Patho Blood Disorders

Blood Composition

• Components of Blood:

  • Plasma:

    • Consists of serum, clotting factors, and fibrin.

  • Formed Elements:

    • Red Blood Cells (RBCs), White Blood Cells (WBCs), and platelets (thrombocytes).

Hemopoiesis

• Definition: Normal cell production, mitosis, and differentiation.

• Location:

  • Initially occurs in the yolk sac and liver primordium during fetal development.

  • Later occurs in the bone marrow.

• Stem Cells:

  • Hematopoietic stem cells give rise to:

    • Myeloid Stem Cells: Produce:

      • Reticulocytes: Become RBCs.

      • Megakaryocytes: Become platelets.

      • Granulocytes: Become eosinophils, basophils, and neutrophils.

      • Monocyte Precursors: Become monocytes.

    • Lymphoid Stem Cells: Produce B and T lymphocytes and plasma cells.

Erythropoiesis

• Definition: Production of RBCs regulated by erythropoietin (hormone from liver and kidney).

• Process:

  • Erythroblast → Reticulocyte → RBC.

  • RBCs lose their nucleus and have a lifespan of about 120 days, with a daily loss of approximately 1%.

• Requirements: Needs hemoglobin synthesis, Vitamin B12, and folic acid.

• Normal Count: Approximately 5 to 6 million RBCs per cubic millimeter.

Leukopoiesis

• Production of WBCs: Approximately 7 million granulocytes and monocytes in circulation, with an equal number in tissues and lymph nodes.

• Lifespan: Granulocytes live for days and monocytes may last months to years.

Thrombopoiesis

• Definition: Production of platelets from megakaryocytes via fragmentation.

• Normal Count: About 250,000 platelets per microliter of blood.

• Regulation: Influenced by growth factors produced by the liver, including thrombopoietin.

Blood Coagulation

• Purpose: Maintaining static volume of blood (hemostasis).

• Clot Formation:

  • Essential for sealing leaks due to injury.

• Coagulation Cascade:

  • Extrinsic Pathway: Tissue factor exposed on endothelium due to injury.

  • Intrinsic Pathway: Factors in blood activated by subendothelial collagen.

• Calcium Ions: Required for clotting; EDTA acts as a coagulant blocker.

• Basic Mechanism: Requires fibrin, platelets, and fibrinogen. Prothrombin converts to thrombin, which turns fibrinogen into fibrin that polymerizes and binds platelets.

Role of Platelets

• Mechanism:

  • When collagen is exposed, von Willebrand factor (vWF) binds collagen and platelets, activating aggregation.

• Releases: ADP, stimulating more platelet aggregation; Thromboxane A2 (TxA2) promotes inflammation and vasoconstriction.

Anticoagulation Factors

• Methods of Stopping Coagulation Cascade:

  • Hemodynamics: Blood flow can dilute activated factors.

  • Endothelial Mediation: Endothelial cells release prostacyclin (PGI2) to inhibit platelet aggregation; degrade thrombin and ADP.

  • Fibrinolytic System: Plasminogen converts to plasmin, degrading fibrin and other clotting factors. Tissue plasminogen activator (t-PA) helps dissolve clots from the inside.

Balance Between Clotting and Anticoagulation

• Interactions: Some factors can affect both hemostasis and anticoagulation:

  • Factor XII: Activates intrinsic pathway and promotes plasmin formation.

  • ADP & Thrombin: Promote both platelet activation and protein C, aiding fibrinolysis.

Coagulation Tests

• PTT (Partial Thromboplastin Time):

  • Normal range: 25-40 seconds; longer indicates problems.

• PT (Prothrombin Time):

  • Normal range: 9-12 seconds; prolonged indicates low factor levels.

Blood Disorders

A. Bleeding Into Tissues

• Terminology of Signs:

  • Petechiae: Pinpoint hemorrhages.

  • Purpura: Larger patches (≥2cm).

  • Ecchymoses: Bruises, larger in size.

  • Hematoma: 3D pooled blood trapped between tissues.

1. Platelet Disorders

• Thrombocytopenia: Insufficient circulating platelets caused by production issues, increased clearance, or immune destruction (e.g., ITP).

• Thrombotic Thrombocytopenic Purpura (TTP): Antibodies damage endothelium leading to widespread platelet binding.

• DIC (Disseminated Intravascular Coagulation): Widespread platelet activation causing hemorrhaging.

• Impaired Platelet Function: Resulting from genetic issues or uremia.

2. Clotting Disorders

• Genetic Causes:

  • Von Willebrand's Disease: Deficiency in vWF affecting collagen binding.

  • Hemophilias: Defects in clotting factors VIII (A) or IX (B).

• Acquired Clotting Disorders: Related to liver synthesis impairments and Vitamin K deficiencies.

3. Small Vessel Fragility

• Results in small hemorrhages; conditions include vasculitis and hereditary telangiectasia.

B. Erythrocyte Disorders

• Definitions:

  • Increased numbers = Polycythemia; Decreased numbers = Anemia.

1. Anemia

• Definition: Reduction in O2 transport efficiency with Hb < 14-18 g/dL (male) or < 12-16 g/dL (female).

• Causes: Ranges from hemolysis and nutritional deficiencies to marrow defects.

2. Polycythemia

• Types:

  • Absolute Polycythemia: Increased erythropoietin secretion due to hypoxia or high altitudes.

  • Relative Polycythemia: Due to plasma deficiency, such as dehydration.

C. Leukocyte Disorders

• Leukopenia: Low WBC count; often neutropenia.

• Leukocytosis: Elevated WBC count due to various conditions.

• Leukemia: Malignant tumors of leukocyte precursors, various types including:

  • Hodgkin’s Lymphoma: Characterized by Reed-Sternberg cells.

  • Non-Hodgkin’s Lymphoma: Lacks Reed-Sternberg cells.

• Bone Marrow Transplant: Requires HLA antigen matching; donor loses 750 mL of marrow.

Anemia

Definition: Reduction in O2 transport efficiency with Hb < 14-18 g/dL (male) or < 12-16 g/dL (female). Causes: Ranges from hemolysis and nutritional deficiencies to marrow defects.

• Types of Anemia:

  • Iron-Deficiency Anemia: Caused by insufficient iron intake, chronic blood loss, or absorption issues.

  • Vitamin B12 Deficiency Anemia: Can lead to megaloblastic anemia due to poor absorption or dietary deficiency, manifesting in neurological symptoms.

  • Folic Acid Deficiency Anemia: Similar to B12 deficiency, often seen in pregnant women or individuals with malabsorption.

  • Hemolytic Anemia: Due to early destruction of RBCs caused by autoimmune diseases, infections, or hereditary conditions like sickle cell disease.

  • Aplastic Anemia: Bone marrow fails to produce sufficient blood cells, often resulting from autoimmune diseases, infections, or exposure to toxins.

• Symptoms: Fatigue, weakness, pale skin, shortness of breath, dizziness, and cold hands/feet.

• Diagnosis: Blood tests measuring hemoglobin levels, reticulocyte count, and assessments of iron and vitamin B12 levels.

• Treatment: Varies based on the cause; iron supplements, vitamin B12 injections, folic acid supplements, or treating underlying conditions may be necessary.