Week 2 Physiology

Equation for Total Peripheral Resistance

TPR = Atrial Pressure/CO

Total Peripheral Resistance in terms of MAP*** (need to remember)

TPR = MAP/CO

two deviations from the ideal laws of hemodynamics in small vessels

The formation of Rouleaux at low flow rates in the microcirculation increases blood viscosity thereby reducing the flow. However, the Fahraeus-Lindqvist effect decreases viscosity in the microcirculation and facilitates flow.

Total Peripheral Resistance

The overall resistance to flow through the circulation is called the total peripheral resistance (TPR). The organs are arranged in parallel network, and the resistance of each organ contributes to the TPR according to the inverse relationship. By this mechanism, blood flow is regulated and balanced throughout the body according to organ needs.

The two types of pressure in the circulatory system

The pressure at any point in the circulatory system is the sum of static and dynamic pressures. 1. Static pressure (present whether the blood is moving or not) is composed of the applied or lateral pressure (ΔP or PL) and force of gravity (ρgh) --> drives fluid out of capillaries 2. Dynamic pressure is that due to kinetic energy (½ρv ^2) important at levels of high cardiac output --> If the energy is constant for blood flowing in a segment of a vessel, then the total pressure is constant. Two important conclusions: 1) As velocity decreases, dynamic pressure becomes a smaller fraction of the total pressure 2) As vessel radius narrows, the dynamic component increases significantly and as a result lateral pressure decreases.

How does coronary circulation protect papillary muscles against ischemia

The redundancy of the coronary distribution to the papillary muscles protects against papillary muscle failure resulting from ischemic heart disease by supplying each papillary muscle from two different coronary arteries. 1. The posterior papillary muscle is supplied form the RCA and the LCX arteries. 2. The anterior papillary muscle is supplied form the LAD and the LCX arteries.

High Pressure baroreceptors

The sensor component of the negative feedback loop consists of a set of mechanoreceptors located at strategic high-pressure sites : Carotid sinus and Aortic arch 1. Stretching of the distensible vessel walls at either site leads to reflex vasodilation and bradycardia (decreased TPR and HR = decreased MAP)

Exercise induced hyperthermia

The steady-state core temp during exercise is not "regulated" at the elevated level* 1. Exercise-induced hyperthermia is due to an initial imbalance between rates of heat production & dissipation

Sympathetic Nervous systems role in heat regulation

The sympathetic nervous system (SNS) supplying the skin vasculature is inhibited (less vasoconstriction=vasodilation + active vasodilation) when the body temperature rises, and activated (more vasoconstriction) when the body temperature falls.

Capillary colloid osmotic pressure

The total osmotic pressure is due to both salts (1/3) and proteins (2/3) and it exerts a force that results in fluid ABSORPTION 1. About 2/3 of the colloid osmotic pressure is due to proteins—albumin, globulins, and fibrinogen. 2. The combined effects of the plasma proteins and the slight excess salt in the plasma together make the colloid osmotic pressure of the plasma about 25 mm Hg.

Sheer stress and atherosclerosis

There is a non uniform distribution of atherosclerotic disease in the body and only occurs at certain points on the arterial tree. 1. Sheer stress is involved in endothelial cell signaling and development of atherosclerosis.

three ways resistance influence perfuscion

Three variables contribute to the resistance in the coronary vessels: R1: epicardial conduit artery resistance R2: arterioles and resistance arteries (metabolic) R3: compressive resistance (mechanical)

Nitroglycerine

Used for acute and chronic Angina Administration: 1-Sublingual (spray or tablet) 2-Transdermal (patch) 3-Intravenous Relieves symptoms of angina through nitric oxide mediated dilation of vascular smooth muscle of veins and at higher doses arteries. While the mechanism of action for nitroglycerine and other drugs in the nitrate family (EX: Glyceryl trinitrate, isosorbide dinitrate, and isosorbide mononitrate) is the production of nitric oxide and dilation of vascular smooth muscle, during ischemia, the coronaries would be maximally dilated as a result of the local metabolic conditions so Nitrates cannot further dilate the coronaries in the ischemic zone. Nitrates effect on myocardial ischemia is largely produced by reduction of preload to the heart (through dilation of the venous system and a reduction of blood return to the right atrium) which reduces myocardial oxygen demand to match the reduced supply.

Pressure and stress in stenosis

Whenever blood velocity increases, a greater proportion of the blood pressure is converted from lateral into dynamic pressure. Thus lateral pressure decreases while dynamic pressure increases. 1. In turn, turbulence and flow separation can occur leading to changes in sheer stress and strain. If Pressure Lateral decreases below the external pressure, the artery will collapse and flow stops momentarily, whereupon the energy is reconverted to lateral pressure, and the artery opens again. This oscillation of pressure may produce a flutter, which could result in rupture of a plaque and the formation of emboli. 2. Heart has to work HARDER to push turbulent flow

Heat Exhaustion

a common heat disorder due to a failure in CARDIOVASCULAR HOMEOSTASIS in a hot environment. There is a decrease in circulating blood volume caused by skin vasodilation and a sweating-induced decrease in central venous pressure (CVP). In the upright person, decreased CVP can allow blood to pool in the limbs, causing syncope (fainting). Collapse may occur during rest or exercise and be preceded by weakness, confusion, ataxia, anxiety, vertigo, headache, nausea or vomiting. The patient typically has dilated pupils and sweats profusely. Rest in a cool environment plus fluid/electrolyte replacement (oral or iv, as indicated by severity). Core temperature may be normal or only mildly elevated. Heat exhaustion can lead to heatstroke.

Interstitial osmotic pressure

a force of 3 mm Hg that favors fluid filtration. - Small additions of interstitial fluid raise Pif, thus opposing further filtration (low compliance system). However, with further additions some tissues such as loose subcutaneous tissue interstitium can accommodate large volume of edematous fluid without much rise in pressure (high compliance system).

Malignant Hyperthermia

a massive increase in metabolic rate, oxygen consumption, and heat production in skeletal muscle that can be lethal. A majority of afflicted individuals have gene mutations in the ryanodine receptor which disrupt calcium homeostasis in skeletal muscles. May be triggered by inhalation anesthetics and some depolarizing muscle relaxants (e.g., succinylcholine). Treatment involves discontinuation of triggering agent, use of ryanodine receptor antagonists (e.g., dantroline), and cooling of the body.

Fåhraeus-Lindqvist effect***

an effect where the viscosity of a fluid, in this case blood, changes with the diameter of the tube it travels through; in particular there's a decrease of viscosity as the tube's diameter decreases (arterioles, capillaries, and venules). This is because erythrocytes move over the center of the vessel, leaving plasma at the wall of the vessel a phenomena called axial streaming --> The result is a lower hematocrit in the smaller vessels, and a consequent reduction of blood viscosity in tubes having small diameters

Describe what microcirculation is

circuit extends from an arteriole to a venule. Arterioles are surrounded by a single layer of vascular smooth muscle cells; venules are surrounded by a discontinuous layer of vascular smooth muscle cells. -- metarterioles are not present in all tissues; when present, they may provide a shunt that bypasses the capillary network. -- precapillary sphincters control local flow within the capillary network; they are not innervated but are responsive to local conditions of oxygen, carbon dioxide, and acidity, in particular dilating in response to hypoxia.

Frost Bite

exposure to extremely low temperatures causes freezing of surface areas, called frostbite. The most vulnerable areas are the earlobes, and digits of the hands and feet. Permanent necrotic damage occurs when extensive ice crystals form in the cells of the skin and subcutaneous areas. Gangrene often follows thawing, and frostbitten areas must be surgically removed. Sudden cold-induced vasodilation is a final protective response-it occurs near freezing temperatures when smooth muscle in the vascular wall becomes paralyzed by the cold itself. This response is better developed in lower animals.

Preoptic area of hypothalamus

heated in experimental subjects, heat sensitive neurons/receptors in the hypothalamus are activated, the skin sweats profusely and the skin vessels vasodilate.

Peripheral Chemoreceptors

located in the carotid and aortic bodies, are in close contact with arterial blood. When arterial pressure falls below a critical level, the receptors become stimulated because diminished blood flow causes decreased oxygen, and excess buildup of carbon dioxide and hydrogen ions that are not removed by the slowly flowing blood. Signals transmitted from the chemoreceptors, along with the baroreceptor fibers, pass through Hering's nerves and the vagus nerves into the vasomotor center to elevate the arterial pressure back toward normal. However, the chemoreceptor reflex is not a powerful arterial pressure controller until the arterial pressure falls below 80 mm Hg (e.g., hemorrhage). Thus, it is at the lower pressures that this reflex becomes important to help prevent further decreases in arterial pressure.

How is the baroreceptor system initiated

stretch receptors, called baroreceptors, located in the walls of several large systemic arteries (in particular the carotid sinus and aortic arch). A rise in arterial pressure stretches the baroreceptors and causes them to transmit more action potentials to the CNS medullary control centers (NTS). 1. Carotid Baroreceptors: Located in the carotid sinus and transmit through small Herings nerves to CN IX (gloss) then to NTS 2. Aortic Baroreceptors: Transmitted via the vagus nerve (X) to the NTS in medulla

Baroreceptor adaption

the baroreceptor reflex ADAPTS to long-term changes in mean arterial pressure. For example, in hypertension, the set point is increased so the curve is parallel and shifted to the right.

Lymphatic Vessels

• During the expansion phase, hydrostatic pressure in the intersitium exceeds the initial lymph causing microvalves to open and fluid to enter • During compression phase, hydrostatic pressure inside the intial lymph rises, clsing the valves and opening valves downstream -> movement. • Initial lymphatics similar to capillaries but with primary one-way lymph valves • Large collecting lymphatics drain into right and left subclavian veins • Lymph flow is 2-4 L/day

Coronary blood flow

1. .225 L and up to 1 LPM during exercise and uses up 5% of CO 2. The Left Circumflex Artery supplies the free wall of the LV between the anterior and posterior papillary muscle. 3. The Left Anterior Descending Artery supplies the free wall of the LV, the anterior 2/3 of the ventricular septum and a small portion of the free wall of the RV 4. The Right Coronary Artery supplies the free wall of the RV, the posterior 1/3 of the interventricular septum and the posterior wall of the LV to the posterior papillary muscle --> LV served by all 3 coronary arteries and arteries need to travel through the thickness of the muscle

The effect of constriction and dilation on capillary hydrostatic pressure

1. Arterial dilation results in a decrease in the resistance of the arterial and the pressure drop upon the arterial is less (high pressure)= increase in hydrostatic pressure in capillaries and FILTRATION -> same as venous constriction 2. Arterial constriction leads to a increase in arterial resistance which causes a drop in pressure which ultimately decreases hydrostatic pressure in the capillaries AND MORE ABSORPTION --> Sam as venous dilation

How is blood pressure in a arteriole affected by dilation and constriction

1. Arteriole constriction leads to a larger blood pressure drop 2. Arteriole dilation leads to a smaller blood pressure drop --> Governed poiussons rules of resistance

Viscosity changes with hematocrit

1. At low hematocrits, viscosity increases because of stickiness of RBCs 2. At higher hematocrits, viscosity increases because of cell deformation

Two ways flow rates are not described as newtonian?

1. At lower flow rates, blood behaves anomalous caused by increased viscosity. --> At low flow rates blood appears to have a higher resistance than at faster flow rates due to formation of Rouleaux. As blood flow increases, Rouleaux tend to break up, thereby decreasing the viscosity and the resistance, thus contributing to anomalous viscosity 2. Polycethemia: When HCT increases from 40% to 60%, as occurs in polycythemia, blood viscosity doubles. Therefore, the resistance to the flow of blood also doubles, and the heart must work harder to maintain normal cardiac output. Nearly one-half of patients with polycythemia develop hypertension

When is autoregulation impaired

1. Autoregulation is impaired in presence of 2. Critical fall in aortic pressure (shock) 3. Chronic hypertension and LV hypertrophy 4. Critical stenosis of coronary arteries

How do baroreceptors react in response to increased MAP

1. Baroreceptors in the carotid sinus and aortic arch are the branched terminals of myelinated and unmyelinated sensory nerve fibers, intermeshed within the elastic layers. They are sensitive to stretch. 2. An increase in transmural pressure difference enlarges the vessel, deforming the receptors, and increasing firing rate of the baroreceptor's sensory nerve (shown in figure). Thus, the signal is frequency-modulated. The response is a graded response whose amplitude is proportional to the degree of stretch

Principles of coronary autoregulation

1. Basal blood flow remains fairly constant despite fluctuations in coronary artery pressure. 2. Given that the myocardium extracts 70% of the oxygen supplied to it at rest, increases in MVO2 increases necessitate an increase in blood flow. Therefore the coronary vessels dialate to increase blood flow, and therefore oxygen delivery, as MVO2 increases

Left sided Coronary flow changes throughout the cardiac cycle

1. Because of the effect of extravascular compression on the coronary arteries, systolic flow is markedly impaired in the left coronary artery such that maximum flow occurs in the LCA during early diastole. In the right coronary artery, the force of external compression is much less from the weaker right ventricle so coronary flow is fairly even during both diastole and systole. --> diastole is shorter when the heart rate is high, left ventricular coronary flow is reduced during tachycardia. --> Because no blood flow occurs during systole in the subendocardial portion of the left ventricle, this region is prone to ischemic damage and is the most common site of myocardial infarction.

How does blood flow change in response to changes in temperature

1. Blood flow from core to skin transfers heat.The rate can vary from near zero to ~30% of cardiac output 2. Skin and subcutaneous fat are heat insulators that help maintain core temperatures. *Note that fat is a poor conductor of heat (~1/3 as effective as other tissues). 3. Blood vessels beneath the skin are profuse and includes a continuous venous plexus supplied by inflow of blood from the skin capillaries. In the most exposed areas (hands, feet, ears) blood is supplied to the plexus directly from small arteries through muscular arteriovenous anastomosis. ---> when hot blood enters the venous plexus to dissipate heat via inhibition of alpha1 (vasoconstricts) 4. High rates of blood flow to skin is a highly efficient means to conduct heat from the core, whereas low rates of flow decrease heat conduction from the core.

4 pressures involved in capillary fluid balance

1. Capillary hydrostatic pressure (25 out) 2. Capillary osmotic pressure (25 in) 3. Interstitial Hydrostatic pressure (-2 out) 4. Interstitial Osmotic pressure (3 in) --> net of 5 mm Hg into the interstitiam

Cardiac function and myocardial oxygen consumption

1. Cardiac function (at rest) = Cardiac Output (CO) ~5 LPM 2. Cardiac reserve (response to exercise) - hearts ability to increase blood flow - 4x-7x increase with strenuous exercise 3. Myocardial Oxygen consumption (MVO2) - 6x-9x increase in oxygen demand - Consumes 70% of oxygen in blood

Compressive resistance summary (R3)

1. Changes in cardiac cycle change coronary perfusion - Shorter diastole = reduced coronary blood flow 2. Changes in ventricular pressures change coronary perfusion - Increased afterload = reduced coronary blood flow 3. Changes in muscle mass change coronary perfusion - Ventricular hypertrophy = reduced coronary flow*

How is skin a highly efficient controlled heat system

1. Changes in environmental temperatures result in ~8-fold increase in heat conductance compared to the fully vasoconstricted state. 2. At relatively low environmental temperatures, the arterioles and arteriovenous anastomosis that supply blood to the venous plexus of the skin are constricted. 3. As the environmental temperature increases, vasodilation subserves heat conductance through the skin.

Types of temperature feedback***

1. Changes in skin temperature reflect the environment, and the resulting reflexes prevent corresponding changes in body core temperature. Hence, these reflexes are termed "anticipatory" feedback. However, changes in core temperature, such as during exercise, result in responses involving "negative" feedback that serve to minimize the change in core temperature. 2. There are also both heat and cold-sensitive neurons in the hypothalamus, with proportionately more heat-sensitive neurons.

Chronic exposure to cold

1. Chronic exposure to cold involves adaptive responses that are poorly understood. Constriction of blood vessels in the skin and inhibition of sweat production help minimize heat loss. Basal metabolic rate may be increased by increased thyroid hormone secretion after exposure to extreme cold for several weeks. 2. The most common cause of lethal hypothermia is immersion in cold water for an extended period (e.g. heart fibrillation or standstill after 30min when the body temp has fallen to ~77ºF). A thick layer of insulating fat/blubber retards heat loss to the water and postpones /prevents hypothermia.

Three types of capillaries

1. Continuous capillaries are most common with interendothelial junctions 10 - 15 nm wide as in skeletal muscle. These junctions are absent in brain capillaries, which have narrow tight junctions that form the blood-brain barrier. 2. Fenestrated capillaries often surround exocrine glands or epithelial membranes such as the small intestine. Their endothelial cells have conduits that permit the flow of fluid and solutes across the capillary endothelial membrane. 3. Discontinuous capillaries are found in liver sinusoids. In addition to fenestrations, they have large gaps between their endothelial cells. --> Capillary density is high in tissues with high oxygen consumption such as the heart, and low in tissues with low oxygen consumption such as joints and cartilage

How does the heart receive more oxygen when it needs it

1. Coronary blood flow reserve - hearts ability to increase coronary flow - Only 3x-4x (Compare to consumption increase of 6-9X)

When does coronary perfusion occur and how does it affect blood flow during exercise?

1. Diastole: During diastole, aortic diastolic pressure is transmitted without resistance to the coronary ostia. 2. During exercise systolic blood pressure increases but diastolic is mostly unchanged. The coronary arteries receive the great majority of their blood flow during diastole (this will be explained in detail in the next objective). So ABP is not the source of increased coronary blood flow during exercise. 3. The increased metabolic need is met by increased coronary perfusion that is facilitated by a reduced resistance to blood flow. The change in resistance is regulated by local metabolic conditions.

How does the endothelium control vascular tone

1. Endothelium produces powerful vasodilators - EDRF endothelium derived relaxing factor - NO - Prostacyclin - EDHF endothelium derived hyperpolarizing factor 2. Powerful vasoconstrictors - Endothelin-1 3. Endothelium can be damaged by atherosclerosis and cardiac risk factors - Its dysfunction leads to imbalance of coronary flow, pathogenesis of myocardial ischemia and is a central factor in evolution of atherosclerosis and thrombosis

Pyrogens

1. Fever is an increase in temperature set point and core temperature, and is usually due to a pathological process such as infection (e.g., viruses, bacteria, endotoxins). 2. When the set point is raised, the mechanisms for raising body temperature are engaged, thereby enhancing heat conservation and heat production. 3. The hypothalamus has a fenestrated capillary endothelium that allows endogenous pyrogens (e.g., cytokines such as interleukins and TNF) to cross the blood-brain-barrier and act to increase the temperature set-point. 4. Endogenous pyrogens are sensed by hypothalamic control neurons, possibly via local release of prostaglandins. 5. Other fever-producing conditions include degenerating body tissues, hypothalamic brain lesions, tumors that compress the hypothalamus, and thyroid storm. 6. Aspirin and acetaminophen (antipyretics) inhibit prostaglandin synthesis and reduce fever, and also attenuate muscle and joint pain that often accompany fever. 7. fever may be beneficial during an infection bc immune cells may operate optimally at the higher temp

How does our body sense the temperature

1. Free nerve endings functioning as thermal sensors are located over the skin surface and in the hypothalamus. These nerves respond to changes in local temperature by altering their frequency of firing action potentials. They anticipate changes in core temp. 2. The skin has anatomically distinct receptors for warmth and cold, with 10-fold more cold receptors in many parts of the skin. Together with distinct deep body receptors (spinal cord, abdominal viscera, great veins) sensitive primarily to cold in the body core, THEY PREVENT HYPOTHERMIA. They project to a control center in the hypothalamus. ---> ANTICIPATORY CHANGES 3. The firing rate of the cold and warmth receptor fibers are equal at a skin temperature of ~37ºC. 4. Up to 44 - 46ºC, the firing rate of the warmth receptor fibers increases. As the temperature decreases below the set point of 37ºC, the firing rate of the cold receptor fibers increases.

The effects on gravity on blood pressure

1. Gravity affects the lateral (or transmural) pressure through a gravitational pressure term, which either adds to or subtracts from the pressure generated by the heart. This gravitational pressure will exist whether or not the heart is beating. Thus, gravity affects the measurement of blood pressure, which should be taken at the level of the heart. 2. Gravity does not affect the flow of blood in a circuit of distensible vessels because gravitational pressure in the arteries is exactly counter-balanced by the same gravitational pressure at the same level in the corresponding veins. While gravity does not affect the driving pressure on the blood, it does affect the distribution of blood throughout the system of distensible vessels and, therefore, it affects the transmural pressure

At what three major points is MAP monitored

1. High pressure arterial baroreceptors (Aortic,coratid) 2. Renal juxtaglomerular apparatus 3. Low presure baroreceptors

2 terms that describe the human temperature regulation

1. Humans (and all mammals) are endotherms; they generate their own body heat, principally through metabolism, an inefficient process. 2. Humans are also homeotherms - they maintain their core body temperature within a narrow range (~0.6ºC/1.0ºF) despite large fluctuations in the environment. Average core temp is 37ºC/98.6ºF, with oral being slightly lower (~1ºF) than rectal readings. However, there is a normal range around this average.

When is the hypothalamus regulation of temperature compromised

1. Hypothalamic regulation of temperature is compromised below ~94ºF/34.4ºC and lost below ~85ºF/29.4ºC. 2. Cellular heat production is decreased ~2-fold for every 10ºF decrease in body temperature. Sleepiness (and later coma) also depress CNS responsiveness 3. Cardiac ―standstill or fibrillation is a threat at low temperatures (e.g. death can occur after 20-30 min exposure to ice water when core temperature falls to ~77ºF/25ºC) 4. Maintenance of a stable body temperature involves negative feedback control with a very high gain (~25-30)

Interstitial fluid hydrostatic pressure

1. In loose tissues like the lungs and subcutaneous tissue, Interstitial fluid hydrostatic pressure is usually -2 mm HG exerting a force that drives filtration 2. In rigid enclosed systems (bone marrow,brain) the Interstitial fluid hydrostatic pressure is usually 1-3 resulting in a force that drives absorption

Feedback mechanisms of temperature regulation

1. Increased body temperature engages skin vasodilation, sweating, and decreased heat production to reduce body heat. 2. Decreased body temperature engages skin vasoconstriction, piloerection (important in lower animals, not humans), and thermogenesis/heat production (shivering, sympathetic/chemical excitation, thyroid hormone production). Curling up reduces the surface area of the skin available for heat loss. Sympathetic/chemical excitation involving epinephrine and norepinephrine may be relevant in infants. ---> Efferent sympathetic nerves are activated to decrease heat loss and increase heat production. 3. Effect of hypothalamic temperature on evaporative heat loss from the body and on heat production caused primarily by muscle activity and shivering.

Ventricular Hypertrophy

1. Increased muscle mass = increased oxygen demand Coronary flow reserve is reduced by ventricular hypertrophy: Stenosis of the aortic valve will force the LV to work harder to pump blood across a smaller orifice. As a result, the left ventricular tissue will hypertrophy and the increased muscle mass will require greater oxygen supply. Additionally, the coronary flow reserve is reduced due to a change in the ratio of blood supply to mass of tissue. Hypertrophic cardiomyopathy is an other pathology which may increase left ventricular muscle mass with much the same effect on blood supply.

The goal of temperature regulation

1. Keep the internal body temperatureremains stable despite wide changes in atmospheric temperature 2. Maintenance of internal body temperature is one of the most important regulated variables in humans because enzymes, cells, and organs function optimally in a narrow range of temperatures, whereas environmental temperatures can vary widely

Turbulent vs Laminar Flow

1. Laminar flow, where flow is proportional to ΔP, breaks down when velocity reaches a critical point. Above this velocity, the flow depends less strongly on pressure gradient, rather √ (ΔP). This is because the effective resistance increases. 2. This region is called turbulent (greater than 3000) flow which causes significant losses of kinetic energy. In turbulent flow, Q is proportional to the √ ΔP. For the same ΔP, there is less flow when flow is turbulent than when laminar. --> High velocity = turbulent and High Viscosity = Laminar (less than 2000)

Properties of the interstitium

1. Made up of both liquids and solids as well as a small amount of free water 2. The hydrostatic pressure of interstitial fluid is sensitive to additional fluids in the interstitium because it can result in solid phase collagen and proteoglycan gel. Especially true in loose subcutaneous tissue which can accomodate edema fluid

Why are net shifts in fluids between the interstitiam and capillaries important***

1. Maintain blood volume 2. Interstitial absorption 3. Tissue Edema formation 4. Saliva, sweat and urine production

Autoregulation of arterioles and resistance arteries (R2)

1. Mechanism of autoregulation 2. Metabolic control: - Adenosine diffuses out of cell and dilates VSM - To a lesser extent, other metabolic products, (CO2 and H+ and others) contribute to dilation - Endothelium responds to sheer forces with production of Nitric Oxide (NO) 3. Myogenic control: arteriolar VSM contracts with increased intraluminal pressure

The sounds of turbulent flow (not too important)

1. Murmurs are audible sounds due to vibrations in heart or vessel walls. They do not usually occur under resting conditions. "Bruit" is another term used. 2. "Innocent" systolic murmurs occur when cardiac output increases during exercise, causing turbulent aortic flow during systole. 3. Korotkoff sounds of sphygmomanometry (blood pressure measurement with inflatable cuff) are also examples of the sound of turbulent flow. 4. Aortic or mitral stenosis (constriction of vessels) may also cause murmurs. Aortic regurgitation (back flow into the heart caused by aortic valve defect) generates turbulence and characteristic sounds. 5. The arterial wall may be damaged by turbulence, and the development of thrombi (blood clots) is more likely in turbulent flow. Also, the resistance to flow is increased with a consequent increased work of the heart.

Epicardial conduit artery resistance (R1)

1. Not a factor in healthy arteries 2. Pathologies can make epicardial resistance significant - CAD (coronary artery diesease) - Coronary Spazm --> sympathetic stimulation of the Alpha receptors on the VSM of the epicardial conduit arteries may be responsible for acute coronary syndrome in some individuals

Major mechanisms of heat loss and gain

1. Radiation transfers heat as electromagnetic waves between objects that are not in contact— the rate of temperature transfer is proportional to the temperature difference between the body surface and the environment. At rest indoors ~60% of body heat is lost by radiation. 2. Conduction is intermolecular thermal heat transfer between solid objects in direct contact. Normally, heat exchange by conduction is minimal in a person wearing shoes and clothing. 3. Convection is loss or gain of heat by movement of air or water over the body. Because heat rises, air carries heat away from the body by convection. A body immersed in water exchanges most heat by convection. 4. Evaporation of water from the skin and respiratory tract can carry large amounts of heat generated by the body because of the amount of heat required to transform water from liquid to gas phase . Air circulation improves the rate of evaporation of sweat from skin, and high humidity makes it less effective. ---> Of these heat removal mechanisms, evaporative losses from the surface of the skin by sweating normally dissipate nearly all of the heat produced during exercise. However, inadequate heat loss upon excessive heat exposure can lead to heat exhaustion, in which the body core temperature rises to 39ºC (102.2°F), or in severe cases to heat stroke when the core temperature reaches 41ºC (105.8°F) or higher.

Effect of increasing the set point on body temperature

1. Raising the set point to 103ºF triggers an error signal that the blood temp is now less than the set point. The hypothalamus thinks' the body is too cold. The person develops chills, and effectors that elevate body temp are activated. Vasoconstriction conserves heat by reducing blood flow to the skin; the skin feels cold; shivering generates heat; curling up conserves heat. 2.Note that body temp can take several hours to reach the new set point 3. When the body temp reaches the higher set point, this higher temp is maintained as the new normal' as long as the pyrogenic substance is present. 4. When the pyrogen is removed, the set point returns to normal and the lower set point activates mechanisms to dissipate heat leading to hot skin, intense sweating, and vasodilation to counteract the higher body temp

Baroreceptor changes in sensitivity

1. The carotid sinus baroreceptors (which transmit impulses in Hering's nerves) are not stimulated by pressures between 0 and 50 to 60 mm Hg. Above these levels, they respond progressively more rapidly and reach a maximum at about 180 mm Hg 2. Aortic baroreceptors are similar to those of the carotid receptors except that they operate, in general, at arterial pressure levels about 30 mm Hg higher (higher threshold means less sensitive) --> In the normal operating range of arterial pressure (~100 mm Hg) even a slight change in pressure causes a strong change in the baroreflex signal to readjust arterial pressure back toward normal

Epicardial coronary arteries vs Arterioles

1. The epicardial coronary arteries act as conductance or conduit vessels --> No appreciable resistance to blood flow with no detectable pressure drop along the length of epicardial arteries 2. The arterioles are 10 - 200 microns diameter --> Act as resistance vessels --> Large pressure drop --> The major variable controlling blood flow is change in coronary vascular resistance.

What does the loss of baroreceptors result in

1. The loss of MINUTE TO MINUTE response to MAP --> increased variability in MAP that results in a broader range of pressures instead of centered around the normal range

Adenosine

1. The most potent coronary vasodilator 2. Released from cardiac myocytes --> when the rate of ATP hydrolysis exceeds its synthesis during ischemia or increased myocardial metabolic demand 3. Extremely short half life <10 secs 4. ENDOTHELIUM INDEPENDENT 5. Primarily dilates vessels less than 100 µm 6. No direct effect on larger arteries 7. Increased production with imbalance of O2 supply demand --> Rise in interstitial adenosine levels parallels coronary flow

Greatest risk of ischemia is in which layer of tissue

1. There is a greater risk of ischemia in the subendocardial tissue: 2. Because no blood flow occurs during systole in the subendocardial portion of the left ventricle, this region is prone to ischemic damage and is the most common site of myocardial infarction.

What does core temperature vary with

1. Time of day - being lowest between 3 and 6am, and highest between 3 and 6pm. 2. Stage of menstrual cycle - increasing ~1ºC during the post-ovulatory phase (progesterone). 3. Level of activity - increasing with exercise and emotional states. 4. Age - being higher in active children and lower in aged adults. --> When the environmental temp decreases, the body generates and conserves heat. When the environmental temp increases, the body reduces heat production and dissipates heat.

What maintains the vasomotor tone

1. Under normal conditions, the vasoconstrictor area of the vasomotor center transmits signals continuously to the SYMPATHETIC vasoconstrictor nerve fibers over the entire body, causing slow firing of these fibers -> vasomotor tone 2. The loss of these fibers leads to hypotension. normal vasoconstriction can be restored with NorEPI

Eccrine sweat glands

1. When exposed to a hot environment, thermal sensors in the skin increase blood flow to the skin and also sweat production, increasing heat loss. 2. If core temperature increases, sweat production can increase profusely to greatly increase heat loss by evaporation (~1L/hr in an unacclimatized person) 3. If evaporation cannot occur or is difficult because the air is saturated with water vapor, sweating is not an effective means of heat loss. 4. Acclimatization to hot weather (1-6 weeks) involves a change in the sweat glands to increase sweating capability (up to 2-3L/hr). 5. With acclimatization, there is also a decrease in the loss of NaCl in the sweat to conserve body salt. This is mainly due to aldosterone secretion from the adrenal cortex. 6. Sweat gland innervated by an acetylcholine-secreting sympathetic nerve.

Where is most of the body's heat generated?

1. deep organs (liver, brain, heart, active skeletal muscle) by cellular metabolism, which is inherently inefficient. Rate of heat production ~ metabolic rate. 2. The rate of heat loss is largely determined by how rapidly the heat is: - carried from the core to the skin; - transferred from the skin to the surroundings. 3. Most heat is transferred from the core to the skin by CONVECTION in the blood, where it is then lost to the air & surroundings. 4. The sympathetic nervous system regulates blood flow to the skin and sweating.

The 4 non ideal rheological effects***

1. formation of Rouleaux: chain-like aggregates of red blood cells which form at low flow rates = Increase in viscosity 2. plasma skimming: the tendency of the cell-free plasma to be skimmed off at a branch point of the microcirculation --> increased viscosity 3. Fåhraeus-Lindqvist effect: tube diameters less than 0.3 mm (arterioles, capillaries, and venules), the apparent viscosity of blood decreases caused by axial streaming. 4. cellular deformity: the ability of the cell membrane to bend, also affects flow in the microcirculation --> sickle cell anemia

Examples of how structure and function of microcirculation differ in different tissue

1. nutritional source and waste removal in most vascular beds 2. filtration in renal glomeruli 3. thermoregulation in the skin

Other pharmacological vasodialators

Angiotensin Converting Enzyme (ACE) Inhibitors: Interacting with the renin angiotensin system and lowering blood volume / pressure (reducing preload and afterload) and reducing myocardial oxygen demand Calcium Chanel Blockers: Blocking calcium channels and reducing blood pressure (reduce afterload) and force of myocardial contraction both of which reduce myocardial oxygen demand Beta blockers : Block Sympathetic beta-adrenergic receptors reducing sympathetic enhancement of heart rate and cardiac metabolism (reducing heart rate and force of contraction and therefore myocardial oxygen demand)

Most important mechanism for SHORT TERM arterial pressure regulation

Arterial Baroreceptor reflex is critical for adequate blood flow to vital organs 1. Acute regulation of arterial pressure is primarily mediated by the high-pressure baroreceptor reflex, with contributions by cardiopulmonary receptors (aka low-pressure baroreceptors) and chemoreceptors (primarily concerned with respiratory control).

Effects of coronary stenosis on coronary flow

As a coronary stenosis grows it will reduce the conronary reserve. Stenosis greater than 70% may reduce coronary reserve and limit the patients ability to exercise without symptoms. Stenosis greater than 90% may reduce coronary flow at rest. These patients may have symptoms at rest. The normal autoregulatory process will maximally dilate the arterial system distal to a critical stenosis. If ischemia persists after maximal dilation, then MVO2 reduction is the only solution to reduce the ischemia.

Heat Stroke

As core temp approaches ~41°C, confusion, then loss of consciousness and convulsions occur . Cell/tissue damage occurs throughout the body. The 2 forms of heatstroke are: classical, whereby environmental stress overwhelms an impaired thermoregulatory system; the person stops sweating (most patients have preexisting chronic disease); and exertional, where the primary factor is high metabolic heat production. Patients are generally young and fit (e.g., soldiers, athletes). If core temp rises over 41°C, neural death and organ system failure may result . The upper limit of temperature that one can stand depends on whether air is wet or dry. If air is dry, convective currents promote rapid evaporative heat loss and the person can withstand several hrs of high temperatures (~130ºF). In very humid air (or water), environmental temperatures above 94ºF can elevate core temperature. With heavy exercise, heatstroke can occur at lower temperatures. Treatment requires rapid lowering of core body temperature (immersion in cold water), vigorous hydration, airway maintenance, avoidance of aspiration.

Coronary Artery Disease (CAD)

Coronary artery disease is the development of coronary stenosis from atherosclerotic plaques that invade the lumen of the artery. Over time these plaques may become the most significant resistance to flow in that arteries distribution. Once the stenosis causes a reduced blood flow, the the supply of oxygen will not meet the demand and the myocardium downstream of the stenosis will: 1-be hypoxic and will suffer reduced function and may die 2-maximally dilate the arterial system in the ischemic area, At this point no further autoregulation is possible and perfusion is proportional to the blood pressure.

Sheer stress on blood vessels

Created by flowing blood on the endothelial wall directed along the long axis of the vessel. Sheer stress on the vessel wall is directly proportional to viscosity and flow rate, and inversely proportional to the cube of the vessel radius. Sheer stress is measured in units of pressure

Diffusion coefficient

D increases with increasing temperature and is inversely proportional to the square root of the molecular weight of a solute. Thus, small solutes diffuse more rapidly than larger solutes

Edema

EDEMA: Excess salt and water in interstitial space • Caused by renal, cardiac, lung and hepatic disease. Some examples are: • Left heart failure (e.g. congestive heart failure) leads to pulmonary edema • Pulmonary hypertension also causes pulmonary edema • Right heart failure leads to edema in lower extremities and abdominal viscera • Fluid from the hepatic and intestinal capillaries may move from the interstitium into the peritoneal cavity, a condition called ascites • Plasma albumin is synthesized in the liver and secreted into the plasma; thus, liver disease leads to hypoalbuminemia and peripheral edema • SIADH (inappropriate secretion of antidiuretic hormone by certain lung tumors) leads to peripheral edema • Lymphatic blockage: malignant neoplasms may cause local edema upstream of the sites of blockage

The affects of sheer stress on the endothelial

Endothelial cells will detach at stress levels >0.3 mm Hg. Changes in shear stress and cyclic strain-stretch produces significant changes on endothelial cells, including altering gene expression and signaling pathways. Shear stress has benefits by promoting adaptive dilatation or structural remodeling of the artery wall via endothelium. CAUSES DAMAGE TO VESSELS

Right sided Coronary flow changes throughout the cardiac cycle

Flow in the right ventricle and atria is not appreciably reduced during systole, because aortic pressure is much higher.

Hypothermia

Hypothermia (core temp <35°C or 95°F) is common after immersion in cold water (water transfers heat ~25x faster than air). In this case, heat production cannot increase enough to compensate for heat loss. Hypothermia leads to drowsiness, slurred speech, bradycardia, and hypoventilation associated with cold-induced decreases in metabolic rate. Severe hypothermia can lead to coma, hypotension, and fatal cardiac arrhythmias (ventricular fibrillation).

Changes to in total peripheral resistance and blood flow (in exercise and Hypertension)

In excercise: The Cardiac Output rises while blood pressure stays the same which results in a decrease in TPR In hypertension: Blood Pressure increases while cardiac out stays the same which results in an increased TPR --> do questions on Hemodynamic lecture slide 7

Central Chemoreceptors

In the medulla are sensitive to decreases in brain pH (reflecting an increase in arterial PCO2) and cause an increase in SNS output.

Medical Management for MI

Lifestyle changes Diet , exercise, reduce stress, weight loss, quit smoking Pharmacologic therapy Reduce MVO2

Local intrinsic mechanisms vs Neural hormonal vascular regulation

Local intrinsic mechanisms are primarily aimed at regulating regional blood flow while neuronal (hormonal) are often aimed at regulating MAP to maintain adequate tissue perfusion MAP = SV x HR x TPR

Microcirculation changes during excercies

Only 20% of muscle capillaries are perfused at rest; during exercise, arteriolar vasodilation and precapillary sphincter relaxation increase muscle blood flow in proportion to the increased consumption of oxygen

Properties of capillary hydrostatic pressure

Pc varies among different tissues. A higher Pc favors FILTRATION. In renal glomeruli, Pc is about 50 mm Hg, large enough to enable glomerular filtration. In pulmonary capillaries, Pc is only 5 -15 mm Hg, thereby preventing filtration and pulmonary edema. Pc like other blood pressures, is influenced by gravity. --> drops from arteries --> veins

What influences the delivery of blood through the coronary arteries?

Q = ∆P/R 1. P = ABP (particularly diastolic pressure) 2. R = Resistance (Mechanical, Metabolic, Pathologic)

Total Peripheral Resistance and Cardiac Output

Q = ∆P/R ≈ CO = ∆P(pressure at L ventricle)/TPR

Fick's Law of Diffusion

Rate = A/T x D x (p1-p2) - the number of moles that diffuse across the membrane during an interval of time, in a direction perpendicular to the membrane, is directly proportional to the area, A, of the membrane, and to the concentration gradient (c2 - c1)/l (moles/cm3/cm) across the membrane, the constant of proportionality being the diffusion coefficient D (cm2 /sec) - Inversely proportional to thickness

Starling forces along a capillary***

Remember that Pc falls along the length of the capillary. • At the arteriolar end of a capillary, the hydrostatic pressure driving filtration exceeds the colloid osmotic pressure driving absorption; hence the net result is filtration (20 L/day) • Fluid leaving the capillary at the proximal end contains plasma protein, resulting in a gradual increase in interstitial colloid osmotic pressure along the length of the capillary bed. The decreased capillary hydrostatic pressure of the plasma dominates, resulting in absorption at the venular end of the capillaries (16-18 L/day) --> net filtration of 2-4 liters a day.

Peripheral circulation flow***

Since the arterioles have the largest resistance compared to other vessels, the overall resistance of any organ is determined by Rarterioles which is in turn controlled by the arteriolar radius. Thus, contraction or relaxation of the smooth muscles in the arteriolar wall is a major control point in cardiovascular physiology.

Cardiovascular transport rates and transcapillary efflux rate***

Substance carried between organs via CONVECTIVE transport Cardiovascular Transport Rate: Flow rate (Q) x Concentration [X] --> only 2 ways to change transport rate are by increasing Q or [X] Transcapillary Efflux Rate: Flow Rate (Q) x [Xart - Xvein]

Sudden Cardiac Deaths

Sudden coronary thrombosis may result any time the endothelial lining of the artery is damaged. Damage to the endothelial lining exposes the subendothelial matrix (and perhaps atherosclerotic plaque) which stimulates the coagulation cascade. Coronary artery atheroma increases the risk of endothelial damage. A slowly developing plaque can become a sudden occlusion if the endothelial cap ruptures. Coronary thrombus will acutely occlude the coronary artery. Depending on the volume of tissue downstream from the occlusion sudden death may result.