Cardiovascular System:

• The material contained in these slides corresponds to your assigned readings found in Chapter 18 of our text.

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Learning objectives

• Know the general functions of blood. • Be familiar with the major components of blood (plasma vs formed elements) when isolated via centrifugation. • Know the components of hematocrit. • Know the three formed elements of blood and their relative abundance. • Know the overall process of hemopoiesis including the role of hematopoietic stem cells and of colony-stimulating factors in mediating blood cell formation. • Be familiar with the function and physical properties of erythrocytes. • Understand the process of erythroctye formation via the actions of EPO.

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Overview of the CV System:

CV system is comprised of: • Heart • Blood vessels (lymphatics) • Blood

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Blood Functions (Sec.18.1a)

• Functions of blood include: • Transport (nutrients, heat, waste products, hormones etc.) • Regulation of body temperature (working in concert with integumentary vasoconstriction/vasodilation) • Fluid balance • Acid/Base-Ph balance (working in concert with urinary and respiratory systems) • Protection (immunological) – WBCs mediate our body’s immune responses

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Properties of Blood (18.1b)

deoxygenated • Color - scarlet oxygenated • Oxygenated= bright red • Deoxygenated = dark red (not blue as commonly referenced in many textbooks) • Volume = avg adult ~ 5 Liters

• Ph 7.35 – 7.45 Avg volume = 4.5 L Avg volume = 5.5 L • Viscosity 4.5 – 5.5X water; can be variable depending on state of hydration e.g dehydrated → viscosity ↑

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Blood composition (Sec.18.1c)

• Whole Blood is a fluid CT. • Upon centrifugation it can be separated into its two main components. 1. Plasma – 55% 2. Formed elements – 45%

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Blood composition (Sec.18.1c) Plasma (a type of ECF is 55% of whole blood) contains: • dissolved solutes (electrolytes, gases, nutrients) • water (92%) – makes blood a solution • Proteins (also makes blood a colloid solution) Formed elements (45% of whole blood) contains: • Erythrocytes (RBCs – 99.9% of Formed elements) • Leukocytes (WBCs- <1% of Formed elements) • Formed elements are seen through blood smear analysis

Fig. 18.1 MCB 246: Human Anatomy and Physiology II Fig. 18.2 © University of Illinois Board of Trustees Blood composition (Sec.18.1c)

Other clinical measures of blood include: Hematocrit (packed cell volume/PCV) = % by volume of formed elements • Adult male = avg 49% (42 – 56%) • Adult female = avg 42% (38-46%)

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Blood composition; Plasma proteins (Sec.18.2a) Most plasma proteins are synthesized in by the liver. Some important and major plasma proteins of blood include: • Albumins – most numerous • Largest contributor to colloid osmotic pressure; serve as transport proteins • Globulins – second largest group • Alpha-globulins and beta-globulins act as transporters for water in-soluble molecules • Gamma-globulins (antibodies) • Fibrinogen – insoluble protein involved in blood clotting • Other proteins include: regulatory proteins (enzymes, hormones, lipid binding proteins [apolipoproteins])

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Formed elements: Hemopoiesis (18.3a)

• Hemopoiesis (hematopoiesis) = production of formed elements (RBCs, WBCs, ) • Occurs in bone marrow • Begins with pluripotent blood stem cell (hemocytoblast) • WBC and production is driven by growth factors (RBCs = hormone dependent)

Figure 18.3 MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Formed elements: Hemopoiesis (18.3a)

From Figure 18.3 Hemocytoblasts further differentiation leads to two developmental lines: • Lymphoid line (lymphoid stem cell) – gives rise to lymphocytes () • Myeloid line (myeloid stem cells) – gives rise to RBCs (), /thrombocytes (thrombopoiesis) and leukocytes( and - excluding lymphocytes) via leukopoiesis

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Formed elements: Hemopoiesis (18.3a)

Within each line (myeloid vs lymphoid) further differentiation is determined by exposure of developing stem cells (‘blasts’) to the appropriate growth factor (colony-stimulating factor). • Multi-colony-stimulating factor (multi-CSF) • Increases formation of erythrocytes, granulocytes, monocytes, and platelets • - colony-stimulating factor (GM-CSF) → granulocytes and monocytes • Granulocyte colony-stimulating factor (G-CSF) → granulocytes • Macrophage colony-stimulating factor (M-CSF) → monocytes • Thrombopoietin (TPO)‡ → megakaryocytes (platelets) • Erythropoietin (EPO)* → RBCs • EPO* - is a hormone produced by the kidneys • TPO ‡ - hormone produced by liver

From Figure 18.3 MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Erythropoiesis:(18.3a) RBCs are the most numerous of the formed elements (99% of total population) at 4.2 – 6.2 million cells/mm. Production is constant (3 million/sec). Unlike WBC (CSF-dependent), RBC synthesis is both CSF and hormone dependent. Day 1 to 5 1. myeloid stem cell + Multi-CSF + EPO → (large nucleated cells) 2. Proerythroblast → erythroblast (smaller cell; begins hemoglobin (Hb)production) 3. Proerythroblast → normoblast (continues Hb production; loses nucleus) 4. Normoblast → (loses organelles except ribosomes – continues Hb production) Day 6-7 6. enter circulation (~2 days) 7. Reticulocyte → erythrocyte (ribosomes lost only Hb remains)

From Figure 18.3 MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Erythropoiesis:(18.3a) In addition to growth factors (CSFs) and hormones (EPO), proper and adequate RBC production is dependent on other factors:

Dietary – (Vitamin B 12 and iron)

From Figure 18.3 MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Leukopoiesis(18.3a) WBCs are the least numerous of the formed elements (<.01% of total population) at 4500 – 11,000 cells/mm. Production is involves 3 separate processes: 1)Granulocyte formation, 2) formation, 3)lymphocyte formation • Granulocytes (, , and ) requires: • Multi-CSF and GM-CSF cause progenitor cell to become that becomes a granulocyte • Monocytes requires: • M-CSF to prompt progenitor → • Monoblast → promonocyte → monocyte • Lymphocytes – derived from lymphoid stem cell line (unique among leukocytes) • Lymphoid stem cells differentiate into B- lymphoblasts and T-lymphoblasts • Lymphoblasts → B-lymphocytes and T-lymphocytes • Some lymphoid stem cells differentiate directly into natural killer (NK) cells

From Figure 18.3 MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Thrombopoiesis(18.3a) Platelets make up <1% of hematocrit and are not cells (fragments of megakaryocytes/thrombocytes): • Myeloid stem cell + Multi-CSF →progenitor cells • Progenitor cells → Megakaryoblast + TPO (thrombopoietin) → (MK/large cells) • Single megakaryocyte produces thousands of platelets (2,000 -10,000) • MK cell - large cells with multilobed nucleus • MK cell produces proplatelets (see inset) —long extensions which extend through blood vessel wall into bloodstream. • Platelet fragments are sliced off (2,000-10,000 per MK cell) and circulate through the bloodstream

Figure 18.4 From Figure 18.3

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Erythrocytes (Sec. 18.3b)

• Most numerous of Formed elements • Structurally each RBC has a biconcave shape (~.75μm at narrow center to ~2.6 μm at edges). Advantages include: • Flexibility (fold to fit through narrow capillaries) • Rapid gas exchange (small diffusion distance) • Ability to stack (“roleau”) in capillaries

Figure 18.5

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Erythrocytes (Sec. 18.3b) Heme group containing porphyrin ring Functions for RBCs (iron shown in red) • Plasma/ECF Acid-Base balance (indirect) • Transport of respiratory gasses (O2 and CO2) • Requires the tetrameric (2 alpha subunits; 2 beta subunits) oxygen-binding protein hemoglobin (Hb)

• 1 Hb binds 1 O2 molecule at the iron-containg ‘heme group’

• Hb bound to O2 – oxyhemoglobin (bright red) • Hb w/o O2 – deoxyhemoglobin (dark red) • Hb bound to CO2 – carbaminohemoglobin • In the absence of any other organelle, RBCs avg ~280 million Hb/RBC, 4 O2binding heme/Hb = >1 billion 21 O2/RBC x 25 trillion RBCs/indiv. = > 25 x 10 O2/indiv.!

Figure 18.5

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Erythrocytes, Erythropoiesis and EPO (Sec 18.3b) • Erythropoiesis works via a negative- feedback system

• ↓PO2 → stimulates kidneys (sensor) • Kidneys → ↑ EPO production (note that EPO production is never completely absent) • EPO → Bone marrow to ↑ RBC production

• RBC → ↑ PO2 (homeostasis is restored!)

Figure 18.7

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Clinical implications: EPO

• EPO is used to treat a variety of illnesses/diseases • Anemias • Renal failure • Chemotherapy (cancer) • HIV

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Clinical implications: EPO abuses -blood doping

Blood doping To gain a competitive edge (particularly in endurance-aerobic activities) individuals would extract and preserve their blood (hematocrit) before a contest. A few days before the event, they would inject (dope up) with their preserved blood thereby boosting their O2 carrying capacity.

Modern day blood doping involves exogenous administration of synthetic EPO.

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees Clinical implications: EPO abuses -blood doping

Blood doping Blood doping has been outlawed by many governing bodies for professional sports.

Negative health consequences include: • Increased risk for heart attack and stroke • Permanent cardiovascular damage • Can be fatal

MCB 246: Human Anatomy and Physiology II © University of Illinois Board of Trustees