Cardiovascular Physiology: Blood Composition

Cardiovascular Physiology: Blood

• Average adult blood volume is about 5 liters, or 6-8% of total body weight, which equals 80-85 ml/kg.
• Blood consists of approximately 45% formed elements (cellular component) and 55% fluid or plasma.
• Hematocrit (Hct) is the percentage of blood volume that is erythrocytes, with normal values being 42% for females and 45% for males.

Fluid Portion of the Blood

• Plasma, the straw-colored/pale-yellow liquid component, makes up 55% of blood volume and remains once cellular components are removed.
• Plasma contains water, electrolytes, hormones, enzymes, antibodies, proteins, and clotting factors.
• Serum is plasma without blood cells and clotting factors.
• Some blood tests, like those for albumin and liver panels, must be conducted only on serum.

Serum Levels and Assessment

• Substances are continuously exchanged between the interstitial fluid (IF) and both the plasma
• Materials are similarly exchanged between the interstitial fluid, organs, and cells
• Assessing blood samples (plasma or serum) provides information not only about the blood but also about the interstitial fluid, organ function, and cell function

Normal Plasma Values

• Blood volume: 80-85 ml/kg body weight.
• Blood osmolality: 285-295 mOsm.
• Blood pH: 7.38-7.44.
• Hematocrit for females: 36%-46%; for males: 41%-53%.
• Hemoglobin for females: 12-16 g/100 ml; for males: 13.5-17.5 g/100 ml.
• Red blood cell count: 4.50-5.90 million/mm³.
• White blood cell count: 4,500-11,000/mm³.

Plasma Proteins: Serum Albumin

• Serum Albumin is the most abundant blood protein, comprising 50% of serum proteins
• Synthesized in the liver.
• Transports hormones (lipid-soluble/non-polar), free fatty acids, and drugs, and bilirubin.
• Responsible for creating colloid osmotic pressure or oncotic pressure.
• Deficiencies are associated with kidney and liver disease, as well as malnutrition.

Oncotic Pressure

• Oncotic pressure, or colloid osmotic pressure, is a form of osmotic pressure induced by the presence of proteins, particularly albumin, in plasma.
• Albumin displaces water molecules and influences fluid pressures.

Other Plasma Proteins: Globulins

• Globulins account for 38% of blood proteins.
• Alpha and beta globulins are synthesized in the liver and transport lipids, hormones, and fat-soluble vitamins.
• Gamma globulins are antibodies that function in immunity, found in this blood fraction.

Plasma Proteins: Fibrinogen

• Fibrinogen is synthesized by the liver.
• Fibrin binds platelets together to form clots.

Blood Cells

• Blood cells include neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, and erythrocytes.

Stem Cell Maturation

• Lymphoid stem cells differentiate into lymphocytes
• Myeloid stem cells can differentiate into erythrocytes, neutrophils, monocytes, eosinophils, basophils, and megakaryocytes

Red Blood Cells (RBCs) or Erythrocytes

• Erythrocytes are flattened, biconcave discs that lack nuclei and mitochondria.
• They contain hemoglobin, which binds CO₂ and O₂
• Erythrocytes carry oxygen and CO₂
• They have a 120-day life span, and their quantity is indirectly defined by hematocrit,
• RBC production: Occurs in the marrow of all bones in children and becomes limited to specific bones as we age.
• Regulation: Hemopoietic growth factors, specifically erythropoietin produced in the kidney and controlled by O₂ availability.

Recycling Erythrocytes

• Aged erythrocytes are phagocytized in the liver and spleen
• Erythrocyte membrane proteins and globin proteins are broken down into amino acids to make new erythrocytes
• Heme components are recycled
• Heme is converted into biliverdin and then to bilirubin and secreted in bile from the liver

Platelets/Thrombocytes

• Platelets are the smallest formed element in the blood and participate in clot formation.
• Fibrin "ties" platelets together to form a mesh or clot over an injured area to limit blood loss.
• Platelets work with factor XIII/XIIa to aid clotting and increase its durability and are activated by thrombin.
• Thrombocytopenia is a deficiency of platelets.

Leukocytes

• Leukocytes have nuclei and mitochondria and include granular and agranular types.
• Granular leukocytes (neutrophils, eosinophils, basophils) are produced in bone marrow.
• Neutrophils are the majority of WBCs.
• WBC count is often used as a surrogate measure of the number of neutrophils.
• WBCs are produced in the bone marrow, while T and B lymphocytes are also produced in the lymph nodes and spleen, and T cells are produced in the thymus.
• WBC counts increase during periods of infection.

Types of Granular Leukocytes: Neutrophils

• Neutrophils are the most abundant WBC type, 50-70% of all WBCs.
• Neutrophils are phagocytic, consume microbes, and foreign particles and are associated with infections and the key component of inflammatory response.

Other Granular Leukocytes: Eosinophils

• Eosinophils protect against parasites
• Eosinophils are involved in inflammation and allergic reactions

Granular Leukocytes: Basophils

• Basophils are also known as secretory leukocytes.
• Basophils contain heparin (anticlotting) and histamine (vasodilator) and are associated with inflammation and allergic reactions.

Agranular Leukocytes: Lymphocytes

• Lymphocytes lack granules in the cytoplasm and are produced in lymphoid tissue (spleen, thymus, lymph nodes).
• Lymphocytes are antibody-producing cells, including natural killer cells, T cells, and B cells.
• Their function is to recognize and eliminate specific "non-self" antigens.

Agranular Leukocytes: Monocytes

• Monocytes lack granules and are produced in bone marrow.
• Monocytes mature into macrophages after entering body tissues, and macrophages are phagocytic.

Hemostasis

• Hemostasis is the prevention of blood loss by clot formation
• It is essential to only get clotting when it is needed

Clot Formation: Prevention

• Clot formation is prevented by physical separation of the blood/platelets from collagen and other activators located in the vessel wall (endothelial lining)
• Clot-repressing molecules like Prostacyclin PGI2 and NO (nitric oxide) are released from the endothelial layer of blood vessels
• Antithrombin III, a molecule that degrades clots is produced

Clot Formation: Needed

• Clot formation is initiated by injury/damage to the endothelium, exposing passing platelets to collagen in the vascular wall, initiating platelet binding, creating a "platelet plug"
• Also by Von Willebrand's factor, a major player, binds to platelets to help platelets stick together
• Degranulation of bound platelets happen, converting them into "activated" platelets
• Platelet Activation: Release ADP → "sticky" platelets, Release Thromboxane A → "sticky" platelets and vasoconstriction, Release serotonin → vasoconstriction

Clot Formation: Net Effect

• Recruitment of more platelets to the site of injury.
• Activation of these platelets to form a platelet plug.
• Reduced blood flow to the area of injury.

Circulating system

• Circulating fibrinogen, made in the liver, is converted to fibrin, a long fibrous protein.
• Thrombin ties platelets together and strengthens the plug/clot

Clot Formation: Stopping

• There is a significant need to limit clot formation and degrade existing clots to avoid issues like DVT's and PE's

Interrupting Factors

• Reactions that drive clot formation are reversed by other reactions that stop the clotting process. Intermediates of clot formation have a short half-life, and receptors for intermediates quickly downregulate.
• Anticlotting molecules include Protein C and Antithrombin III:

Anticlotting Molecules

• Protein C, combines with thrombin to inactivate some clotting factors
• Antithrombin III is Produced in the liver, inactivates several intermediates of the coagulation cascade

Degradation

• Fibrinolysis: Clot degradation
• Plasmin, an enzyme that digests fibrin, is converted from plasminogen by tissue plasminogen activator (TPA).
• Clotting can be prevented by certain drugs: Streptokinase, Calcium chelators (sodium citrate or EDTA), Heparin (blocks thrombin), and Coumadin (inhibits vitamin K).

Virchow's Triad

• Hypercoagulable State
• Vascular Wall Injury
• Circulatory Stasis