Blood Physiology PDF

# Introduction Of Blood - Blood is a red fluid contained within a closed system (cardiovascular system). - It circulates through this system by the pumping action of the heart. - The normal total blood volume is about 5-6 liters in man (70 Kg) or 80/0 of body weight. - About 55% of this volume is p...

# Introduction Of Blood - Blood is a red fluid contained within a closed system (cardiovascular system). - It circulates through this system by the pumping action of the heart. - The normal total blood volume is about 5-6 liters in man (70 Kg) or 80/0 of body weight. - About 55% of this volume is plasma and 45% is blood cells (hematocrite value). ## Blood Components Blood consists of: 1. **Plasma** 2. **Blood Cells:** - Red blood cells (RBCs) - White blood cells (WBCs) - Blood platelets ## Composition of Blood The composition of blood can be described as follows: | Component | Description | | ------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------- | | **Whole Blood** | This refers to the complete blood, including both plasma and formed elements. | | **Plasma** | This is the liquid portion of blood, comprising approximately 55% of the blood volume. It includes components such as amino acids, proteins, electrolytes, etc. | | **Formed Elements** | This part of the blood consists of various cells, including platelets, leukocytes (white blood cells), and erythrocytes (red blood cells). | | **Platelets** | They play a crucial role in blood clotting. | | **Leukocytes** | These are white blood cells that contribute to the immune system's defense against infections and diseases. | | **Erythrocytes** | These are red blood cells responsible for carrying oxygen to tissues and removing carbon dioxide. | | **Granulocytes** | These are a type of leukocyte that includes neutrophils, basophils, and eosinophils. | | **Agranulocytes** | This group of leukocytes includes lymphocytes and monocytes. | | **Neutrophils** | They are the most abundant type of granulocyte and effectively fight bacterial infections. | | **Basophils** | These cells release histamine, which contributes to allergic reactions and inflammation. | | **Eosinophils** | They combat parasitic infections and play a role in allergic reactions. | | **Lymphocytes** | These participate in the body's immune response by recognizing and eliminating foreign invaders. | | **Monocytes** | They develop into macrophages, which engulf and destroy foreign particles and cellular debris. | ## Functions of Blood - **Transport:** - Transports substances absorbed from the alimentary canal to the tissues. - Transports oxygen from the lungs to the tissues. - Returns carbon dioxide from the tissues to the lungs. - Returns the other products of metabolism from the tissues to the kidneys. - Distributes hormones from the endocrine glands that regulate cell function. - **Regulate body temperature.** - **Clotting of blood:** to stop bleeding from wounds. - **Fighting against invading organisms.** ## The Specific Gravity of Blood - Whole blood: 1060 - Red cells: 1090 - Plasma: 1030 - The cells are heavier than the plasma, so they sediment to the bottom when blood is centrifuged. - Using a special centrifugation rate, white cells and platelets can be separated into a middle layer between the red cells and plasma because they are lighter than red cells but heavier than the plasma. ## Composition of Blood: Diagram A diagram shows a test tube of blood that has been centrifuged. The following composition is shown: - Plasma (55%) - White blood cells & platelets (4%) - Red blood cells (41%) ## Plasma - Plasma is the fluid portion of the blood. - Normal plasma volume is about 5% of the body weight or 3500 ml in a 70-kg man. - Plasma clots on standing. - Plasma remains fluid only if an anti-coagulant is added. - If the whole blood is allowed to clot and the clot is removed, the remaining fluid is called serum. ## Plasma Components - Water: 90% - Plasma proteins: 7.1% - Nutrient materials and waste products: 2% - Inorganic constituents: 0.9% as Na+, K+, Cu++, and Mg++. ## Plasma Proteins - The plasma proteins consist of: - **Albumin**: 55% - **Globulin**: 38% (The globulin fraction is subdivided into α1, α2, β1, β2, and γ globulin) - **Fibrinogen**: 7% - The **Albumin/Globulin ratio** is about 1.5, but it can vary under pathological conditions. These variations are important for the diagnosis of some diseases. ## Origin of Plasma Proteins - **Tissue proteins** contribute. - **Dietary proteins**, especially those with high biological value, play a role. ## Site of Synthesis - Most plasma proteins, such as serum albumin, fibrinogen, and prothrombin, are synthesized in the **liver.** - However, **globulins** are also formed in other tissues, like the reticulo-endothelial cells and lymphoid tissue. ## Functions of Plasma Proteins - **Tissue metabolism**: Plasma proteins can be used by the tissues for their metabolism, especially in cases of starvation. - **Blood coagulation**: Some plasma proteins like fibrinogen, prothrombin, and thromblastin, are essential for blood clotting. - **Regulation of blood volume**: The capillary walls are impermeable to the proteins found in plasma. This means the proteins are present in higher concentrations in plasma compared to tissue fluids, creating an osmotic pressure that pulls water from the tissues into the blood. This pressure is about 25 mmHg. ## Diagram of Exchange at the Capillaries A drawing shows the exchange of substances at the capillary beds. The diagram shows the following: - At the **arterial end** of a capillary, the blood pressure pushes fluid outward due to higher blood pressure than osmotic pressure. This fluid contains oxygen, amino acids, and glucose. - At the **venous end**, the osmotic pressure draws fluid back towards the capillary due to a higher osmotic pressure than blood pressure. This fluid contains waste products like carbon dioxide and water. ## Viscosity of Blood - Whole blood is five times more viscous than water. - Plasma proteins are responsible for the viscosity of blood. - This is a key factor in maintaining arterial blood pressure. ## Buffer Action - Plasma proteins help maintain a constant pH of the blood. - They are responsible for 7% of the buffering power of the blood. ## Immunity - **Immunoglobulins** (antibodies), found in the γ - globulins protect against microorganisms and their toxins. ## Transport Functions - Plasma proteins play a crucial role in the transport of hormones. - Albumin serves as a carrier for: - Ca++, - Iron, - Fatty acids, - Amino acids, - Enzymes, and - Vitamins. ## Hypoproteinemia - **Definition**: Hypoproteinemia indicates low plasma protein levels. - **Causes**: - Prolonged starvation - Intestinal disease (e.g., malabsorption) - Liver disease (reduced hepatic protein production) - Renal disease (loss of albumin in the urine) - Because of the decrease in plasma osmotic pressure, **edema** tends to develop. ## Red Blood Cells - **Other names:** Red blood cells are also known as **erythrocytes**. - **Description**: They are normally circular non-nucleated biconcave discs, with a diameter of about 7.5 µm and a thickness of 2 µm. - **Shape change**: Their shape can change as they pass through capillaries. - **Composition**: Red blood cells contain: - 60% Water - 34% Hemoglobin (HB) - 6% Stroma and inorganic substances ## Erythrocyte Count - The average normal red cell count is: - 5.4 million/cubic mm in men - 4.8 million/cubic mm in women ## Life Span - RBCs survive in the circulation for an average of 120 days. - At the end of their life, they are broken down. - Broken RBCs are removed from the circulation by reticulo-endothelial cells in the lymph glands, liver, and spleen. ## Hemoglobin Content of the Blood - **Values**: - 15.6 gm/100 ml for adult men - 14.8 gm/100 ml for adult women - **Composition**: Hemoglobin (HB) is composed of: - **Globulin**: Contributes 95% of the molecule. - **Haem**: Contributes 5% of the molecule. The haem portion contains **four atoms of iron**. - The combination of globulin and haem gives hemoglobin its important physiological properties: - **Solubility**: Hemoglobin is soluble in the blood. - **Oxygen binding**: Hemoglobin can reversibly bind to oxygen without the help of oxidizing or reducing agents. - The hemoglobin of different animals is not identical, but the differences are primarily in the globulin portion. - Fetal hemoglobin is different from that of its mother. ## Functions of RBCs - **Transport:** - RBCs transport oxygen from the lungs to the tissues; this is called **oxygenated hemoglobin,** and it gives arterial blood its red color. - RBCs carry carbon dioxide from the tissues back to the lungs; this is called **reduced hemoglobin,** and it gives venous blood its blue color. - **Protection of Hemoglobin**: RBCs keep hemoglobin inside them, providing the following benefits: - **Protection from Reticulo-endothelial cells:** Hemoglobin is protected from being broken down by these cells. - **Prevention of Kidney Blockage:** Hemoglobin will not precipitate in kidney tubules if it remains inside red blood cells. - **Regulation of Osmotic Pressure:** Free hemoglobin in the circulation would increase osmotic pressure, hindering the formation of tissue fluid. - **Surface area**: The biconcave shape of RBCs gives them a large surface area, facilitating the rapid exchange of gases with hemoglobin. - **Flexibility**: RBCs can squeeze their way through narrow capillaries without permanent damage due to the flexible nature of their cell wall. - **Inactivation of Substances**: RBCs can inactivate physiologically active substances that could potentially pass into cells, such as histamine. - **Carbonic Anhydrase**: RBCs contain carbonic anhydrase enzyme, which catalyzes the reaction between carbon dioxide and water. This allows blood to transport carbon dioxide from tissues to the lungs in the form of bicarbonate ions (HCO3-). ## Genesis of RBCs - Erythropoiesis - **Sites of erythropoiesis**: The process of red blood cell formation, erythropoiesis, occurs in different sites depending on age: - **Fetal Life**: The spleen and liver are primary sites. - **Children**: All bone marrow is active in this process. - **Adults**: Erythropoiesis primarily occurs in the bone marrow of flat bones, including the: - Skull - Vertebrae - Ribs - Sternum - Iliac crests - Proximal ends of long bones - **Stages of erythropoiesis**: 1. **Proerythroblast**: The initial stage of red blood cell formation involves the proerythroblast. 2. **Basophilic Erythroblast**: The proerythroblast divides to create the basophilic erythroblast. This cell has low amounts of hemoglobin, and it stains heavily with basic dyes. 3. **Polychromatic Erythroblast**: The basophilic erythroblast further divides, becoming polychromatic, containing a higher amount of hemoglobin and displaying a mixture of basophilic and acidophilic staining properties. 4. **Orthochromatophilic Erythroblast**: This stage is characterized by a loss of basophilia and the presence of acidophilic staining. 5. **Reticulocyte**: The orthochromatophilic erythroblast nucleus shrinks further, forming a reticulocyte. These cells show a meshwork of blue-stained ribosomal RNA remnants. 6. **Mature Erythrocyte**: The reticulocyte proceeds to lose its remaining ribosomes, becoming a mature red blood cell, lacking a nucleus. Typically, 1-2% of circulating blood cells are reticulocytes. ## Functions of Erythropoietin - **Erythropoietin**: This hormone plays a vital role in stimulating red blood cell production. - **Production**: Erythropoietin is produced by the kidney in response to low blood oxygen levels. The liver can also contribute to erythropoietin production. - **Mechanism**: Erythropoietin promotes red blood cell production in three ways: - **Pronormoblast production**: Erythropoietin stimulates the production of pronormoblasts, the precursors of erythrocytes. - **Shortened time in the normoblast stage**: The time spent in the normoblast stage of development is shortened, accelerating the process of red blood cell formation. - **Early release of reticulocytes**: The early release of reticulocytes into the bloodstream increases the oxygen-carrying capacity of the blood. ## Dietary Factors - **Dietary proteins**: Animal proteins found in the liver and muscles are especially beneficial for hemoglobin regeneration compared to other protein sources. - **Iron**: Iron is crucial for the formation of hemoglobin: - It is absorbed from the small intestine in the ferrous state. - The mucosa of the small intestine forms a protein called **apoferritin**. Apoferritin binds with iron to create **ferritin**. - Ferritin then releases iron into the blood, which is transported as **transferritin** to the bone marrow. - Iron deficiency can lead to **iron deficiency anemia**. - **Copper**: Copper is essential for hemoglobin synthesis. ## Vitamins - **Vitamin B12 and folic acid**: These vitamins are essential for erythrocyte maturation. - **Mechanism**: Vitamin B12 and folic acid play a vital role in DNA synthesis, which is crucial for cell division. - Vitamin B12 (extrinsic factor) is absorbed from the intestines. - The stomach mucosa produces a protein called **intrinsic factor**, which is required for the absorption of vitamin B12. - A deficiency of Vitamin B12 results in **pernicious anemia**. - This can occur due to: - A lack of the vitamin in the diet - A failure in its absorption (commonly due to the atrophy of the gastric mucosa) ## Hormones - **Androgens, thyroxine, and cortical hormones**: These hormones, at physiological doses, can increase erythropoiesis. ## The Liver - The liver plays a significant role in the regeneration of red blood cells. - Its roles include: - Storing iron, copper, and vitamin B12. - Contributing to the formation of globulin, which is used by bone marrow in globulin synthesis. ## The Bone Marrow - The bone marrow is the primary site for erythropoiesis. - If bone marrow is destroyed by X-rays, chemical toxins, or bacterial toxins, **aplastic anemia** can occur. ## Anemia - **Definition**: Anemia is characterized by either low red blood cell count or low hemoglobin content. - **Types of Anemia**: 1. **Blood loss anemia**: This arises from rapid hemorrhage. The body replaces the lost plasma fluid in 1-3 days. However, if the blood loss is chronic, iron cannot be absorbed from the intestines as quickly as it is lost, leading to the production of smaller, hemoglobin-deficient red blood cells, which are **microcytic and hypochromic.** 2. **Aplastic anemia**: This type of anemia results when bone marrow aplasia occurs. This means there is a lack of functioning bone marrow, leading to reduced production of all blood cells, RBCs, WBCs, and platelets. This can happen due to exposures to excessive X-rays, gamma radiation, industrial chemicals, or even drugs. 3. **Hemolytic anemia**:This occurs due to the rapid destruction of red blood cells, as seen in sickle cell anemia. Sickle cell anemia results from an abnormal type of hemoglobin called **hemoglobin S**. 4. **Megaloblastic anemia**: This results from a deficiency in vitamin B12, folic acid, or intrinsic factor, leading to the production of large red blood cells known as **megaloblasts**. These cells are **macrocytic (larger) and hyperchromic (richer in hemoglobin content)**. A common cause might be atrophy of the stomach mucosa, which is seen with pernicious anemia. Surgical removal of the stomach can also lead to megaloblastic anemia. 5. **Hemolytic anemia**: This type of anemia results from the destruction of red blood cells, primarily due to abnormalities. - **In hereditary spherocytosis**: The red blood cells are spherocytic, meaning they have a spherical shape. They are also smaller in size and extremely fragile. They hemolyze easily in a hypotonic sodium chloride solution. This fragility makes hereditary spherocytosis one of the most common causes of hereditary hemolytic anemia. - **In thalassemia**: The red blood cells are small in size due to reduced hemoglobin production. - **In sickle cell anemia**: The red blood cells contain abnormal hemoglobin, called hemoglobin S, which causes them to become sickle-shaped, leading to issues with blood flow and hemolysis. The red blood cells are also more prone to destruction. - **In erythroblastosis fetalis**: This condition occurs when an Rh-positive fetus is exposed to antibodies from an Rh-negative mother. The antibodies attack Rh-positive red blood cells, making them more fragile and leading to hemolysis, causing the newborn to have serious anemia. ## Red Cell Fragility - **Osmotic Pressure**: The osmotic pressure of the surrounding solution determines whether red blood cells shrink or swell. - In a **hypertonic solution** (higher osmotic pressure than that of normal blood plasma), RBCs lose water and shrink. - In a **hypotonic solution** (lower osmotic pressure than that of normal blood plasma), RBCs gain water and swell, potentially becoming spherical and losing hemoglobin (hemolysis). - A **0.9% sodium chloride solution** is isotonic with normal blood plasma. This means the solution and the red blood cells have equal osmotic pressure. - **Normal Fragility**: Red blood cells normally begin to lyse in a 0.5% saline solution; 50% lysis occurs in 0.4% saline, and complete lysis happens in 35% saline. ## Diagram of Red Blood Cell Response to Osmotic Pressure A diagram shows a red blood cell's response to different osmotic pressures. - **Hypertonic Solution**: The red blood cells shrink and become crenated (having a notched or scalloped surface). - **Isotonic Solution**: The red blood cells maintain a normal shape and size. - **Hypotonic Solution**: The red blood cells swell and potentially lyse (burst).