Blood Physiology – Human Physiology Notes Free Pdf

Blood is a part of the inner medium of an organism and plays a great role in keeping homeostasis in our body. Basically, blood is a circulating fluid tissue composed of fluid plasma and formed cellular elements. Blood physiology is very important topic in human physiology and main functions of blood: transport, homeostasis, defence.

Blood system is consist of: Blood, Hemopoietic organs, Organs of blood destruction (spleen, liver), Neurohumoral apparatus.

Blood Composition

Blood is made up of two parts:

• Plasma which is 55% of blood volume. Plasma is the fluid part of blood without the formed elements. It is made up of 90% water, 7-8% soluble proteins (albumins, globulins, clotting proteins), 1% carbon dioxide and 1% of salt which helps in maintaining pH of the blood.
• Formed cellular elements (erythrocytes, leukocytes, platelet cells) which makes 45% of the blood.
• Serum: it is the part of plasma but without clotting factors.

Hematocrit : % of total blood volume that blood cells occupy. Normal value is for male = 40-50%, for female = 37-48%, for newborn = 55%. It depends on sex, age, life conditions. Increase in hematocrit levels leads to blood stickiness that increase the load on heart function. Hematocrit levels increases in dehydration, polycythaemia and decreases in over-hydration and anemia.

Plasma Proteins

Types of plasma proteins

1. Albumin (35-50 g/L): it is the most common soluble protein which is produced in liver. Its main function is to maintain osmotic pressure between blood and tissue fluid, transport different types of materials like vitamins etc. Albumin also plays an important role in creation of oncotic pressure, decrease of which can lead to development of edema.
2. Globulins (20-40 g/L): It is of three types alpha, beta and gamma, also synthesized in mainly in liver. The main function is transport and protection.
3. Clotting factors: They are 12 types; important one is fibrinogen (2-4 g/L). They participate in clotting process. Fibrinogen plays important role in process of formation of blood clot and fibrin plug.

Functions of plasma proteins

1. Transport function- They bind with inorganic substances (ions, water) and organic substances (hormones, biologically active substances) and transport them to different sites in our body.
2. Trophic function- Proteins are source of amino acids and energy. The breaking down of plasma proteins provide amino acids which with peripheral tissues is used for formation of specific organ proteins.
3. Enzymatic function- There are lot of protein-enzyme in the plasma eg. Enzymes of blood clotting.
4. Hemostatic function- Plasma proteins have biochemical system of blood plasma, blood clotting system, anticoagulatory system, fibrinolytic system.
5. Maintaining pH of blood- Proteins form protein buffer system which helps in maintaining pH of blood by acting as base in acidic medium and acid in basic medium.
6. Source of biologically active substances. Eg. kinins, angiotensin etc.
7. Protective function- participate in nonspecific and specific immune responses. Eg. Complement protein system, interferons, inhibitors.
8. Making connections- Proteins participate in transferring of information that affects genetic data of cells, provide growth factors, differentiation of cells and tissues.
9. Create oncotic pressure- albumin creates oncotic pressure P_onc=25-30mmHg.

Properties of blood

Osmotic blood pressure

The main function of blood plasma is to create osmotic pressure which P_osm= 7.5atm. Osmosis is flow of solvent from low concentration of solute to higher concentration of solute through semi permeable membrane. NaCl plays important role in creation of osmotic pressure in our body.

• Solutions which have same osmotic pressure as our blood plasma are known as isotonic solutions. For example, 0.9% NaCl solution, Ringers solution etc.
• Solutions having higher osmotic pressure are called hypertonic solution. In this case water from erythrocytes leaves and shrink the cells causing plasmolysis.
• In hypotonic solution, water enters the erythrocyte cell causing swelling and leads to hemolysis of erythrocytes.

pH of the Blood

pH is measurement of acidity of a solution. Normal pH of blood is 7.45 (arterial blood) and 7.35 (venous blood).

If pH is more than 7.5, it is called alkalosis and less than 7.3 is called acidosis.

The constant normal level of pH is very important for functioning of biological systems. In our body, pH is maintained by different types of buffer systems.

Buffer System of Blood

Protein buffer system (in blood) – Protein buffer system is either intracellular or extracellular. They include basic group and acidic group of proteins which act as hydrogen ion donor to maintain the pH level.

Hemoglobin buffer system (inside erythrocytes) – It consist of HHb (acid) and KHb (base). It accounts for 75% of blood-buffer.

HHb + KOH –> KHb + H₂O (in acidosis)        KHb + HCl –> HHb + KCl (in alkalosis)

Phosphate buffer system (in kidneys) – This buffer system is comprised of two ions hydrogen phosphate HNa₂PO₄ (base) and dihydrogen phosphate ion H₂NaPO₄ (acid)

H₂NaPO₄ + NaOH –> HNa₂PO₄ + H₂O (in acidosis)      HNa₂PO₄ + HCl –> H₂NaPO₄ + NaCl (in alkalosis)

Bicarbonate buffer system (in lungs) – consist of H2CO3 (acid) and NaHCO3 (base)

HCl + NaHCO₃ –> H₂CO₃ + NaCl (in alkalosis)      NaOH + H₂CO₃ –> NaHCO₃ + H₂O (in acidosis)

Erythrocytes

They are formed in bone marrow (process – erythropoiesis), have biconcave disc shape and lack nucleus upon maturation. In embryonic life, produced by yolk sac and later by liver and spleen. After birth erythrocytes only produced by bone marrow. Production of RBC is stimulated by erythropoietin hormone produced by kidney and liver, principle stimulus is decrease of oxygen level. Vitamin B12 and folic acid is essential for maturation of erythrocytes. On average, 2 million RBCs are produced per second. RBCs have a lifespan of 120 days after which they undergo eryptosis, erythrocyte programmed cell death.

Average no. of RBCs in male = 3.9-5.5*10⁶ per mm³ and in female = 3.9-4.7*10⁶ per mm³

Main functions of Erythrocytes

The main function of RBCs is to transport oxygen with the help of hemoglobin throughout the body and carry CO2 out and maintain pH of blood.

Regulation of erythropoiesis

• Nervous – Sympathetic nervous system = stimulates erythropoiesis

Parasympathetic nervous system = inhibits erythropoiesis

• Humoral – Growth hormone, ACTC, Thyroxin and male hormones = stimulates, and female hormones = inhibits.

Destruction of erythrocytes

Red blood cells are broken down and hemoglobin is released. The globin part is converted to amino acids and reused. Iron is recycled and returned to bone marrow. The heme portion undergoes chemical changes and converted to bile pigments which gives color to feces and skin color when bruised.

Three types of RBC destruction

1. Mechanical – erythrocyte loses its elasticity and cannot pass through narrow vessels like in the spleen where it gets stuck and engulfed by macrophages.
2. Phagocytosis – there is mononuclear phagocyte system in liver and spleen. Macrophages detects erythrocytes which have sialic acid on their surface.
3. Hemolysis – destruction of erythrocyte with release of hemoglobin into the blood plasma. It is of five types; osmotic, chemical, mechanical, thermal, biological.

Leukocytes

Also known as white blood cells, they are translucent, have nuclei. Normal value is 4*10⁹ – 9*10⁹ per liter of blood. They are subdivided into granular and agranular leukocytes.

Main functions are protection, transport, metabolic and regeneration.

Neutrophils

lifespan 12-48 hours, stained with neutral dyes. Important role in nonspecific cellular immunity against microorganisms. First line of defense. Active phagocytes, capable of phagocyting 20-30 bacteria.

• Diapedesis – passage of neutrophils through the blood capillary into surrounding tissue.
• Chemotaxis – attraction of neutrophils and macrophages to the potential site of trauma.

Eosinophils

plays important role in parasitic infection, destruction of antigen-antibody complex, produce histaminase which destroys ingested histamine. It is chemo toxic and kill parasites.

Basophils

mediates hypersensitive reactions, binds with IgE and upon reaction with corresponding antigen releases vasoactive substances like histamine, heparin.

Monocytes

responsible for phagocytosis, appears at the site of inflammation after neutrophils. In tissues, they are known as macrophages and release cytokines. Show highest activity in acidic medium.

Lymphocytes

of two types; B-lymphocytes and T-lymphocytes and responsible for specific immune reactions.

• B-lymphocytes: produced in bone marrow and matured in lymphoid tissue of gut, appendix, tonsils. Plays important role in humoral immunity and producing immunoglobulins (antibodies).
• T-lymphocytes: produced in bone marrow and maturation in thymus gland. Essential for cellular immunity. Four types, T-killer, T-helper, T-suppressor, T-regulator (T-memory cells and T-amplifiers)

Blood Groups (ABO blood types)

Agglutinogens

they are the specific antigens, which are present on erythrocyte membrane.

Agglutinins

they are specific antibodies, which are present in blood plasma.

Type I (O) blood group

it has no agglutinogen but have both α,β agglutinins. They are known as universal donor and receive only from O blood group.

Type II (A) blood group

it has A agglutinogen and β (anti B) agglutinin. They can donate blood to A and AB blood group and can receive blood only from A blood group.

Type III (B) blood group

it has B agglutinogen and α (anti A) agglutinin. They can donate blood to B and AB blood group and can receive blood only from B blood group.

Type IV (AB) blood group

it has both A,B agglutinogen and no agglutinin. They are known as universal recipient and donate to only AB blood group.

Agglutination

process of clumping of erythrocytes to a particular antibody.

Types of agglutination

1. Direct – donor’s agglutinogen reacts with agglutinin of recipient.
2. Indirect (reversible) – recipient’s agglutinogen reacts with agglutinin of donor.

Rh factor

In 1940, Landsteiner and Winner found one more antigen on erythrocyte membrane of Macaque Rhesus monkey, thus named Rh-factor.

There are two blood groups in Rh system:

Rh+ – blood has antigen D

Rh- – blood does not have antigen D

Rules of blood transfusion

1. The blood should have same group and same rhesus factor.
2. The blood should be cross matched to prevent combination of same agglutinins of recipient and agglutinogens of donor.
3. According to rule of dilution, agglutinins of donor can be disregarded if transfused in small quantities (less than 250 mL) of blood.
4. Blood should not be transfused from same donor more than once.

Hemostasis

It is prevention of blood loss from a broken vessel and provides maintenance of blood fluidity.

Structure of hemostasis system

• Blood vessels wall
• Formed blood cells
• Biochemical systems of blood
  • Blood coagulation system
  • Anticoagulation system
  • Fibrinolytic system
  • Calicrein-kinine system

Mechanisms of Hemostasis

1. Vascular-platelet (primary, microcirculatory)

Provide stoppage of bleeding in the vessels of microcirculatory system. A vessel well and thrombocytes (platelet) participate in formation of clot.

Stages of vascular-platelet hemostasis:

• Spasm of damaged vessels – primary; under the influence of sympathetic nervous system and appears in first second of damage. Secondary; due to action of vasoconstriction substances (serotonin, epinephrine, norepinephrine) and appears after few seconds of damage.
• Adhesion of thrombocytes – adhesion occurs with the help of two factors that is negative charge of vessels at the site to damage is changes to positive charge and negatively charged platelets adhere to it. Second is slow down of movement of blood. Before attachment, platelets undergo shape change.
• Reversible platelet aggregation – is the aggregation of thrombocytes in the damage site and conglutination of platelet to one another and formation of platelet plug. It begins simultaneously with adhesion.
• Irreversible platelet aggregation – is platelet plug, under the influence of thrombin becomes impermeable to blood. Thrombin causes destruction of platelet membrane and its content is released into blood.
• Retraction of platelet plug – under the influence of thrombosthenin, platelet plug loses extra water and becomes hard.

2. Coagulatory hemostasis (secondary, microcirculatory)

It dominates in medium and large vessels. It includes in three phases:

• Formation of prothrombin factor – can be formed with the help of two mechanisms:
• Extrinsic = fast mechanism, lasts for 5-20 seconds. Reaction occurs on membrane of damaged cells. It is initiated by phospholipids which is released from damaged cells of vessels or connective tissue.
• 
• Intrinsic = slow mechanism, lasts for 5-7 minutes. Reaction occurs on membrane of damaged blood cells. Collagen fibers initiate the process.
• 
• Formation of thrombin – the prothrombin activator catalyzes conversion of prothrombin to thrombin. This is fast stage (2-5 seconds).
• Formation of fibrin – thrombin acts as an enzyme to convert fibrinogen to fibrin fibers that enmesh platelets, blood cells and plasma to form clot.
• Retraction – fibrin fibers are loose(soft). The process of retraction packs thrombus by contraction of protein thrombocystein. After retraction clot is packed two times and serum is removed and plasma cannot pass through it.
• Fibrinolysis – it is decomposition of fibrin clot. It begins simultaneously with retraction but proceeds at lower rate. The content of fibrinolytic system:
  • Plasminogen = not active but present always in blood plasma.
  • Plasmin = active enzyme, which is produced in result of effect to active proteases on plasminogen
  • Activators of fibrinolysis
  • Inhibitors of fibrinolysis

There is internal and external mechanism of fibrinolysis activation.

• Internal mechanism includes activation of factor XII and formation of kallikrein, which causes large amount of fibrinolysis activators to appear in blood.
• External mechanism is associated with tissue plasminogen activator (t-PA) and urokinase.

Anticoagulation System

Blood fluidity is maintained by several mechanisms:

1. Smooth surface of a vessel wall
2. Negative charge of vessel wall and formed blood elements, so they repeal each other
3. Thin fibrin layer on vessel wall which absorbs factors of blood clotting
4. Presence of anticoagulants in bloodstream.

Classification of anticoagulants

• Primary – antithrombin III, heparin, alpha-1 antithropsin, alpha-2 macroglobin
• Secondary – factor XI, antithrombin I, fibrin fibers, peptides

System of blood coagulation

• Blood
• Tissues
• Neurohumoral apparatus