Physiology 1.2. - Cardiovascular System

Give the properties of the following smooth muscle cell types: (A) Inner medial cells (B) Outer medial cells

(A) - Single unit - Not innervated - Spontaneous pacemaker cells generate APs - Good propagation of APs - Respond actively to mechanical stretch (B) - Multi unit - Innervated - Excited by neural activity - Poor propagation of APs - Relatively unresponsive to stretch

Give the duration (in ms) of the action potentials in the following cells: (A) Normal atrial cardiomyocytes (B) Normal ventricular cardiomyocytes (C) Purkinje cells

(A) 150ms (B) 400ms (C) 450ms

What is the variation in pressure between the (A) Arterial and (B) Venous end of a capillary and what function does this gradient serve? (C)

(A) 35 mmHg (B) 15 mmHg (C) The pressure gradient exists to facilitate capillary blood flow & exchange of fluid with tissues (filtration at arterial end and absorption at venous end)

Describe the two factors that cause the decay of the pacemaker potential prior to the generation of an action potential (A and B)

(A) A current of Na+ ions that flows slowly into the cell (funny current) causing gradual depolarization. (B) Membrane permeability to K+ gradually falls and as a result the outflow of K+ gradually falls, allowing inward currents to dominate increasingly.

Name the neurotransmitter and receptor type used at preganglionic nerve terminals for: (A) Parasympathetic nerves (B) Sympathetic nerves

(A) ACh and nicotinic ACh receptors (B) ACh and nicotinic ACh receptors

Name the key proteins in cardiac myocyte which are crucial for muscle contraction.

(A) Actin (thin filaments) (B) Myosin (thick filaments) - ATP powered ratchet during contraction (C) Tropomyosin - long thick regulatory protein that is wrapped around the actinfilament & covers the active binding sites during the time between contractions (D) Troponin - attached to the tropomyosin. When Ca combines with troponin, a conformation change in the molecule causes tropomyosin to expose the myosin-binding sites on actin.

The process whereby there is an increase in coronary flow produced by increased myocardial oxygen consumption (MV̇O2) is referred to as (A).

(A) Active or functional hyperemia

Name five vasodilators that are present in response to hypoxia in the brain (A - E)

(A) Adenosine (B) Potassium and Hydrogen ions (C) Prostaglandins (D) Nitric oxide (E) Excitatory amino acids

Explain the effect of temperature on: (A) Heart rate (B) Ventricular contractile capacity

(A) An increase in body temperature (such as that associated with fever) will cause the HR to increase, while lower temperatures decrease heart rate. (B) Upper and lower thermal limits exist (e.g. 26 and 44 degC for the dog). As the heart approaches either of these limits, myocardial conduction and contractility are both depressed.

What are the two major effects of ADH that are important in the regulation of blood volume and pressure? (A and B)

(A) Antidiuresis (B) Vasoconstriction

How does ventricular systole affect coronary blood flow to the: (A) Left ventricle (B) Right ventricle

(A) As the ventricular muscle contracts during systole it compresses arteries, and therefore coronary blood flow is less to the left ventricle during systole and more during diastole. (B) Blood flow to the right ventricle is not highly affected during systole. This is because the pressure difference between aorta and right ventricle is greater during systole than during diastole, therefore more blood flow to the right ventricle occurs during systole.

Name the six phases of the cardiac cycle

(A) Atrial systole (atrial contraction) (B) First phase of ventricular systole (isovolumteric contraction) (C) Second phase of ventricular systole (ventricular ejection) (D) Ventricular diastole - early (E) Ventricular diastole - late

Name three rapidly acting mechanisms for the control of blood pressure (A - C)

(A) Baroreceptor feedback mechanisms (B) Central nervous system ischemic mechanism (C) Chemoreceptor feedback mechanism

What are the four most important hemodynamical parameters in the circulatory system? (A - D)

(A) Blood pressure (B) Blood volume (C) Blood flow (D) Resistance.

(A) What happens if resistance at the venous end of the capillary increases? (B) How is this rectified?

(A) Capillary blood pressure will increase. (B) Via autoregulation - an increase in capillary pressure will lead to active contraction of the precapillary sphincter & arteriolar smooth muscle to reduce blood flow to the capillary beds, thus reducing the pressure in the capillaries.

What are the dominant forces that facilitate the following in a capillary: (A) Filtration of fluid into the tissues at the arterial end? (B) Reabsorption of fluid at the venous end?

(A) Capillary hydrostatic pressure (due to blood pressure in capillaries) (B) Capillary oncotic pressure (due to reduced blood pressure and increased pressure from proteins in plasma)

Name three types of circulatory shock and what causes each (A - C)

(A) Cardiogenic shock - hypotension and hypoperfusion caused by heart failure due to severe heart disease (end stage result of progressive heart failure whereby the primary mechanism is the failure of cardiac output). (B) Hypovolemic shock is a condition in which severe blood or other fluid loss makes the heart unable to pump enough blood to perfuse the tissues of the body. (C) Septic shock is a severe and potentially fatal condition that occurs when sepsis from an infection leads to life-threatening low blood pressure.

(A) What effect does adrenalin have on the heart? (B) How does this occur?

(A) Causes an increase in the contractile force of the heart. (B) Adrenalin activates the β-adrenergic signaling cascade, which results in the activation of PKA which in turn activates voltage-gated calcium channels, increasing the amount of intracellular Ca2+ and CICR, which increases contractility of the heart.

(A) What effect does verapamil have on the heart? (B) How does this occur?

(A) Causes weakening of the force of contraction of the heart. (B) Verapamil blocks calcium channels in cardiac myocytes and hence there is less influx of Ca2+ during cardiac action potentials, which causes attenuation of the plateau, thus weakening the force of contraction of the heart.

The cerebral circulation is important for the production of (A), primarily formed at the (B) through processes of filtration and active cellular secretion.

(A) Cerebrospinal fluid (CSF) (B) Choroid plexus

What are the two forms of pathological hypertrophy? (A and B)

(A) Concentric hypertrophy (B) Eccentric hypertophy

What is the effect of stimulation of the following receptors in coronary vessels? (A) Alpha adrenergic receptors (B) Beta adrenergic receptors

(A) Constriction of vessels (B) Dilation of vessels

Describe the two major groups of cardiomyocytes and their functions.

(A) Contractile cardiomyocytes - form the majority of the cells of the heart and are specialised to perform mechanical work. (B) Specialised cardiomyocytes - these form the conducting system of the heart and consist of SA and AV nodal cells, transitional cells and Purkinje fibres.

Which cells in the heart have: (A) Rapid initial depolarization (B) Slow initial depolarization

(A) Contractile myocytes (Non-pacemaker cells) (B) Pacemaker cells (SA and AV nodes)

Name four substances that are associated with increased metabolism that would result in increased cerebral blood flow (A - D)

(A) Decreased pO2 (B) Increased pCO2 (C) Decreased pH (increased H+ ions) (D) Increased adenosine concentration

Give four transport functions performed by the circulatory system (A - D).

(A) Delivering oxygen to tissues and CO2 to the lungs (B) Carrying absorbed products of digestion from the intestine to the liver and tissues (C) Carrying metabolic wastes to kidneys to be excreted (D) Distribution of body fluids

What three methods are used in the transport of substances from blood in capillaries to tissues? (A - C)

(A) Diffusion (B) Transcytosis / cytopempsis (C) Bulk flow

Give four characteristics of lymphatic collecting channels that aids in their function (A - D).

(A) Display pumping / sucking action for uptake of lymph (B) Spontaneously motile to aid in movement of lymph (C) Have one way valves to prevent backflow of lymph (D) Movement of lymph can be aided by mechanical movement of tissues.

Name four ways of measuring cardiac output in animals (A - D)

(A) Echocardiography (transthoracic or esophageal) (B) Indicator dilution technique: indicator may be a dye (e.g., indocyanine green), radioisotope, ion (e.g., lithium), or a thermal mass (e.g., cold saline). (C) Fick principle: Cardiac output = oxygen consumption/(arterial - venous oxygen content) (D) Electromagnetic flow meter (accuracy in animals has yet to be determined)

Hydrostatic pressure in the lungs is half that elsewhere to protect against (A).

(A) Edema

Name three tissues that contain fenestrated capillaries (A - C)

(A) Endocrine and exocrine glands (B) Gall bladder (C) Choroid plexus in the brain

Give five effects of stimulation of beta adrenergic receptors in the heart by the sympathetic nervous system (A - E)

(A) Enhance myocardial contractility (increases force of contraction of the heart muscle) (B) Dilate coronary arteries (increase blood flow to the heart muscle) (C) Mediate positive chronotropic effects (increase heart rate) (D) Speed up AV conduction (E) Increase automaticity

Large coronary arteries course along the (A) and coronary artery branches then penetrate into the (B) to supply all layers and regions of the heart.

(A) Epicardium (epicardial surface) (B) Myocardium

Give five functions of vascular endothelium (A - E)

(A) Exchange & transport of metabolites and waste products between blood & tissues (B) Prevention of adherence of platelets, leukocytes & monocytes (C) Activation & inactivation of circulatory hormones & other plasma constituents (D) Synthesis & secretion of vasodilator (NO) & vsoconstrictor(ET-1) substances (E) Production of growth factors/inhibitors involved in the regulation of growth of vascular smooth muscle

Name three specialisations of intercalated discs that allow them to perform their function in facilitating a functional syncytium.

(A) Fascia adherens - form strong connections between fibres, and are anchoring sites for actin, connecting the sarcolemma to the nearest sarcomere of each cell. (B) Desmosomes - function as rivets that "weld" the sarcolemma of adjacent fibres, allowing transmission of the force of contraction = mechanical syncytium (C) Gap junctions - form channels for free diffusion of ions between cells, and thus have low electrical impedence = electrical syncytium

(A) What are the main determinants of the rate of lymph flow? (B) What does an increase in these parameters cause?

(A) Filling pressure (preload) & outflow resistance (afterload) (B) When preload & afterload are increased there is increased stretch of the lymph vessel that results in an increase in the rate and strength of myogenic contractions.

Explain the action of the following in treating heart failure: (A) Loop diuretics (such as furosemide) (B) ACE inhibitors (such as captopril) (C) Cardiac glycosides (such as digoxin) (D) Cardio-selective beta blockers (such as atenolol) (E) Arteriolar vasodilators (such as hydralazine) (F) Reduced sodium in the diet

(A) Fluid removal to reduce ECF (B) Inactivate the RAAS system to reduce blood volume and thus reduce volume overload of the left ventricle (C) Have a positive ionotropic effect and hence increase contractility of the heart (D) Reduce cardiac arrhythmias, HR and SV (E) Reduce total peripheral resistance (TPR) and SV (F) Reduction in ECF

Give three compensatory mechanisms that take place in the event of heart failure (A - C)

(A) Frank-Starling relationship: within physiological limits, added preload will pre-stretch myocardial fibres, leading to an increase in the force of contraction & an increase in stroke volume. (B) Neurohumoral response to heart failure -the baroreceptor system responds to cardiac failure by stimulating sympathetic outflow & reducing parasympathetic outflow (to the heart) to effectively increase stroke volume. (C) ADH secretion may also be enhanced in heart failure (angiotensin II & also through baroreceptor reflex) resulting in further expansion of the ECF volume that then leads to volume overload.

Name four substances that the phospholipid bilayer of cell membranes is permeable to.

(A) Gases (CO2, O2, N2) (B) H2O (C) Lipids (Hydrophobic molecules) (D) Small, neutral molecules such as urea

Name the four primary components of the circulatory system and their respective functions (A - D).

(A) Heart = the driving force (pump) (B) Arteries = the distribution channels (C) Capillaries = exchange points between blood and tissues (D) Veins = collection channels

In all parts of the circulatory system, blood flow is always from a region of (A) to one of (B).

(A) Higher pressure (B) Lower pressure.

List three substances that contribute to vasodilation and increased capillary porosity during inflammation.

(A) Histamine (B) Prostaglandins (C) Bradykinin

Give four regulatory functions performed by the circulatory system (A - D).

(A) Hormonal - carries hormones from sites of secretion to target organs (B) Immune - carries antibodies, leucocytes, and cytokines to sites of infection, and aids the body defense mechanism against pathogens. (C) Protection - carries platelets and clotting factors to protect the body and blood vessels via the blood clotting mechanism. (D) Thermoregulation - Helps in regulation of body temperature by diverting blood to cool or warm the body.

Give two categories of endogenous substances that contribute to the chemical regulation of heart rate and/or contractility (A and B)

(A) Hormones - e.g. catecholamines and thyroid hormones increase HR and contractility. (B) Cations - plasma levels of ions such as Ca2+, K+ and Na+ will alter HR and contractility.

Name three factors that can contribute to increased capillary pressure.

(A) Hypertension (increased arterial pressure) (B) Increased venous pressure secondary to heart failure (C) Decreased arteriolar resistance (loss of sympathetic tone)

What do the following terms mean with regards to effects on the heart: (A) Chronotropic (B) Ionotropic

(A) Increase in heart rate (B) Increase in contractility

What are the general effects on the heart of: (A) Sympathetic stimulation (B) Parasympathetic stimulation

(A) Increase in heart rate and contractility (innervates SA node, AV node, and ventricular myocardium) (B) Decrease in heart rate, little impact on contractility (innervates SA and AV node only)

How does the capillary fluid shift mechanism contribute to regulating blood pressure in the case of: (A) Elevated blood pressure (C) Reduced blood pressure

(A) Increased arterial pressure will increase the hydrostatic pressure within capillaries and more fluid will be filtered through the capillary wall into the interstitial space, thus reducing blood volume and hence BP. (B) The opposite occurs - lower hydrostatic pressure leads to absorption of fluid from tissues into capillaries. Increase in blood volume leads to increase in BP.

List four factors that can lead to edema.

(A) Increased capillary permeability (burns) (B) Decreased concentration of plasma proteins (poor diet or loss during renal disease) (C) Increased capillary pressure leading to increased filtration of fluid (D) Obstruction of lymphatic vessels (tumors, trauma)

Name four mechanisms of increased blood flow to skeletal muscle during moderate exercise (A - D)

(A) Increased cardiac output (B) Increased arterial blood pressure (C) Decreased vascular resistance in target tissues (D) Constriction of other vascular beds

Name five factors that increase preload of the heart (A - E)

(A) Increased central venous pressure that can result from decreased venous compliance (e.g., caused by sympathetic activation of venous smooth muscle) or increased thoracic blood volume. (B) Increased ventricular compliance-results in greater expansion of the chamber during filling at a given filling pressure (C) Increased atrial force of contraction resulting from sympathetic stimulation of the atria or from increased filling of the atria and therefore increased atrial contractile force through the Frank-Starling mechanism (D) Reduced heart rate, which increases ventricular filling time (E) Increased aortic pressure, which increases the afterload on the ventricle, reduces stroke volume by increasing end-systolic volume, and leads to a secondary increase in ventricular preload.

Name three changes in heart parameters that may increase stroke volume.

(A) Increased preload (B) Increased contractility (C) Decreased afterload

Explain the ionic effect of the following in the SA node: (A) Sympathetic nervous system (B) Parasympathetic nervous system

(A) Increases the rate of inflow of Na+ and Ca2+ ions which increases rate of depolarizations = increased HR. The increase in Ca2+ also increases contractility. (B) Decreases rate of inflow of Na+ and Ca2+ ions which decreases rate of depolarizations = decreased HR. Less Ca2+ decreases atrial contractility.

What two effects does cardiac dilation have? (A and B)

(A) Increasing sarcomere length, which increases the contractile strength of myocardial fibers (Frank-Starling relationship) (B) Increasing chamber diameter, which increases the wall stress for a given intra-cardiac pressure in accordance with the Laplace law

The long term blood pressure set point is dependent on the (A), whereby arterial pressure is set at a level which will maintain (B) balance

(A) Kidneys (via the renin-angiotensin system) (B) Sodium

The blood flow to the heart is supplied by the (A) and (B) which arise from the (C) at the level of the (D).

(A) Left coronary artery (B) Right coronary artery (C) Aorta (D) Aortic sinus

Name two conditions that can lead to pulmonary edema, and the mechanisms by which these occur (A & B).

(A) Left-sided heart failure or mitral valvular disease - results in a large increase in pulmonary venous pressure and pulmonary capillary pressure and the flooding of the interstitial spaces and alveoli with fluid. (B) Pneumonia - damages capillary membrane leading to the rapid leakage of both plasma protein and fluid out of the capillaries into the interstitial spaces and the alveoli

List two common causes of pulmonary edema (A and B)

(A) Left‐sided heart failure or mitral valvular disease (leads to large increase in pulmonary venous pressure and pulmonary capillary pressure and the flooding of the interstitial spaces and alveoli with fluid). (B) Damage to the capillary membrane by infections such as pneumonia (results in rapid leakage of both plasma protein and fluid out of the capillaries into the interstitial spaces and the alveoli).

Name three tissues that contain sinusoid capillaries (A - C)

(A) Liver (B) Spleen (C) Bone marrow

Cerebral blood flow is regulated primarily by (A) mechanisms, with (B) mechanisms playing only a secondary and comparatively minor role

(A) Local vascular regulatory (B) Autonomic

The coronary circulation is predominantly controlled via (A), with little dependence on (B) regulation

(A) Local vascular regulatory mechanisms. (B) Autonomic

Excess ECF, macromolecules & particles that are not returned to the bloodstream through capillary absorption can return through the (A)

(A) Lymphatic system

(A) What does the term "local control" mean with regards to blood flow? (B) What agents are used to achieve this?

(A) Mechanisms independent of nerves or hormones by which organs and tissues alter their own arteriolar resistances, thereby self-regulating their blood flows. (B) Autocrines and paracrines

(A) Where is the cardiovascular centre located in the CNS? (B) What type of sensory receptors convey afferent signals to the CVS centre?

(A) Medulla oblongata (B) Chemoreceptors (monitor acidity of blood), proprioreceptors (monitor joint movements), baroreceptors (monitor blood pressure).

The arterioles, capillaries, and venules are collectively termed the (A)

(A) Microcirculation.

Name the key organelles that make up a cardiac myocyte which are crucial for muscle contraction.

(A) Mitochondria (25 - 30% of cell volume for ATP production) (B) Glycogen granules and lipid droplets (C) Transverse tubular system (T-tubules) - continuous with sarcolemma and facilitate spread of electrical impulses to interior of cell. (D) Sarcoplasmic reticulum - uptake and storage of Ca2+ which is necessary for muscle contraction. Terminal cisternae form diads with T-tubules.

Define the following: (A) Bathmotropic (B) Dromotropic

(A) Modifying the degree of excitability (specifically of the heart) (B) Modifying the rate of conductivity (i.e. speed of conduction)

With regards to autoregulation of vessels in skeletal muscle, the (A) response appears to play an important role in the skeletal muscle circulation at rest, while the (B) response plays a greater role during exercise

(A) Myogenic (B) Metabolic (active hyperemia)

Name two ways calcium is removed from the cell after repolarization

(A) Na+ / Ca2+ pumps on the sarcolemma - pump 1 Ca2+ out for every 3 Na+ in (3/4 of calcium removed this way). NB - not powered by ATP, relies on electrochemical gradients. (B) Sarcolemma also has Ca+-ATPase pumps (1/4 of calcium removed this way).

Name the three different types or sections of the sarcoplasmic reticulum (SR), and where these occur on myocytes.

(A) Network SR - Courses over the myofibrils (B) Junctional SR - lies close to T-tubules or sarcolemma (C) Corbular SR - comprised of sac like expansions along the network SR in the I band

Name three extrinsic factors that may influence stroke volume?

(A) Neurohormonal influence - SNS and PSNS (B) Chemical influence - drugs / stimulants (C) Pathological states - ischemia, hypocalcemia

Although NE is the major chemical transmitter released by sympathetic nerves at the smooth muscle cell, (A) and ATP can be co-released with NE from many sympathetic fibers.

(A) Neuropeptide Y

With regards to the group of non-cholinergic, non-adrenergic autonomic neurons: (A) What NT do these neurons use? (B) Where do they primarily occur? (C) What is their function?

(A) Nitric oxide, and possibly others. (B) GIT - particularly prominent in the enteric nervous system. (C) Primarily vasodilation of blood vessels associated with the GIT.

Name four drugs that cause increased coronary blood flow (A - D)

(A) Nitrites (B) Caffeine (C) Aminophylline (D) Khellin

With regard to fluid pressures and distribution within the body, what is: (A) 1st space shifting (B) 2nd space shifting (C) 3rd space shifting

(A) Normal distribution of fluid in both the ECF compartment and ICF compartment (B) Excess accumulation of interstitial fluid (edema) (C) Fluid accumulation in areas that are normally have no or little amounts of fluids (ascites)

Define the following: (A) Myogenic autoregulation (B) Metabolic autoregulation

(A) Occurs in response to changes in blood pressure, with stretch of vessels being a key trigger of autoregulation. Increase in intramural pressure leads to increased contraction of vascular smooth muscle (vasoconstriction) to regulate blood flow, while a decrease in intramural pressure leads to decreased contraction of vascular smooth muscle (vasodilation). (B) Metabolic autoregulation is controlled by the concentration of certain metabolites in the tissues surrounding the vessels. For example, a decrease in oxygen, an increase in H, K, adenosine, osmolarity, adenosine nucleotides, etc leads to vasodilation, while the opposite will lead to vasoconstriction.

Give three types of passive transport and an example of substances that use these methods in the circulatory system (A - C)

(A) Osmosis - movement of water from low solute region to high solute region (B) Simple diffusion - small noncharged molecules or lipid soluble molecules move through plasma membrane between phospholipids, e.g. O2 and CO2 (C) Facilitated diffusion - via channel proteins (in the case of ions such as K+ and Na+) or carrier proteins (in the case of glucose and amino acids)

Give the relative number of gap junctions (high / low) according to function in the following cell types: (A) SA nodal cells (B) AV nodal cells (C) Purkinje fibres

(A) Pacemaker activity - low number of gap junctions (B) Conduction delay - low number of gap junctions (C) Rapid impulse conduction - high number of gap junctions

(A) What is stocking edema? (B) What causes this condition? (C) What is the treatment for stocking edema?

(A) Peripheral edema in the legs of horses. (B) Deficiency of venous massage to aid in the return of venous blood from pendant blood capillaries and inability of the lymphatic system to remove this excessive interstitial fluid. (C) Exercise - muscle massage decreases venous pressure and aids in lymph return.

Define the following: (A) Peripheral edema (B) Pulmonary edema

(A) Peripheral edema is a pathologic increase in the fluid volume of the interstitium of soft tissue typically affecting the head and neck, forelimbs, or hindlimbs. (B) Pulmonary edema refers to a build up of fluid in the lung interstitium and alveoli.

Name and briefly describe the five phases of the cardiac (myocyte) action potential

(A) Phase 0 - Rapid depolarization due to opening of fast voltage-gated sodium channels. These become inactivated almost immediately after opening. (MP reaches between 0 and +40 mV) (B) Phase 1 - Rapid repolarization due to opening of K+ channels. (C) Phase 2 - Plateau phase due to action of slow L-type Ca2+ channels (which open at -35mV) and Calcium induced calcium release which balances the K+ leaving the cell and results in the plateau. Na+ also enters the cell via action of the Ca2+ / Na+ exchanger. (D) Phase 3 - Repolarisation as Ca2+ channels close and rate of K+ efflux from the cell increases, causing repolarisation back towards the RMP. Na+ also still entering cell but at lower rate (Ca2+ gradient less pronounced due to closure of Ca2+ channels). (E) Phase 4 - Resting: RMP re-established via action of K+ channels and Na+-K+-ATPase ( -90 mV)

Name the four categories of factors that affect coronary blood flow (A - D).

(A) Physical factors (B) Chemical factors (C) Neural factors (D) Neurohormonal factors

The physiological function, performance of the heart, and the status of the vascular system depend on what four parameters of the heart?

(A) Preload (B) Afterload (C) Heart rate (chronotropic effect) (D) Contractility (ionotropic effect)

Name five factors that affect ventricular function (A - E)

(A) Preload (B) Afterload (C) Ionotropic state (D) Chronotropic state (E) Lusitropic reserve

What three factors influence stroke volume? (A - C)

(A) Preload (increased preload = increased SV) (B) Afterload (increased afterload = decreased SV) (C) Contractility (increased contractility = increased SV)

Because the baroreceptor system opposes either increases or decreases in arterial pressure, it is called a (A) system and the nerves from the baroreceptors are called (B) nerves.

(A) Pressure buffer (B) Buffer

What are the two main circulatory routes of the CVS?

(A) Pulmonary (B) Systemic

Left sided heart failure leads to (A) in the lungs whereas right sided heart failure would cause (B).

(A) Pulmonary edema (build up of fluid in the lung tissue and alveoli) (B) Hydrothorax ( build up of serous fluid within the pleural cavities)

Name four factors that determine arterial blood pressure.

(A) Pumping action of the heart (cardiac output) (B) Peripheral resistance to blood flow (C) Volume of blood in arterial system (D) Elasticity of arterial walls

Give two types of active transport that are used in the movement of substances between the blood and tissues (A - C)

(A) Pumps - materials moved from low to high concentration against gradient, e.g. Na+-K+-ATPase (B) Endocytosis / Exocytosis (e.g. phagocytosis for large molecules and pinocytosis for liquids)

Blood flow to muscle increases immediately with onset of exercise, due to a phenomenon known as (A)

(A) Rapid‐onset vasodilation (ROV).

List three functions of lymph. (A - C).

(A) Reabsorbs excess interstitial fluid (removes large molecules such as plasma proteins from ISF that would otherwise accumulate and exert oncotic pressure on capillary fluid = edema) (B) Transport of dietary lipids via lacteals that drain into larger lymph vessels and eventually into veins (C) Lymphocyte development, and the immune response.

(A) What is the function of the cardiovascular centre in the medulla? (B) How is this accomplished?

(A) Regulation of heart rate and stroke volume (cardiac output) to meet the metabolic requirements of the body (homeostasis). (B) Through interconnected negative feedback systems that control BP and blood flow by adjusting heart rate, stroke volume, vascular resistance, and blood volume. Efferent signals are effected by sympathetic innervation of the heart (increases HR and contractility) and blood vessels (increases vasoconstriction) and parasympathetic innervation of the heart (decreases heart rate).

Cardiac output and BP are primarily regulated by (A) control of extra-cellular fluid volume via the (B) mechanism.

(A) Renal (B) Pressure natriuresis / diuresis

The majority of cardiac venous drainage empties into the (A) through the (B).

(A) Right atrium (B) Coronary sinus

The right coronary artery supplies the majority of flow to the (A) while the left coronary artery supplies primarily the (B), although there can be overlap.

(A) Right atrium and ventricle (B) Left atrium, left ventricle and interventricular septum.

In which three tissues is active hyperemia most highly developed? (A - C)

(A) Skeletal muscle (B) Cardiac muscle (C) Glands

Give three effects of vagal stimulation of the heart (A - C)

(A) Slows the discharge rate of the AV node (negative chronotropic effect) (B) Slows or blocks AV conduction (negative dromotropic effect) (C) Decreases atrial and ventricular contractility (negative ionotropic effect).

Name three substances that the phospholipid bilayer of cell membranes is impermeable to.

(A) Small charged molecules (ions) (B) Hydrophilic molecules such as glucose (C) Macromolecules such as proteins

Name four tissues that contain continuous capillaries (A - D)

(A) Smooth, skeletal and cardiac muscle (B) Placenta (C) Lungs (D) Central nervous system

During pacemaker action potentials, what are the primary ions responsible for: (A) Prepotential (A) Depolarization (B) Repolarization

(A) Sodium (B) Calcium (C) Potassium

What effect do the following have on lymph vessels? (A) Stimulation of α‐adrenergic sympathetic receptors (B) Stimulation of β‐adrenergic receptors (C) ACh

(A) Stimulate motor activity and local lymph flow (B) Reduce motor activity and lymph flow (C) Reduce motor activity and lymph flow - causes nitric oxide synthesis by endothelial cells (vasodilator)

Explain how veins play a role in regulating arterial blood pressure in the case of: (A) A rapid increase in blood volume (B) A rapid decrease in blood volume

(A) Stress relaxation mechanism leads to stretching of the veins (reduced tone) to accommodate excess blood in response to a rapid increase in blood volume. Leads to increased blood in venous "reservoirs" = reduced preload = reduction in arterial pressure. (B) Increased venous contraction leads to more blood being forced into the heart chambers = increased preload = increased arterial blood pressure.

Name one structural and one functional change that takes place in skeletal muscle circulation in response to exercise training (A and B).

(A) Structural - capillary density increases in those muscles that experience the greatest increase in activity during training (B) Functional - blood flow capacity is increased in trained muscle

Name the two systems of venous drainage of the heart and the veins drained by each (A and B).

(A) Superficial system: drains the left ventricle. It is formed by the coronary sinus and the anterior cardiac veins that open into the right atrium. (B) Deep system: drains the rest of the heart. It is formed of thebesian veins and arterio-sinusoidal vessels that open directly into the heart chamber

Explain the chemical changes that will occur in the ECF surrounding arterioles in a tissue in response to: (A) Decreased blood pressure in the tissue (B) Increased blood pressure in the tissue

(A) Supply of oxygen to the organ diminishes, and the local extracellular oxygen concentration decreases. Simultaneously, the extracellular concentrations of carbon dioxide, hydrogen ions, and metabolites all increase because the blood cannot remove them as fast as they are produced. (B) Increase in pressure removes the local vasodilator chemical factors faster than they are produced and also increases the local concentration of oxygen.

Define the following in reference to cells of the heart: (A) Automatism (B) Conductibility (C) Excitability

(A) The ability to initiate an electrical impulse (B) The ability to transmit impulses from one cell to the next (C) The ability to respond to an electrical impulse

At which two sites do major arterial baroreceptors occur? (A and B)

(A) The carotid sinuses (B) The aortic arch

List the nervous factors that influence coronary blood flow.

(A) The effect of the autonomic nerves to the heart on the coronary arteries is indirect through their effect on cardiac metabolism, as follows: > Stimulation of sympathetic nervous system: increased cardiac metabolism resulting in vasodilation (metabolic autoregulation) and increased coronary blood flow. > Stimulation of parasympathetic nervous system: decreased cardiac metabolism resulting in vasoconstriction (metabolic autoregulation) and decreased coronary blood flow. (B) Sympathetic stimulation of alpha adrenergic receptors in coronary vessels can directly lead to vasoconstriction, but this effect is overshadowed by the increase in cardiac metabolism from sympathetic stimulation of beta adrenergic receptors in the heart, which leads to vasodilation of coronary arteries.

What sites in the cardiovascular system will the following drugs act, and what will their function be? (A) Beta adrenergic antagonists (B) Alpha adrenergic antagonists

(A) The heart - block action of NE, reduce heart rate and contractility (B) The blood vessels - block action of NE, vasodilation

Define the following with regard to the heart: (A) Heterometric autoregulation (B) Homeometric autoregulation

(A) The heart's ability to alter its output in response to altered myocardial fiber length. (B) The ability of the ventricle to alter its vigor of contraction without altering the initial myocardial length e.g in the presence of adrenaline.

Transfer of electrical impulses from the SA node undergoes a delay in the AV node before spreading to the ventricles. (A) What causes this delay? (B) Why is this delay important in the functioning of the heart?

(A) The low density of Na+ channels in the AV node (B) The delay in impulse conduction between the atria and ventricles important for sequential excitation and contraction of atria and then the ventricles to ensure normal cardiac function.

Explain the function of vasopressin in: (A) Normal body function (B) Severe hemorrhage

(A) The normal physiological role of vasopressin related to long‐term regulation of blood pressure is through its influence on water reabsorption in the collecting ducts of the renal tubules. (B) Vasopressin can be released in large quantities and both its vasoconstrictor and fluid‐retaining actions contribute to restoring blood pressure toward normal levels.

Define the following: (A) Pulmonary blood volume (B) Central blood volume

(A) The volume of blood in the vessels of the lungs (B) Pulmonary blood volume plus the volume of blood in the heart and great vessels

Define the following: (A) Cardiac output (B) Total cardiac output

(A) The volume of blood pumped out of either the left or right ventricle in a given period of time. (B) The volume of blood pumped out of both ventricles in a given period of time.

Name three lymphatic organs in the body (A - C)

(A) Thymus (B) Tonsils (C) Spleen

Name two neurohormonal factors that influence coronary blood flow and explain their effects (A and B)

(A) Thyroxin - increases cardiac metabolism and thus causes vasodilation (metabolic autoregulation) and increases CBF. (B) Vasopressin - leads to vasoconstriction, resulting in decreased CBF.

Hydrostatic pressure in glomerulus is twice that elsewhere to facilitate (A).

(A) Ultrafiltration

Name three hormones that are important in renal regulation of blood pressure, and their sites of secretion.

(A) Vasopressin (ADH) - secreted by the neurohypophysis (B) Aldosterone - secreted by the adrenal cortex (C) Atrial natriuretic peptide - secreted by the atria of the heart

What causes the following in the heart? (A) First heart sound (B) Second heart sound

(A) Vibrations from closure of the AV valves (B) Vibrations from closure of the semilunar valves

Name the three ion channels that are responsible for the cardiac action potential and which explain its unique shape (A - C)

(A) Voltage-gated sodium channels (fast) (B) Variable potassium channels (C) Slow Calcium channels

Name metabolic changes (chemical factors) that cause vasodilation of coronary arteries.

(A) lack of O2 (B) Increase in local concentration of CO2 (C) Increase in local concentration of H+ ions (D) Increase in local concentration of K+ ions (E) Increase in local concentration of lactate, prostaglandins, adenosine, etc (F) Increase in local concentration of nitric oxide.

What do the following chemoreceptors primarily monitor: (A) Peripheral chemoreceptors (B) Central chemoreceptors

(A) paO2 (B) paCO2

Explain the mechanism by which parasympathetic stimulation causes a decrease in depolarization in the SA and AV nodes and thus a decrease in HR

- ACh is released from postganglionic vagal efferent nerve terminals at the level of the heart SA and AV nodes, where it binds to muscarinic acetylcholine receptors - These receptors are negatively coupled via Giα to adenylyl cyclase and cAMP, and inhibit activation of calcium channels, thus reducing the rate of diastolic depolarization and making action potential threshold more positive - Muscarinic receptors are also coupled to G protein βγ subunits to directly open potassium channels that hyperpolarize the cell and decrease the frequency of action potentials. - These receptors also activate the phospholipase C pathway to produce nitric oxide that inhibits calcium channels.

Explain how the respective neurotransmitters used by the SNS and PSNS are capable of affecting the secretion of the other.

- ACh released from vagal endings reacts with presynaptic muscarinic receptors on sympathetic nerve endings to reduce the amount of norepinephrine released from sympathetic efferent terminals - In addition to norepinephrine released from sympathetic terminals, transmitters such as neuropeptide Y are also released which inhibits the release of Ach from vagal nerve endings

Explain the progression of compensatory reflex mechanisms in the circulatory system in the case of a severe hemorrhage.

- Activation of neural and hormonal compensatory mechanisms as discussed in moderate to mild hemorrhage - With more severe hemorrhage, peripheral chemoreceptors sense hypoxia (decreased Pao2) due to inadequate blood flow to the carotid body and contribute to further increases in sympathetic outflow. - If cerebral ischemia occurs, elevated Paco2 and decreased blood pH activate chemosensitive neurons in the brain, which results in a massive activation of the sympatho-adrenal systems.

Name four methods of self-regulation used to regulate blood flow.

- Active hyperemia - Reactive hyperemia - Flow autoregulation - Local response to injury (inflammation)

Explain the intracellular mechanism involved in sympathetic regulation of myocardial contractility.

- Adrenergic receptors activate a G-protein coupled cascade that includes the production of cAMP and activation of a protein kinase (PKA). - Several proteins involved in excitation-contraction coupling are phosphorylated by the kinase, which alters their activity. These include: > DHP receptors (L-type calcium channels) in the plasma membrane (increase in intracellular Ca2+) > The ryanodine receptor and associated proteins in the sarcoplasmic reticulum membrane (Ca2+ release from SR) > Thin filament proteins - i.e. troponin (activation of actin) > Thick filament proteins (crossbridge formation and cycling - force generation) > Proteins involved in pumping calcium back into the sarcoplasmic reticulum.

How is heart rate affected by the autonomic nervous system?

- An increase in parasympathetic activity via M2 cholinergic receptors in the heart will decrease the heart rate - An increase in sympathetic activity via B1 and B2 adrenergic receptors throughout the heart will increase the heart rate.

Describe the actions of the m gate and h gate of sodium channels over the course of an action potential in cardiac muscle cells

- At RMP the h gate is open but the m gate remains closed, thus the channel is closed but available for activation - Adequate depolarization causes voltage-mediated activation of the channel by opening of the m gate, and Na+ enters cell as both gates are open - However, depolarization causes the h gate to close with a 1-2 ms delay, which inactivates the Na+ channel. - The h gate cannot be reopened while depolarization of the cell is taking place = absolute refractory period - During repolarization, at about -50 mV, the h gates of some cells will open, meaning another AP can be generated if a sufficiently large stimulus is delivered = relative refractory period. - At RMP the h gate of all cells will open but the m gate will remain closed - therefore cells are in a resting state but available for activation.

Explain the neural response from the CV centre in the event of a rise in blood pressure.

- Baroreceptors increase firing frequency to CV centre - The cardioinhibitory centre increases firing of parasympathetic signals via the vagus nerve = decrease in HR - Also inhibits sympathetic signals = dilation of arterioles - Combined effect is lowering of arterial BP.

Describe what happens during depolarization of the cardiac myocyte, with reference to sliding filament theory

- Calcium enters the cell through the ECF and SR (calcium induced calcium release) - Ca2+ binds to troponin causing a conformational change which exposes active sites on actin - Myosin heads bind with active sites on actin filaments, forming cross bridges. - Filaments are propelled past each-other by power stroke of myosin, powered by ATP - Myosin then disconnects and process repeats at another active site (functions as a ratchet) - Causes thin filaments of the I-band to slide into the spaces between the thick filaments of the A-band (sliding filament theory) - Results in shortening of the I-band and resultant contraction of muscle - The number of cross bridges and therefore the force of contraction depends directly on the concentration of free Ca2+ inside the myocyte

Name six differences between cardiac and skeletal muscle.

- Cardiac muscle behaves as functional syncytium, while skeletal muscle cells are individually innervated - Duration of contraction and refractory period is longer in cardiac muscle - Maximum tension in cardiac muscle is 30 - 50% of that of skeletal muscle - Skeletal muscles are capable of wave summation and tetany - Cardiac muscle behaves in "all-or-none" fashion during contraction whereas in skeletal muscle, a variable number of fibres can contract depending on stimulus. - Cardiac muscle has a major ability to alter contractility by altering initial fibre length (Frank-Starling mechanism), whereas in skeletal muscle it is the number of fibres contracting that affects the force of contraction.

What are the physical factors that affect coronary circulation?

- Cardial cycle and myocardial pressure (the phasic variation): coronary blood flow not only varies in time during cardiac cycle but also varies with depth in the wall of the heart - Aortic pressure - Coronary vascular resistance - Heart rate - Right atrial pressure

Describe the effect of the slow calcium channels on the progression of the cardiac action potential.

- Cardiomyocytes uniquely possess a type of slow calcium channel known as the long, L-type calcium channel. - Slow to open following the rapid depolarization phase but remain open for a long time afterwards. - Causes an influx of calcium into the cardiomyocyte which initiates cardiac excitation-contraction coupling - Most responsible for the Plateau Phase - allow a long time-scale influx of positive ions which exactly balances the initially low efflux of potassium - Eventually the slow calcium channels close and the potassium channels continue to open, resulting in the final rapid repolarization phase

Name three factors that influence the rate of movement of a substance across a membrane

- Concentration gradient - Membrane permeability - Type and number of charges on compound

Describe the renal response to heart failure.

- Heart failure results in a drop in NaCl being delivered to the macula densa of the distal tubule - Results in increased renin secretion and thus activation of the RAAS system - Angiotensin II has two primary effects: > stimulates secretion of aldosterone which increases sodium and H2O reabsorption and thus blood volume > causes vasoconstriction thus increasing blood pressure.

Explain how renal response to heart failure can lead to further complications in the late stages of heart failure.

- Increase in sodium and water retention can negatively effect heart due to rise in volume and increased preload which leads to overdistension of the myocardium (eccentric hypertrophy), thus resulting in decreased stroke volume. - Increased blood pressure due to arteriolar vasoconstriction increases afterload and puts strain on the heart due to high arterial pressure and increased peripheral resistance, also leading to decreased SV. (Sustained high pressure = concentric hypertrophy = reduction in preload and ventricular compliance = further reduced SV)

Explain how concentric hypertrophy leads to heart failure.

- Increased afterload associated with heart failure leads to compensatory cardiac hypertrophy. - Initially this results in improved tissue perfusion - With time concentric hypertrophy results in thickening of ventricular wall and narrowing of lumen (decreased ventricular compliance) - Results in decreased preload, which ultimately worsens existing heart failure.

Explain the progression of compensatory reflex mechanisms in the circulatory system in the case of a mild to moderate hemorrhage.

- Increased sympathetic nerve activity, especially to the kidney, results in vasoconstriction, decreased glomerular filtration rate, and decreased urine volume - Discharge in arterial baroreceptors decreases and contributes to increased sympathetic nerve activity and decreased parasympathetic nerve activity: heart rate, cardiac contractility, and total peripheral resistance increase and venous constriction promotes venous return to the heart. - Decreased stretch of the atrium due to reduced blood volume results in diminished secretion of ANP - Decreased renal perfusion pressure promotes secretion of renin and activation of the renin-angiotensin-aldosterone system to restore blood volume - Cardiopulmonary and arterial baroreflex mechanisms promote increased circulating levels of ADH (vasopressin), angiotensin II, and aldosterone

Describe the effect of the variable potassium channels on the progression of the cardiac action potential.

- Induced to open following rapid depolarization and allow outflow of positively-charged K+ from the cell which is responsible for the cell's eventual repolarization. - However, initially display low potassium conductance which increases gradually but slowly. - Initially, low potassium conductance only allows for a partial repolarization of the membrane, partially contributing to making the plateau phase of the cardiomyocyte AP possible. - As the potassium conductance builds, it overwhelms all other ion conductances and thus causes the rapid repolarization phase.

Describe the innervation of cerebral blood vessels.

- Innervated primarily by sympathetic nervous system, with mediation of vasoconstriction through NE and NPY - Density of α‐adrenergic receptors in the cerebral circulation is low relative to other vascular beds, therefore sympathetic control of cerebral blood vessels is relatively weak. - Innervation by the parasympathetic nervous system arises from the facial nerves but its effects on blood flow are minor. - Sensory nerves containing substance P and calcitonin generelated peptide (CGRP) also supply the distal cerebral vessels (both substances are potent vasodilators)

Name two sources of input into the CV centre of the brain, which will alter efferent signals to the heart.

- Input from higher brain centres (cerebral cortex, limbic system, hypothalamus) - Sensory input from the peripheral nervous system (chemoreceptors, baroreceptors and proprioreceptors)

Describe the pathway of sympathetic innervation of the heart.

- Myelinated preganglionic sympathetic fibers originate from the central nervous system in the intermediolateral (IML) column of the spinal cord. - The IML column is under the control of pre-sympathetic regions, including the rostral ventrolateral medulla (RVLM) of the brainstem and paraventricular nucleus (PVN) of the hypothalamus. - Preganglionic fibers leave the thoracic and lumbar spinal cord between T1 and L3 via the ventral roots - Cardiac preganglionic fibers pass into peripheral ganglia of the sympathetic chain located adjacent to the vertebral column, from which unmyelinated postganglionic fibers leave the ganglia to innervate the heart. - The majority of sympathetic nerve impulses reach the heart through the stellate ganglia

Describe the effect of the fast, voltage-gated sodium channels on the progression of the cardiac action potential.

- Opening of these channels is responsible for the initial, rapid depolarization of the cardiomyocyte. - Allow rapid influx of positive, Na+ ions into the cells which depolarize the membrane potential with incredibly quick kinetics. - However, these channels also quickly close and thus eliminate the Na+ influx soon after maximum depolarization of +20mV is achieved

Describe the pathway of parasympathetic innervation of the heart.

- Parasympathetic preganglionic cell bodies originate in the brainstem primarily in the dorsal motor nucleus of the vagus (DMnX) and nucleus ambiguus (nA). - Myelinated preganglionic fibers leave the central nervous system via the vagus nerve, and travel to terminal ganglia on or near the epicardial surface of the heart where they form a synapse with short postganglionic neurons - The postganglionic fibres of the right and left vagus nerves differentially innervate the SA and AV node.

Explain the pathway by which angiotensin II is produced.

- Renin secreted by the juxtaglomerular apparatus of the kidney - Renin catalyzes the conversion of angiotensinogen (plasma protein produced by liver) to angiotensin I - Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE) mostly in pulmonary capillaries

Describe the pathway of the baroreflex in response to an increase in blood pressure

- Stimulation of afferent nerves of baroreceptors increases activity of the brainstem nucleus tractus solitarius (nTS). - Increases in nTS activity causes discharge of inhibitory neurons in the caudal ventrolateral medulla (CVLM) to reduce activation of the RVLM (rostral ventrolateral medulla) and IML (Intermediolateral) column of the spinal cord, and result in a reduction in sympathetic nervous system activity, blood pressure, and heart rate. - Depending on species, activation of the nTS to either the nA (nucleus ambiguus) or DMnX (dorsal motor nucleus of the vagus) increases vagal tone to also reduce heart rate.

Describe what happens on repolarization of the sarcolemma of the cardiomyocyte.

- Voltage gated Ca2+ channels on the sarcolemma close - Intracellular Ca2+ reaccumulates in the SR - Ca2+-troponin complexes disassociate - Troponin returns to its original shape and tropomyosin again inhibits or covers the myosin-binding sites on the actin filament - Cross bridges between actin and myosin are broken - Sarcomere returns to resting length and muscle relaxes.

What are the immediate responses effected by the nervous system in response to a drop in arterial blood pressure?

- Widespread vasoconstriction in arterioles - Strong vasoconstriction of veins (displaces blood out of the large peripheral blood vessels toward the heart, thus increasing the volume of blood in the heart chambers) - Increased sympathetic stimulation of the heart muscles to increase heart rate and contractility.

What percentage of cardiac output do the heart vessels receive at rest?

5%

Define ischemia reperfusion injury

A condition whereby after a period of poor perfusion due to vascular obstruction, the restoration of blood flow delivers oxygen which is partly converted into toxic superoxide radicals by xanthine oxidase (produced during the anoxic phase) in the metabolically altered tissue. The free radicals damage the endothelium, leading to inflammation and impairment of tissue recovery.

What stimulates the secretion of renin from the juxtaglomerular apparatus?

A drop in blood volume (decreased renal perfusion).

Define cytopempsis

A mechanism for transcellular transport in which a cell encloses extracellular material in an invagination of the cell membrane to form a vesicle (endocytosis), then moves the vesicle across the cell to eject the material through the opposite cell membrane by the reverse process (exocytosis), without utilization of the substance by the cell.

What is heart block?

A pathological condition where there is a blockage of normal electrical conduction across the annulus fibrosis. This prevents the SA from dominating the bundle of His.

What is a portal system?

A portal system is defined as two capillary beds connected in series between an artery and a vein

How is the rapid "off" response of vagal stimulation of the heart brought about?

ACh is rapidly broken down by cholinesterase into choline and acetate. The rapid "off " response to parasympathetic nervous system activation is due to the abundant cholinesterase in the SA and AV nodes of the heart, allowing the rapid breakdown of ACh.

Define edema.

Abnormal accumulation of fluid in interstitial spaces of tissues, accompanied by swelling.

Explain how cardiopulmonary stretch receptors in the atria, ventricles and pulmonary vessels contribute to regulation of blood volume.

Activation (stretching) of these receptors results in a reflex decrease in renal sympathetic nerve activity, decreased renin secretion, decreased angiotensin II and inhibition of vasopressin (ADH) secretion. Because of these reflex humoral changes, an increase in blood volume is compensated for by a loss of fluid into the urine.

What is active dilation of blood vessels?

Active dilation refers to a further reduction in vascular contractile tone below the level of tone present in the absence of sympathetic vasoconstrictor activity.

Define active hyperemia

Active hyperemia is the increase in organ blood flow (hyperemia) that is associated with increased metabolic activity of an organ or tissue, for example blood flow to exercising skeletal muscle increases in direct proportion to the increased activity of the muscle. Active hyperemia is the direct result of arteriolar dilation in the more active organ or tissue.

What is the primary function of the heart?

Acts as a muscular pump that is responsible for: - maintaining adequate levels of blood flow throughout the cardiovascular system by pumping blood under pressure into the vascular system - the mass movement of fluid in the body

Define afterload of the heart.

Afterload is the pressure that the heart must work against to eject blood during systole (ventricular contraction). Afterload is proportional to the average arterial pressure. As aortic and pulmonary pressures increase, the afterload increases on the left and right ventricles respectively.

How does the heart maintain the balance in ventricular volume?

An increase in output of one ventricle will lead to an increase in venous return to the other ventricle. The increased return will result in a stronger contraction and increased output of the other ventricle Thus, left and right ventricular outputs balance.

List five chemical factors that increase when metabolic activity exceeds blood flow, which will stimulate active hyperemia (A - E)

Any five of the following: (A) Carbon dioxide (waste productive of oxidative metabolism) (B) Hydrogen ions (causing decreased pH from e.g. lactic acid) (C) Adenosine (breakdown product of ATP) (D) K+ ions (accumulated from repeated action potential repolarization) (E) eicosanoids (breakdown products of membrane phospholipids) (F) Changes in osmolarity (G) Bradykinin (a peptide generated locally from a circulating protein called kininogen by the action of an enzyme, kallikrein, secreted by active gland cells) (H) Nitric oxide (gas released by endothelial cells)

What is the mechanism of active hyperemia?

Arterial dilation stimulated by local chemical changes in the extracellular fluid surrounding the arterioles, which result from the increased metabolic activity in the cells near the arterioles.

What is the primary mechanism that causes flow autoregulation?

Arterial vasoonstriction / vasodilation in response to local chemical changes in the extracellular fluid surrounding the arterioles (same mechanism as active hyperemia), which result from increased or decreased blood pressure.

What are shunt vessels?

Arteriovenous anastomoses that allow blood to bypass capillary beds.

Why is the strength of myocardial contraction influenced by heart rate?

As the rate (frequency) of contractions increases, there is an increase in the peak tension and maximum shortening that develops over the physiological range (the staircase effect). This is due to increased intracellular calcium due to the increase in the number of action potential plateaus. In addition, elevated frequency enhances the amount of calcium that enters through L‐type calcium channels as well as slowing channel inactivation.

Describe what happens during the early phase of ventricular diastole (including which valves are open)

As the ventricles relax and the pressure falls below arterial pressure, blood flows back against the semi-lunar valves, forcing them to close. The pressure in the ventricles still remains higher than that of the atria, therefore the AV valves remain closed. Ventricles are closed chambers once more (isovolumetric relaxation)

Describe what happens during the first phase of ventricular systole (including which valves are open)

As ventricular contraction begins, pressure in the ventricles exceeds that of atria, and this backwards pressure forces the AV valves to close. During this phase, the aortic and pulmonary pressure remains greater than that of the ventricles, and thus the semi-lunar valves remain closed. The contraction of the ventricles therefore builds up the pressure within the ventricles, but as all valves are closed there is no net movement of blood, so this phase is known as isovolumetric contraction.

Describe what happens in the phase of atrial systole (including which valves are open)

At the start of atrial systole, the atrioventricular valves are already open, and blood is flowing passively into the ventricles. Atrial systole involves the contraction of the atria to force a small amount of additional blood into the ventricles.

Why is the slope of the pacemaker potential important?

Because this will determine the interval between action potentials and thus heartbeats.

Define blood pressure

Blood pressure is the measure of pressure exerted by blood on the walls of a blood vessel

What consequence would arise from pumping unequal volumes of blood from the ventricles of the heart for an extended period?

Blood would accumulate either in the lung or in the body's peripheral veins leading to edema.

What serves as the link between excitation and contraction coupling in cardiac myocytes?

Calcium

How is the heart muscle adapted to maintain its work over long periods of time without rest?

Cardiac muscle contains large numbers of mitochondria for ATP production and the myoglobin content is large, favoring oxygen diffusion into muscle fibres.

How is cardiac output calculated?

Cardiac output (CO) = Stroke volume x Heart rate

What is the relationship between cardiac output, stroke volume and heart rate?

Cardiac output = stroke volume x HR

What is cardiac reserve?

Cardiac reserve is the difference between resting and maximal cardiac output

Define heart failure.

Cardiogenic circulatory failure with a sustained inability of the heart to produce a stroke volume that adequately meets tissue metabolic demands

What is the function of chemoreceptor reflexes in the circulatory system?

Chemoreceptor reflexes buffer changes in arterial blood gases by controlling breathing.

Explain why the adrenal medullae are also considered a part of the sympathetic nervous system.

Chromaffin cells in the adrenal medulla function like postganglionic sympathetic neurons, with the exception that the catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) are released directly into the bloodstream.

Define circulatory shock

Circulatory shock is the severe, acute failure of tissue perfusion resulting in cardiovascular collapse and leading to organ & tissue dysfunction

What is concentric hypertrophy?

Concentric hypertrophy consists of an increased thickness of the ventricular wall without an increase in size of the ventricular chamber. Results from long‐standing pressure overload, myocardial cells respond by adding more myofibrils in parallel.

What generates blood pressure?

Contraction of the ventricles

What is the function of Windkessel vessels? Give an example of such a vessel.

Convert pulsatile inflow into smooth outflow. E.g. the aorta.

What is the action of Ca2+ channel blockers such as verapamil on nodal cells?

Decreases both the size of the action potential (decreasing contractility) and the rate of depolarization (decreasing heart rate)

What is the consequence of heart block on the heart?

Due to the lack of influence of the SA, cells in the bundle of His then take over the pacemaker role, driving the ventricles at their own intrinsic rate of 40 beats/min, which is inadequate for a daily activity

Why are pacemaker cells capable of spontaneous depolarization so frequently?

Due to the unstable resting potential (prepotential or pacemaker potential). The initial membrane potential of the SA cell is only about -60mV and it decays spontaneously due to the slow influx of Na+ ions until a threshold potential (around -40 mV) is reached and an action potential is generated via opening of voltage-gated Ca2+ channels.

How does the lusitropic reserve influence ventricular function?

During exercise the time interval for ventricular filling is reduced and the heart's ability to increase cardiac output depends partly on rapid relaxation. An increased ionotropic state and heart rate normally initiates lusitropic reserve, which shortens the process of myocardial muscle relaxation.

How does reactive hyperemia occur?

During the period of no blood flow, the arterioles in the affected organ or tissue dilate, owing to build up of local factors from cellular metabolism that are not removed via blood flow. Blood flow, therefore, increases greatly through these wide-open arterioles as soon as the occlusion to arterial inflow is removed.

What occurs in the coronary arteries during sympathetic stimulation in the presence of beta blockers used on the heart?

During β‐adrenergic blockade to eliminate effects of sympathetic activation on heart rate and contractility, vasoconstriction from activation of alpha adrenergic receptors in coronary vessels is unmasked, resulting in coronary vasoconstriction and a decrease in blood flow.

What is eccentric hypertrophy?

Eccentric hypertrophy consists of an enlarged ventricular chamber with a relatively small increase in wall thickness. Results from long‐standing volume overload, myocardial cells respond by adding more sarcomeres in series.

What is the ejection fraction and how is it calculated?

Ejection fraction (EF) is the percentage of ventricular end diastolic volume (EDV) which is ejected with each stroke. EF = SV / EDV (x100 for percentage).

How is stroke volume of the ventricle calculated?

End diastolic volume - end systolic volume

Explain the process of functional sympatholysis in skeletal muscle during moderate exercise.

Exercise is associated with an increase in sympathetic nerve activity proportional to the intensity of exercise. While increased sympathetic activity would be expected to produce vasoconstriction through norepinephrine release at α1 and α2 receptors, local metabolites inhibit this effect, a condition termed functional sympatholysis. Metabolic substances cause vasodilation via metabolic autoregulation.

What do pacemaker cells lack that makes their action potentials less steep than those of cardiac muscle cells?

Fast Na+ channels. Action potentials are generated solely by the slow Ca2+ channels.

Coronary flow can increase ______fold during strenuous exercise.

Four to seven

What does an increase in paCO2 cause when detected by central chemoreceptors?

Generally causes increased ventilation, increased sympathetic outflow, and increased blood pressure mediated by projections within the brainstem to respiratory and sympathetic outflow pathways.

Describe changes in the three primary cardiac parameters characteristic of heart failure, and possible conditions that may cause these changes.

Heart failure is normally caused by inadequate stroke volume which may result from: (A) Decreased myocardial contractility - due to cardiac lesions (hypoxia, myocarditis, cardiomyopathy) or decreased sympathetic tone. (B) Decreased preload - due to AV valvular stenosis, pericardial effusion, or arrhythmias that shorten diastole (ventricular filling). (C) Increased afterload (pressure overload) - due to elevated blood pressure, total peripheral resistance, or haematocrit, semi-lunar valvular stenosis, heart worm disease (adult worms in lung vessels) & aortic stenosis

What is hemodynamics?

Hemodynamics is the study of the physical laws of blood circulation

Define circulatory failure.

In circulatory failure, cardiac output fails to meet tissue perfusion needs. When acute and severe, this may lead to circulatory shock.

How does heart rate affect ventricular function?

In the isolated muscle, an increase in stimulation frequency leads to an increase in developed tension (staircase, Bowditch, or treppe phenomenon). Since cardiac output is the product of heart rate (HR) and stroke volume (CO = HR × SV), the cardiac output of a slowly beating heart can be potentially doubled by doubling the heart rate.

What does a decrease in PaO2 cause when detected by peripheral chemoreceptors?

Increased discharge in the afferent chemoreceptor nerves, which promotes increased ventilation.

How does preload affect stroke volume?

Increased preload increases stroke volume, whereas decreased preload decreases stroke volume due to changes in the force of cardiac muscle contraction .

What is flow autoregulation?

Locally mediated changes in arteriolar resistance that occur when a tissue or organ suffers a change in its blood supply resulting from a change in blood pressure. This is done to maintain constant blood flow to the tissue following a change in blood pressure.

Describe the innervation of blood vessels and the neurotransmitter and receptor types involved.

Most blood vessels throughout the body receive sympathetic postganglionic innervation, and release of NE results in vasoconstriction via activation of postsynaptic vascular α1 receptors. α2‐adrenergic receptors are present in certain arterioles and their activation also mediates vasoconstriction. In some species arterioles in skeletal muscle also receive specialized sympathetic innervation in which ACh is released from the postganglionic nerve terminals and mediates vasodilation.

How are impulses from pacemakers spread throughout the contractile cells of the heart to ensure simultaneous contraction?

Myocardial cells form a branching, anastomosing network and are connected by specialised leaky tight junctions, the intercalated discs, which allow electrical continuity and the spread of impulses between cells, and thus the muscle tissue acts as a functional syncytium.

What is the effect of neuropeptide Y on blood vessels?

Neuropeptide Y (NPY) is one of the important co-transmitters released along with NE from sympathetic nerve terminals and, since it is a strong vasoconstrictor, contributes to the vasoconstrictor response especially during intense sympathetic activation.

Can the heart function well under anaerobic conditions?

No. Cardiac muscle = red muscle. In white skeletal muscle the enzymes responsible for anaerobic glycolysis are more abundant, whereas cardiac muscle is richer in enzymes providing for oxidative metabolism. Under anaerobic conditions the heart has a very limited capacity to use glycolysis for energy release, and its slender reserve of phosphocreatine is quickly depleted.

Is the functional syncytium of cardiomyocytes continuous throughout the heart?

No. The atrial functional syncytium is separated (insulated) from the ventricular functional syncytium by the fibrous cardiac skeleton. The atrioventricular node acts as the electrical relay station between the upper and lower chambers of the heart.

Describe what happens during the second phase of ventricular systole (including which valves are open)

Once the pressure in the ventricles exceeds arterial pressure, the semi-lunar valves open and blood is forcefully ejected from the ventricles into the vessels. This phase can also be divided into maximum ejection and slower ejection once peak ventricular pressure is reached, and the rate of blood flow declines. AV valves remain closed during this phase.

What is the definition of a heart beat?

One complete pulsation of the heart - i.e. it is composed of the atrial contraction and relaxation and the ventricular contraction and relaxation.

What fraction of the central blood volume is in the lungs?

One third.

What effects does the sympathetic nervous system have outside of the skeletal muscle circulation during moderate exercise?

Outside the skeletal muscle circulation, sympathetic vasoconstriction due to stimulation of alpha adrenergic receptors during exercise and increased cardiac output due to sympathetic stimulation of beta adrenergic receptors in the heart leads to a moderate increase in systemic arterial blood pressure.

Explain why a coronary blood flow reserve is necessary in the heart.

Oxygen extraction by the myocardium is very high (approximately 75%) in comparison to other tissues. An increase in oxygen demand by the myocardium therefore must be met primarily by an increase in coronary blood flow. The increase in blood flow during strenuous exercise is known as the coronary flow reserve.

When does peak coronary blood flow in the left coronary artery occur?

Peak left coronary flow occurs during early diastole, when aortic pressure is still high but the ventricle has relaxed, eliminating extravascular compressive forces.

Contrast physiological and pathological myocardial hypertrophy

Physiologic hypertrophy, as seen in exercise training, is characterised by: > a normal or enhanced contractile state > proportional growth of cellular constituents > normal myosin ATPase activity. Pathologic hypertrophy, seen in diseased hearts, is characterised by > a decrease in contractile state > decreased myosin ATPase activity > diminished cyclic AMP > disproportionate biosynthesis of subcellular structures (e.g., mitochondria).

What is the most important parameter that regulates ADH secretion?

Plasma osmolarity: increased osmolarity = increased ADH secretion to promote fluid retention.

Name the neurotransmitter and receptor type that characterize postganglionic terminals of the parasympathetic NS in the SA and AV node of the heart.

Postganglionic nerve terminals release acetylcholine (ACh) which activates M2‐type muscarinic cholinergic receptors and decreases heart rate and atrial contractile force.

According to the Frank-Starling law, what is the most important factor influencing cardiac output?

Preload - If ventricular end diastolic volume (preload) is increased, it follows that the ventricular myocardial fibre length is also increased, resulting in increased force of contraction during systole and hence a greater cardiac output.

How does preload influence ventricular function?

Preload in the isolated muscle stretches the muscle and determines the resting fiber length of myocytes. Increasing the preload of an isolated muscle causes an increased force of contraction and thus increased stroke volume or cardiac output (Starling's law of the heart).

What is the function of anastomoses between arteries?

Provide alternate routes for blood flow known as collateral circulation.

What effects does ANP have?

Reduces blood volume via the following mechanisms: - ANP acts directly on the inner medullary collecting ducts of the kidney to inhibit sodium reabsorption. - Acts on the renal arterioles to increase glomerular filtration rate (more sodium excreted due to increased flow rate through the renal tubules) - Inhibits the secretion of renin, and it acts directly on the adrenal cortex to inhibit angiotensin‐induced aldosterone secretion (less sodium and water reabsorbed in renal tubules).

What is the primary function of baroreflex pathways?

Regulation of blood pressure: - a rise in blood pressure leads to a marked slowing of heart rate, vasodilation, and a fall in blood pressure via afferent signals sent from baroreceptors to the CV centre in the medulla - a drop in blood pressure causes cardiac acceleration, vasoconstriction, and a rise in arterial pressure.

What are the effects of angiotensin II in the circulatory system?

Restores blood volume and pressure by: - acts on vascular smooth muscle to increase vasoconstriction - stimulates sympathetic NS which further increases vasoconstriction and cardiac output - stimulates secretion of aldosterone from the adrenal cortex - Acts directly on renal tubules and arteries to increase Na+ reabsorption and thus H2O retention - Stimulates ADH secretion from the neurohypophysis which increases H2O absorption in renal collecting ducts - Stimulates thirst centre in brain promoting fluid intake

What effect does complete obstruction of lymphatics have on myogenic contractions?

Significantly increases amplitude & frequency of contractions, raising peak lymphatic pressure to 60mmHg or higher (normal = 25 mmHg).

How does sympathetic innervation of blood vessels contribute to vasodilation in the vessels of skeletal muscle?

Skeletal muscle vessels possess β2 receptors that produce vasodilation in response to moderate levels of circulating epinephrine. The net effect of functional sympatholysis and β2‐receptor activation is to spare the circulation of exercising muscle from vasoconstriction typically produced by a generalized increase in sympathetic nervous system activity.

What other mechanism (other than chemical changes in the ECF around arterioles) can cause flow autoregulation to a tissue?

Some arteriolar smooth muscle responds directly to increased stretch, caused by increased arterial pressure, by contracting to a greater extent. Conversely, decreased stretch due to a drop in blood pressure will result in greater vasodilation.

What is a sphincter vessel?

Sphincter vessels occur at the terminal segments of precapillary arterioles, and can constrict/shut off capillary flow. Therefore, they determine rate of blood flow to capillaries, number of open capillaries & area of capillary exchange surface

What stimulates the secretion of Atrial natriuretic peptide (ANP)?

Stretching of mechanoreceptors in the atria, as may occur with an increase in blood volume, causes release of ANP into the circulation.

How are the rhythmic contractions of smooth muscle in lymph vessels influenced by lymph volume?

Stretching of the vessels due to an increase in the volume of lymph causes rhythmic contractions to increase in rate and strength, depending on the degree of stretch.

Name the neurotransmitter and receptor type that characterize postganglionic terminals of the sympathetic NS in the heart.

Sympathetically mediated increases in heart rate and cardiac contractility are due to release of norepinephrine (NE) from nerve terminals and activation of β1‐adrenergic receptors in the heart

State the Fick principle with regards to the uptake of substances from circulation by the body.

The Fick principle states that the amount of a substance taken up by an organ (or by the whole body) per unit of time is equal to the arterial level of the substance minus the venous level (A-V difference) times the blood flow

State the Frank-Starling law of the heart

The Frank-Starling Law states that the stroke volume of the left ventricle will increase with increased venous return (i.e. preload) due to the increased myocyte stretch causing a more forceful systolic contraction.

Describe the gradient of automaticity in the conducting system of the heart, and the consequences this has for establishing the rate of impulse conduction in the heart.

The SA node has the highest level of automaticity (at a rate of 60 - 90 impulses per minute), followed by the AV node (at a rate of 40 - 60 impulses per minute) and then the bundle of His (20 - 40 ipm) and finally the Purkinje fibres (less than 20 ipm). The SA node therefore imposes its rhythm on the rest of the heart, thus making it the primary pacemaker of the heart. In the event the SA node fails, the other elements will take over in hierarchal order of automaticity.

How does afterload affect ventricular function?

The arterial pressures determine the afterload, influencing the velocity and length by which muscles will contract during ventricular systole, and therefore the afterload sets the amount of work needed to eject blood. If arterial pressure rises, afterload will increase.

What is the difference between active hyperemia and flow autoregulation?

The difference is the cause of changes in vascular resistance. In the case of hyperemia it is altered metabolism, while for flow autoregulation it is altered blood pressure. Additionally, active hyperemia always results in vasodilation to the tissue (due to increased metabolic demands), whereas flow autoregulation can cause vasodilation (if blood pressure drops) or vasoconstriction (if blood pressure increases).

What is lusitropy?

The inactivation of the myocardial contractile process and the return of the muscle to a relaxed state.

How is the plateau phase related to the strength of contraction in cardiac muscle?

The influx of calcium ions during the plateau phase influences the size of the intracellular calcium store. Large plateau currents such those stimulated by adrenaline and noradrenaline are therefore associated with more forceful contractions.

How does the ionotropic state of the heart affect ventricular function?

The inotropic state affects muscle performance independent of preload and afterload. Increasing the inotropic state increases the peak (isometric) tension developed at each preload and the velocity of fiber shortening. Increasing the contractility but keeping preload and afterload constant results in an increased stoke volume and decreased left ventricular end systolic volume.

Why is lusitropy important for cardiac output?

The lusitropic state of the myocardium is important for adequate ventricular filling before the next cardiac contraction.

What is the m gate of a sodium channel and where is it located?

The m gate is the activation gate, located at the entrance on ECF side of the ion channel

What is the h gate of a sodium channel and where is it located?

The m gate is the inactivation gate, located at the entrance of the ion channel on the interior of the cell.

Where are arterial chemoreceptors located?

The peripheral chemoreceptors are located in the same general regions as the arterial baroreceptors (carotid sinuses and aortic arch) and their afferent nerves travel in the same nerve bundles as the arterial baroreceptors. There are also neurons within the central nervous system that are chemosensitive (central chemoreceptors)

Define preload of the heart.

The preload is the end diastolic volume that stretches the right or left ventricle of the heart to its greatest dimensions under variable physiologic demand. Simply, it is the volume of blood in the ventricle prior to contraction.

Describe what happens during the late phase of ventricular diastole (including which valves are open)

The pressure in the ventricles declines rapidly until it falls below that of the atria and the AV valves open once more. All chambers are now relaxed, resulting in the refilling of the ventricles from blood in the atria, which have been refilling during ventricular systole. This phase can be divided into the rapid filling and slow filling or diastasis, in which minimal filling takes place due to the ventricles already being almost full. Semi-lunar valves remain closed.

Why does vagal activation of the heart have a more rapid response than sympathetic activation?

The rapid "on" response of vagal activation is due to the direct coupling of muscarinic receptors to potassium (IK,ACh) channels that allow a rapid response whereas sympathetic stimulation requires activation of the second messenger adenylyl cyclase and cyclic AMP system.

What is the function of the refractory period in cardiomyocytes?

The refractory period prevents cardiac cells from undergoing another action potential for a certain period after they are stimulated by the first action potential. This prevents cardiac myocytes from being re-stimulated by action potentials occurring in adjacent cells to which the action potential has just been spread. It also serves to prevent wave summation and tetanus in the heart muscle, which would have lethal consequences.

What subcellular system in the myocyte is responsible for initiating contraction, regulating tension & achieving relaxation of the muscle?

The sarcoplasmic reticulum

In which cardiac cells is the T-tubule system most well developed?

The t-tubule system is well developed in the ventricular myocytes, but is scant in the atrial and Purkinje cells.

What is cardiac dilation?

The term cardiac dilation refers to an increase in the volume or capacity of the heart chambers.

What is the major function of the microcirculation?

The transport of oxygen and nutrients to the tissues and the removal of waste products from the tissues.

What is the stroke volume?

The volume of blood pumped from a ventricle at each systole, which equates to the end diastolic volume in the ventricle minus the residual volume left behind in the ventricle after systole.

State Laplace's Law with regards to the heart

The wall stress during ventricular contraction (systole) is a function of the intraventricular pressure, radius of the ventricular cavity, and the thickness of the myocardial wall.

Why is the relationship between preload and stroke volume important in heart function?

This relationship is important in maintaining an equal output of both ventricles.

Explain what occurs in arterioles in response to local tissue injury / inflammation.

Tissue injury causes a variety of substances to be released locally from cells or generated from plasma precursors. These substances make arteriolar smooth muscle relax and cause vasodilation in an injured area.

What is the primary mechanism that facilitates the flow of lymph in lymph vessels?

Tonic and phasic contractions of smooth muscle cells that occur in response to pacemaker activity from within the smooth muscle layer of the vessel wall.

What is the function of transitional cells in the heart?

Transitional cells connect the conductive tissues to the contractile tissues within the heart.

What nerve is responsible for the parasympathetic innervation of the heart?

Vagus nerve

What is the mechanism of vasodilation for the majority of blood vessels?

Vasodilation, particularly of a reflex nature, is predominantly due to removal of existing vasoconstrictor tone.

What are capacitance vessels?

Veins that can effect marked shifts in blood volume to the heart (through diameter changes) thereby altering venous return.

How is coronary blood flow regulated when aortic pressure fluctuates?

Via myogenic autoregulation - the intrinsic tendency of vascular smooth muscle in coronary arteries to shorten in response to stretch produced by arterial distending pressure. Minimizes changes in coronary flow despite significant changes in coronary arterial pressure.

A major contribution of cardiopulmonary reflexes to circulatory control involves regulation of blood (A).

Volume.

Define reactive hyperemia

When an organ or tissue has had its blood supply completely occluded, a profound transient increase in its blood flow occurs as soon as the occlusion is released.

What happens to the contractions in lymph vessels when lymph volume is zero

When no lymph is present, its smooth muscle becomes quiescent, contractions cease, and lymph pressure falls to zero.

What safety mechanism exists to prevent pulmonary edema?

When the pulmonary capillary pressure remains chronically elevated, the lungs become even more resistant to pulmonary edema because the lymph vessels expand, increasing their ability to carry fluid away from the interstitial spaces as much as tenfold