Physiology 7 Cardio 2

Summation of resistance: Parallel vs Series

Series: Rt = R1 + R2 + R3 + Rn Parallel: 1/Rt = 1/R1 + 1/R2 + 1/R3 + 1/Rn Adding similar-sized vessels in parallel reduces resistance

Peripheral vascular system veins and arteries.

Start with elastic artery -> muscular artery -> arteriole -> continuous capillary -> fenestrated capillary -> venule -> medium-sized vein -> Large vein.

Cardiac function measurements

Stroke Volume (SV): volume of blood ejected from heart each cycle. SV = EDV - ESV. Cardiac Output (CO): amount of blood ejected from heart each minute. CO = SV x HR Ejection Fraction (EF): Fraction of EDV that is ejected during systole. EF = (EDV-ESV)/EDV Pulse Pressure (PP): Pressure changes during cardiac cycle. PP = Systolic BP - Diastolic BP

Effects of increased afterload on SV?

Stroke volume goes down while ESV goes up (volume in left ventricle after contraction). On the next cardiac cycle- heart again fills but now with the extra blood left over from last cycle means increase in EDV on this subsequent cycle which means increase in preload and activating Frank-Starling Mechanism, increase in SV also on this subsequent cycle.

Mechanisms of inotropy (contractility)

*Regulate intracellular calcium, Inotropy has nothing to do with changing the length of the sarcomere* -Increasing Ca2+ influx - Increasing Ca2+ release from the SR - Increasing troponin sensitivity to Ca2+ More cross-bridges!

Factors that influence vascular compliance

*Sympathetic stimulation*- decreases compliance. - Important for regulation of venous pressure and cardiac preload. - Reduced aortic compliance with age or disease. Dotted line symbolizes sympathetic stimulation, for the same pressure there is a decrease in volume in vein due to venoconstriction (major effect in veins). Also, for the same pressure there is a decrease in volume in artery due to vasoconstriction (smaller effect than in veins).

In a given capillary the following set of conditions exists: Blood hydrostatic pressure = 12 mmHg Blood osmotic pressure = 28 mmHg Interstitial hydrostatic pressure = -3 mmHg Interstitial osmotic pressure = 1 mmHg What is the net filtration pressure? -18 mmHg -12 mmHg -14 mmHg +38 mmHg

(12 + 1) - (28 + -3) = 13 - 25 = -12 mmHg, re-absorption.

If B means increase and C means decrease, how would these factors influence sarcomere length (preload)?: Decrease total blood volume. Increased heart rate. Increased CVP Decreased ventricular compliance Venocontriction Active skeletal muscle pump Atrial fibrillation

(C is low side on black line, A is in the middle on black line, and B is at the top of black line. Decrease total blood volume. (Goes to C). Increased heart rate. (Goes to C) Increased CVP (Goes to B) Decreased ventricular compliance (Goes to C) Venocontriction (Goes to B) Active skeletal muscle pump (Goes to B) Atrial fibrillation (Goes to C)

Types of capillaries (3)

*Continuous*- Small pores, allow glucose and small molecules. *Tight* *Fenestrated*- Larger clefts, less selective - no protein. (Found in kidneys and small intestines, filtering. Have large pores in them) *Leaky* *Sinusoids*- Discontinuous endothelium, pass blood cells and protein. (found in liver or bone marrow. Has incomplete basement membranes, intracellular gaps). *Leakiest*

Venous return

*Venous Return*: the flow of blood back to the heart. Over time, venous return must equal cardiac output. This balance is largely achieved by the Frank-Starling mechanism. If venous return does not equal cardiac output then that means blood is backing up somewhere, either in periphery or lungs.

Venules (collection vessels)

- Collect blood from capillary bed - Low resistance

Veins (Capacitance vessels)

- Thin- walled (little smooth muscle) - Low pressure (0-2 mmHg) - High compliance - Blood reservoir (most blood stored here, Capacitance = storage). *Compliance* is the ability of a hollow organ (vessel) to distend and increase volume with increasing transmural pressure.

Capillaries (Exchange Vessels)

-Endothelium (one cell thick) and basement membrane. - Pores which allow for exchange of nutrients. - Areas with high metabolic requirements have extensive capillary networks (muscles, liver, kidneys, nervous system). - Areas with very low metabolic requirements lack capillaries. (cornea and lens of eye, nails, hair follices, cuticles, cartilage)

1. Given: Pc = 40, πi = 3, Pi = 2, and πc = 25, what is the net filtration rate? 2. Given: Pc = 10, πi = 3, Pi = 2, and πc = 25, what is the net filtration rate?

1. (40 + 3) - (2 + 25) = +16, filtration is favored. (arteriolar end) 2. (10 + 3) - (2+ 25) = -14, re-absorption is favored. (venous end)

What factors increase lymph flow (6)

1. Increase Pc 2. Decrease πc 3. Increase πi 4. Decrease Pi 5. Increase Capillary surface area 6. Increase Capillary permeability (histamine, burns) (Many of these factors are same as those that favor capillary filtration).

Stretching of cardiomyocytes results in?

1. Increased sensitivity of troponin for binding Ca2+. 2. Increased Ca2+ release from SR 3. Decreased spacing between thin/thick filaments More cross-bridges = more force

What 3 factors regulate Stroke Volume?

1. Preload (sarcomere length)- Initial stretch of the ventricles at the end of diastole. Is related to EDV (the amount of volume of blood in the ventricles at the end of diastole) Sometimes related to EDP. (EDV and EDP in the left ventricle). - Increase in preload causes increase in stroke volume. 2. Afterload- related to the pressure the ventricle must generate in order to eject blood into the aorta during systole (frequently related to aortic pressure) - Increase in afterload causes decrease in stroke volume. 3. Inotropy- "Contractility". alteration of the force of muscle contractions (Positive inotropes strengthen force of contraction) - Increase in contractility causes an increase in stroke volume.

Mechanisms to maintain venous return (4)

1. Regulate venous compliance (sympathetic nervous system): Increase in sympathetic nervous system = increase venoconstriction = decrease venous compliance = increases venous return. 2. Venous valves: Make sure that the blood goes one way back to the heart, defect in valves, like in vericose veins, causes blood to pool back and increases the size of the vein (that's why you can see them). Decrease venous return when not working. 3. Skeletal muscle pump: Contraction creates the pressure needed to open up the valve above it and allow the blood to move upwards (valve below stays closed). Increase in skeletal muscle pump = increase in venous pressure = increase in venous return. 4. Respiratory pump: When breathing in, the diaphragm moves down and the chest expands lowering the pressure in the chest as a result. The new pressure difference between chest (lower) and rest of body pushes blood in the veins towards the heart. Decrease pressure in chest = increase in pressure gradient = increase in venous return.

What is the main contributor of capillary oncotic/osmotic pressure?

Albumin

Arteries vs veins

Arteries are thicker and have more smooth muscle, appear rounded. (vaso constriction/relaxation) Veins are thinner and have less smooth muscle, appear floppy. (veno constriction/relaxation)

Regulation of cardiac output

Cardiac output is increased by Heart Rate and Stroke Volume. Stroke volume: Increased by increase in contractility (Inotropy) and preload. Decreased by increase in afterload. (Afterload is the pressure against which the heart must work to eject blood during systole.)

Central blood volume

Blood volume = intrathoracic + Extrathoracic. Central (Intrathoracic) blood volume = blood in the right atrium/ventricle, pulmonary circulation, left atrium, superior vena cava and intrathoracic portions of the inferior vena cava. (Basically all the blood in the heart). Central Blood Volume can be increased or decreased by shifts in blood to and from the extrathoracic blood volume (veins in extremities and abdominal cavity) Veins are primary factors of central blood volume: Venoconstrict = decrease in venous compliance = Increase central venous pressure -> blood goes to the heart. Venodilation = Increase in venous compliance = Decrease in central venous pressure -> blood goes to veins in extremities and abdominal cavity.

Capillary fluid exchange

Bulk flow- filtration (reabsorption) of fluids and their solutes. Capillary to tissue is called filtration. Tissue to capillary called re-absorption. Filtration = Kf x NFP *NFP = (Pc + πi) - (Pi + πc)* Kf = capillary permeability/surface area NFP = net filtration pressure Starling forces = Hydrostatic pressure and Osmotic/oncotic pressure ------------------------------ *Hydrostatic pressure (P)* = *Pushing* pressure (exerted by water in the blood) due to volume from fluid. *Pc* = hydrostatic pressure in capillary = push fluid out of capillary and into tissue *Pi* = hydrostatic pressure in interstitium = push fluid out of tissues and into capillary. ------------------------------ *Oncotic/Osmotic pressure*= *Pulling* pressure, due to solutes. *πc* = Oncotic pressure in capillary (plasma proteins- albumin) = pull fluid into capillary and out of tissues. *πi* = Oncotic pressure in interstitium = pull fluid into tissue and out of capillary. ------------------------------ High hydrostatic capillary pressure and high oncotic interstitial pressure favors filtration (capillaries -> tissues) High hydrostatic interstitial pressure and high oncotic capillary pressure favors reabsorption (tissues -> capillaries)

How does an increase in preload cause a higher stroke volume?

By stretching the cardiomyocytes, you increase the amount of cross bridges and increase their calcium sensitivity and therefore are able to generate more tension and eject more blood from the heart.

Central venous pressure

Central venous pressure (CVP) = pressure in thoracic vena cava near the right atrium (reflects right atrial pressure) - Major determinant of filling pressure (preload) of right ventricle. This regulates stroke volume through Frank-Starling mechanism. ΔCVP = ΔV/Cv ΔV = change in volume of blood within thoracic veins Cv = compliance of the thoracic veins (C=ΔV/ΔP) Increase in Central Venous Pressure = Increase in EDV = Increase in SV.

Effects of decreased afterload on SV

Decrease in afterload causes increase in SV and decrease in ESV. On subsequent cycle there is a decrease in EDV and therefore preload and subsequently stroke volume.

Effects of decreased inotropy on SV

Decreased inotropy causes decrease in stroke volume and increase in ESV. Causes increased EDV on subsequent cycle.

Capillary transport

Diffusion of solutes: Lipid-soluble substances pass through the endothelial cells. (O2, CO2) Bulk flow (Pores, Intercellular clefts): Small water soluble substances pass through the pores (Na+, K+, glucose, amino acids) Vesicular transport (exocytosis, endocytosis, pinocytosis): Exchangeable proteins are moved across by vesicular transport. Plasma proteins generally cannot cross the capillary wall.

What is used to indicate preload?

EDV (end diastolic volume) and EDP (end diastolic pressure) in the left ventricle. The more the ventricle stretches, the higher the preload = the higher the stroke volume = the higher the cardiac output. Stretches to ideal overlap of actin and myosin.

Frank-Starling Law

Frank-Starling Law: the strength of the heart's systolic contraction is directly proportional to its diastolic expansion with the result that under normal physiological conditions the heart pumps out of the right atrium all the blood returned to it without letting any back up in the veins. - This results in numerous possible curves, depending on the inotropic state, preload, and afterload. Important mechanism by which the heart keeps the blood moving and not backing up. Decrease in venous return = decrease in EDV.

How blood pressure can be heard

If blood pressure is 120/80 then: When the cuff is over 120 mmHg: you can't hear anything because no blood flows through the vessel. Between 120 -80: blood flow through the vessel is turbulent whenever the blood pressure exceeds cuff pressure. Intermittent sounds heard as blood pressure fluctuates through cardiac cycle. Below 80: Blood flows through the vessel in smooth laminar fashion, no sound is heard. (listent to korotkoff sounds in brachial artery)

Factors affecting afterload.

Increase in *Systemic vascular resistance* causes increase in *aortic pressure* which causes an increase in *afterload.* Decrease in Aortic Compliance causes increase in *aortic pressure* which causes increase in *afterload.* (Both increase in systemic vascular resistance and decrease in aortic compliance causes increase in aortic pressure which increases afterload)

Effects of afterload/inotropy on Frank-Starling

Increase in Afterload: Decrease in SV. Increase in ESV. New curve down and to the right. Increase in Inotropy: Increase in SV. Decrease in ESV. New curve up and to the right. Increase in afterload or decrease in inotropy causes a subsequent increase in EDV which should activate Frank-Starling on next cardiac cycle to attempt to compensate. Moving up and to the left means either: Increase in Inotropy or decrease in Afterload. Moving down and to the right means either: Increase in Afterload or decrease in Inotropy

How does afterload affect length-tension relationship

Increase in afterload causes decrease in stroke volume, increase in ESV. (SV = EDV - ESV) Makes the line move up and to the left.

Effect of contractility on force-velocity curves

Increase in inotropy = increase in contractility. Can increase Fmax and Vmax (unlike preload)

Inotropy effects on Stoke Volume

Increase in inotropy causes the line to shift up and to the left. Increase in inotropy causes increase in SV and decrease in ESV. Causes decrease in EDV on subsequent cycle.

Factors regulating inotropy

Increase in sympathetic nervous system (norepinephrine) and increase in circulating catecholamines causes an increase in ionotropy. Decrease in parasympathetic nervous system (acetylcholine) causes increase in inotropy.

Factors that affect Central Venous pressure

Increase in venous blood volume or increased venous tone (decreased venous compliance) Increase venous blood volume and it increases on the line. Decrease in venous compliance (increased venous tone) and the line goes down and to the right.

Factors affecting preload.

Increase in ventricular compliance, atrial contractility, central venous pressure, thoracic venous blood volume, total blood volume, and venous return (respiration, muscle contraction, gravity) all increase ventricular filling (preload). Increase in heart rate or increase in venous compliance decreases Ventricular Filling (preload).

Factors affecting preload

Increases preload (ventricular filling)via increase in: Atrial contractility *Ventricular compliance (ventricles)* Central venous pressure -Thoracic venous blood volume - Total blood volume - Venous return -Respiration -Muscle contraction -Gravity Decreases preload (ventricular filling) via increase in: Heart rate *Venous compliance (Veins, venodilation decreases central venous pressure which decreases preload)

Effect of length (preload) on Force-Velocity curves

Increasing length increases the velocity with force is kept the same. Decrease afterload = increase in velocity Increase in preload = increase in velocity Increase in Inotropy = increase in velocity

Length-tension relationship: Cardiac

Increasing the sarcomere length (preload) generates higher tension. There is an optimal resting length for the heart.

Factors that influence venous return short term vs long term.

Long term = blood volume Short term = respiratory pump, skeletal muscle pump, sympathetic vasoconstrictor activity.

Lymphatic system

Lymphatics help recover excess fluid and protein loss and return it to the central circulation. Not everything that gets filtered gets reabsorbed. That which is not reabsorbed picked up by the lymphatic system and put back into the veins later on. Filtration = reabsorption + lymph flow.

Calculate the MAP, SV, CO, EF, and TPR given: Systolic pressure (aorta) = 124 mmHg Diastolic pressure (aorta) = 82 mmHg R-R interval = 800 msec LV EDV = 140 mL LV ESV = 70 mL Mean pulmonary artery pressure = 15 mmHg Right atrial pressure = 2 mmHg Left atrial pressure = 5 mmHg

MAP = 2/3 diastolic + 1/3 systolic = 96 SV = EDV - ESV = 70 CO = SV x HR (HR = 60/ r-r interval (.8) = 75) = 5,250 EF = (EDV - ESV)/ EDV = 50% TPR = MAP/CO = .018

Mean Arterial Pressure (MAP)

MAP = 2/3 diastolic pressure + 1/3 systolic pressure. Measures the average blood pressure in the arteries. Heart spends 2/3 of its time in diastole (filling up) and only 1/3 of its time in systole.

Net Filtration Pressure

NFP = (Pc + πi) - (Pi + πc) If (Pc + πi) > (Pi + πc): then positive number and filtration occurs (Capillaries -> tissues, seen at arterial end) If (Pc + πi) < (Pi + πc): then negative number and reabsorption occurs (Tissues -> capillaries, seen at venous end). Hydrostatic pressure drops along the length of the capillary, so hydrostatic pressure drops and explains why arteriolar end cause filtration while venous end causes reabsorption.

Fluid movement equation

Ohm's Law: Delta P = QR or Q = delta P/R Delta P = Pi - Po (pressure, mmHg) (Pi is inlet pressure, Po is outlet pressure) Q = flow rate (Q, volume/time) R = resistance to flow (mmHg/volume/time) 2 ways blood flow through organ can be changed. - Heart generates Pi Increase in pressure means increase in flow. Resistance is inverserly proportional to flow, increase in resistance means decrease in flow.

Large arteries and pulse pressure

Pressure changes during cardiac cycle: Pulse pressure (PP) = systolic pressure - diastolic pressure It is dependent on the ratio: - SV/arterial compliance Therefore: - Increase SV = increase in pulse pressure - Increase arterial compliance = decrease in pulse pressure. Alter these factor and you change the pulse pressure.

Ventricular volumes

Primary function of the heart: Impart energy to blood in order to generate and sustain an arterial blood pressure necessary to provide adequate perfusion of organs. End diastolic volume (EDV)= Volume of blood in the ventricle at the end of diastole. End systolic volume (ESV)= Volume of blood in the ventricle at end of systole. Stroke volume (SV) = volume of blood ejected from heart each cycle.

Arterioles

Resistance vessels (arteries main control over the blood pressure, not veins) - Regulate vessel diameter - High resistance to blood flow - Change Q *Metarterioles*- connect arterioles and capillaries *Precapillary Sphincters*- smooth muscle cells which regulate flow into capillary beds. Thoroughfare channel- Same as metarterioles but the venous side of it. Precapillary sphincters are basically smooth muscles lying at the beginning of the capillaries (at junction between metarterterioles and capillaries) that can constrict and stop blood flow to a certain region. Important in regulating blood flow. Instead, the blood would just collect in the thoroughfare channel and then leave through the venule.

Vascular resistance.

Rsistance to flow depends on: r = radius inside the tube L = length of tube n = fluid viscosity (RBCs) Poiseuille's Law: R = (8Ln)/pi(r)^4 So the radius has the biggest effect on resistance. Increasing the radius by 2 means decreasing resistance by the 4th power and vice versa. (Resistance is proportional to the reciprocal of the 4th power of radius.) Increasing length or fluid viscosity is proportional with increasing resistance.

Blood functions

Transport (long distance)- dissolved or bound substrates. - O2, Co2, antibodies, acids/bases, ions, vitamins, hormones, nutrients, metabolites, minerals - Heat Hemostasis - arrest of bleeding after injury Homeostasis- Maintains optimal internal environment - pH, ion concentrations, osmolality, temperature, nutrient supply, vascular integrity. Immunity - Leukocytes in the blood fight infection by microorganisms.

Vascular compliance

Vascular Compliance: distensibility of a vessel (how much it can stretch). - Compliance (slope) decreases at higher P and V (hits max but before then High V low P huge slope, rise over run). - Veins are much more compliant that arterioles. The large compliance in veins allows them to accommodate high volumes with little change in pressure. C=ΔV/ΔP

Composition of blood

Whole blood (approximately 5 L in an adult) - 55% liquid plasma (dissolved substances, plasma proteins) - 45% cellular/formed elements portion (RBCs, WBCs, platelets) Plasma = serum + clotting factors.

Total peripheral resistance

the resistance of the entire cardiovascular system, also known as systemic vascular resistance. MAP = CO x TPR so TPR = MAP/CO Pressure in the arteries is equal to the amount of blood pushes out of the arteries every minute multiplied by the resistance of those arteries. (P = QR) so (R = P/Q)