1. Aims Blood clotting (cont.). –Coagulation cascade Regulation of blood pressure. Regulation of blood volume. Reading; Sherwood, Chapters 10 &11, Chapter 15 pages 569-570 ; Robbins, pages 84-90

2. Coagulation Cascade Very complex –>50 substances effect coagulation –procoagulants –anticoagulants Key Steps –Formation and/or Activation of prothrombin activator/s (Factor X) –Conversion of prothrombin to _________________ –Conversion of fibrinogen to ___________________.

3. Sherwood’s Human Physiology 11-12 Coagulation Cascade Activation of Prothrombin activator/s is the rate limiting step.

4. Guyton’s Textbook of Medical Physiology 36-4 Intrinsic Pathway

5. Guyton’s Textbook of Medical Physiology 36-3 Extrinsic Pathway

6. Sherwood’s Human Physiology 11-13 Summary

7. Fibrinolytic System Limits the size of the clot. Plasminogen is a plasma protein trapped in the clot. It is cleaved into plasmin by tPA. Plasmin breaks down __________________ and interferes with its polymerization. Robbins’ Basic Pathology 4-12

8. Leukocytes White blood cells (WBC’s) that serve in the immune system. Primary functions: –Defend against pathogens via phagocytosis. –Identify and destroy cancer cells. –Phagocytose debris resulting from dead or injured cells.

9. Sherwood’s Human Physiology 10-35 (10-34 6th Edition) Factors Involved in Blood Pressure mean arterial pressure = cardiac output X total peripheral resistance

10. Sherwood’s Human Physiology 10-35 (10-35 6th Edition) Factors Involved in Blood Pressure There are both short term and long term adjustments made to normalize blood pressure. Short Term (within seconds to minutes) –Alterations in cardiac output and total peripheral resistance (______________________________) Long Term (minutes to days) –Adjusting total blood volume

11. Sherwood’s Human Physiology 10-36 (10-36 6th Edition) Arterial Baroreceptors Constantly monitor mean arterial pressure and pulse pressure. Mechano-receptors in the walls of several large arteries.

12. Guyton’s Textbook of Medical Physiology 18-5 Arterial Baroreceptors Cardiovascular Control Center Located in the __________________ Autonomic nervous system “feedback”

13. Guyton’s Textbook of Medical Physiology 18-6 Arterial Baroreceptor Increased arterial pressure => Increased CNS signal. Decreased arterial pressure => decreased CNS signal.

14. Sherwood’s Human Physiology 10-37 (10-36 6th Edition) Arterial Baroreceptor

15. Baroreceptor Reflex Increased CNS signal (increased BP) –Inhibit vasoconstrictor center of medulla. Vasodilation of veins and arteries => decreasing peripheral resistance. –Excite vagal parasympathetic center. Sherwood’s Human Physiology 10-38 (10-37 6th Edition)

16. Baroreceptor Reflex Decreased CNS signal (decreased BP) –Excite vasoconstrictor center of medulla. Vasoconstriction of veins and arteries => increasing peripheral resistance. –Excite vagal _____________________________________ center. Sherwood’s Human Physiology 10-38 (10-37 6th Edition)

17. Effects of changing body position on the arterial baroreceptor Standing from a supine position (lying down) -BP in upper body and head decreases and can cause a loss of consciousness. -Decreased pressure elicits a an immediate reflex resulting in a strong sympathetic response.

18. Guyton’s Textbook of Medical Physiology 18-8 Arterial baroreceptor as a pressure buffer system Important in maintaining pressure during changes in body position. Functions as a “pressure buffer system” since without an arterial baroreceptor there is an increase in pressure variability.

19. Guyton’s Textbook of Medical Physiology 18-9 Arterial baroreceptors are responsible for reducing the minute by minute variations in arterial pressure by 1/2-1/3. ____________ Term Regulation Arterial baroreceptor is a short term regulator

20. Sherwood’s Human Physiology 10-39 (10-38 6th Edition) Summary of Baroreceptor Reflex Increased BP

21. Sherwood’s Human Physiology 10-39 (10-38 6th Edition) Summary of Baroreceptor Reflex Decreased BP

22. Guyton’s Textbook of Medical Physiology 18-5 Chemoreceptor Reflex Located in the ______________________ and adjacent to the aorta. Sensitive to: –Decreased O 2 –Excess CO 2 –Excess H + (low pH)

23. Chemoreceptor Reflex Excite nerve fibers in the vasomotor center of the brain stem. Decreased pressure => decreased O 2, increased CO 2, increased H + => stimulates chemoreceptors => maintain vasoconstrictor tone => increased pressure back to normal. Not a powerful reflex –Because it is only activated at pressures below 80mm Hg.

24. Guyton’s Textbook of Medical Physiology 19-15 Blood Pressure Control Mechanisms

25. CNS Ischemic Response “Last ditch stand” Control of arterial pressure in response to diminished brain blood flow. Neurons in the vasomotor center respond directly and strongly. Their stimulation results in systemic arterial pressure as high as the heart can pump. –Due to elevated level of CO 2 stimulating sympathetic nervous system in medulla. –One of the most powerful activators of the sympathetic vasoconstrictor system.

26. Guyton’s Textbook of Medical Physiology 19-15 Blood Pressure Control Mechanisms

27. Cushing Reaction In response to elevated cerebrospinal fluid pressure. When cerebrospinal fluid pressure > arterial pressure, the brain’s vessels collapse and blood flow stops. This initiates the CNS ischemic response and the elevation of arterial pressure > than the cerebrospinal fluid pressure.

28. Volume Reflex Sherwood’s Human Physiology 15-4 Left atrial volume receptors and osmoreceptors are involved in H 2 O and NaCl balance. They play a role in ___________________ Term regulation of BP by increasing blood volume & vasoconstriction.

29. Renal-Body Fluid System for Arterial Pressure Control Primitive: dates back to the hag fish. Long Term regulation of BP. Pressure diuresis is the increase in output volume as arterial pressure rises.

30. Guyton’s Textbook of Medical Physiology 19-1 Renal-Body Fluid System for Arterial Pressure Control

31. Guyton’s Textbook of Medical Physiology 19-15 Blood Pressure Control Mechanisms

32. Equilibrium point Water and salt intake Renal output of water and salt Arterial pressure Intake or output (fold) 1 4 8 10015050 More output than input More input than output Water and Salt Intake vs. Renal Output

33. Guyton’s Textbook of Medical Physiology 19-2 Blood Volume Increases If you increase the volume of blood there is an immediate response to increase CO, Urine out flow, and arterial pressure.

34. Renin-Angiotensin System When the Kidneys experience ________________ arterial pressure their Juxtaglomerular cells release a small protein, Renin. Renin is not a vasoactive substance it is an enzyme which cleaves a plasma protein angiotensinogen to angtensin I which is a mild vasoconstrictor. Angiotensin I is cleaved in the lungs into Angiotensin II which is a strong vasoconstrictor and decreases renal excretion of both water and salt.

35. Decreased arterial pressure Renin release from Kidneys AngiotensinogenAngiotensin I (mild vasoconstriction) Angiotensin II Converting enzyme (in lung) Renal retention of salt and water Strong vasoconstriction (inactive) Angotensinase Renin-Angiotensin System

36. Next Time Cardiovascular pathology –Hypertension –Atherosclerosis Readings; Robbins, Atherosclerosis 328- 338, Hypertension 338-341.

37. Objectives 1.Describe the coagulation cascade. 2.Describe how blood pressure is regulated (short term vs long term). 1.Baroreceptors and baroreceptor reflex 2.Chemoreceptors and chemoreceptor reflex 3.Ischemic response 4.Volume reflex and the role of the kidney (renin- angiotensin system)