1. 4 The Cardiovascular System Vascular Function Curves

2. Flow versus driving force Venous return MAP This curve is pretty easy to understand – more driving force gives more flow. Thought question: Why doesn’t the arterial pressure fall to zero when flow falls to zero? The slope of the curve is 1/TPR

3. Changes in the VR/MAP curve with change in TPR and blood volume VR MAP normal Arteriolar dilation (decreased TPR) Arteriolar constriction (increased TPR) Blood volume changes would move VR along the normal curve – they would also change the stop-flow pressure, but the magnitude of the changes would be small relative to the scale of MAP

4. Flow versus venous pressure This one is harder to grasp…. Pressure that would exist if there were no flow

5. Understanding the vascular function curve with respect to RAP This is the stop-flow pressure It helps to do a thought experiment. Imagine bringing the heart to a stop. Cardiac output will fall to zero. Aortic pressure will plummet – venous pressure will rise slightly – capillary pressure will remain almost constant. The 3 pressures will converge on the stop-flow pressure. Now, restart the heart. Imagine the pressure values tracking back along the curves to their normal values.

6. Now look back at the curve of VR versus RAP, and remember that CO=VR Stop flow pressure When the heart is restarted, the RAP curve will follow the red curve from right to left, ending up somewhere in the normal range indicated by the arrows. If the heart is stimulated and becomes hypereffective, the RAP value will move further to the left. Ultimately, as the heart starts to apply suction to the venous supply, RAP enters the negative range (i.e. is less than atmospheric pressure), and the great veins leading to the heart start to collapse – this is why the curve flattens out. Normal range

7. Changes in the VR/RAP curve with change in TPR Arteriolar dilation Arteriolar constriction Venous Return RAP These curves say: Arteriolar dilation improves venous return – arteriolar constriction impedes it.

8. Blood-volume changes move the VR/RAP curve right or left Venous Return RAP Decreased BV Increased BV BV changes change the stop-flow pressure, but not the slope of the curve

9. Integration of the cardiac and vascular function curves

10. Some definitions for the CV system model System Properties –TPR –Blood volume/Venous capacitance –Cardiac functionality (inotropic state, HR) System Variables –RAP –MAP –CO

11. The RAP curves VR=CO RAP System operating point When we overlay the two curves that relate to the RAP, we are allowing the two parts of the CV system to interact. The intersection of the two curves describing potential values determines the real system variables of CO and RAP for a system with a specific set of system properties. Any change in a system property would shift one or the other of the curves and thus change the operating point.

12. The MAP curves MAP CO Operating point When the MAP curves are overlain, the two parts of the system interact to determine the real values of CO and MAP. If the system properties are the same as for the RAP curves in the previous slide, the CO value will be the same for both slides.

13. Using the model The model can be used to predict the effects on system variables of any change or set of changes in system properties. These would include changes imposed from outside (disease, therapeutic drugs, toxins), changes in physical activity levels, and reflexive responses to homeostatic challenge. For example, the following situations can be modeled: –The onset of hemorrhagic shock and the reflexive response to it –chronic heart disease –Effects of epinephrine and other cardiotonic drugs –Effects of vasoconstrictor or vasodilator drugs –exercise Some of these situations will be modeled in class (be there or be square!) – some will be assigned for you to model.

14. System Responses to Stress and Disease

15. Hemodynamic changes in response to hemorrhage A drop in systemic arterial pressure initiates the baroreceptor reflex and greatly increases sympathetic outflow. This accounts for the increases in heart rate and TPR. Remember that the regulated variable here is mean arterial pressure. In this example, the blood loss is mild (no more than about 1 liter for a 60-70 Kg person) and the reflexive compensation is able to protect MAP while slower responses can restore the lost fluid, electrolytes and blood cells. Note that cardiac output is not a regulated variable and cannot return to normal until volume restoration occurs.

16. Irreversible Hemorrhagic Shock If the immediate responses were inadequate, a rapid positive-feedback cycle would cause hemorrhagic shock. Cardiac depression: heart fails to pump enough blood to meet the needs of itself and the CNS, leading to Vasomotor Failure: depressed blood flow to brain is the most potent of sympathetic stimulants, but after a few minutes of depressed blood flow, sympathetic outflow drops and those arterioles that had been constricted by their adrenergic inputs then dilate, causing a collapse of MAP.

17. Hemodynamic changes during exercise Organ Resting Perfusion (L/min) Perfusion during Exercise (L/min) Dominant effect Brain11autoregulation Heart0.51autoregulation Skeletal Muscle112autoregulation + beta adrenergic effect Skin0.54thermoregulation Splanchnic21Alpha adrenergic effect Kidney21Alpha adrenergic effect TOTAL CO720

18. How is a 3X increase in CO possible during exercise? Can it be the result of cardiac effects only? Use the model to find out. CO RAP

19. Exercise responses are multifactorial The magnitudes of MAP, CO and TPR changes in exercise are affected by multiple factors, including Conditioning Muscle mass Exercise intensity level Environmental temperature In some highly muscular individuals, MAP may decrease significantly in intense exercise, due to a profound decrease in diastolic pressure.

20. Capillary Filtration, Interstitial Fluid and the Lymphatic System

21. Capillaries and Capillary Filtration Capillaries are the major sites of exchange of materials between tissues and bloodstream Materials may move across capillary walls by diffusion and bulk flow Ordinarily, capillary slits are not permeable to molecules as large as plasma proteins, but in order for protein hormones to enter the bloodstream and to reach their targets, there is extensive protein movement across capillary endothelial cells by pinocytosis.

22. Capillary filtration Arteriolar end Venular end 35 ~0 3 28 15 ~0 3 28 Osmotic pressure gradient is due to plasma proteins and doesn’t change along capillary length – little protein is filtered. Capillary hydrostatic pressure decreases along capillary length due to friction Total pressure = 10 outward Total pressure = 10 inward

23. Edema is an excess of ISF that reflects an imbalance between rates of formation and drainage of ISF Hydrostatic factors that promote systemic edema: –Hypertension –Vasodilation –Increased venous pressure –Erect posture or compression of central veins –Lymphatic blockage –Right Heart failure Osmotic factors that promote systemic edema: Loss of serum proteins (protein undernutrition) inflammation with increased capillary leakiness and release of tissue proteins

24. Edema and congestive heart failure “Congestive” refers to the fact that the disease-weakened heart must operate in a larger range of EDV and ESV to be able to generate enough force to sustain MAP. The edema results from increased venous pressure that backs up to increase capillary hydrostatic pressure, favoring filtration over absorption. Patients with generalized congestive heart failure typically experience peripheral edema during the day and pulmonary edema at night.

25. The Lymphatic System Lymphatic capillaries are blind-ended tubes with flap valves that permit entry of ISF Lymphatic veins have 1- way valves like blood veins, so periodic compression of lymphatics improves lymph flow. Ultimately, lymph drains back into the blood vascular system through two ducts – the thoracic duct (to left subclavian vein) and right lymphatic duct (right subclavian vein).

26. Lymph drainage opposes edema recovers proteins that escape across capillary walls delivers information about presence of infectious agents and non-self antigens to lymph nodes for immune surveillance