Human Physiology: Blood Clotting and Disorders

Blood Physiology Overview

• Blood is a connective tissue in fluid form, considered the "fluid of life" due to its role in transporting oxygen and carbon dioxide throughout the body.

Blood Properties

• Color: Arterial blood is scarlet red (due to oxygenated hemoglobin), and venous blood is purple-red (due to higher carbon dioxide levels).
• Volume: An average adult has 5 liters of blood, while a newborn has 450mL. Blood volume increases during growth and reaches adult levels around puberty. In females, the average volume is slightly lower (around 4.5 liters). The volume is approximately 8% of body weight in a healthy adult.

Blood Composition

• Cellular Components: Erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets).
• Plasma: Composed primarily of water (about 98%), ions, and plasma proteins (e.g., albumin, globulins, fibrinogen). It has a similar ionic composition to interstitial fluid.

Functions of Blood

• Transport: Oxygen, carbon dioxide, nutrients, hormones, and waste products.
• Homeostasis: Regulation of body temperature and extracellular fluid (ECF) pH.
• Protection: Defense against infections by white blood cells and antibodies.
• Clot Formation: Prevents blood loss.

Blood Cell Formation

• Erythropoiesis: Formation of red blood cells (RBCs)
• Leucopoiesis: Formation of white blood cells (WBCs)
• Thrombopoiesis: Formation of platelets (thrombocytes)

Hematopoiesis

• Blood cell formation begins early in embryonic development and continues throughout life.
• Locations of red blood cell (RBC) production change during development (yolk sac, liver, spleen, and bone marrow).
• In adults, red bone marrow in the axial skeleton, pelvic and pectoral girdles, and proximal epiphyses of long bones is the primary site of RBC production.. Different bones produce RBCs at different ages.

Blood Cell Characteristics

• Red Blood Cells (Erythrocytes):

  • Biconcave disks 7.5 micrometers across
  • Flexible cell membrane
  • No mitochondria or ribosomes (anaerobic glycolysis)
  • Life span: 120 days.
  • Normal count of 4.7–5.2 million per mm³.
  • Hemoglobin (Hb) concentration of 14–16 g/dL.

• Function: Transport of O2 and CO2, and acts as a buffer.

• Platelets:

  • Irregular shape, smaller than RBCs.
  • 150,000 - 450,000 per mm³,
  • Short lifespan 8-12 days
  • Formed from the cytoplasm of megakaryocytes.
  • Crucial role in blood clotting.

• White Blood Cells (Leukocytes):

  • Various types with different functions in the immune system and
  • protective mechanisms.
  • Granulocytes: neutrophils (most common), eosinophils, basophils.
  • Agranulocytes: lymphocytes, monocytes (developing to macrophages).
  • Normal white blood cell count: 4,000 – 11,000/µL

RBC Development (Erythropoiesis)

• RBC development is characterized by:
  • Decrease in cell size.
  • Disappearance of the nucleus.
  • Appearance of hemoglobin (Hb).
• Controlled by erythropoietin (EPO), a hormone primarily produced by the kidney in response to low oxygen levels in the blood (hypoxia).

Erythropoietin (EPO)

• EPO is a glycoprotein.
• Primarily produced by the kidney in response to hypoxia (low oxygen), and to a small degree by the liver.
• Stimulates the growth of early stem cells, but does not affect red blood cell (RBC) maturation.
• Its level can be measured in plasma and urine.

Hemoglobin

• Composed of four globin protein chains, each with a heme group that contains iron.
• Iron is important to hemoglobin, myoglobin, and other structures ( ~65% of total iron in hemoglobin).
• Normal hemoglobin types include Hb A (most adult form), Hb A2, and Hb F (fetal).

Platelet Formation and Structure

• Platelets are fragments of cytoplasm from megakaryocytes.
• Megakaryocytes are large cells with multiple DNA copies in the nucleus.
• Platelet count (normal) 150,000-450,000/mm³
• Platelets have membrane glycoproteins that serve as receptors, mediate adhesion and contraction.
• Platelet production is highly regulated.

Hemostasis

• A series of mechanisms that stop blood loss from damaged blood vessels.
• Three main phases:
  • Vasoconstriction: Immediate contraction of the damaged blood vessel to reduce blood flow.
  • Platelet plug formation: Platelets stick together to form a temporary plug.
  • Coagulation: Formation of a stable blood clot through a series of reactions involving multiple blood clotting factors.

Blood Coagulation

• A complex process initiated by the intrinsic or extrinsic pathways.
• Involves multiple coagulation factors (proteins) that act in a cascading manner.
• The final common pathway leads to the conversion of fibrinogen to fibrin, forming a mesh that traps blood cells and platelets to form a clot.

Anticoagulants

• Substances that inhibit blood clotting. Important to prevent clots in undamaged blood vessels.
• Important intravascular system factors to prevent clot formation in the normal vascular system include endothelial surface factors like thrombomodulin, prostacyclin and nitric oxide (NO).
• Anticoagulants in vitro like EDTA, oxalate, heparin, sodium citrate, and sodium fluoride/potassium oxalate are used to prevent clotting of blood samples for testing purposes.

Clot Retraction

• Fibrin fibers shorten, pulling the edges of the damaged vessel together to further reduce further bleeding. Involves the interaction of platelets.

Fibrinolysis

• The breakdown of a blood clot following a healing process.
• Activated by plasminogen-plasmin sequence.

Jaundice

• Condition characterized by a yellowish pigmentation of the skin and eyes.
• Occurs when there is excessive bilirubin in the blood (hyperbilirubinemia).
• Bilirubin is a byproduct of red blood cell breakdown that is normally processed and excreted by the liver.
• Types of jaundice include prehepatic, intrahepatic, and posthepatic, depending on the cause of the bilirubin buildup.

Anemia

• A condition characterized by a decrease in the oxygen-carrying capacity of blood due to a deficiency or abnormality in red blood cells (RBCs) or hemoglobin.

• Several types of anemia exist, caused by various factors like blood loss, malnutrition, genetic disorders, and bone marrow problems. The result is reduced numbers of RBCs, reduced hemoglobin, and a decreased packed cell volume.

Increased Blood Viscosity and Anemia/Polycythemia

• Increased blood viscosity may occur in conditions like polycythemia, causing sluggish blood flow. In anemia, decreased red blood cell count and hemoglobin reduce blood viscosity, possibly increasing blood flow and cardiac output to compensate for the reduced carrying capacity.

WBC Disorders

• Leukocytosis: Increased white blood cell count due to infection
• Leukemia: Uncontrolled abnormal increase in white blood cell production, causing various complications.

This quiz focuses on the physiological processes involved in blood clotting, including the role of thrombin and various pathways of clot formation. It also delves into blood disorders such as leukemia and polycythemia, offering insights into their characteristics and impacts on health.