OPTOMETRY · SEMESTER 1
Blood Physiology
Human Anatomy and Physiology
BLOOD PHYSIOLOGY
PART I
INTROD CONT …
- BLOOD: Is a liquid connective tissue or viscous fluid that:
- Circulates in a virtually “CLOSED” system of blood vessels
Blood, a connective tissue, that is composed of plasma and formed elements.
INTRODUCTION
Blood is a specialized body fluid that circulates through the cardiovascular system of humans and other vertebrates.
It serves multiple critical functions, including the delivery of necessary substances such as oxygen and nutrients to cells, as well as the removal of metabolic waste products.
INTRODUCTION cont …
- It circulates continually around the body, allowing constant
- communication between tissues distant from each other.
Blood makes up about 7% of body weight (about 5.6 litres in a 70 kg man).
This proportion is less in women and considerably greater in children, gradually decreasing until the adult level is reached.
Blood in the blood vessels is always in motion because of the pumping action of the heart.
INTRODUCTION cont …
The continual flow maintains a fairly constant environment for body cells.
Blood volume and the concentration of its many constituents are kept within narrow limits by homeostatic mechanisms.
COMPONENTS OF BLOOD
Composition of blood is divided into two aspects, the formed elements part and fluid part, namely;
- Blood Plasma (Fluid part) – occupies 55% of blood
Blood Cells (Formed Element part) – occupies 45% of blood
COMPONENTS OF BLOOD CONT …
Blood is composed of a clear, straw-coloured, watery fluid called plasma in which several different types of blood cell are suspended.
- Plasma normally constitutes 55% of the volume of blood.
The remaining 45% is accounted for by the cellular fraction of blood.
The two fractions of blood, blood cells and plasma, can be separated by centrifugation (spinning) or by gravity when blood is allowed to stand.
Because the cells are heavier than plasma, they sink to the bottom of any sample.
BLOOD PLASMA
Blood plasma is the liquid component of blood that constitutes approximately 55% of its total volume.
It is a light amber-colored fluid that serves several critical functions in the body.
Plasma is primarily composed of water (about 92%), with the remaining content consisting of plasma proteins, electrolytes, hormones, nutrients, and waste products.
Plasma proteins
Plasma proteins, which make up about 7% of plasma, are normally retained within the blood, because they are too big to escape through the capillary pores into the tissues.
They are largely responsible for creating the osmotic pressure of blood, which keeps plasma fluid within the circulation.
If plasma protein levels fall, because of either reduced production or loss from the blood vessels, osmotic pressure is also reduced, and fluid moves into the tissues (oedema) and body cavities.
Plasma proteins CONT …
- Plasma Proteins include albumin, immunoglobulins, fibrinogen
- Plasma viscosity (thickness) is due to plasma proteins, mainly albumin and fibrinogen.
Plasma proteins, with the exception of immunoglobulins, are formed in the liver.
Albumins
These are the most abundant plasma proteins (about 60% of total) and their main function is to maintain normal plasma osmotic pressure.
Albumins also act as carrier molecules for free fatty acids, some drugs and steroid hormones.
Globulins
Their main functions are:
as antibodies (immunoglobulins), which are complex proteins produced by lymphocytes that play an important part in immunity.
They bind to, and neutralise, foreign materials (antigens) such as microorganisms.
Transportation of some hormones and mineral salts, e.g. thyroglobulin carries the hormone thyroxineand transferrin carries the mineral iron inhibition of some proteolytic enzymes, e.g. α2 macroglobulin inhibits trypsin activity.
BLOOD CELLS
Blood cells are specialized cells produced through a process known as hematopoiesis, primarily found in the blood.
They play crucial roles in various physiological functions, including oxygen transport, immune defense, and blood clotting.
- There are three main types of blood cells:
- Red blood cells (erythrocytes)
- White blood cells (leukocytes)
Platelets (thrombocytes).
SUMMARY OF BLOOD CONSTITUENTS
FUNCTIONS OF BLOOD
- The major functions of blod includes;
Oxygen Transport
Nutrient Distribution
Waste Removal
Hormone Transport
Temperature Regulation
- pH Balance
Fluid Balance
Immune Response
Clotting Mechanism
CLASSIFICATION OF BLOOD CELLS
Blood cells can be classified into three main types: red blood cells, white blood cells, and platelets. Each type has distinct functions and characteristics.
RED BLOOD CELLS
Red blood cells are the most abundant type of blood cell, accounting for approximately 40 to 45 percent of the blood’s volume.
Their primary function is to transport oxygen from the lungs to the body’s tissues and return carbon dioxide from the tissues back to the lungs for exhalation.
Red blood cells contain hemoglobin, a protein that binds oxygen and gives blood its red color.
They are characterized by their biconcave disk shape, which allows for flexibility as they navigate through various sizes of blood vessels.
RED BLOOD CELLS CONT..
Red blood cells are biconcave discs; they have no nucleus, and their diameter is about 7 micrometres.
Their main function is in gas transport, mainly of oxygen, but they also carry some carbon dioxide.
Their characteristic shape is suited to their purpose; the biconcavity increases their surface area for gas exchange, and the thinness of the central portion allows fast entry and exit of gases.
RED BLOOD CELLS CONT..
The cells are flexible so they can squeeze through narrow capillaries, and contain no intracellular organelles, leaving more room for haemoglobin.
Haemoglobin is the large pigmented protein responsible for gas transport.
erythroPOIESIS
The process of development of red blood cells from stem cells takes about 7 days and is called erythropoiesis.
Erythrocytes are produced in red bone marrow, which is present in the ends of long bones and in flat and irregular bones.
- They pass through several stages of development before entering the blood.
Their life span in the circulation is about 120 days.
SITES FOR ERYTHROPOIESIS
Prior to birth, hemopoiesis occurs in a number of tissues, beginning with the yolk sac of the developing embryo, and continuing in the fetal liver, spleen, lymphatic tissue, and eventually the red bone marrow.
Following birth, most hemopoiesis occurs in the red marrow, a connective tissue within the spaces of spongy (cancellous) bone tissue.
In children, hemopoiesis can occur in the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus.
SITES FOR ERYTHROPOIESIS
Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements.
This process is referred to as extramedullary hemopoiesis (meaning hemopoiesis outside the medullary cavity of adult bones).
When a disease such as bone cancer destroys the bone marrow, causing hemopoiesis to fail, extramedullary hemopoiesis may be initiated.
erythroPOIESIS CONT…
The immature cells are released into the bloodstream as reticulocytes, and then mature into erythrocytes over a day or two within the circulation.
During this time, they lose their nucleus and therefore become incapable of division.
MATURATION OF ERYTHROCYTE
Both vitamin B12 and folic acid are required for red blood cell synthesis.
They are absorbed in the intestines, although vitamin B12 must be bound to intrinsic factor to allow absorption to take place.
Both vitamins are present in dairy products, meat and green vegetables.
The liver usually contains substantial stores of vitamin B12, several years’ worth, but signs of folic acid deficiency appear within a few months.
MATURATION OF ERYTHROCYTE
PICTURE SHOWING RED BLOOD CELLS
Differentiation of Formed Elements from Stem Cells
All formed elements arise from stem cells of the red bone marrow.
Recall that stem cells undergo mitosis plus cytokinesis (cellular division) to give rise to new daughter cells: One of these remains a stem cell and the other differentiates into one of any number of diverse cell types.
Stem cells may be viewed as occupying a hierarchal system, with some loss of the ability to diversify at each step.
Differentiation of Formed Elements from Stem Cells
- The totipotent stem cell is the zygote, or fertilized egg.
The totipotent (toti- = “all”) stem cell gives rise to all cells of the human body.
The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting fetal membranes.
Differentiation of Formed Elements from Stem Cells
Beneath this level, the mesenchymal cell is a stem cell that develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood, but not epithelium, muscle, and nervous tissue.
One step lower on the hierarchy of stem cells is the hematopoietic stem cell, or hemocytoblast.
All of the formed elements of blood originate from this specific type of cell.
HAEMATOPIOESIS
Hemopoiesis begins when the hematopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate.
- One daughter cell remains a hematopoietic stem cell, allowing hemopoiesis to continue.
The other daughter cell becomes either of two types of more specialized stem cells.
Hemopoietic Growth Factors
Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels.
Thrombopoietin, another glycoprotein hormone, is produced by the liver and kidneys. It triggers the development of megakaryocytes into platelets.
Cytokines are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. Stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease.
Haemoglobin
Haemoglobin is a large, complex protein containing a globular protein (globin) and a pigmented iron containing complex called haem. Each haemoglobin molecule contains four globin chains and four haem units, each with one atom of iron.
As each atom of iron can combine with an oxygen molecule, this means that a single haemoglobin molecule can carry up to four molecules of oxygen.
An average red blood cell carries about 280 million haemoglobin molecules, giving each cell a theoretical oxygen-carrying capacity of over a billion oxygen molecules.
Haemoglobin CONT …
Control of erythropoiesis
Red cell numbers remain fairly constant, because the bone marrow produces erythrocytes at the rate at which they are destroyed.
This is due to a homeostatic negative feedback mechanism. The hormone that regulates red blood cell production is erythropoietin, produced mainly by the kidney.
Control of erythropoiesis CONT …
The primary stimulus to increased erythropoiesis is hypoxia, i.e. deficient oxygen supply to body cells.
This occurs when: the oxygen-carrying power of blood is reduced by, e.g., haemorrhage or excessive erythrocyte breakdown (haemolysis) due to disease the oxygen tension in the air is reduced, as at high altitudes.
Control of erythropoiesis CONT …
function of erythrocytes
Oxygen transport
When all four oxygen-binding sites on a haemoglobin molecule are full, it is described as saturated.
Haemoglobin binds reversibly to oxygen to form oxyhaemoglobin, according to the equation:
WHICH SYRINGE CONTAINS MORE OXYGENATED BLOOD, 2 TOPS OR 3 BOTTOMS?
function of erythrocytes CONT …
As the oxygen content of blood increases, its colour changes too. Blood rich in oxygen is bright red because of the high levels of oxyhaemoglobin it contains, compared with blood with lower oxygen levels, which is dark bluish in colour because it is not saturated.
The association of oxygen with haemoglobin is a loose one, so that oxyhaemoglobin releases its oxygen readily, especially under certain conditions.
Destruction of erythrocytes
The life span of erythrocytes is about 120 days and their breakdown, or haemolysis, is carried out by phagocytic reticuloendothelial cells.
These cells are found in many tissues but the main sites of haemolysis are the spleen, bone marrow and liver.
As erythrocytes age, their cell membranes become more fragile and so more susceptible to haemolysis.
Iron released by haemolysis is retained in the body and reused in the bone marrow to form new haemoglobin molecules.
Destruction of erythrocytes CONT ..
Biliverdin is formed from the haem part of the haemoglobin.
It is almost completely reduced to the yellow pigment bilirubin, before being bound to plasma globulin and transported to the liver.
In the liver it is changed from a fat-soluble to a water-soluble form to be excreted as a constituent of bile.
Blood groups
Individuals have different types of antigen on the surfaces of their red blood cells. These antigens, which are inherited, determine the individual’s blood group.
In addition, individuals make antibodies to these antigens, but not to their own type of antigen, since if they did the antigens and antibodies would react, causing a transfusion reaction, which can be fatal.
These antibodies circulate in the bloodstream and the ability to make them, like the antigens, is genetically determined and not associated with acquired immunity.
Blood groups CONT …
If individuals are transfused with blood of the same group, i.e. possessing the same antigens on the surface of the cells, their immune system will not recognise them as foreign and will not reject them.
However, if they are given blood from an individual of a different blood type, i.e. with a different type of antigen on the red cells, their immune system will mount an attack upon them and destroy the transfused cells.
This is the basis of the transfusion reaction; the two blood types, the donor and the recipient, are incompatible.
Blood groups CONT …
There are many different collections of red cell surface antigens, but the most important are the ABO and the Rhesus systems.
The ABO system
About 55% of the population has either A-type antigens (blood group A), B-type antigens (blood group B) or both (blood group AB) on their red cell surface.
The remaining 45% have neither A nor B type antigens (blood group O).
The ABO system
The corresponding antibodies are called anti-A and anti-B.
Blood group A individuals cannot make anti-A (and therefore do not have these antibodies in their plasma), since otherwise a reaction to their own cells would occur; they do, however, make anti-B.
Blood group B individuals, for the same reasons, make only anti-A. Blood group AB make neither, and blood group O make both anti-A and anti-B
PART II
Leukocytes (white blood cells)
These cells have an important function in defence and immunity. Leukocytes are the largest blood cells but they account for only about 1% of the blood volume. They contain nuclei and some have granules in their cytoplasm. There are two main types:
- granulocytes (polymorphonuclear leukocytes)
- neutrophils, eosinophils and basophils
- agranulocytes
- monocytes and lymphocytes.
Rising white cell numbers in the bloodstream usually indicate a physiological problem, e.g. infection, trauma or malignancy.
Granulocytes (polymorphonuclear leukocytes)
During their formation, granulopoiesis, they follow a common line of development through myeloblast to myelocyte before differentiating into the three types.
- All granulocytes have multilobed nuclei in their cytoplasm.
- Their names represent the dyes they take up when stained in the laboratory.
- Eosinophils take up the red acid dye, eosin;
- Basophils take up alkaline methylene blue;
Neutrophils are purple because they take up both dyes.
Granulocytes (polymorphonuclear leukocytes)
Neutrophils
These small, fast and active scavengers protect the body against bacterial invasion, and remove dead cells and debris from damaged tissues.
They are attracted in large numbers to any area of infection by chemical substances called chemotaxins, which are released by damaged cells. Neutrophils are highly mobile, and squeeze through the capillary walls in the affected area by diapedesis.
Neutrophils CONT …
Their numbers rise very quickly in an area of damaged or infected tissue. Once there, they engulf and kill bacteria by phagocytosis.
Their nuclei are characteristically complex, with up to six lobes, and their granules are lysosomes containing enzymes to digest engulfed material.
Neutrophils live on average 6–9 hours in the bloodstream. Pus that may form in an infected area consists of dead tissue cells, dead and live microbes, and phagocytes killed by microbes.
Eosinophils
Eosinophils, although capable of phagocytosis, are less active in this than neutrophils; their specialised role appears to be in the elimination of parasites, such as worms, which are too big to be phagocytosed.
They are equipped with certain toxic chemicals, stored in their granules, which they release when the eosinophil binds to an infecting organism.
Eosinophils CONT …
Eosinophils are often found at sites of allergic inflammation, such as the asthmatic airway and skin allergies.
There, they promote tissue inflammation by releasing their array of toxic chemicals, but they may also dampen down the inflammatory process through the release of other chemicals, such as an enzyme that breaks down histamine
Basophils
Basophils, which are closely associated with allergic reactions, contain cytoplasmic granules packed with heparin (an anticoagulant), histamine (an inflammatory agent) and other substances that promote inflammation.
Usually the stimulus that causes basophils to release the contents of their granules is an allergen (an antigen that causes allergy) of some type. This binds to antibody-type receptors on the basophil membrane.
A cell type very similar to basophils, except that it is found in the tissues, not in the circulation, is the mast cell. Mast cells release their granule contents within seconds of binding an allergen, which accounts for the rapid onset of allergic symptoms following exposure to, for example, pollen in hay fever
Agranulocytes
- The monocytes and lymphocytes make up 25 to 50% of the total leukocyte count.
They have a large nucleus and no cytoplasmic granules.
Monocytes
These are the largest of the white blood cells.
Some circulate in the blood and are actively motile and phagocytic while others migrate into the tissues where they develop into macrophages.
Both types of cell produce interleukin 1, which: acts on the hypothalamus, causing the rise in body temperature associated with microbial infections stimulates the production of some globulins by the liver enhances the production of activated T-lymphocytes.
Macrophages have important functions in inflammation and immunity.
The monocyte–macrophage system
This is sometimes called the reticuloendothelial system, and consists of the body’s complement of monocytes and macrophages.
Some macrophages are mobile, whereas others are fixed, providing effective defence at key body locations.
The monocyte–macrophage system CONT ..
Collections of fixed macrophages include:
synovial cells in joints, Langerhans cells in the skin, microglia in the brain, hepatic macrophages (Kupffer cells) in the liver, alveolar macrophages in the lungs, sinus-lining macrophages (reticular cells) in the spleen, lymph nodes and thymus gland, mesangial cells in the glomerulus of nephrons in the kidney, osteoclasts in bone.
Macrophages have a diverse range of protective functions.
They are actively phagocytic and are much more powerful and longer-lived than the smaller neutophils.
Lymphocytes
Lymphocytes are smaller than monocytes and have large nuclei. They circulate in the blood and are present in great numbers in lymphatic tissue such as lymph nodes and the spleen.
Lymphocytesdevelop from pluripotent stem cells in red bone marrow and from precursors in lymphoid tissue, then travel in the blood to lymphoid tissue elsewhere in the body where they are activated, i.e. they become immunocompetent which means they are able to respond to antigens (foreign material).
Examples of antigens include:
cells regarded by lymphocytes as abnormal, e.g. cells that have been invaded by viruses, cancer cells, transplanted tissue, pollen from flowers and plants fungi, bacteria some large molecule drugs, e.g. penicillin, aspirin.
Although all lymphocytes originate from one type of stem cell, when they are activated in lymphatic tissue, two distinct types of lymphocyte are produced – T-lymphocytes and B-lymphocytes.
Platelets (thrombocytes)
These are very small non-nucleated discs, 2 to 4 μm in diameter, derived from the cytoplasm of megakaryocytes in red bone marrow.
They contain a variety of substances that promote blood clotting, which causes haemostasis (cessation of bleeding)
Platelets (thrombocytes) CONT …
The normal blood platelet count is between 200 × 109/l and 350 × 109/l (200 000 to 350 000/mm3).
The control of platelet production is not yet entirely clear but one stimulus is a fall in platelet count.
The kidneys release a substance called thrombopoietin, which stimulates platelet synthesis.
Platelets (thrombocytes) CONT …
The life span of platelets is between 8 and 11 days and those not used in haemostasis are destroyed by macrophages, mainly in the spleen.
About a third of platelets are stored within the spleen rather than in the circulation; this is an emergency store that can be released as required to control excessive bleeding.
Haemostasis
Hemostasis is the body’s natural process to prevent and stop bleeding when an injury occurs.
When a blood vessel is damaged, loss of blood is stopped and healing occurs in a series of overlapping processes, in which platelets play a vital part.
The more badly damaged the vessel wall is, the faster coagulation begins, sometimes as quickly as 15 seconds after injury.
1 Vasoconstriction
When platelets come into contact with a damaged blood vessel, their surface becomes sticky and they adhere to the damaged wall.
- They then release serotonin (5-hydroxytryptamine), which constricts
(narrows) the vessel, reducing blood flow through it.
Other chemicals that cause vasoconstriction, e.g. thromboxanes, are released by the damaged vessel itself
2 Platelet plug formation
The adherent platelets clump to each other and release other substances, including adenosine diphosphate (ADP), which attract more platelets to the site.
Passing platelets stick to those already at the damaged vessel and they too release their chemicals.
This is a positive feedback system by which many platelets rapidly arrive at the site of vascular damage and quickly form a temporary seal – the platelet plug. Platelet plug formation is usually complete by 6 minutes after injury.
3 Coagulation (blood clotting)
This is a complex process that also involves a positive feedback system and only a few stages are included here.
The factors involved are 12 in number but are named from I-XIII, where number VI is universally unavailable. Their numbers represent the order in which they were discovered and not the order of participation in the clotting process.
3 Coagulation (blood clotting)
These clotting factors activate each other in a specific order, eventually resulting in the formation of prothrombin activator, which is the first step in the final common pathway. Prothrombin activates the enzyme thrombin, which converts inactive fibrinogen to insoluble threads of fibrin.
As clotting proceeds, the platelet plug is progressively stabilised by increasing amounts of fibrin laid down in a three-dimensional meshwork within it. The maturing blood clot traps blood cells and is much stronger than the rapidly formed platelet plug.
CLOTTING FACTORS
I Fibrinogen
- II Prothrombin
III Tissue factor (thromboplastin)
CLOTTING FACTORS CONT …
- IV Calcium (Ca2+)
- V Labile factor, proaccelerin, Ac-globulin
- VII Stable factor, proconvertin
- VIII Antihaemophilic globulin (AHG), antihaemophilic factor A
- IX Christmas factor, plasma thromboplastin component (PTA), antihaemophilic factor B
- X Stuart Prower factor
- XI Plasma thromboplastin antecedent (PTA), antihaemophilic factor C
- XII Hageman factor
- XIII Fibrin stabilising factor
- (There is no factor VI)
Vitamin K is essential for synthesis of factors II, VII, IX and X
CLOTTING PATHWAYS
The final common pathway can be initiated by two processes which often occur together: the extrinsic and intrinsic pathways.
The extrinsic pathway is activated rapidly (within seconds) following tissue damage.
Damaged tissue releases a complex of chemicals called thromboplastin or tissue factor, which initiates coagulation.
The intrinsic pathway is slower (3–6 minutes) and is triggered when blood comes into contact with damaged blood vessel lining (endothelium).
