ↑ production
of RBCs – polycythaemia vera (primary
polycythaemia)
 Conditions causing hypoxia (through EPO) –
secondary polycythaemia:
 Natives living in high altitudes
 Heart disease
 Lung disease
ERYTHROCYTE SENDIMENTATION RATE
(ESR)
 When blood to which an anticoagulant has been
added is allowed to stand in narrow tube, the
RBCs form a pile of aggregates (rouleaux)
 Rouleaux gradually sediment leaving a clear
zone of plasma above
 The length (mm) of the column of clear plasma
after one hour is the measure of ESR
 Normal ESR values:
 Male: 3 – 5 mm
 Female: 4 – 7 mm
FACTORS AFFECTING ESR

 Surface area of falling RBC

 Reduced by rouleaux formation, thus ESR ↑
 Composition of plasma proteins
 Increased plasma proteins (fibrinogen, 2- and -
globulins) → ↑ ESR
 RBC count
 ↑ RBC count → ↓ ESR
 Size and shape of RBC
 ESR is low in sickle cell anaemia and congenital
spherocytosis because abnormal RBCs fail to form
rouleaux
IMPORTANCE OF ESR

 Non-specific indicator of the presence of organic

diseases
 Useful in the evaluation of treatment of various
rheumatic diseases
 Not used for diagnosis of diseases