1-4: Hematologic System and Blood Composition

Blood maintains a delicate balance between clot formation (hemostasis) and fibrinolysis (the breakdown of clots).
Whole Blood Composition (by volume): - Plasma: $55\%$ of whole blood volume. - Formed Elements: $45\%$ of whole blood volume, consisting of Erythrocytes (RBCs), Leukocytes (WBCs), and Platelets.
Formed Elements Normal Counts: - Platelets: $150,000 - 450,000\,\mu L$ - Leukocytes: $4 - 11 \times 10^3\,\mu L$ - Erythrocytes: $4 - 6 \times 10^6\,\mu L$
Leukocyte Differential (Percentage Breakdown): - Neutrophils: $50 - 70\%$ - Lymphocytes: $20 - 40\%$ - Monocytes: $4 - 8\%$ - Eosinophils: $2 - 4\%$ - Basophils: $0 - 2\%$

Bone Marrow: - Serves as the primary site for the production of all blood cells, including RBCs, WBCs, and Platelets. - It is predominantly located within flat bones, such as the pelvis and the sternum.
Hematopoiesis (The process of blood cell production): - Stem cells differentiate into two primary lineages: - Myeloid stem cells: These differentiate into most blood cells. - Lymphoid stem cells: These differentiate specifically into lymphocytes.

General Characteristics: - Normal RBC Count: $4.5 - 5.0 \times 10^6$ cells. - Essential Function: Transportation of oxygen ( $O_2$ ) and carbon dioxide ( $CO_2$ ). - Content: Erythrocytes contain hemoglobin, which fundamentally requires iron ( $Fe$ ) for its formation and function.
Reticulocytes: - These are the immature form of red blood cells. - Clinical Significance of Reticulocyte Levels: - Low levels suggest a failure in the bone marrow's ability to produce cells. - High levels indicate a compensatory increase in red blood cell production, typically due to the destruction of cells or significant blood loss.
RBC Production (Erythropoiesis): - Erythropoiesis is stimulated by hypoxia (low oxygen levels). - The process is controlled by Erythropoietin (EPO), a hormone produced by the kidneys. - Regulatory Feedback Loop: 1. Kidneys detect low oxygen ( $O_2$ ) levels. 2. Kidneys release Erythropoietin (EPO). 3. EPO stimulates the bone marrow. 4. Result: $\uparrow$ RBC production.
Nutritional Requirements for RBC Production: - Iron - Vitamin $B_{12}$ - Vitamin $B_6$ - Folic acid

Normal Leukocyte Count: $4,000 - 11,000\,\text{cells}/\mu L$
Granulocytes: - This category includes Neutrophils, Eosinophils, and Basophils. - Neutrophils: These act as first responders during an infection. They utilize phagocytosis to engulf and destroy foreign bodies and cellular waste.
Lymphocytes: - These manage the immune response by producing antibodies to neutralize foreign bodies. - They are specifically responsible for fighting viruses and cancer cells.

Normal Platelet Count: $150,000 - 450,000\,\mu L$
Function and Activation: - Primary Function: Clotting. - Clotting Cascade mechanism: Upon injury, platelets adhere to the damaged vessel wall, clump together, and form a platelet plug to initiate the clotting cascade.

Function of Plasma: Transports essential proteins, nutrients, clotting factors, and metabolic wastes.
Key Plasma Proteins (Produced in the Liver): - Albumin: Maintains oncotic pressure to keep fluid within the blood vessels. - Clinical Implication: Decreased albumin ( $\downarrow$ albumin) leads to edema as fluid leaks out of the vessels. - Fibrinogen: An essential clotting factor that remains inactive until an injury occurs. - Clinical Implication: A decrease in clotting factors ( $\downarrow$ clotting factors) creates a significant bleeding risk.

Hemostasis: The physiological process that stops bleeding.
Primary Hemostasis: - Involves immediate vasoconstriction lasting approximately $20 - 30\,\text{min}$ . - Platelets adhere, activate, and aggregate to form a temporary platelet plug. - This process is triggered by the exposure of collagen.
Secondary Hemostasis: - Involves the activation of the clotting factor cascade: - Prothrombin $\rightarrow$ Thrombin - Fibrinogen $\rightarrow$ Fibrin - The end result is the formation of a fibrin mesh. - This mesh traps RBCs, WBCs, and platelets to create a strong, stable clot.

Definition: The process that breaks down clots once healing has occurred.
Mechanism: - Plasminogen is converted into Plasmin. - Plasmin subsequently breaks down the fibrin clot. - This process produces fibrin degradation products.

Spleen: - Unlike many organs, the spleen can be removed without causing major harm to the body. - Functions: - Produces RBCs during fetal development. - Filters and removes aged or damaged RBCs. - Recycles iron and sends it back to the bone marrow. - Acts as a storage site for blood and platelets. - Performs immune functions via lymphocytes.
Liver: - The primary site for the production of most clotting factors. - Clinical Implication: Liver dysfunction can severely impair coagulation and significantly increase the risk of bleeding.

Pediatrics: - Infants have an elevated count ( $\uparrow$ ) of RBCs and WBCs at birth. - Infants have a decreased count ( $\downarrow$ ) of platelets at birth. - Vitamin K is administered at birth to facilitate clotting factor production.
Aging: - There is a decrease ( $\downarrow$ ) in bone marrow and stem cell activity. - There is a reduced ability to handle physiological stress such as blood loss or infection. - Hemoglobin levels typically decrease ( $\downarrow$ ) with age.

Medications and Herbal Influences: - Certain herbs can affect clotting: Garlic, Ginger, Chamomile, Primrose, and St. John's Wort. - St. John's Wort specifically decreases the effectiveness of Coumadin.
Surgical History: - Important factors include a history of Splenectomy (removal of the spleen) or the presence of a prosthetic heart valve.
Lymph Node Palpation: - Normal Status: Lymph nodes are usually not palpable. - Abnormal Status: Hard, fixed, enlarged, or tender nodes. - Tender nodes usually indicate inflammation. - Non-tender nodes may indicate a possible malignancy.