Aims

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

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

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

6. Summary Sherwood’s Human Physiology 11-13

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

10. 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 Sherwood’s Human Physiology 10-35 (10-35 6th Edition)

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

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

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

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

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. 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. Guyton’s Textbook of Medical Physiology 18-8

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

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

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

22. Chemoreceptor Reflex • Located in the ______________________ and adjacent to the aorta. • Sensitive to: • Decreased O2 • Excess CO2 • Excess H+ (low pH) Guyton’s Textbook of Medical Physiology 18-5

23. Chemoreceptor Reflex • Excite nerve fibers in the vasomotor center of the brain stem. • Decreased pressure => decreased O2, increased CO2, 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. Blood Pressure Control Mechanisms Guyton’s Textbook of Medical Physiology 19-15

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 CO2 stimulating sympathetic nervous system in medulla. • One of the most powerful activators of the sympathetic vasoconstrictor system.

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

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 • Left atrial volume receptors and osmoreceptors are involved in H2O and NaCl balance. • They play a role in ___________________ Term regulation of BP by increasing blood volume & vasoconstriction. Sherwood’s Human Physiology 15-4

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

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

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

32. More output than input More input than output Water and Salt Intake vs. Renal Output Renal output of water and salt 8 4 Intake or output (fold) Equilibrium point Water and salt intake 1 50 100 150 Arterial pressure

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

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

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

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