Blood Physiology and Pathophysiology - Fall 2023

Blood Physiology and Pathophysiology

• This presentation covers blood physiology and pathophysiology.
• The course is for the faculty of Pharmacy, Fall 2023, at Galala University.

Objectives

• Students will be able to describe cellular and non-cellular blood components.
• Students will be able to recognize blood functions.
• Students will be able to define erythropoiesis, leucopoiesis, and thrombopoiesis.
• Students will be able to recognize sites of RBC formation across different developmental ages.
• Students will be able to describe different stages of RBC differentiation.
• Students will be able to describe RBC maturation features.
• Students will be able to describe RBC production regulation and erythropoietin hormone secretion in response to hypoxia.
• Students will be able to recognize clinical conditions with high erythropoietin levels in the blood.

Blood Components

• Plasma makes up 55% of blood.
• Blood cells make up 45% of blood.
• Blood cells include three main types:
  • Erythrocytes/RBCs
  • Leukocytes/WBCs
  • Thrombocytes/Platelets

Blood Volume

• In an average 70 kg man, blood volume is 5-6 liters.
• Roughly 8% of total body weight.
• Female: 4-5 liters.
• Male: 5-6 liters.

Hematocrit (PCV)

• Hematocrit is the percentage of erythrocytes in whole blood.
• Also known as packed cell volume (PCV).
• Average values differ between genders.

Functions of Blood

• Transport: Gases, nutrients, hormones, waste products.
• Regulation: Acid-base balance, blood pressure.
• Defense: Against infection (white blood cells and immune system).
• Hemostasis: Stoppage of bleeding (platelets and clotting factors).

Plasma

• Plasma is a yellow, clear liquid.
• On standing, blood clots; the remaining fluid is called serum.
• Serum is plasma lacking clotting factors.
• Plasma is 90% water and 9% organic constituents.
• Plasma also contains inorganic constituents and blood proteins.

Plasma Proteins

• Plasma proteins include:
  • Albumin (3.5-5.0 g/dL, liver)
  • Globulins (2.5 g/dL, liver and white blood cells)
  • Fibrinogen (0.4 g/dL, liver)
  • Prothrombin (0.01 g/dL, liver)

Functions of Plasma Proteins

• Albumin- Maintains osmotic pressure and transports hormones.
• Globulins- Transport hormones and fat-soluble vitamins (α and β) and bind to foreign substances (γ).
• Fibrinogen- Converted to fibrin to form blood clots.
• Prothrombin- Plays a role in blood clotting.

Leukocytes (White Blood Cells)

• Leukocytes (WBCs): 4,000-11,000 per microliter.
• Categories:
  • Granulocytes (contain granules
  • Neutrophils, eosinophils, basophils):
  • Agranulocytes (lack granules
  • Lymphocytes, monocytes)

Neutrophils

• 40-70% of WBCs.
• 6-9 day development.
• 6 hours-few days life span.
• Function: Phagocytose bacteria

Eosinophils

• 1-4 % of WBCs.
• 6-9 day development.
• 8-12 days Life Span.
• Function: Kill parasitic worms, destroy antigen-antibody complexes.

Basophils

• 0.5% of WBCs.
• 3-7 days development.
• A few hours-few days Life Span.
• Function: Release histamine and other inflammatory mediators, contain heparin.

Lymphocytes

• 20-45% WBCs.
• Development: Days to weeks.
• Life span: Hours to years.
• Function: Mount immune response (T cells direct cell attack, B cells via antibodies).

Monocytes

• 4-8% WBCs.
• 2-3 days development.
• Life span: Months.
• Function: Phagocytosis, develop into macrophages in tissues.
• Role of Leukopenia during chemotherapy
• Cancerous cells grow rapidly. Chemotherapy targets fast-growing cells.
• Chemotherapy also affects normal fast-growing cells, including leukocytes, hair, and intestinal epithelial cells.

Erythrocytes (Red Blood Cells, RBCs)

• Average: 5 million/mm³.
• Shape: Biconcave disc for gas exchange, flexible for small vessels (capillaries).
• Structure: Hemoglobin (protein binding oxygen and carbon dioxide), no nucleus or mitochondria.

Hemoglobin

• Each molecule consists of four protein chains (globins) and four heme groups.
• Heme groups contain a ferrous ion (Fe²⁺) for oxygen binding.
• Globins comprise two alpha and two beta chains.
• 5% of CO₂ in blood is bound to globin.

Functions of RBCs

• Carry hemoglobin.
• Transport oxygen.
• Transport carbon dioxide.
• Buffer (pH regulation).
• Counts: Males (4.8-5.8 million cells/mm³), Females (4.2-5.2 million cells/mm³).
• Life span: 120 days.

Erythropoiesis

• Process of RBC formation.
• Intrauterine life: Liver and spleen.
• Post-natal life:
  • Children: Primarily in the red bone marrow of the axial and appendicular skeleton.
  • Adults: Red bone marrow of axial skeleton.

Life Span and Fate of RBCs

• Life span: 120 days.
• Fate: RBCs cannot reproduce. They rupture easily, especially in the spleen.
• Breakdown: Globin (protein metabolism), heme (iron stored in liver as ferritin), and protoporphyrin (yellow bile pigments).

Factors Regulating Erythropoiesis

• Decreased oxygen supply (hypoxia): Stimulates RBC production.
• Erythropoietin (EPO): Hormone produced by the kidney (85%) and liver (15%) to stimulate RBC formation.

Role of Nutrients for Erythropoiesis

• Cobalamin (Vitamin B12): RBC maturation (liver).
• Folic acid: RBC maturation (leaves, fish).
• Vitamin B6: Hemoglobin synthesis (eggs, whole grains, potatoes).
• Amino acids: Nucleoproteins (eggs, meat, milk).
• Vitamin C: Converts folic acid to active form.
• Iron: Essential for hemoglobin synthesis.

Factors Affecting Erythropoiesis

• Hormones:
  • Testosterone: Stimulates EPO secretion.
  • Thyroid hormones: Increase cell metabolism
  • Cortisol: Increases RBC formation.
• Healthy Liver: Forms globin, stores iron and Vitamin B12, produces 15% of erythropoietin.
• Healthy Bone Marrow: Site of erythropoiesis, can be destroyed by irradiation or tumors

Anemias

• Decrease in red blood cell count or hemoglobin concentration.
• Leads to decreased oxygen supply to tissues.

Hemostasis

• Process to stop bleeding.
• Stages:
  • Vascular spasm (vasoconstriction)
  • Platelet plug formation
  • Coagulation (blood clotting)
• Fibrinolysis: Breakdown of fibrin clot by plasmin.

Anticoagulants

• Heparin: Commercial, extracted from animals.
• Coumarins: Warfarin, competitive with vitamin K (decreases factors II, VII, IX, X).
• Oxalate, Citrate, EDTA: Decrease blood calcium ion concentration.

This quiz focuses on the cellular and non-cellular components of blood, their functions, and the processes involved in erythropoiesis, leucopoiesis, and thrombopoiesis. Students will also explore RBC formation and maturation, as well as clinical conditions associated with erythropoietin levels. This content is designed for Pharmacy faculty at Galala University.