BIOL 410 EXAM 3

What are the 5 types of leukocytes and

(1) basophils in the blood and related mast cells in the tissues (2) eosinophils (3) neutrophils (4) monocytes and their derivative macrophages, dendritic cells (5) lymphocytes and their derivative plasma cells

What factors disrupt the normal balance between capillary filtration and absorption?

1. An increase in capillary hydrostatic pressure: Increased capillary hydrostatic pressure usually indicative of elevated venous pressure; One common cause of increased venous pressure is heart failure, condition in which one ventricle loses pumping power and can no longer pump all blood sent to it by other ventricle; When capillary hydrostatic pressure increases, filtration greatly exceeds absorption, leading to edema. 2. A decrease in plasma protein concentration: concentrations may decrease as result of severe malnutrition or liver failure; liver is main site for plasma protein synthesis, and these proteins are responsible for colloid osmotic pressure component (p) of blood 3. An increase in interstitial proteins: excessive leakage of proteins out of blood decreases the colloid osmotic pressure gradient and increases net capillary filtration.

Describe pulmonary circulation

1. Deoxygenated blood from systemic veins enters R atrium from the superior and inferior vena cava 2. Blood flows from R atrium through R AV valve (tricuspid) into R ventricle 3. Blood them pumped through pulmonary semilunar valve into the pulmonary arteries to lungs, where it is oxygenated 4. From lungs, blood travels to left side of heart through pulmonary veins

Describe the propagation of the AP throughout the atria and ventricles.

1. Depolarization begins in SA node; autorhythmic cells in R atrium that serve as main pacemaker of heart; electrical signal for contraction begins when SA node fires AP and depolarization wave spreads rapidly through specialized conducting system of non-contractile autorhythmic fibers 2. Branched internodal pathway connects SA node to AV node; group of autorhythmic cells near floor of R atrium; electrical conduction rapid through internodal conducting pathways 3. electrical conductio slower through contractile cells of atria 4. As APs spread across atria, they encounter fibrous skeleton of heart at junction of atria and ventricles; barricade prevents transfer of electrical signals from atria to ventricles; makes AV node only pathway that APs can reach contractile fibers of ventricles; electrical signal passes from AV node through AV bundle and bundle branches to apex of the heart 5. From AV node, depolarization moves into ventricles; Purkinje fibers, specialized conducting cells of ventricles, transmit electrical signals very rapidly down AV bundle aka bundle of His in ventricular septum. A short way down septum, AV bundle fibers divide into L and R bundle branches; bundle branch fibers continue downward to apex of heart, where they divide into smaller Purkinje fibers that spread outward among contractile cells; all contractile cells in apex contract nearly simultaneously

What are the 3 major functions of the immune system?

1. It tries to recognize and remove abnormal "self" cells created when normal cell growth and development go wrong. 2. It removes dead or damaged cells, as well as old RBCs; Scavenger cells of immune system patrol EC compartment, gobbling up and digesting dead or dying cells. 3. It protects the body from disease-causing pathogens. Microorganisms (microbes) that act as pathogens include bacteria and viruses, fungi and one-celled protozoans. Larger pathogens include multicellular parasites.

Describe systemic circulation

1. Oxygenated blood from lungs enters heart @L atrium and passes through the L AV valve (bicuspid) into L ventricle 2. Blood pumped out of L ventricle passes through aortic semilunar valves and enters aorta 3. Aorta branches into series of smaller and smaller arteries that finally lead into networks of capillaries 4. After leaving the capillaries, blood flows into venous side of circulation, moving from small veins into larger and larger veins 5. Veins from upper part of body join to form superior vena cava; those from lower part of body form inferior vena cava; venae cavae empty into R atrium

Explain the cardiac cycle in detail

1. The heart at rest: atrial and ventricular diastole. atria filling w/blood from veins, and ventricles have just completed a contraction. As ventricles relax, AV valves between atria and ventricles open. Blood flows by gravity from atria into ventricles. Relaxing ventricles expand to accommodate entering blood 2 Completion of ventricular filling: atrial systole. Most blood enters ventricles while atria are relaxed, but last 20% of filling is accomplished when atria contract and push blood into ventricles. Atrial systole begins following wave of depolarization that sweeps across atria. Pressure increase that accompanies contraction pushes blood into ventricles. During atrial systole small amount of blood forced backward into veins b/c no one valves to block backward flow (openings of veins narrow during contraction). @end of atrial systole ventricles contain largest volume they will hold during cycle; maximal volume= end-diastolic volume (EDV) b/c it occurs @end of ventricular diastole 3 Early ventricular contraction and the first heart sound. While atria are contracting, depolarization wave moving slowly through conducting cells of AV node then down Purkinje fibers to apex of heart. Ventricular systole begins there as spiral bands of muscle squeeze blood upward toward base. Blood pushing against underside of AV valves forces them closed so blood cannot flow back into atria. Vibrations following closure of AV valves create first heart sound, S1, (lub). W/both sets of AV and semilunar valves closed, blood in ventricles has nowhere to go; ventricles continue to contract squeezing on blood; phase = isovolumic ventricular contraction. While ventricles begin to contract, atrial muscle fibers repolarizing and relaxing. When atrial pressure falls below veins, blood flows from veins into atria again. Closure of AV valves isolates upper and lower cardiac chambers 4 The heart pumps: ventricular ejection. ventricles contract; generate enough pressure to open semilunar valves and push blood into arteries; pressure created by ventricular contraction becomes blood flow driving force. High-pressure blood forced into arteries displacing low-pressure blood; pushes it farther into vasculature. AV valves remain closed and atria continue to fill. Heart does not empty itself completely of blood each time ventricle contracts. Volume of blood left in ventricle @end of contraction = end- systolic volume (ESV) . 5 Ventricular relaxation and the second heart sound. @end of ventricular ejection ventricles begin to repolarize and relax; ventricular pressure decreases. Once ventricular pressure falls below pressure in arteries blood starts to flow backward into heart; backflow of blood fills cuplike cusps of semilunar valves forcing them together into closed position. Vibrations created by semilunar valve closure = second heart sound, S2, (dup) Once semilunar valves close, ventricles again become sealed chambers; AV valves remain closed b/c ventricular pressure (although falling) still higher than atrial pressure. Period = isovolumic ventricular relaxation b/c volume of blood in ventricles not changing. When ventricular relaxation causes ventricular pressure to become less than atrial pressure, AV valves open; blood accumulated in atria during ventricular contraction rushes into ventricles

What does an elevated WBC indicate?

A high white blood cell count may indicate that the immune system is working to destroy an infection. It may also be a sign of physical or emotional stress. People with particular blood cancers may also have high white blood cells counts.

What does a coronary bypass operation do?

Restores blood flow to heart muscle by diverting flow of blood around a section of a blocked artery in heart

How do anticoagulants work?

‣2 mechanisms limit extent of blood clotting w/in a vessel: (1) inhibition of platelet adhesion and (2) inhibition of coagulation cascade and fibrin production ‣Anticoagulants: prevent coagulation from taking place; Most act by blocking one or more reactions in coagulation cascade ‣Body produces 2 anticoagulants, heparin and antithrombin III, which work together to block active factors IX, X, XI, and XII. ‣Protein C, another anticoagulant in body, inhibits clotting factors V and VIII. ‣One option for dissolving blood clots is to use fibrinolytic drugs— such as streptokinase (from bacteria) and tissue plasminogen activator (tPA)—to dissolve the clots; These drugs are now being combined w/antiplatelet agents to prevent further platelet plug and clot formation; Some antiplatelet agents act as antagonists to platelet integrin receptors and prevent platelets from adhering to collagen ‣People at risk of developing small blood clots sometimes told to take one aspirin every other day "to thin the blood"; prevents clots from forming by blocking platelet aggregation

Explain the generation of the action potential of the heart through EC-coupling

‣APs originate spontaneously in heart's pacemaker cells and spreads into contractile cells through gap junctions 1. An AP that enters a contractile cell moves across sarcolemma and into t-tubules 2. Voltage-gated L-type Ca2+ channels in cell membrane are opened and Ca2+ enters cell moving down its electrochemical gradient 3. Ca2+ entry opens ryanodine receptor Ca2+ release channels (RyR) in SR 4. When RyR channels open, stored Ca2+ flows out of SR and into cytosol creating Ca2+ "spark" 5. Multiple sparks from different RyR channels sum to create a Ca2+ signal Calcium released from SR provides ~90% of Ca2+ needed for muscle contraction, w/remaining 10% entering the cell from ECF. 6. Ca2+ diffuses through cytosol to contractile elements, where ions bind to troponin and initiate cycle of crossbridge formation and movement (contraction takes place by same type of sliding filament movement that occurs in skeletal muscle) 7. As cytoplasmic Ca2+ concentrations decrease, Ca2+ unbinds from troponin, myosin releases actin, and contractile filaments slide back to relaxed position 8. Ca2+ transported back into SR w/help of Ca2+@ATPase 9. Ca2+ exchanged w/Na+ by NCX antiporter; 1 Ca2+ out of cell against electrochemical gradient in exchange for 3 Na+ entering cell down electrochemical gradient 10. Na+ that enters cell during transfer is removed by Na+-K+-ATPase to maintain Na+ gradient

What portal systems occur in the systemic circulation?

‣Abdominal aorta supplies blood to trunk, legs, and internal organs such as liver (hepatic artery), digestive tract, and the kidneys (renal arteries) ‣Hepatic portal system: the two capillary beds of digestive tract and liver, joined by hepatic portal vein; blood leaving digestive tract goes directly to liver by means of hepatic portal vein; liver is important site for nutrient processing and plays major role in detoxifying foreign substances; most nutrients absorbed in intestine are routed directly to liver, allowing processing by liver before release into general circulation; ‣In kidneys: where two capillary beds are connected in series. ‣Hypothalamic-hypophyseal portal system: connects hypothalamus and anterior pituitary

What is angiogenesis?

‣Angiogenesis: process by which new blood vessels develop, especially after birth ‣In adults, angiogenesis takes place as wounds heal. Angiogenesis also occurs w/endurance exercise training, enhancing blood flow to heart muscle and to skeletal muscles. In women, growth of uterine lining after menstruation and development of placenta during pregnancy require angiogenesis. ‣Controlled by cytokines (angiogenic and antiangiogenic): promoted by vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF); Inhibited by angiostatin and endostatin ‣Regulating angiogenesis could prevent disease: Inhibiting malignant tumor growth; Promoting collateral circulation in coronary heart disease

What is mean arterial pressure?

‣Arterial blood pressure, or simply "blood pressure," reflects driving pressure created by pumping action of heart ‣Mean arterial pressure (MAP): represents driving pressure; estimated as diastolic pressure + 1/3 pulse pressure; MAP closer to diastolic pressure than to systolic pressure b/c diastole lasts twice as long as systole. ‣Abnormally high or low arterial BP can be indicative of problem in CV system. If BP falls too low (hypotension), blood flow unable to overcome opposition by gravity; if BP chronically elevated (hypertension) high pressure on walls of BVs may cause weakened areas to rupture and bleed into tissues.

How does MAP influence Cardiac Output?

‣Arterial pressure is balance between blood flow into arteries and blood flow out of arteries; If flow in exceeds flow out blood volume in arteries increases, and MAP increases; If flow out exceeds flow in, volume decreases and MAP falls ‣Blood flow into aorta is equal to CO of L ventricle ‣Blood flow out of arteries influenced primarily by peripheral resistance (resistance to flow offered by arterioles) ‣MAP proportional to cardiac output (CO) X resistance (R) of arterioles ‣If CO increases, heart pumps more blood into arteries per unit time; If resistance to blood flow out of arteries does not change, flow into arteries greater than flow out, blood volume in arteries increases, and arterial blood pressure increases.

Compare veins, arteries, and capillaries.

‣Arteries: thick, smooth muscle layer and large amounts of elastic and fibrous connective tissue; arteries and arterioles characterized by divergent pattern of blood flow. As major arteries divide into smaller and smaller arteries, character of wall changes, becoming less elastic and more muscular. Walls of arterioles contain several layers of smooth muscle that contract and relax under influence of various chemical signals. Low- volume vessels that usually contain only ~11% of total blood volume at any one time ‣Veins: blood flows from capillaries into small vessels called venules. Smallest venules are similar to capillaries, w/thin exchange epithelium and little connective tissue. They are distinguished from capillaries by convergent pattern of flow. Smooth muscle begins to appear in walls of larger venules. From venules, blood flows into veins that become larger in diameter as they travel toward heart. Venae cavae empty into R atrium. To assist venous flow some veins have internal one-way valves; once blood reaches vena cava, there are no valves. high-volume vessels that hold ~60% of circulating blood volume @any one time, making them the volume reservoir of circulatory system. Veins lie closer to surface of body than arteries, have thinner walls than arteries, w/less elastic tissue ‣Capillaries: smallest vessels in cardiovascular system; primary site of exchange between blood and interstitial fluid; lack smooth muscle and elastic or fibrous tissue reinforcement; walls consist of flat layer of endothelium, one cell thick, supported on basal lamina. Many capillaries closely associated w/cells known as pericytes. In most tissues, these highly branched contractile cells surround capillaries, forming meshlike outer layer between capillary endothelium and interstitial fluid. Pericytes contribute to "tightness" of capillary permeability: more pericytes = less leaky capillary endothelium. Pericytes secrete factors that influence capillary growth, and some can differentiate to become new endothelium or smooth muscle cells

Describe resistance in the arterioles

‣Arterioles are main site of variable resistance in systemic circulation and contribute more than 60% of total resistance to flow in system ‣Resistance in arterioles is variable b/c of large amounts of smooth muscle in arteriolar walls; When smooth muscle contracts or relaxes, radius of arterioles changes. ‣Arteriolar resistance influenced by local and systemic control mechanisms: 1. Local control of arteriolar resistance: matches tissue blood flow to metabolic needs of tissue; in heart and skeletal muscle local controls often take precedence over reflex control by CNS. 2. Sympathetic reflexes mediated by the CNS: maintain MAP and determine blood distribution to various tissues to meet homeostatic needs (I.e., temp regulation) 3. Hormones: particularly those that regulate salt and water excretion by kidneys influence BP by acting directly on arterioles and by altering autonomic reflex control

What is atherosclerosis, why is it a problem?

‣Atherosclerosis: ("hardening of arteries"); which fatty deposits form inside arterial BVs. ‣CHD accounts for majority of CV disease deaths and is single largest killer of Americans, both men and women; atherosclerosis is underlying cause ‣Increased blood cholesterol and triglycerides ‣High-density lipoprotein-cholesterol (HDL-C) is "healthy" cholesterol ‣Low-density lipoprotein-cholesterol (LDL-C) is "lethal" cholesterol ‣Atherosclerosis considered inflammatory process in which macrophages release enzymes that convert stable plaques to vulnerable plaques

Describe blood pressure

‣BP highest in arteries and decreases continuously as blood flows through circulatory system; decrease in pressure occurs b/c energy is lost as result of resistance to flow offered by vessels; resistance to blood flow also results from friction between blood cells. ‣In systemic circulation, highest pressure occurs in aorta and results from pressure created by the left ventricle ‣Aortic pressure reaches an average high of 120 mm Hg during ventricular systole (systolic pressure), then falls steadily to a low of 80 mm Hg during ventricular diastole (diastolic pressure) ‣High diastolic pressure in arteries reflects ability of those vessels to capture and store energy in elastic walls.

Where is blood pressure controlled, and where are the sensors (barorecptors) located?

‣Baroreceptor reflex: primary reflex pathway for homeostatic control of MAP; Stretch-sensitive mechanoreceptors (baroreceptors) located in walls of carotid arteries and aorta where they continuously monitor pressure of blood flow to brain (carotid baroreceptors) and to body (aortic baroreceptors); increased BP in arteries stretches baroreceptor membrane increasing AP firing rate; decreased BP decreases receptor firing rate; change in BP changes frequency of APs traveling from baroreceptors to medullary cardiovascular control center ‣Carotid and aortic baroreceptors tonically active stretch receptors that fire APs continuously @normal BPs; ‣CVCC integrates sensory input and initiates an appropriate response; response of baroreceptor reflex is rapid; output signals from CVCC carried by both sympathetic and parasympathetic autonomic neurons

Describe basophils and mast cells

‣Basophils: rare in circulation; easily recognized by the large, dark blue granules in cytoplasm; related to mast cells of tissues ‣Mast cells: fixed and concentrated in connective tissue of skin, lungs, and GI tract; locations where they are ideally situated to intercept pathogens ‣Both basophils and mast cells release chemicals (histamine) that contribute to inflammation and the innate immune response.

What is bulk flow across the capillaries?

‣Bulk flow: a third form of capillary exchange; refers to mass movement of fluid as result of hydrostatic or osmotic pressure gradients; ‣Absorption: fluid movement if direction of bulk flow is into capillary ‣Filtration: fluid movement if direction of flow is out of the capillary; caused by hydrostatic pressure that forces fluid out of capillary through leaky cell junctions. ‣Most capillaries show transition from net filtration @arterial end to net absorption @venous end ‣ Capillaries in part of kidney filter fluid along entire length; some capillaries in intestine are only absorptive, picking up digested nutrients that have been transported into interstitial fluid from lumen of intestine ‣Two forces regulate bulk flow in the capillaries: hydrostatic pressure, the lateral pressure component of blood flow that pushes fluid out through capillary pores; and osmotic pressure; forces are sometimes called Starling forces

Why does cardiac muscle contract without innervation?

‣Bulk of heart is composed of myocardium; most is contractile, but ~1% specialized to generate APs spontaneously ‣Autorhythmic cells: signal for myocardial contraction comes not from the nervous system but from specialized myocardial cells (myogenic origination) ‣Pacemakers: autorhythmic cells are also called; they set rate of heartbeat ‣Myocardial autorhythmic cells anatomically distinct from contractile cells: autorhythmic cells are smaller and contain few contractile fibers, don't have organized sarcomeres, don't contribute to contractile force of heart

What other systems influence cardiovascular function?

‣CV function can be modulated by input from peripheral receptors other than baroreceptors ‣Arterial chemoreceptors: activated by low O2 → increased cardiac output; Adaptive integration between respiratory and CV systems ‣BP modulated by hypothalamus and cerebral cortex: Learned and emotional responses ‣BP closely tied to fluid balance in kidneys

Compare cardiac muscle to skeletal muscle

‣Cardiac muscle fibers smaller than skeletal muscle fibers and usually have a single nucleus per fiber ‣Individual cardiac muscle cells branch and join neighboring cells end-to-end to create a complex network; cell junctions (intercalated disks) consist of interdigitated membranes. Intercalated disks have two components: desmosomes and gap junctions; desmosomes are strong connections that tie adjacent cells together, allowing force created in one cell to be transferred to adjacent cell ‣Gap junctions in intercalated disks electrically connect cardiac muscle cells to one another; allow waves of depolarization to spread rapidly from cell to cell, so that all heart muscle cells contract simultaneously; in this respect, cardiac muscle resembles single-unit smooth muscle ‣T-tubules of myocardial cells larger than those of skeletal muscle, and they branch inside myocardial cells ‣Myocardial SR smaller than skeletal muscle; reflects that cardiac muscle depends in part on EC Ca2+ to initiate contraction; in this respect cardiac muscle resembles smooth muscle ‣Mitochondria occupy ~1/3 cell volume of cardiac contractile fiber; reflection of high energy demand cells

What factors influence arterial pressure?

‣Cardiac output ‣Distribution of blood in systemic circulation: arteries are low-volume vessels that usually contain only ~11% of total blood volume; veins are high-volume vessels that hold ~60% of circulating blood volume ‣Total blood volume: veins act as volume reservoir for circulatory system holding blood that can be redistributed to arteries if needed; if arterial blood pressure falls, increased sympathetic activity constricts veins, decreasing holding capacity; constriction of veins redistributes blood to arterial side of circulation and raises MAP

What is cardiac output (CO)?

‣Cardiac output (CO): volume of blood pumped by one ventricle in a given period of time; b/c all blood that leaves heart flows through tissues, CO indicator of total blood flow through body ‣Cardiac output (CO) = HR (bpm) X SV (mL/beat, or /contraction)

How does coagulation convert a platelet plug into a clot?

‣Coagulation divided into 2 pathways that eventually merge into 1 ‣Intrinsic pathway: begins when damage to tissue exposes collagen; also known as contact activation pathway; pathway uses proteins already present in plasma; Collagen activates 1st enzyme (factor XII) to begin cascade ‣Extrinsic pathway: starts when damaged tissues expose tissue factor (tissue thromboplastin or factor III); also called cell injury pathway or tissue factor pathway; Tissue factor activates factor VII to begin extrinsic pathway. ‣Common pathway: once started, thrombin converts fibrinogen into insoluble fibrin polymers, and Fibrin fibers become part of the clot ‣To remove: Fibrinolysis: removal when injury is repaired; Fibrin broken by enzyme plasmin; Inactive plasminogen activated to plasmin by tissue plasminogen activator (tPA)

Explain the competing pressures contributing to the bulk flow of fluid across both ends of the capillary.

‣Colloid osmotic pressure: colloid osmotic pressure constant along length of capillary, atp = 25mmHg; higher in plasma (pcap = 25 mm Hg) than in interstitial fluid (pIF = 0 mm Hg); osmotic gradient favors water movement by osmosis from interstitial fluid into plasma ‣Capillary hydrostatic pressure (PH): decreases along length of capillary as energy is lost to friction; Avg values for capillary hydrostatic pressure are 32 mm Hg @arterial end of capillary and 15 mm Hg @venous end; hydrostatic pressure of interstitial fluid PIF is very low (we consider it to be essentially zero); water movement due to hydrostatic pressure directed out of capillary w/pressure gradient decreasing from arterial end to venous end ‣Net pressure driving fluid flow across capillary determined by difference between hydrostatic pressure PH and colloid osmotic pressure (p); positive value for net pressure indicates net filtration and negative value indicates net absorption ‣@arterial end, PH>p; net filtration pressure ‣@venous end, PH<p; net pressure favors absorption

Describe the function of colloid osmotic pressure for fluid bulk flow.

‣Colloid osmotic pressure: osmotic pressure determined by solute concentration of compartment; main solute diff between plasma and interstitial fluid due to proteins, which are present in plasma but mostly absent from interstitial fluid ‣Colloid osmotic pressure not equivalent to total osmotic pressure in capillary; is measure of osmotic pressure created by proteins ‣B/c capillary endothelium is freely permeable to ions and other solutes in plasma and interstitial fluid, these other solutes do not contribute to osmotic gradient ‣Colloid osmotic pressure higher in plasma (pcap = 25 mm Hg) than interstitial fluid (pIF = 0 mm Hg); osmotic gradient favors water movement by osmosis from interstitial fluid into plasma

What are the types of capillaries?

‣Continuous capillaries: endothelial cells joined to one another w/leaky junctions; found in muscle, connective tissue, and neural tissue; continuous capillaries of brain have evolved to form blood-brain barrier, w/tight junctions that help protect neural tissue from toxins that may be present in bloodstream ‣Fenestrated capillaries: large pores that allow high vol of fluid to pass rapidly between plasma and interstitial fluid; found primarily in kidney and intestine where they are associated w/absorptive transporting epithelia ‣Sinusoids: as much as 5x wider than a capillary; sinusoid endothelium has fenestrations, and there may be gaps between cells; found in locations where blood cells and plasma proteins need to cross endothelium to enter blood (bone marrow, liver, and spleen); In liver sinusoidal endothelium lacks basal lamina, which allows even more free exchange between plasma and interstitial fluid

How can pressure in the circulatory system change?

‣Contraction of blood-filled ventricles creates pressure which is transferred to blood; high-pressure blood then flows out of ventricle and into BVs, displacing lower-pressure blood already in vessels; pressure created in ventricles is called driving pressure because it is the force that drives blood through BV's ‣When heart relaxes and expands, pressure in fluid-filled chambers falls ‣In BV's: if BV's dilate, BP inside circulatory system falls; if BV's constrict, BP in system increases

What is erythropoietin (EPO)?

‣Controls RBC production (erythropoiesis) ‣Erythropoietin (EPO): glycoprotein; assisted by several cytokines; made primarily in kidneys of adults. ‣Stimulus for EPO synthesis and release is hypoxia, low oxygen levels in tissues; hypoxia stimulates production of transcription factor called hypoxia-inducible factor 1 (HIF-1), which turns on EPO gene to increase EPO synthesis. ‣EPO pathway, like other endocrine pathways, helps body maintain homeostasis; By stimulating synthesis of RBCs, EPO puts more Hb into circulation to carry O2

Describe coronary circulation

‣Coronary arteries: run across surface of heart in shallow grooves, branching into smaller and smaller arteries until finally arterioles disappear into heart muscle itself oRight coronary artery (RCA): runs from aorta around right side of heart in coronary sulcus between RA and RV; RCA branches feed RA, most of RV and some of LV, and posterior portion of interventricular septum oLeft coronary artery (LCA): leaves left side of aorta and divides into 2 main branches; circumflex branch which continues around left side of heart to posterior surface, and anterior interventricular branch (LAD) which runs in groove toward apex of heart; LCA supplies blood to LA, most of LV and interventricular septum, and some of RV ‣Coronary veins: run in parallel w/coronary arteries oMost venous blood (∼85%) leaves myocardium through cardiac veins that empty into coronary sinus on posterior aspect of heart; blood in coronary sinus empties directly into RA oDeep in heart muscle, smaller blood channels empty their blood directly into heart's chamber; few small veins on anterior portion of RV drain directly into RA

What is the function of cytokines?

‣Cytokines: peptides or proteins released from one cell that affects growth or activity of another cell; controls production and development of blood cells ‣Cytokines in hematopoiesis: colony-stimulating factors, molecules made by endothelial cells and WBCs; interleukins such as IL-3, cytokines released by one WBC to act on another WBC, play important roles in immune system; erythropoietin controls RBC synthesis

Define systole and diastole

‣Diastole: time during which cardiac muscle relaxes ‣Systole: time during which muscle contracts

How is blood distributed to the tissues?

‣Distribution of systemic blood varies by metabolic needs of individual organs; governed by combination of local control mechanisms and homeostatic reflexes ‣Blood flow to individual organs set by number and size of arteries feeding organ; usually more than 2/3 of CO routed to digestive tract, liver, muscles, and kidneys ‣Variations in blood flow to individual tissues possible b/c arterioles in body arranged in parallel; all arterioles receive blood @same time from aorta; total blood flow through all arterioles of body always equals CO ‣Flow thru individual arterioles in branching system of arterioles depends on resistance (R); higher resistance in arteriole = lower blood flow; flow diverted away from constricted arteriole distributed to other arterioles keeping total flow through system constant ‣Arteriolar resistance in most tissues balance between autonomic control by brain and local control by tissue metabolites and paracrine signals. In brain and heart tissue metabolism is primary factor that determines arteriolar resistance

What are the functions of blood?

‣Distribution: O2 and nutrients to body cells, metabolic wastes to lungs and kidneys for elimination, hormones for endocrine grands to target organs ‣Regulation: body temp by absorbing and distributing heat, normal pH using buffers, adequate fluid volume in circulatory system ‣Protection against: blood loss (plasma proteins and platelets to initiate clot formation), and infection (antibodies, complement proteins, WBC's)

Describe eosinophils

‣Easily recognized by bright pink-staining granules in cytoplasm ‣Normally, few eosinophils found in peripheral circulation ‣Most functioning eosinophils found in digestive tract, lungs, urinary and genital epithelia, and connective tissue of skin; locations reflect role in defense against parasitic invaders ‣Eosinophils attach to large antibody-coated parasites and release substances from their granules that damage or kill parasites. ‣Participate in allergic reactions, where they contribute to inflammation and tissue damage by releasing toxic enzymes and oxidative substances

What is edema, and what are some causes?

‣Edema: swelling caused by excess interstitial fluid trapped in the body's tissues; a sign that normal exchange between circulatory system and lymphatics has been disrupted ‣Causes: (1) inadequate drainage of lymph or (2) blood capillary filtration that greatly exceeds capillary absorption. ‣Inadequate lymph drainage: occurs w/obstruction of lymphatic system, particularly @lymph nodes; Parasites, cancer, or fibrotic tissue growth caused by therapeutic radiation can block movement of lymph through system; drainage may be impaired if lymph nodes are removed during surgery

Describe an ECG

‣Electrocardiograms (ECGs): show summed electrical activity generated by all cells of heart; an extracellular recording that represents tsum of multiple ApPs taking place in many heart muscle cells ‣Waves of ECG: oP wave: corresponds to depolarization of atria oQRS complex: represents progressive wave of ventricular depolarization; Q wave sometimes absent on normal ECGs; includes atrial repolarization oT wave: represents repolarization of ventricles. ‣Segments of ECG: oP-R segment: conduction through AV node and AV bundle oS-T segment: represents beginning of ventricular repolarization and corresponds w/"plateau" phase of AP of ventricular myocytes

Define "essential hypertension" and the risk factors associated with it.

‣Essential (primary) hypertension: more than 90% of all patients w/hypertension; no clear-cut cause other than heredity; CO usually normal and elevated BP appears to be associated w/increased peripheral resistance; SV remains constant up to mean BP of ~200 mmHG ‣Carotid and aortic baroreceptor adapt to higher pressure, w/subsequent down-regulation of activity; W/out input from baroreceptors, CV control center interprets high BP as "normal," and no reflex reduction of pressure occurs ‣Risk factor for atherosclerosis b/c high pressure in arteries damages endothelial lining of vessels and promotes formation of atherosclerotic plaques ‣High arterial BP puts additional strain on heart by increasing afterload; When resistance in arterioles is high myocardium must work harder to push blood into arteries

Describe the mechanisms for transfer of gases and solutes across the walls of capillaries, in tissues and organs.

‣Exchange between plasma and interstitial fluid takes place by movement between endothelial cells (paracellular pathway) or through cells (endothelial transport) ‣Smaller dissolved solutes and gases move by diffusion between or through cells depending on lipid solubility; Larger solutes and proteins move mostly by vesicular transport ‣Diffusion rate for dissolved solutes determined primarily by concentration gradient between plasma and interstitial fluid; O2 and CO2 diffuse freely across thin endothelium; Their plasma concentrations reach equilibrium w/interstitial fluid and cells by time blood reaches venous end of capillary. ‣In capillaries w/leaky cell junctions most small dissolved solutes diffuse freely between cells or through fenestrations ‣In continuous capillaries blood cells and most plasma proteins are unable to pass through junctions between endothelial cells; proteins do move from plasma to interstitial fluid and vice versa ‣Transcytosis: larger molecules (including selected proteins) in most capillaries are transported across endothelium; endothelial cell surface appears dotted w/numerous caveolae and noncoated pits that become vesicles for transcytosis; in some capillaries chains of vesicles fuse to create open channels that extend across endothelial cell

How does blood flow related to changes in pressure and resistance?

‣Flow of blood in CV system directly proportional to pressure gradient in system and inversely proportional to resistance of system to flow; if pressure gradient remains constant, flow varies inversely w/resistance ‣Pressure: blood flow thru CV system requires pressure gradient; flow thru tube directly proportional to pressure gradient (∆P); higher pressure gradient=greater fluid flow ‣Resistance: resistance to flow is tendency of CV system to oppose blood flow; blood flow takes path of least resistance; increase in resistance of BV = decrease in flow thru vessel; flow inversely proportional to resistance: resistance increase = flow decrease; resistance decrease = flow increases

Where are blood cells formed, from what progenitors?

‣Formed in: In adult bone marrow of pelvis, spine, ribs, cranium, and proximal ends of long bones ‣Progenitor cells: differentiate into RBC's, lymphocytes, other WBCs, and megakaryocytes (parent cells of platelets); committed to developing into 1 or 2 cell types

What is transported through the body via the cardiovascular system?

‣From external environment: O2, nutrients, water ‣Materials between cells: wastes, stored nutrients, hormones, immune cells, antibodies, clotting proteins ‣Waste eliminated by cells: metabolic wastes, CO2, heat

What are the types of leukocytes?

‣Granulocytes: WBCs whose cytoplasm contains prominent granules; include basophils, eosinophils, and neutrophils ‣Agranulocytes: WBCs that have no distinct granules in cytoplasm; lymphocytes and monocytes

What can an expert read from an ECG?

‣HR: normally timed either from beginning of one P wave to beginning of next P wave or peak of one R wave to peak of the next R wave; A faster-than-normal rate = tachycardia, and slower-than-normal rate = bradycardia ‣Rhythm: arrhythmia can result from benign extra beat or from more serious conditions such as atrial fibrillation, in which SA node has lost control of pacemaking ‣Wave normality: Is there one QRS complex for each P wave? If yes, is P-R segment constant in length? If not, problem w/conduction of signals through AV node may exist

What is hematocrit?

‣Hematocrit: ratio of RBCs to plasma; expressed as a percentage of total blood volume; determined by drawing blood sample into narrow capillary tube and spinning it in centrifuge so heavier RBCs go to bottom, leaving thin "buffy layer" of lighter leukocytes and platelets in middle, and plasma on top. ‣Normal range: 40-54% for a man, 37-47% for a woman

Describe hematopoiesis

‣Hematopoiesis: synthesis of blood cells; begins early in embryonic development and continues throughout a person's life ‣Active bone marrow is red b/c it contains hemoglobin ‣Inactive marrow is yellow b/c of abundance of adipocytes (fat cells) ‣Blood synthesis in adults is limited to liver, spleen; inactive (yellow) regions of marrow can resume blood cell production in times of need. ‣In regions of marrow actively producing blood cells, ~25% of developing cells are RBCs, while 75% are destined to become WBCs; life span of WBCs considerably shorter than RBCs so WBCs must be replaced more frequently

What are the major types of blood disorders and their causes?

‣Hemolytic anemia: rate of RBC destruction exceeds rate of production; usually hereditary membrane defects (example: hereditary spherocytosis), enzyme defects, and Hb (example: sickle cell anemia); Several are acquired diseases such as parasitic infections (example: malaria), drugs, and autoimmune reactions ‣Sickle cell anemia: result of abnormal Hb molecules; genetic defect in which glutamate, the sixth amino acid in the 146-amino acid beta chain of hemoglobin, is replaced by valine; result is abnormal Hb (form referred to as HbS) that crystallizes when it gives up O2; crystallization pulls RBCs into sickle shaped cell that become tangled w/other sickled cells as they pass through smallest BVs, causing cells block blood flow to tissues; blockage creates tissue damage and pain from hypoxia ‣Iron-deficiency anemia: failure of bone marrow to make adequate amounts of hemoglobin; low RBC count (reflected in a low hematocrit) or low Hb content in blood; RBCs often smaller than usual and lower Hb content may cause cells to be paler than normal ‣Polycythemia vera: stem cell dysfunction that produces too many blood cells (white and red); patients may have hematocrits as high as 60-70% (normal is 37-54%); increased number of cells causes blood to become more viscous and more resistant to flow through circulatory system ‣Relative polycythemia: person's RBC number normal, but hematocrit is elevated b/c of low plasma vol due to dehydration; or low hematocrit due to over-hydration

What is hemostasis?

‣Hemostasis: process of keeping blood w/in a damaged blood vessel ‣3 major steps: 1 vasoconstriction; immediate constriction of damaged vessels to decrease blood flow and pressure w/in vessel temporarily, normally caused by paracrine molcs released from endothelium 2 temporary blockage of a break by a platelet plug; formation begins w/platelet adhesion, adhered platelets become activated, releasing cytokines into area around injury; platelet factors reinforce local vasoconstriction and activate more platelets, which aggregate to form loose platelet plug. 3 coagulation, formation of a clot that seals hole until tissues are repaired; exposed collagen and tissue factor(protein-phospholipid mixture) initiate formation of fibrin protein mesh that stabilizes platelet plug to form clot ‣Eventually, as damaged vessel repairs itself, clot retracts when fibrin slowly dissolved by enzyme plasmin. ‣Body must maintain proper balance during hemostasis: too little hemostasis allows excessive bleeding; too much creates thrombus, a blood clot that adheres to undamaged wall of a BV; A large thrombus can block lumen of vessel and stop blood flow

What are the functions of heparin, and plasminogen and plasmin?

‣Heparin: anticoagulant; medication and naturally occurring glycosaminoglycan; also used in treatment of heart attacks and unstable angina ‣Plasminogen: inactive form of plasmin; activated by tissue plasminogen activator (tPA) ‣Plasmin: enzyme that breaks down fibrin through fibrinolysis

How do physicians treat hypertension?

‣If resistance remains high over time, heart muscle cannot meet workload and begins to fail: CO by left ventricle decreases; If CO of the right heart remains normal while output from left side decreases, fluid collects in lungs, creating pulmonary edema ‣Treatments: calcium channel blockers, diuretics, beta-blocking drugs, ACE* inhibitors, and angiotensin receptor blockers

How do paracrine signals influence vascular smooth muscle?

‣In tissue, blood flow into individual capillaries regulated by precapillary sphincters; When sphincters constrict, they restrict blood flow into capillaries; When sphincters dilate, blood flow into capillaries increases; mechanism provides additional site for local control of blood flow ‣Local regulation also takes place by changing arteriolar resistance in tissue; accomplished by paracrine molecules (including the gases O2, CO2, and NO) secreted by vascular endothelium or by cells to which arterioles supply blood ‣Active hyperemia: process in which increase in blood flow accompanies increase in metabolic activity; Concentrations of many paracrine molecules change as cells become more or less metabolically active (E.g., if aerobic metabolism increases, tissue O2 levels decrease while CO2 production goes up; Both low O2 and high CO2 dilate arterioles; vasodilation increases blood flow into tissue bringing additional O2 to meet increased metabolic demand and removing waste CO) ‣Reactive hyperemia: increase in tissue blood flow following a period of low perfusion (blood flow); If blood flow to tissue occluded, O2 levels fall and metabolic paracrine signals such as CO2 and H+ accumulate in interstitial fluid; Local hypoxia causes endothelial cells to synthesize vasodilator NO; When blood flow to tissue resumes, increased concentrations of NO, CO2, and other paracrine molecules immediately trigger significant vasodilation; As vasodilators metabolized or washed away by restored tissue blood flow, radius of arteriole gradually returns to normal

Compare innate and acquired immune responses

‣Innate immunity: present from birth; body's immediate immune response to invasion; not specific to any one pathogen, so it begins w/in minutes to hours; Inflammation, visible on skin as a red, warm, swollen area, is classic sign of innate immunity; innate immune response to pathogen not remembered by immune system and must be triggered anew w/each exposure; cells responsible for rapid innate response are circulating and stationary leukocytes that are genetically programmed to respond to broad range of material that they identify as foreign ‣Adaptive immunity (acquired immunity): directed @particular invaders and is body's specific immune response; steps needed to launch a specific immune response following first exposure to pathogen may take days to weeks; upon reexposure. certain immune cells called memory cells "remember" their prior exposure to pathogen and react more rapidly; can be divided into cell-mediated immunity and antibody-mediated immunity; Cell-mediated immunity requires contact-dependent signaling between immune cell and receptors on target cell; Antibody-mediated immunity, aka humoral immunity, uses antibodies to carry out immune response; Antibodies bind to foreign substances to disable them or make them more visible to cells of immune system

How is contractility controlled by the nervous and endocrine systems?

‣Ionotropic agent: any chemical that affects contractility; influence is called an inotropic effect; if chemical increases force of contraction, it is said to have a positive inotropic effect (EX epi- and norepinephrine enhance contractility and are therefore considered to have a positive inotropic effect); chemicals w/negative inotropic effects decrease contractility. ‣Contractility increases as amount of Ca2+ available for contraction increases ‣Catecholamines increase Ca2+ storage through use of a regulatory protein called phospholamban ‣Catecholamines shorten duration of contraction; enhanced Ca2+@ATPase speeds up removal of Ca2+ from cytosol shortening time that Ca2+ bound to troponin and decreases active time of myosin crossbridges

What is leukopoiesis?

‣Leukopoiesis: WBC production; production of new WBCs regulated in part by existing WBCs; allows leukocyte development to be very specific and tailored to body's needs; When body's defense system called on to fight foreign invaders, both absolute number of WBCs and relative proportions of diff types of WBCs in circulation change ‣Colony-stimulating factors (CSFs): regulate leukopoiesis; stimulate growth of leukocyte colonies in culture; made by endothelial cells, marrow fibroblasts, and leukocytes ‣CSFs induce cell division (mitosis) and maturation in stem cells; Once leukocyte matures, it loses ability to undergo mitosis

What is the function of the lymph nodes and the spleen?

‣Lymph nodes: @intervals along way, vessels enter; bean-shaped nodules of tissue w/fibrous outer capsule and internal collection of immunologically active cells, including lymphocytes and macrophages ‣The speen: works as part of lymphatic system to protect body, clearing worn-out RBCs and other foreign bodies from bloodstream to help fight off infection

How does lymph return fluid to the heart?

‣Lymphatic system has no single pump like heart; flow depends primarily on waves of contraction of smooth muscle in walls of larger lymph vessels ‣Flow of lymph aided by contractile fibers in endothelial cells, by one-way valves, and external compression created by skeletal muscles ‣Lymphatic vessels drain into collecting ducts, which empty contents into the 2 subclavian veins located under collarbones; These veins join to form superior vena cava that drains blood from upper body into heart ‣Returning filtered fluid to circulation allows recycling of plasma proteins

What is hemoglobin (Hb)?

‣Main component of RBCs; best known for role in O2 transport ‣Large, complex protein w/4 globular protein chains, each of which is wrapped around an iron-containing heme group; several isoforms of globin proteins in Hb ‣The four heme groups in Hb molecule are identical; each consists of carbon-hydrogen-nitrogen porphyrin ring w/iron atom (Fe) in center; ~70% of iron in body is found in heme groups of Hb ‣Hb synthesis requires adequate supply of Fe in diet; carrier protein transferrin binds Fe and transports in blood; bone marrow takes up Fe and uses to make heme group of Hb for developing RBCs ‣Excess ingested Fe is stored, mostly in liver; Iron stores found inside spherical protein called molecule ferritin

What is mean arterial pressure (MAP)?

‣Mean Arterial Pressure (MAP): primary driving force for blood flow; arteries act as pressure reservoir during heart's relaxation phase ‣MAP influenced by 2 parameters: cardiac output (volume of blood the heart pumps per minute) and peripheral resistance (resistance of BV's to blood flow through them) ‣Mean Arterial Pressure (MAP) ∝ Cardiac Output (CO) X Total Peripheral Resistance (TPR) ‣MAP = Diastolic P + 1/3 (Pulse pressure), where pulse pressure = systolic - diastolic pressure

What are some indicators of RBC problems?

‣Morphology of RBCs can provide clues to presence of disease; Sometimes cells lose flattened disk shape and become spherical (spherocytosis); In sickle cell anemia, cells shaped like a sickle ‣Mean corpuscular volume (MCV): In some disease states, size of RBCs may be either abnormally large or abnormally small; For ex, RBCs can be abnormally small, or microcytic, in iron-deficiency anemia ‣If RBCs are pale due to lack of red Hb; described as hypochromic

Describe the characteristics of capillaries

‣Most cells located w/in 0.1 mm of nearest capillary, and diffusion over short distance proceeds rapidly ‣Capillary density in any given tissue is directly related to metabolic activity of tissue's cells; Tissues w/higher metabolic rate require more oxygen and nutrients; have more capillaries per unit area ‣Subcutaneous tissue and cartilage have lowest capillary density; Muscles and glands have highest ‣Thinnest walls of all BVs; composed of single layer of flattened endothelial cells supported on basal lamina ‣Diameter of capillary is barely that of RBC; RBCs squeeze through single file

What is myogenic autoregulation?

‣Myogenic autoregulatin: ability of vascular smooth muscle to regulate its own state of contraction ‣In absence of autoregulation, an increase in BP increases blood flow through an arteriole. However, when smooth muscle fibers in wall of arteriole stretch b/c of increased BP, arteriole constricts. This vasoconstriction increases resistance offered by arteriole, automatically decreasing blood flow through vessel; arterioles have limited ability to regulate own blood flow. ‣Myogenic autoregulation work @cellular level: when vascular smooth muscle cells in arterioles are stretched, mechanically gated channels in muscle membrane open. Cation entry depolarizes cell opening voltage-gated Ca2+ channels, and Ca2+ flows into cell down electrochemical gradient. Ca2+ entering cell combines w/calmodulin and activates myosin light chain kinase; MLCK increases myosin ATPase activity and crossbridge activity resulting in contraction.

Under what circumstances does cardiac out-put change? Since the volume of blood is a fixed amount, how can CO increase during exercise?

‣Normally, CO same for both ventricles; if one side of heart begins to fail and unable to pump efficiently, CO becomes mismatched; blood pools in circulation behind weaker side of heart ‣During exercise, CO may increase to 30-35 L/min ‣Homeostatic changes in CO accomplished by varying heart rate, stroke volume, or both. Both local and reflex mechanisms can altercardiac output.

What are risk factors for cardiovascular disease?

‣Not controllable: sex, age, family history ‣Controllable: smoking, obesity, sedentary lifestyle, untreated hypertension ‣Diabetes mellitus contributes to development of atherosclerosis ‣Some genetic factors can be modified by lifestyle

How does orthostatic hypotension trigger the baroreceptor reflex?

‣Orthostatic hypotension: decrease in blood pressure upon standing; normally triggers baroreceptor reflex; result is increased CO and increased peripheral resistance, which together increase MAP and bring it back up to normal w/in 2 heartbeats ‣Skeletal muscle pump also contributes to recovery by enhancing venous return when abdominal and leg muscles contract to maintain an upright position. ‣Baroreceptor reflex not always effective: during extended bed rest, blood from lower extremities distributed evenly throughout body rather than pooled in lower extremities; even distribution raises arterial pressure, triggering kidneys to excrete what body perceives as excess fluid; over course of 3 days of bed rest, excretion of water leads to 12% decrease in blood volume.

What are myocardial autorhythmic cells?

‣Pacemaker potential: unstable membrane potential; gives myocardial autorhythmic cells unique ability to generate AP spontaneously in absence of input from nervous system; starts at -60 mV and slowly drifts upward toward threshold. ‣Whenever pacemaker potential depolarizes to threshold, autorhythmic cell fires AP ‣If channels (funny current): allow current (I) to flow and b/c of unusual properties; belong HCN channel family (hyperpolarization-activated cyclic nucleotide-gated channels); ‣When If channels open @neg membrane potentials, Na+ influx exceeds K+ efflux; net influx of + charge slowly depolarizes autorhythmic cell; As membrane potential becomes more positive, If channels gradually close and one set of Ca2+ channels opens; resulting influx of Ca2+ continues depolarization and membrane potential moves steadily toward threshold ‣When membrane potential reaches threshold, diff subtype of voltage-gated Ca2+ channels opens; Ca2+ rushes into cell creating steep depolarization phase of AP ‣When Ca2+ channels close @peak of AP, slow K+ channels have opened; repolarization phase of autorhythmic AP is due to resultant efflux of K+ ‣Speed that pacemaker cells depolarize determines rate that the heart contracts at (HR); interval between APs can be modified by altering permeability of autorhythmic cells to diff ions, which in turn changes duration of pacemaker potential

What factors affect heart rate?

‣Parasympathetic Control: acetylcholine (ACh) slows HR; ACh activates muscarinic cholinergic receptors that influence K+ and Ca2+ channels in pacemaker cell. K+ permeability increases, hyperpolarizing cell so that pacemaker potential begins @more neg value. @Same time, Ca2+ permeability of pacemaker decreases. Decreased Ca2+ permeability slows rate that pacemaker potential depolarizes. Combination of effects causes cell to take longer to reach threshold, delaying onset of AP in pacemaker and slowing HR ‣Sympathetic Control: stimulation of pacemaker cells speeds up HR. norepinephrine (from sympathetic neurons) and epinephrine (from adrenal medulla) increase ion flow through both If and Ca2+ channels. More rapid cation entry speeds up rate of pacemaker depolarization, causing cell to reach threshold faster and increasing rate of AP firing. When pacemaker fires APs more rapidly, HR increases. ‣Tonic Control: normally tonic control of HR dominated by parasympathetic branch. Increase in HR can be achieved in two ways. Simplest method for increasing rate is to decrease parasympathetic activity. As parasympathetic influence is withdrawn from autorhythmic cells, they resume intrinsic rate of depolarization, and HR increases to 90-100 bpm. Sympathetic input required to increase HR above intrinsic rate. Norepinephrine (or epinephrine) on b1-receptors speeds up depolarization rate of autorhythmic cells and increases HR. Both autonomic branches also alter rate of conduction through AV node. ACh slows conduction of APs through AV node, thereby increasing AV node delay. Epi- and norepinephrine enhance conduction of APs through AV node and conducting system

Describe the anatomy of the heart in detail

‣Pericardium: encases heart in tough membranous sac; thin layer of clear pericardial fluid inside pericardium lubricates external surface of heart as it beats w/in sac ‣Myocardium: cardiac muscle that composes heart itself; covered by thin outer and inner layers of epithelium and connective tissue. ‣Aorta and pulmonary trunk (artery) direct blood from heart to tissues and lungs ‣Venae cavae and pulmonary veins return blood to heart ‣Atrioventricular valves: between atria and ventricles; R AV valve (tricuspid) and L AV valve (bicuspid or mitral); formed from thin flaps of tissue joined @base to a connective tissue ring. Flaps are slightly thickened @edge and connect on ventricular side to collagenous tendons (chordae tendineae) ‣Chrodae tendineae: most fasten to edges of valve flaps; opp ends of chordae are tethered to moundlike extensions of ventricular muscle (papillary muscles) ‣Papillary muscles: provide stability for chordae, but cannot actively open and close AV valves ‣Semilunar valves: between ventricles and the arteries; aortic and pulmonary semilunar

What are the 2 functional groups of leukocytes?

‣Phagocytes: ingest material from ECF using a large vesicle; include neutrophils, macrophages, dendritic cells ‣Antigen-presenting cells (APCs): have ability to display bits of antigen on their surface as signal to other immune cells; primary APCs are the macrophages and dendritic cells

Describe the action potential of a cardiac contractile cell

‣Phase 4: resting membrane potential: myocardial contractile cells have stable resting potential of ~-90 mV. ‣Phase 0: depolarization: when a wave of depolarization moves into contractile cell through gap junctions, membrane potential becomes more positive; voltage-gated Na+ channels open allowing Na+ to enter cell and rapidly depolarize it; membrane potential reaches ~+ 20 mV before Na+ channels close; (double-gated Na+ channels) ‣Phase 1: initial repolarization: when Na+ channels close, cell begins to repolarize as K+ leaves through open K+ channels. ‣Phase 2: the plateau: initial repolarization very brief; AP flattens into plateau as result of two events: decrease in K+ permeability and increase in Ca2+ permeability; Voltage-gated Ca2+ channels activated by depolarization have been slowly opening during phases 0 and 1; when finally open, Ca2+ enters cell and some "fast" K+ channels close; combination of Ca2+ influx and decreased K+ efflux causes AP to flatten out into plateau ‣Phase 3: rapid repolarization: plateau ends when Ca2+ channels close and K+ permeability increases once more; "slow" K+ channels responsible for this phase are similar to those in neuron: activated by depolarization but slow to open; When slow K+ channels open, K+ exits rapidly, returning cell to resting potential

What are the cellular and noncellular components of blood?

‣Plasma: fluid matrix of the blood, w/in which cellular elements are suspended ○(~92%)Water ○(7%)Proteins ○(1%) dissolved organic molecules (amino acids, glucose, lipids, and nitrogenous wastes), ions (Na+, K+, Cl-, H+, Ca2+, and HCO3-), trace elements and vitamins, and dissolved O2 and CO2 ‣Plasma proteins: made mostly by liver, some globulins (immunoglobulins or antibodies) are synthesized and secreted by specialized blood cells; participate in blood clotting and defense against foreign invaders; act as carriers for steroid hormones, cholesterol, drugs, and certain ions such as iron (Fe2+); some act as hormones or EC enzymes ○(~90%) Albumins, globulins = clotting protein, fibrinogen, and transferrin = iron-transporting protein ○(~60%) Albumin ‣Cellular elements: RBCs (erythrocytes), WBCs (leukocytes), and platelets (thrombocytes)

What are platelets and how are they formed?

‣Platelets: cell fragments produced in bone marrow from huge cells called megakaryocytes; smaller than RBCs, colorless, have no nucleus; cytoplasm contains mitochondria, smooth ER, and numerous membrane-bound vesicles called granules that are filled w/variety of cytokines and growth factors ‣Outer edges of marrow megakaryocytes extend through endothelium into lumen of marrow blood sinuses, where cytoplasmic extensions fragment into platelets ‣Platelets always present in blood and typical life span is ~10 days

How is the formation of a clot an example of positive feedback?

‣Plug formation begins w/platelet adhesion; when platelets adhere or stick to exposed collagen in the damaged area ‣Adhered platelets become activated, releasing cytokines into area around injury; these platelet factors reinforce local vasoconstriction and activate more platelets, which aggregate or stick to one another to form a loose platelet plug. ‣Platelets activating more platelets are an example of a positive feedback loop

How does a pressure-volume curve represent one cardiac cycle?

‣Point a: ventricle has completed a contraction and contains minimum amount of blood that it will hold during cycle; relaxed and pressure @minimum value; blood flowing into atrium from pulmonary veins. Once pressure in atrium exceeds pressure in ventricle, mitral valve opens ‣Point A to B: Atrial blood flows into ventricle increasing its volume ‣Point A' to B: As blood flows in, relaxing ventricle expands to accommodate entering blood; vol of ventricle increases, but pressure in ventricle goes up very little; last portion of ventricular filling completed by atrial contraction ‣Point B: ventricle now contains maximum vol of blood; end-diastolic volume or EDV ‣B to C:When ventricular contraction begins, mitral (AV) valve closes. Blood in ventricle nowhere to go w/AV and semilunar valves closed. Ventricle continues to contract causing pressure in chamber to increase rapidly during isovolumic contraction ‣Point C: once ventricular pressure exceeds pressure in aorta, aortic valve opens ‣C to D: Pressure continues to increase as ventricle contracts further, but ventricular volume decreases as blood is pushed out into aorta ‣Point D: end-systolic volume (ESV); minimum volume of blood ventricle contains during one cycle ‣D to A: @end of each ventricular contraction ventricle begins to relax; ventricular pressure decreases; Once pressure in ventricle falls below aortic pressure, semilunar valve closes, and ventricle becomes sealed chamber; Remainder of relaxation occurs w/out change in blood volume, AKA isovolumic relaxation; ‣When ventricular pressure falls below atrial pressure, mitral valve opens and cycle begins again

What is Pouiselle's law?

‣Poiseuille's law: (1) resistance to fluid flow offered by tube increases as length of tube increases, (2) resistance increases as viscosity of fluid increases, but (3) resistance decreases as tube's radius increases ‣Length of systemic circulation determined by anatomy of system and is essentially constant ‣Blood viscosity determined by ratio of RBC's to plasma and how much protein is in plasma; normally viscosity constant ‣Small changes in length or viscosity have little effect on resistance ‣Changes in radius of BVs is main variable that affects resistance in systemic circulation ‣Vasoconstriction: decrease in BV diameter; decreases blood flow through a vessel ‣Vasodilatation: increase in BV diameter; increases blood flow through a vessel

What are the major molecules that contribute to plasma osmolarity?

‣Presence of proteins in plasma makes osmotic pressure of blood higher than that of interstitial fluid ‣Osmotic gradient tends to pull water from interstitial fluid into capillaries and offset filtration out of capillaries created by blood pressure

Describe pressure generated by the heart and through the circulatory system

‣Pressure gradient (𝚫P): flow from regions of higher pressure to regions of lower pressure; blood can flow in CV system only if one region develops higher pressure than other regions ‣Heart creates high pressure when contracts; blood flows out of heart (region of highest pressure) into closed loop of BVs (region of lower pressure); as blood moves thru system, pressure is lost b/c of friction between fluid and BV walls. ‣Pressure falls continuously as blood moves farther from heart; highest pressure in vessels of CV system found in aorta and systemic arteries as they receive blood from L ventricle; lowest pressure in venae cavae just before they empty into R atrium

What is pressure and hydrostatic pressure??

‣Pressure: in fluid is force exerted by fluid on its container; in heart and BVs, pressure is commonly measured in mm Hg ‣Hydrostatic pressure: pressure exerted by fluid not moving; force exerted equally in all directions; in a system in which fluid is flowing, pressure falls over distance as energy is lost b/c of friction ‣Pressure exerted by moving fluid has 2 components: a dynamic, flowing component that represents kinetic energy of system, and a lateral component that represents hydrostatic pressure (potential energy) exerted on the walls of system ‣Pressure w/in our cardiovascular system is usually called hydrostatic pressure even though it is a system in which fluid is in motion

Describe the anatomy of the immune system

‣Primary lymphoid tissues: thymus gland and bone marrow; Both organs are sites where cells involved in immune response form and mature. ‣Secondary lymphoid tissues: encapsulated and unencapsulated diffuse lymphoid tissues ‣Encapsulated lymphoid tissues: spleen and lymph nodes; Both have fibrous collagenous capsule walls and immune cells positioned so they monitor EC compartment for foreign invaders; Phagocytic cells in spleen trap and remove aging RBCs; lymph nodes are part of lymphatic circulation, which is closely associated w/capillaries of CV system. ‣Unencapsulated diffuse lymphoid tissues: cells in skin and tonsils of the posterior nasopharynx, cells associated w/mucosal surfaces exposed to external environment; mucosa-associated lymphoid tissue (MALT), include gut-associated lymphoid tissue (GALT), which lies just under epithelium of esophagus and intestines, and clusters of lymphoid tissue associated w/respiratory, urinary, and reproductive tracts

What are the functions of prothrombin and thrombin, and fibrinogen and fibrin?

‣Prothrombin: protein present in blood plasma that is converted into active thrombin during coagulation ‣Thrombin: enzyme that converts fibrinogen into insoluble fibrin polymer ‣Fibrinogen: a thrombin-coagulable glycoprotein; Forms fibrin threads essential to blood clotting ‣Fibrin: insoluble protein formed from fibrinogen during the clotting of blood; forms fibrous mesh that impedes the flow of blood

What is pulse pressure?

‣Pulse pressure: measure of strength of pressure wave (pulse); defined as systolic pressure - diastolic pressure ‣By time blood reaches veins, pressure has decreased b/c of friction, and pressure wave no longer exists; venous blood flow steady rather than pulsatile, pushed along by continuous movement of blood out of capillaries ‣Low-pressure blood in veins below heart must flow against gravity to return to heart; venous return aided by valves (respiratory and skeletal muscle pump)

What are normal values for RBC count, hematocrit, and WBC count?

‣RBC count: Male, 4.35-5.65 trillion cells/L* (4.35-5.65million cells/mcL**); Female, 3.92-5.13 trillion cells/L (3.92-5.13 million cells/mcL) ‣Hematocrit: 40-54% for a man, 37-47% for a woman ‣WBC count: 3.4-9.6 billion cells/L (3,400 to 9,600 cells/mcL)

What is the importance of the refractory period in cardiac cells?

‣Refactory period: time following an AP during which a normal stimulus cannot trigger a second action potential ‣In cardiac muscle, long AP means the refractory period and contraction end almost simultaneously ‣By time a second action potential can take place, myocardial cell has almost completely relaxed; consequently, no summation occurs

What is the Frank-Starling Law of the Heart?

‣Relationship between stretch and force in an intact heart ‣Relationship between stretch and force in intact heart is plotted on a Starling curve; x-axis represents EDV. EDV is measure of stretch in ventricles, which in turn determines sarcomere length. Y-axis of Starling curve represents SV and indicates force of contraction ‣Stroke volume proportional to EDV ‣Frank-Starling law of the heart: as additional blood enters, heart contracts more forcefully and ejects more blood; w/in physiological limits, heart pumps all blood that returns to it

What factors affect stroke volume of the heat?

‣SV directly related to force generated by cardiac muscle during contraction. Normally, as contraction force increases, SV increases. ‣In isolated heart, force of ventricular contraction affected by 2 parameters: length of muscle fibers @beginning of contraction and contractility of heart ‣EDV determines length of muscle. ‣Contractility: intrinsic ability of cardiac muscle fiber to contract @any given fiber length and is a function of Ca2+ interaction w/contractile filaments. ‣Length-Tension Relationships: as stretch of ventricular wall increases, so does SV; if additional blood flows into ventricles, muscle fibers stretch then contract more forcefully, ejecting more blood. Degree of myocardial stretch before contraction begins=preload on heart b/c this stretch represents load placed on cardiac muscles before contraction ‣The Frank-Starling Law of the Heart: SV proportional to EDV; as additional blood enters heart, heart contracts more forcefully and ejects more blood; heart pumps all blood returned to it

Describe coagulation disorders

‣Several inherited diseases affect coagulation process; Patients w/coagulation disorders bruise easily; In severe forms, spontaneous bleeding may occur throughout body; Bleeding into joints and muscles can be painful and disabling; If bleeding occurs in the brain, it can be fatal ‣Hemophilia: name given to several diseases in which one of the factors in coagulation cascade either defective or lacking; Hemophilia A, a factor VIII deficiency, is most common form, occurring in about 80% of all cases. This disease is a recessive sex-linked trait that usually affects only males

How can cardiac muscle contraction be graded and how do action potentials vary?

‣Single muscle fiber can execute graded contractions, in which fiber varies amount of force it generates; force generated by cardiac muscle proportional to number of crossbridges active; number of active crossbridges determined by how much Ca2+ bound to troponin ‣If cytosolic Ca2+ concentrations low, some crossbridges not activated and contraction force small; if additional Ca2+ enters cell from ECF, more Ca2+ released from SR; additional Ca2+ binds troponin enhancing ability of myosin to form crossbridges w/actin and creating additional force ‣Sarcomere length @beginning of contraction affects force of contraction; in intact heart, stretch on individual fibers is function of how much blood is in chambers of heart ‣Each of the two types of cardiac muscle cells has distinctive AP that vary somewhat in shape depending on where in heart it's recorded; in both autorhythmic and contractile myocardium, Ca2+ plays important role in AP, in contrast to APs of skeletal muscle and neurons which depend solely on Na+ and K+ movement

What is Stroke Volume (SV)?

‣Stroke volume (SV): amount of blood pumped by one ventricle during contraction; measured in mL per beat ‣Blood vol before contraction - Blood vol after contraction = stroke volume EDV - ESV = stroke volume

Describe red blood cells in terms of structure, function, and "life cycle."

‣Structure: mature RBCs lack nucleus, mitochondria, and ER; in isotonic solution are biconcave disks; membranous "bags" filled w/enzymes and hemoglobin; membrane held in place by complex cytoskeleton composed of filaments linked to transmembrane attachment proteins; remarkably flexible allowing shape change to squeeze through narrow capillaries of circulation; disk-like structure of allows modification of shape in response to osmotic changes in blood ‣Function: play a key role in transporting O2 from lungs to tissues, and CO2 from tissues to lungs ‣Life cycle: (1) small intestine absorbs essential nutrients, (2) Blood transports nutrients to red bone marrow, (3) in marrow, RBCs arise from division of progenitor cells, (4) Mature RBCs released into bloodstream, where they circulate for ~120 days, (5) Macrophages destroy damaged RBCs in spleen and liver, (6) Free Hb broken down into heme and globin, (7) Iron from heme returns to red bone marrow and is reused, (8) Biliverdin and bilirubin are exerted in bile

What is thrombopoietin (TPO)?

‣Thrombopoietin (TPO): glycoprotein that regulates growth and maturation of megakaryocytes, the parent cells of platelets. ‣TPO produced primarily in liver.

Explain how vasoconstriction and vasodilation alter flow rate. Which vessels are mainly involved in regulating blood flow and resistance, affecting blood pressure?

‣Vasoconstriction: narrows diameter of BV lumen; increases flow rate ‣Vasodilatation: widens diameter of BV lumen; decreases flow rate ‣Arteries and arterioles: in systemic circulation highest pressure occurs in aorta and results from pressure created by L ventricle; high diastolic pressure in arteries reflects ability of those vessels to capture and store energy in their elastic walls.

Compare the vessels of the systemic circulation in terms of total cross sectional area and velocity of flow.

‣Velocity slowest where total cross‐sectional area is greatest ‣Each time an artery branches, total cross‐sectional area of all its branches is greater than cross‐sectional area of the original vessel, so blood flow becomes slower and slower as blood moves further away from the heart, and is slowest in the capillaries. ‣When venules unite to form veins, total cross‐sectional area becomes smaller and flow becomes faster

What determines venous return?

‣Venous return: amount of blood that enters heart from venous circulation; normally determines EDV ‣3 factors affect venous return: (1) contraction or compression of veins returning blood to heart (the skeletal muscle pump), (2) pressure changes in abdomen and thorax during breathing (the respiratory pump), and (3) sympathetic innervation of veins. ‣Skeletal muscle pump: skeletal muscle contractions that squeeze veins (particularly in legs), compressing them and pushing blood toward heart. During exercise that involves lower extremities, skeletal muscle assists venous return. During motionlessness skeletal muscle pump does not assist venous return ‣Respiratory pump: created by movement of thorax during inspiration (breathing in). As chest expands and diaphragm moves toward abdomen, thoracic cavity enlarges and develops subatmospheric pressure; low pressure decreases pressure in inferior vena cava as it passes through thorax, which helps draw more blood into vena cava from veins in abdomen. Respiratory pump aided by higher pressure placed on outside of abdominal veins when abdominal contents are compressed during inspiration. Combination of increased pressure in abdominal veins and decreased pressure in thoracic veins enhances venous return during inspiration. ‣Constriction of veins by sympathetic activity: when veins constrict, volume decreases, squeezing more blood out of them and into heart. W/larger ventricular volume @beginning of next contraction, ventricle contracts more forcefully, sending blood out into arterial side of circulation. Sympathetic innervation of veins allows body to redistribute some venous blood to arterial side of circulation

Describe the lymphatic system

‣Vessels of lymphatic system interact with: CV system, digestive system, and immune system ‣Functions of lymphatic system: (1) returning fluid and proteins filtered out of capillaries to circulatory system, (2) picking up fat absorbed @small intestine and transferring it to circulatory system, and (3)filter to help capture and destroy foreign pathogens ‣Lymphatic system allows one-way movement of interstitial fluid from tissues into circulation ‣Lymph vessels in tissues: join to form larger lymphatic vessels that progressively increase in size; vessels have system of semilunar valves; largest lymph ducts empty into venous circulation just under collarbones, where the left and right subclavian veins join the internal jugular veins ‣Blind-end lymph vessels: (lymph capillaries) lie close to all blood capillaries except those in kidney and CNS ‣Smallest lymph vessels: composed of single layer of flattened endothelium that is thinner than capillary endothelium; walls anchored to surrounding CT by fibers that hold thin-walled vessels open

What are the parts of the CV system?

‣Vessels: also known as the vasculature; BVs that carry blood away from heart = arteries; BV's that return blood to heart=veins, capillaries and portal system ‣Portal systems: valves in heart and veins ensures that blood flows in one direction only ‣Heart: essentially a pump that drives circulation; pressure generated in heart propels blood through system continuously ‣Blood: cells and plasma; blood picks up O2 @lungs and nutrients in intestine and then delivers these substances to body's cells while simultaneously removing cellular wastes and heat for excretion

How is lymph formed? How does it differ from plasma?

‣When fluid, interstitial proteins, and particulate matter such as bacteria to be swept into lymph vessels (lymphatics) through large gaps between cells by bulk flow; Once inside lymphatics, clear fluid is called lymph ‣Plasma is fluid portion of whole blood and carries substances such as nutrients, oxygen, and hormones to bathe cells and tissues; Lymph comes from plasma but is different from plasma in that it is made up of more water, sugar, and electrolytes and less of larger proteins found in plasma

Describe the pacemakers of the heart

‣cells of SA node set pace of heartbeat ‣Other cells in conducting system, such as AV node and Purkinje fibers have unstable resting potentials and can also act as pace- makers under some conditions; b/c their rhythm is slower than SA node they do not usually have chance to set heartbeat ‣SA node = 70 BPM, AV node = 50 BPM, Purkinje fibers = 35 BPM