Blood (part I)

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 (Formed Elements)

Erythrocytes (red blood cells, RBC)

Leukocytes (white blood cells, WBC)

Fluid Component (Plasma)

Thrombocytes (platelets)

CHARACTERISTICS OF BLOOD Properties Colour

Bright red (oxygenated) 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

 Regulation

& transport

(maintenance of homeostasis)

 Protection

FUNCTIONS OF BLOOD Distribution & transport 

Respiration  O2

from lung to tissues  CO2 from tissues to lung 

Nutrition  Nutrients

from 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  



Index of the amount of plasma in relation to RBCs  



Lower red cell mass (anaemia) → lower Hct Higher red cell mass (polycythaemia) → higher Hct

 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 (Percentage by weight)

Albumins ~60 %

Proteins 7 %

Globulins ~34 %

Percentage by volume

Fibrinogen ~4%

Water 91 % Ions

Other solutes 2 %

Plasma 55 %

Formed Elements 45 %

Formed elements (number per mm3) Platelets 150 – 400 thousand Leukocytes 5 - 9 thousand

Erythrocytes 4.2 – 6.5 million

Nutrients Waste products Gases Regulatory Substances

Neutrophils 60 – 70 % Lymphocytes 20 – 40 % Monocytes 2–6% 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: – O2 & CO2  Electrolytes – Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, phosphate, etc  hormones, nutrients, trace elements, waste products  plasma proteins  Gases

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

 Partially

responsible 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   



Gamma (γ) 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 Immunoglobulins (antibodies) Crucial to the body’s defense mechanism

Fibrinogen 

Inactive precursor for the fibrin meshwork of a clot

Plasma proteins are synthesised by liver, except -globulins, which are produced by lymphocytes

HYPOPROTEINAEMIA  



 plasma protein (< 5 g/dL) [normal: 7- 8 g/dL]  plasma colloid osmotic pressure → excessive fluid accumulation in interstitial space → oedema Causes: -  protein in diet  Small intestinal disease -  absorption of protein  Liver disease -  synthesis of plasma protein  Kidney disease – protein lost in urine  Malnutrition

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 : 4.6 – 6.5 x 106 / µl blood  Females: 3.9 – 5.6 x 106 / µl blood  Males



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 (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  New-born



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 O2carrying 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

4 The additional erythrocytes

5 4

increase the O2-carrying 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 

Results from blood loss

 Haemolytic 

anaemia

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 concentration < 11 – 12 g/dL blood  Hb molecules are normal, but RBC content < normal  Megaloblastic anaemia  Microcytic anaemia  Hb

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 • large immature and dysfunctional RBCs • hypersegmented or multisegmented neutrophils

Microcytic Anaemia • RBCs are smaller and paler

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 βchain 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 



Composition of plasma proteins 



Increased plasma proteins (fibrinogen, 2- and globulins) → ↑ ESR

RBC count 



Reduced by rouleaux formation, thus ESR ↑

↑ 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