Exam 5 6 and 7 physiology lecture

• Blood consists of plasma and cellular elements.

Blood Composition

• The fluid matrix of blood is composed of 92% water, 7% proteins, and 1% ions, organic molecules, gases, trace elements, and vitamins.
• Plasma proteins include albumins (regulating osmotic pressure and fat movement), globulins (antibodies), fibrinogen (for coagulation), and transferrin (short half-life).
• Cellular elements include red blood cells (RBCs or erythrocytes) for O2 and CO2 transport, platelets from megakaryocytes, and white blood cells (WBCs or leukocytes).

Types of White Blood Cells

• Lymphocytes, also called immunocytes, provide immune responses against invaders.
• Monocytes develop into phagocytic macrophages.
• Neutrophils are mobile phagocytes that ingest foreign substances and pathogens; they are phagocytes and granulocytes.
• Eosinophils are granulocytes producing toxic compounds against invading pathogens.
• Basophils are granulocytes and include tissue basophils (mast cells).
• Platelets are cell fragments essential for blood clotting (coagulation).
• Blood cells are produced in bone marrow and have a higher yield of ATP.

Hematopoiesis

• Hematopoiesis is the creation of all blood cells.
• Red bone marrow is red because it contains hemoglobin and is active (25% RBCs, 75% WBCs).
• Yellow bone marrow contains adipose cells and is inactive.
• Hematopoiesis is controlled by cytokines like interleukins and colony-stimulating factors (CSFs).
• Colony stimulating factors regulate leukopoiesis
• CSFs are produced by cells in the bone marrow.
• Leukopoiesis is the production of white blood cells only.
• Thrombopoietin (TPO) regulates platelet production.
• TPO is produced in the liver.
• Erythropoietin (EPO) regulates red blood cell production and is produced in the kidney.
• Erythropoiesis: production of red blood cells only.

Red Blood Cells

• RBCs need a high diffusion area = high surface area.
• Hematocrit is the ratio of red blood cells to plasma, expressed as a percentage, indicating the percentage of RBCs in blood.
• Low hematocrit indicates anemia, high indicates polycythemia vera.
• Mature RBCs lack a nucleus; morphology can provide clues to disease presence.
• Mean corpuscular volume (MCV) is the size of red blood cells.
• RBCs live for ~120 days (3-4 months).
• Older RBCs rupture or are phagocytized in the spleen.
• Amino acids from globin are incorporated into new proteins while some iron from heme groups is reused in new heme groups.
• Remnants of heme groups convert to bilirubin and are excreted as bile. Bilirubin metabolites are excreted in urine. Jaundice results from elevated bilirubin levels.
• RBC disorders decrease oxygen transport, leading to anemia, assessed via hematocrit and hemoglobin values.
• Examples of anemia are hemolytic anemia (e.g., hereditary spherocytosis), sickle cell disease, and iron deficiency anemia.

Erythrocytes

• The cytoskeleton creates shape of RBCs.
• In hypertonic solutions, erythrocytes shrink but the cytoskeleton stays intact, resulting in a spiky surface (crenated).
• In hypotonic solutions, erythrocytes swell and lose their disk shape.
• Abnormal hemoglobin in sickle cell disease causes RBCs to change shape.

Hemoglobin

• Hemoglobin requires iron and plays a role in oxygen transport
• Hemoglobin has 4 polypeptide chains (2 pairs) and 4 heme groups
• Heme is a porphyrin ring with an iron (Fe) atom at its center, with iron coming from diet.
• Iron is transported in the blood by transferrin and is taken up in bone marrow, with excess iron stored in the liver by ferritin.
• Hemoglobin is structured with 4 protein globin chains centered around a heme group (containing porphyria ring w/ iron atom).

Platelets and Megakaryocytes

• Platelets stop blood loss, aid immunity, and assist inflammation with a 10-day life span.
• Platelets are smaller than RBCs.
• Activated platelets develop spiky outer surfaces to adhere to each other, while inactive platelets are small disk-like cell fragments.
• Megakaryocytes are giant cells with multiple copies of DNA in their nucleus.

Hemostasis and Coagulation

• Hemostasis prevents blood loss from damaged vessels and involves 3 major steps.
• Vasoconstriction occurs due to paracrine secretion by the damaged endothelium and platelets (+ visceral reflex, increases pressure).
• Platelet plug begins with platelet adhesion. Platelets adhere to exposed collagen of the damaged BV wall, activate, swell, become stickier, and secrete paracrine to reinforce vasoconstriction and cause more platelet aggregation.
• Coagulation (clot formation) occurs with exposed collagen binds and activates platelets, which then release platelet factors that attract more platelets to aggregate into the platelet plug.
• Intact endothelium releases prostacyclin and nitric oxide (NO), which prevent platelet adhesion.
• Coagulation converts a platelet plug into a clot (fibrinogen)
• Coagulation (clot formation) involves reinforcing the platelet plug with the protein fibrin (fibrin threads).
• There are 2 pathways the body uses to form fibrin (intrinsic and extrinsic), both triggered simultaneously due to BV damage.
• The 2 pathways come together to form thrombin, an enzyme that converts fibrinogen to fibrin. Clots are a temporary fix.

Fibrinolysis

• As the damaged wall repairs itself, the clot disintegrates = fibrinolysis.
• Thrombin works with tissue plasminogen activator to convert inactive plasminogen into plasmin, which breaks down the fibrin mesh.
• Factor X regulates thrombin, and thrombin regulates fibrinogen.

Coagulation Cascade

• Includes the Intrinsic Pathway (Contact Activation).
• Extrinsic Pathway (Cell Injury).
• Conversion of fibrinogen into fibrin & subsequent fibrinolysis.
• If tPA is inhibited = more clotting.
• Thrombin inhibited = less clotting.

Hemophilia

• Hemophilia is several diseases in which one of the factors in the coagulation cascade is defective or lacking.
• Hemophilia A is the most common form (usually affects males).
• Uncontrolled bleeding can lead to death.

Overview of Cardiovascular System (CVS)

• The CVS consists of the heart (pump), blood (fluid), and blood vessels + capillaries (tubes).
• It transports materials from the external environment (nutrients, water, gases), between cells (hormones, immune cells, antibodies), and waste eliminated by cells (CO2, heat metabolic waste).
• Blood Vessels (vasculature) include Arteries (carries away from heart) vs. veins (carries towards heart), capillaries (responsible for gas exchange), and the portal system (joins two capillary beds in series).

Heart Structure

• The septum divides heart into two halves (left/right). The atrium receives blood returning to heart while the ventricle pump blood out of the heart.
• Blood is made of cells and plasma
• Pulmonary (right side of heart) vs. systemic circulation (left side of heart)
• Pulmonary arteries vs. pulmonary veins
• Aorta (cardiac output) vs. inferior vena cava/ superior vena cava (venous return)

Pressure Gradient

• Blood pressure of systemic circulation range from: high 93 mm Hg in aorta to a low of a few mm Hg in the venae cavae.
• Arteries – hydrostatic pressure (prime regulator of moving flow).
• Veins - have a shunt system to bring blood back to heart.
• Vessels: if blood vessels dilate, blood pressure decreases
• If blood vessels constrict, blood pressure increases

Pressure and Volume

• Volume changes affect blood pressure in the cardiovascular system:
• Vasoconstriction increases BP
• Vasodilation decreases BP
• Blood flows from higher pressure to lower pressure
• HIGHER the pressure gradient = GREATER fluid flow
• Fluid flows only if there’s (+) pressure gradient

Physics of Flow

• Flow depends on pressure gradient, NOT absolute pressure
• Flow through a tube is inversely proportional to resistance: Flow decreases as resistance increases
• Resistance is proportional to length (L) of the tube (blood vessel). Resistance increases as length increases (linear related) `Resistance is proportional to viscosity (η)/thickness, of the fluid (blood). Resistance increases as viscosity increases.
• Resistance is inversely proportional to tube radius to the fourth power

Resistance

• Resistance decreases as radius increases. Vasoconstriction vs. vasodilation
• Flow increases as the pressure gradient increases (directly proportional) or as resistance to flow decreases (inversely proportional)

Mean Arterial Pressure (MAP)

• The average arterial pressure throughout one cardiac cycle, systole, and diastole.
• MAP is influenced by cardiac output and systemic vascular resistance.
• MAP ∝ cardiac output (CO)  peripheral resistance (PR)
• Cardiac output = amount of blood ejected by the ventricles each min (L/min)

Heart

• The heart (4 Chambers:) contains paired atria (thin-walled upper chambers) and paired ventricles (thick-walled lower chambers).
• The right side carries deoxygenated blood while the left side carries oxygenated blood.
• Blood vessels emerge from the base of the heart and includes the aorta and pulmonary trunk (carries blood from heart). Vena cava and pulmonary veins return blood to the heart.
• Deoxygenated: vena cava → right atrium → right ventricle → pulmonary trunk
• Oxygenated: pulmonary veins → left atrium → left ventricle → aorta

Heart Valves

• Creates one way flow through heart.
• Atrioventricular valves (A-V valves) is between atria and ventricles
• Chordae tendineae (keeps everything shunt) prevents eversion during ventricular contraction (prevents regurgitation of blood into the atria).
• The tricuspid valve is on the right side and Bicuspid valve (mitral valve) is on the left side
• Semilunar valves has the aortic valve (between the left ventricle and aorta) and the pulmonary valve (between the right ventricle and pulmonary trunk).
• Stenosis: can lead to excessive opening/congestive heart failure

Coronary Circuit

• This is the pathway of blood being supplied to the heart (systemic)
• Autorhythmic cells (conducted pacemakers): e.g Sinoatrial node (SA node) Initiates the cardiac action potential Smaller and fewer contractile fibers compared to contractile cells and No organized sarcomeres
• Contractile cells are striated fibers organized into sarcomeres
• Cardiac muscle vs. skeletal muscle: Is smaller, has a single nucleus per fiber, branch and join neighboring cells through intercalated disks, and the intercalated disks contain gap junctions and desmosomes

Cardiac Contraction

• The spiral arrangement of ventricular muscle allows ventricular contraction to squeeze the blood upward from the apex of the heart.
• Intercalated disks contain desmosomes (transfer force from cell to cell) and gap junctions (allow electrical signals to pass rapidly from cell to cell)
• Contraction = Graded and is determined by how much calcium is bound to troponin Sarcomere length affects force of contraction (length-tension relationship in “Dilated Cardiomyopathy”)

Myocardial Cells

• Phase 4: Resting Membrane Potential
• Phase 0 (depolarization): Na+ voltage gated channels open resulting in Na+ influx, slow K+ and Ca++ channels begin to open
• Phase 1: initial repolarization with Na+ channels close. Different type of K+ channels opens briefly (fast K+ channels) then close
• Phase 2: plateau with those slow. Ca++ channels fully open causing Ca++ influx and this sustains refractory period and prevents tetanus
• Phase 3: rapid repolarization due to K+ efflux from the opening of those slow K+ channels
• Phase 4: Resting Membrane Potential

Myocardial Autorhytmic Cells

• Have Unstable membrane potential called pacemaker potential
• At -60 mv, so-called “funny channels” open briefly allowing increased Na+ influx and slight K+ efflux. This slowly depolarizes the SA node
• As the membrane potential becomes more +, funny channels close and one set of calcium voltage-gated channels open briefly. This continues the depolarization as the membrane potential steadily moves towards threshold
• At threshold, a different set of calcium channels open causing massive calcium influx creating a steep depolarization phase
• At peak of AP, calcium channels close and K+ voltage-gated channels open leading to K+ efflux and repolarization
• The SA node (70-100 bpm) depolarizes
• The electrical activity goes rapidly to AV node (slows down) via internodal pathways
• Depolarization spreads more slowly across atria so conductions slows through AV Node (pace setter)
• Depolarization moves rapidly through ventricular conducting system to bundle of his with Purkinje fibers allowing complete contraction

Electrocardiogram (ECG)

• Show the summed electrical activity generated by all the cells of the heart that is not the same as an action potential
• Includes the P wave (atrial depolarization), the QRS complex (wave of ventricular depolarization, a trial repolarization is part of QRS), and the T wave (ventricular repolarization) ① Heart at rest: atrial and ventricular diastole where the atria are filling with blood from the superior vena cava, inferior vena cava, coronary sinus, and pulmonary veins. The AV valves open → ventricles fill ② Completion of ventricular filling: atrial systole where the atria contract at the end of ventricular diastole to push a little more blood into the ventricles and the end-diastolic volume (EDV): volume in ventricle at the end of ventricular diastole ③ Early ventricular contraction and the first heart sound where the AV valves close (vibrations following closure of the AV valves, “Lub”), no blood in or out (isovolumic ventricular contraction), increasing pressure due to ventricular muscle contraction, and concurrent atrial diastole (atria relaxes and blood flows in the atria) In the fourth step the ventricles contract (ventricular systole) where semilunar valves open and blood is ejected into arteries with the End-systolic volume (ESV): volume in ventricle at the end of ventricular contraction

Heart Sounds

• The Fifth Step contains Ventricular relaxation and the second heart sound:
• Arterial blood flows back towards heart with Semilunar valves shutting → second heart sound (“Dup”).
• Ventricular muscles relax pressure drops (still higher than atrial pressure) where no blood enters or exits (isovolumic ventricular relaxation).
• Arterial blood flows back towards heart with Semilunar valves shutting (resulting inthe “Dup” second heart sound)

Stroke Volume

• Stroke Volume = amount of blood ejected by the ventricle each time it contracts (determine cardiac output). So stroke volume (SV) = EDV-ESV:
• Average is 70 mL (70-kg man at rest)
• Cardiac output is a measure of cardiac performance Volume of blood pumped by one ventricle in a given period of time (per minute) with: Cardiac out put (CO) = heart rate stroke volume and has Average = 5 L/min
• Heart Rate (is determined by rate of depolarization in authorhythmic cells) and Stroke Volume (is determined by force of contraction in ventricular myocardium influenced by contractility and end-diastolic volume)

Autonomic Division

• AD modulates heart rate by modulating the pacemaker potential
• Parasympathetic control (cholinergic/ acetylcholine neurotransmitter) slows the heart rate and the muscarinic receptors on the SA node resulting in lower depolarization. It also hyperpolarizes membrane potential due to higher K+ permeability, lower pacemaker potential, and lower Ca2+ permeability (also slows rate of pacemaker depolarization making it take longer to reach threshold) Sympathetic control (release epinephrine neurotransmitter) increases the heart rate where the sympathetic stimulation and epinephrine depolarize autorhythmic cell & speed up pacemaker potential with B1-adrenergic receptors on the SA Node (higher Na+ & Ca2+ permeability increases rate of pacemaker depolarization)

Vascular

• The 5 Types of Blood Vessels includes artery (the pressure reservoir of efficient circulation of O2 and nutrients), arteriole (distributes blood flow into capillary bed), capillaries greatest in diffusion (transfer nutrients/gases), venule (collects blood from capillaries and transfer nutrients), and the vein (returns deoxygenated blood)
• Pericytes allows regeneration by secreting paracrine factors to promote vascular growth
• Capillary beds large in volume to increase surface area
• Metarterioles is a shunt path
• Allows blood volume compensation

Blood Pressure (BP)

• This measurementis highest in arteries & lowest in veins and includes: MAP = diastolic pressure + 1/3(systolic pressure – diastolic pressure)
  • Blood flows if a pressure gradient is present
  • Blood flows in the following order HIGH -> LOW
  • Blood flows if there is resistance
• There are 3 Factors affecting Blood Flow: Radius of blood vessel, length (L) of blood vessels, and viscosity (n)
• The baroreceptor reflex allows blood pressure volume control

Fluid Movement and Regulation

• Includes what can be measured via Compensation of Increased Blood Volume
• Includes regulation of Cardiovascular Function where baroreceptor Reflex control Blood pressure and Orthostatic Hypotension triggers baroreceptor reflex

Capillary Action

• There is a bulk which is the fluid movement that includes Filtration and Absorption. With Filtration, there is fluid movement out of capillaries due to hydrostatic pressure where the hydrostatic pressure of IF is Negligible and PH decreases over length of capillary due to friction
• In Absorption there is fluid movement into capillaries due to colloid osmotic pressure (π), also called oncotic pressure with fluid proteins at 25mgHg. IF has none
• Net pressure determines direction of bulk flow: filtration at arterial end and at venous end due to arterial constriction where constriction is the effect
• The average is 3l/day in fluid filtering; with the determination Net pressure = hydrostatic pressure - colloid osmotic pressure