paul.brand@utoledo.edu

1. From Mars, With Love Photograph taken by NASA Mars Global Surveyor paul.brand@utoledo.edu

2. Basic Principles of Cardiovascular Physiology The circulation provides flowing blood for exchange of CO2, O2, nutrients, hormones, & wastes with body cells in proportion the metabolic activity of the cells CO2, O2, nutrients and wastes exchange between blood & body cells at the capillaries by passive diffusion along concentration gradients Differences in blood pressure in the circulation drive blood flow against the resistance offered by the blood vessels Arterial blood pressure depends on cardiac output and total peripheral (systemic) resistance.

3. Rt atrium Lft atrium Rt ventricle Lft ventricle systemic arteries Gut, spleen, pancreas pulmonary arteries Portal vein pulmonary capillaries systemic capillaries Hepatic sinusoids pulmonary veins systemic veins Hepatic vein Pathway of blood flow in the Circulation What is the pressure gradient (DP) that drives blood around the systemic circulation? Around the pulmonary circulation?

4. Intracellular fluid Interstitial fluid capillaries Plasma osmosis NFP Circulation of water in the body NFP = net filtration pressure Lymph vessels Water leaves capillaries following a hydraulic pressure gradient and is returned to the blood via the lymphatics. In addition, water moves readily across cell membranes in either direction following osmotic pressure gradients.

5. CO2 O2 mitochondrion lungs blood tissues metabolism RBC O2 O2 O2 O2 CO2 CO2 CO2 CO2 circulation alveolar capillary membrane interstitial fluid Diffusion drives exchange of respiratory gases, nutrients and wastes Metabolism drives diffusion of O2 & CO2 & other nutrients & wastes Metabolism and blood flow are tightly coupled.

6. The rate of diffusion of a molecule is proportional to area & concentration gradient, & inversely proportional to distance: n = amount, t = time, D = diffusion coefficient, A = area, dC = concentration gradient, dx = distance. The negative sign shows that diffusion occurs in the direction away from the higher concentration. D, the diffusion coefficient, includes temperature and molecular size. Smaller molecules diffuse faster; & diffusion increases with increasing temperature. Fick equation for rate of diffusion In the circulation, when metabolism increases, diffusional exchange increases by:  1)  Area (more capillaries recruited) 2)  Diffusion Distance (shorter intercapillary distance) 3)  Time in Exchange Area (decreased blood velocity) 4)  Concentration Gradient (increased metabolism in tissue cells).

7. Distance (m) Time 1 0.5 msec 10 (RBC ~ 7 m) 50.0 msec 100 5 sec 1,000 8.3 min 10,000* 14 hrs Diffusion is rapid over short distances, for example, between red blood cells and cells of other tissues *10,000 meters = 0.39 inches Caution: Do not memorize.

8. Flow is the quantity of a liquid (volume) passing a point per unit time: Flow = volume/time An energy gradient in the form of a pressure difference will create flow. P1 – P2 is the difference in hydrostatic pressure (blood pressure) between two points in the circulation: P1 P2 Flow  Flow (F) is directly proportional to the pressure difference (P1 – P2) between two points and inversely proportional to the resistance (R): Pressure is created by contraction of cardiac muscle squeezing the blood. The blood pressure drives the blood around the circulation against the resistance offered by the blood vessels. Flow, pressure and resistance

9. Arteriolar Resistance and arteriolar radius • R (resistance) is proportional to length and viscosity, and inversely proportional to the radius (r) of the vessel according to the Poiseuille’s equation: • R = resistance • L= length • = viscosity r = radius Viscosity is the property of a fluid that resists a force tending to cause the fluid to flow. • Note that resistance is inversely proportional to the fourth power of the radius. Therefore resistance to flow in any individual vessel is determined mainly by vessel radius. Small changes in radius cause large changes in resistance. • Conductance (C) is the inverse of resistance:

10. The curve represents the equation For a single vessel. Resistance/length Vessel radius venules Arterioles capillaries Role of arterioles in regulation of vascular resistance Although the radius of an individual capillary is less than that of an arteriole, total capillary resistance in a vascular bed is less than arteriolar resistance because there are many more capillaries than arterioles. Arteriolar resistance is regulated by changes in radius mediated by autonomic nerves, tissue metabolism and various hormones in order to meet tissue metabolic needs and maintain arterial blood pressure.

11. Cardiac output at rest Normal Flows Cardiac Output (CO) ~ 5 L/min  Cardiac Index (CI) = CO/Body Surface Area CI = 5 L/min per 1.7 M2 = 2.9 L/min per M2 Percent of cardiac output at rest Circulation Splanchnic 24% Renal 19 Cerebral 13 Coronary 4 Skeletal muscle 21 Skin 9 Other 10

12. Calculation of total peripheral resistance in a normal resting adult Mean arterial pressure = ~ 102 mm Hg Venous pressure near the heart = ~ 2 mm Hg. Cardiac output = 5 L/,in F = DP/R R = DP/F Resistance for the entire systemic circulation is called “total peripheral resistance”, or TPR.

13. Aorta functions as a pressure reservoir Arteries distribute flow to various organs Pressure is nearly the same in all large arteries Differences in arteriolar radius determine differences in resistance and therefore in flow. Large radius Low resistance High flow Small radius High resistance Low flow The distribution of blood flow to different vascular beds is regulated by varying the radius of the arterioles by nerves, hormones and metabolism.

14. ECG 200 100 A B Pressures in the circulation Left ventricle 120/0 – 5 mm Hg Arteries 120/80 Capillaries 35 - 25 Venules 25 - 15 Large veins 15 - 0 Right atrium 0 - 5 Right ventricle 30/0 – 5 Pulmonary artery 30/10 Pulmonary capillary ~10 Left atrium ~5 – 10 portal vein ~10 Note the large pressure drop between arteries and capillaries, that is, across the arterioles Where in the circulation are pressure curves A and B measured?

15. Systolic pressure Mean arterial pressure (MAP) Diastolic pressure CO = cardiac output, MAP = mean arterial pressure, CVP = central venous pressure (blood pressure at entrance to right atrium). TPR = total peripheral resistance (total resistance of all systemic blood vessels). F = DP/R CO = (MAP – CVP)/TPR; since CVP is normally ~ 0 it can be ignored: CO = MAP/TPR, rearranging: MAP = CO x TPR. Regulation of CO and TPR sets the level of MAP. Arterial pressure is regulated by changes in CO and TPR Pulse pressure = systolic pressure – diastolic. Clinically MAP is determined electronically

16. Autonomic nerves Tissue metabolism hormones Blood volume Arteriolar radius SV HR CO TPR MAP = CO x TPR MAP Blood volume is determined by NaCl and water balance Determinants of mean arterial pressure Arterial Pressure (AP) is the prime regulated cardiovascular variable MAP is the product of Total Peripheral Resistance (TPR) and Cardiac Output (CO): MAP = CO x TPR

17. Definitions of flow and velocity Velocity (v) is the rate of displacement of a particle with time (cm/s).Flow (Q) is the rate of displacement of a volume of fluid with time (cm3/s).In a tube of constant cross-sectional area A: Q

18. Velocity is affected by the cross sectional area of a vessel Q = vA; rearranging v = Q/A, velocity is inversely related to area.In an unbranched segment of an artery with a constriction, velocity is greater in the constricted region: The presence of a congenital coarctation or an atherosclerotic plaque will increase velocity & likely cause turbulence, bruits (sounds), and contribute to damaging the vessel wall in the area of constriction. Q A1 > A2 v1 < v2

19. Velocity Total Cross sectional area Velocity of blood in the systemic circulation Aorta & large arteries Capillaries & venules Large veins & vena cava Small arteries & arterioles Small veins As arterial blood flow is distributed to more vessels (arterioles, capillaries) velocity decreases. The lowest velocity, in the capillaries & venules, maximizes time for diffusion between blood and tissue cells.

20. Cardiac output is a function of whole body oxygen consumption Regulation of the cardiovascular system by nerves, hormones and local metabolism matches blood flow to metabolic needs. Consequently cardiac output is a linear function of whole body oxygen consumption.

21. (F)[ml O2/ml venous blood] (F) [ml O2/ml arterial blood] capillaries O2 in venous blood O2 inarterial blood F = flow, ml min VO2 = O2 consumed by mitochondria Oxygen consumption and blood flow The oxygen consumption of an organ or tissue equals the amount in the arterial blood minus the amount in the venous blood draining the organ or tissue. The oxygen extraction of an organ or tissue is the difference between arterial and organ venous oxygen concentration: In response to increased metabolic demand, oxygen consumption may be increased by increasing blood flow or increasing oxygen extraction or both.

22. Calculating cardiac output using whole body oxygen consumption Whole body VO2 = (cardiac output) (whole body oxygen extraction) or VO2 = oxygen consumption O2A = ml O2 per ml arterial blood O2V = ml O2 per ml mixed venous blood. Cardiac output may be measured by measuring oxygen consumption from expired air and sampling arterial and mixed venous blood. Extraction for any substance is the difference in concentration between arterial blood and venous blood. Consumption is blood flow times extraction.

23. VO2 = O2 inhaled minus O2 exhaled Advantage: accuracy Disadvantage: invasive (arterial puncture, cardiac catheter) lungs Pulmonary arteries Pulmonary veins Systemic veins Systemic arteries Peripheral tissues Fick principle for measuring cardiac output using O2 consumption

24. Indicator dilution method for measuring cardiac output Add a known amount (A) of a tracer to an unknown volume (V) of fluid. After mixing occurs measure the concentration (C) of the tracer and calculate the volume: By definition: Solving for volume To measure cardiac output (L/min) The volume passing a point in the circulation during a known time (that is, the flow) is determined. The tracer must mix in the central circulation where all of the blood flow from the body becomes mixed, in the right or left heart. Common tracers used for CO: Cold saline solution Cold saline mixes with and cools the blood. The average blood temperature during the interval immediately after the injection is analogous to average tracer concentration.

25. t1 time t2 Rt atrium 38 C Pulmonary artery Thermistor Blood temperature Arrow: cold saline injection Inject cold saline Thermodilution for measuring CO No arterial catheter needed. Repeated measurements can be made. Saline is safe. A small bolus of saline at ~10o C is injected into the right atrium via a venous catheter. The saline mixes with blood and the blood temperature is measured by a thermistor in the pulmonary artery. Knowing the volume and temperature of the saline bolus and the average blood temperature during the interval between t1 and t2, the volume of blood flowing during the interval (= cardiac output) can be calculated.