A Study of Blood Vessels

1. A Study of Blood Vessels Mike Clark, M.D.

2. Types of Blood Vessels Arteries Capillaries Veins Three Generic Circulations in the Body Systemic – blood goes from left ventricle to Right Atrium Pulmonary – blood goes from right ventricle through lungs to left atrium Hepatic Portal – venous circulation – drains blood from portions of gastrointestinal tract (intestines) and takes it to the liver

3. Schematic System Circulation Figure 19.2

4. Pulmonary Circulation Figure 19.18a

5. Hepatic Portal Circulation

6. Cross Section of Typical Blood Vessel Figure 19.1b

7. Tunica interna (intima) • composed of endothelium cells (simple squamous) - these cells must be smooth in order to not to activate the intrinsic clotting cascade – additionally these cells secrete various paracrine chemicals • Basement membrane or basal lamina • Small amount of loose connective tissue • In some vessels have an internal elastic lamina composed of elastin – particularly in muscular arteries

8. Tunica Media • Composed of various amounts of smooth muscle depending on the blood vessel type • Composed of some loose connective tissue • Larger muscular arteries have an external elastic lamina

9. Tunica Adventitia • Outermost layer of blood vessels – composed of fibroblasts, collagen and elastic fibers. This layer becomes continuous with the connective tissue elements surround the blood vessel – so the vessel in held in place. • Vasa Vasorum – in the walls of the larger thicker blood vessels – the cells of the vessel wall itself needs a blood supply – thus “a vessel to a vessel”. Since veins generally have less oxygen than arteries – the larger veins need more vasa vasorum vessels than the larger arteries • Note: larger thick lymphatic vessels also have vasa vasorum vessels

10. Types of Blood Vessels • Arteries • Arterioles (resistance vessels) • Capillary Bed (inclusive of capillaries) – exchange vessels • Post Capillary Venules – location where most white blood cells leave circulation (diapedesis) • Venules • Small, Medium and Large Veins (capacitance vessels)

11. Figure 19.1

12. Arteries • Artery – a blood vessel that transports blood away from the heart. The arteries branch considerably as they get further from the heart and the diameter gets smaller. There different types of arteries. Types of Arteries • Elastic (Conducting) Arteries – arteries proximal to the heart that can easily stretch and conduct blood from the heart ( aorta, common carotids, subclavian, common iliac arteries and pulmonary trunk • Muscular (Distributive) Arteries –arteries with considerable smooth muscle in the walls – thus can vasoconstrict and channel (distribute) blood to organs that need it. The muscular arteries include almost all of the arteries in the body besides those of the elastic – these arteries are large, medium and small. • Arteriole – (resistance vessel) very, very tiny artery with a diameter of 0.1mm or less – but considerable smooth muscle in the wall – can perform considerable vasoconstriction (resistance).

13. Table 19.1 (1 of 2)

14. Figure 19.1a

15. Capillaries and Capillary Bed • Capillaries (exchange vessels) are short length (0.25 μm – 1 μm) and thin diameter (10 μm - 30 μm) small vessels. There walls are very thin and sometimes porous (fenestrated, sinusoidal) – thus providing great diffusive ability. The three anatomical types of capillaries will be discussed later in this PowerPoint. • True capillaries are generally located in capillary beds. There are millions of capillary beds in the body. Each population cells needs a capillary bed in order to get oxygen and nutrients. • Capillary beds contain metarterioles and thoroughfare channels.

16. Table 19.1 (2 of 2)

17. Figure 19.4

18. Venules and Veins • Vein (capacitance vessels) – a blood vessel that returns blood back to the heart. As with arteries – there are different types of veins. Types of Veins • Post capillary venule – A tiny (15 μm – 20 μm) blood vessel that has a wall as thin as the capillaries – this is where most white blood cells leave the circulation (diapedesis) • Small, medium (less than 1 cm) and large veins Veins generally have a wider inside lumen diameter than an artery – and have less smooth muscle in their walls. It was this reason that veins easily stretch and hold onto to more blood. Most of the blood (around 60%) in the body is located in the veins (high capacitance) at any given time.

19. Table 19.1 (2 of 2)

20. Figure 19.1a

21. Secretions and receptors of Endothelial Cells • Collagens Type II, IV, and V • Lamin – type of intermediate filament • Endothelin – causes vasoconstriction • Nitric Oxide – (Endothelial Derived Relaxing Factor) has many actions like vasodilation and keeps platelets off wall of blood vessels • Von Willebrand Factor – used to assist Clotting Factor VIII to work • Angiotensin Converting Enzyme – converts angiotensin I to angiotensin II • Enzymes that degrade Bradykinin, Serotonin, Prostaglandins, Thrombin and Norepinephrine • Can Bind Lipoprotein Lipase

22. Normally the intact endothelium produces prostacyclin (PGI2)and Nitric Oxide, which inhibit platelet aggregation. It also blocks coagulation by the presence of thrombomodulin and heparin-like molecule on its surface membrane. These two membrane-associated molecules inactivate specific coagulation factors. • Injured endothelial cells release Von Willebrand factor and tissue thromboplastin and cease the production and expression of inhibitors of coagulation and platelet aggregation. They also release endothelin, a powerful vasoconstrictor.

23. Factors Preventing Undesirable Clotting • Unnecessary clotting is prevented by endothelial lining the blood vessels • Platelet adhesion is prevented by: • The smooth endothelial lining of blood vessels • Heparin and PGI2 secreted by endothelial cells • Vitamin E quinone, a potent anticoagulant

24. Smooth Muscle For an understanding of smooth muscle excitation- contraction please refer To my PowerPoint Smooth Muscle Excitation Contraction under A&P II Figure 9.25

25. Figure 9.26

26. Smooth muscle like cardiac muscle receives some calcium from the outside of the cell for contraction - thus it too can be slightly relaxed by administering calcium channel blocker medications. Figure 9.27

27. Classes of Calcium Channel Blockers Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance "-dipine". Amlodipine (Norvasc) Nifedipine (Procardia, Adalat) Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed. Verapamil (Calan, Isoptin) Gallopamil (Procorum, D600

28. Benzothiazepine calcium channel blockers are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines. Diltiazem (Cardizem)

29. Mathematical Analysis of the Circulatory System • Discussion of Pressure • Discussion of Pressure in a pipe without an external compression device (pressure in the blood vessels without the heart) known as “Mean Circulatory Filling Pressure”. Discuss unstressed and stressed blood volume • Discuss pressure in blood vessels with heart compression • Discuss Flow – velocity of flow versus rate of flow • Discuss Resistance – • resistance in pipes arranged in series versus those arranged in parallel • Total Peripheral Resistance • Examine Diffusion Formula • Examine Capacitance (Compliance) Formula • Examine the Mean Arterial Pressure Formulas • Wall Tension

30. Formulas of importance Flow = ∆P/ R, ∆P is the change in pressure from one area to another (P1 – P2) – in the direction of flow, R is the resistance (Note: pressure drops off as a fluid or gas passes further down the pipe – thus the pressure in proximal area 1 (P1) is higher than the pressure is distal area 2. The more pressure drop off the more the flow. Also, the less the resistance the better the flow. • Rate of Flow = amount of gas or liquid/time (example ml/min) • Velocity of flow = amount of gas or liquid/time/cross sectional area (another way of looking at it is Vf = rate of flow/cross sectional area) example of velocity of flow ml. /min per cm2 Note: Area of a circle (like the inside of a vessel ) = equals pi (π) times the radius squared (π⋅r2), example ml. /min per cm2 Flow formula derived Ohm’s Law

31. Formulas of Importance • Resistance –a force of impedance (holding back) R = 8ηL/πR4 , η is viscosity of the gas or liquid, L is the length of the vessel, and R is the resistance raised to the 4th power • Summation (∑) of Resistances – adding up the resistors in flow arrangement a series arrange • Resistors in series – one resistor in front of another ∑ = R1 + R2 + R3 + …… • Resistors in parallel – a pipe leads into a branching set of pipes ∑ = 1/R1 + 1/R2 + 1/R3 +.. • Note: resistors in parallel give less total resistance than those in series (think of the capillary arrangement)

32. Total Peripheral Resistance (Systemic Vascular Resistance) • The TPR (SVR) is the summation (∑ ) of all the resistors in the systemic (Left Ventricle – to Right Atrium) circulation. Some of the blood vessel resistors are in series (R1 + R2 + R3 + ……) and some are in parallel (1/R1 + 1/R2 + 1/R3 )– thus the two different formulas must be used. • Since R is raised to 4th power it numerically is the most significant contributor to Total Peripheral Resistance – thus vasoconstriction and vasodilation are the most important contributors to TPR. • Alternate calculations are Total Pulmonary Resistance which is resistance in the pulmonary circulation – as well as other organ and circulatory resistances can be calculated

33. Formulas of Importance Diffusion – net movement of certain particles from a region of high concentration of those certain particles to region of low concentration of those certain particles D = A x Dc /t (Co – Ci) • A is the area of the membrane being diffused through, Dc is the diffusion coefficient, t- is the thickness of the membrane being diffused through, Co – Ci is the concentration difference between the o (outside) and I (inside) of the container • The diffusion coefficient = solubility coefficient divided by the square root of the molecular weight of the substance diffusing (this applies more to gases) • Analysis- the greater the area and/or diffusion coefficient – the faster the rate of diffusion. The more the concentration difference the faster the rate of diffusion. However, the thicker the membrane to diffuse through the slower the rate of diffusion.

34. Formulas of Importance • Capacitance (Compliance) C – is the ease at which a container can stretch to accommodate increased volumes of gases or liquids. C = ∆V/∆P, • ∆P is change in pressure, and ∆V is change in volume • The more volume change without a change in pressure (due to compression of atoms and molecules in a minimally stretchable container) the greater the capacitance (compliance) • Thus a balloon would have greater capacitance (compliance) that a leather container.

35. Laminar Flow Versus Turbulent Flow Laminar flow, sometimes known as streamline flow, occurs when a fluid flows in parallel layers, with no disruption between the layers. It is the opposite of turbulent flow. In nonscientific terms laminar flow is "smooth," while turbulent flow is "rough."

36. Laminar Flow is a quiet smooth flow through blood vessels – whereas turbulent flow makes a noise as it flows – the more turbulent the flow the louder the noise. Turbulent flow produces murmur like sounds in the heart. A Bruit is the unusual sound that blood makes when it rushes past an obstruction (called turbulent flow) in an artery when the sound is auscultated with the bell portion of a stethoscope. A related term is "vascular murmur", which should not be confused with a heart murmur.

37. Note- that once laminar flow hit the obstruction (like blood wall atherosclerotic plaque – it converted to turbulent flow. Reynolds number (Re) is the ratio of inertial forces to viscous forces and is given by the formula: Re = ρVD/μ where ρ = density of the fluid, V = velocity, D = pipe diameter, and μ = fluid viscosity. Reynolds number is used to determine whether a flow will be laminar or turbulent. If Re is high (>2100), inertial forces dominate viscous forces and the flow is turbulent; if Re number is low (<1100), viscous forces dominate and the flow is laminar.

38. Determining if flow is Laminar versus Turbulent Re = ρVD/μ where ρ = density of the fluid, V = velocity, D = pipe diameter, and μ = fluid viscosity. If Re is high (>2100), inertial forces dominate viscous forces and the flow is turbulent; if Re number is low (<1100), viscous forces dominate and the flow is laminar. The Reynolds number is used to determine whether a flow will be laminar or turbulent. Reynolds number (Re) is the ratio of inertial forces to viscous forces and is given by the formula:

39. Mean Arterial Pressure It is defined as the average arterial pressure during a single cardiac cycle. MAP (SYSTEMIC) = CO X TPR (SVR) MAP (SYSTEMIC) is the average pressure in the systemic circulation (Left Ventricle to Right Atrium). Thus MAP (pulmonic) can be calculated also as well as other circulations. CO is the cardiac output = heart rate x stroke volume (stroke volume is End Diastolic Volume – End Systolic Volume) TPR (SVR) is the total resistance in the systemic circulation

40. MAP (SYSTEMIC) = CO X TPR (SVR) • This formula is an excellent one to use to understand pressures in the blood vessels. It can explain hypertensive pressures, normotensive pressures and hypotensive pressures. However, it cannot be actually calculated in that the TPR cannot be calculated. TPR in involves calculating the radius of the blood vessels at each millimeter along the circulation – the human body has approximately 60,000 miles of blood vessels – thus this is impossible to calculate. • The algebraic formula used to calculate MAP is MAP = DBP + 1/3 (SBP – DBP) DBP is the Diastolic Blood Pressure, and SBP is the Systolic Blood Pressure SBP – DBP is the Pulse Pressure

41. MAP = DBP + 1/3 (SBP – DBP) Systolic Blood Pressure – occurs during Ejection Contraction Time The Diastolic Blood Pressure has more weight (significance) in this formula – because during one cardiac cycle there is more time spent in diastole in the blood vessels than is systole. The actual way MAP is calculated by the computer (arterial line) is using differential Calculus. Differential calculus exactly calculates the area under a curve.

42. Blood Vessel Wall Tension • Tension = Pressure inside vessel x r/ 2 • r is radius of the vessel • Interpretation: For a given blood pressure, increasing the radius of the blood vessel leads to a linear increase in tension. This implies that large arteries must have thicker walls than small arteries in order to withstand the level of tension.

43. Arteries • Elastic (Conducting) Arteries – first vessels to leave heart – act as a second pump – since the heart is an intermittent pump. (Aorta, Common Carotids, Subclavian, Common iliacs and pulmonary trunk)

44. 2. Muscular (Distributive) Arteries arteries with considerable smooth muscle in the walls – thus can vasoconstrict and channel (distribute) blood to organs that need it. The muscular arteries include almost all of the arteries in the body besides those of the elastic – these arteries are large, medium and small.

45. 3. Arterioles (Resistance Vessels) • very, very tiny artery with a diameter of 0.1mm or less – but considerable smooth muscle in the wall – can perform considerable vasoconstriction (resistance).

46. 4. Capillary and Capillary Bed • True capillary (three types) continuous, fenestrated and sinusoidal – degree of permeability makes the difference • Metarteriole – tiny blood vessel with space intermittent smooth muscle in its wall – generally its entrance is guarded by a precapillary sphincter • Precapillary sphincter – valve type structure comprised of surrounding smooth muscle at the entrance of metarterioles and true capillaries • Thoroughfare channels – anatomic structure with very low resistance and not guarded by a precapillary sphincter – leads to venules

47. Capillaries are the exchange (diffusion) vessels. There are millions of capillary beds in the body. Each population cells needs a capillary bed in order to get oxygen and nutrients. The true capillary and the associated capillary bed are excellent for diffusion because (1) they have very thin walls (2) a large cross sectional area to diffuse through and (3) the large cross sectional area slows the velocity of flow (4) they are narrow in diameter (10 μm - 30 μm) therefore less distance from lumen to membrane. Because they are narrow in diameter – this could significantly increase the resistance – but the parallel arrangement reduces this. D = A x Dc /t (Co – Ci)

48. Capillary • The the peripheral circulation of the whole body has about 10 billion capillaries with a total surface area estimated to be 500 -700 square meters (about 1/8th the surface area of a football field). It is rare for any functional cell of the body to be more than 20 – 30 micromillimeters from a capillary – definitely no more than 100 micromillimeters.

49. Blood Flow Through Capillaries • Vasomotion • Slow and intermittent flow • Reflects the on/off opening and closing of precapillary sphincters

50. Parallel arrangement of vessels reduces resistance. R = 1/R1 + 1/R2 + 1/R3 Capillary bed has very slow velocity of flow due to its large cross sectional area. Figure 19.13