Mike Clark, M.D.

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

Schematic System Circulation
Figure 19.2

Pulmonary Circulation
Figure 19.18a

Hepatic Portal Circulation

Cross Section of Typical Blood Vessel
Figure 19.1b

• 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

• 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

• 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

• 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)

Figure 19.1

• 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
1. 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
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.
3. 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).

Figure 19.1a

• 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.
• 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 .

Figure 19.4

• 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
1. 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)
2. 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.

Figure 19.1a

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

1. Normally the intact endothelium produces prostacyclin (PGI
2
)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.
2. 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.

• Unnecessary clotting is prevented by endothelial lining the blood vessels
• Platelet adhesion is prevented by:
– The smooth endothelial lining of blood vessels
– Heparin and PGI
2 cells secreted by endothelial
– Vitamin E quinone, a potent anticoagulant

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

Figure 9.26

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

Classes of Calcium Channel Blockers
1. Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance "-dipine".
Amlodipine (Norvasc)
Nifedipine (Procardia, Adalat)
2. 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

3. 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)

Mathematical Analysis of the Circulatory System
1.
Discussion of Pressure
2.
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
3.
Discuss pressure in blood vessels with heart compression
4.
Discuss Flow – velocity of flow versus rate of flow
5.
Discuss Resistance –
• resistance in pipes arranged in series versus those arranged in parallel
• Total Peripheral Resistance
6.
Examine Diffusion Formula
7.
Examine Capacitance (Compliance) Formula
8.
Examine the Mean Arterial Pressure Formulas
9.
Wall Tension

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 cm 2
Note: Area of a circle (like the inside of a vessel ) = equals pi
(π) times the radius squared (π ⋅ r 2 ), example ml. /min per cm 2
Flow formula derived Ohm’s Law

• Resistance –a force of impedance (holding back) R = 8ηL/πR 4 , η is viscosity of the gas or liquid, L is the length of the vessel, and R is the resistance raised to the 4 th 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)

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 4 th 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

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.

• 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.

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

• 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

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.

• 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 .

Table 19.1

1. 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)

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.

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

• 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

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)

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

Continuous capillary Fenestrated capillary
Sinusoidal Capillary
Figure 19.3

Continuous capillary
Least permeable capillaries found in skin and muscles. Blood – Brain barrier and Blood- Thymic Barrier have even less permeability.
Figure 19.3a

Have more permeability – found in small intestine and endocrine glands
Figure 19.3b

Have considerable permeability – found in liver, spleen, bone marrow and adrenal medulla
Figure 19.3c

Routes of movement through capillaries
Figure 19.15

Capillary Exchange of Water – Starling’s Law of the Capillaries
Should put out from capillary as much fluid as is brought back in. If more out
Than in – edema – if more in than out – dehydration in the area.
Net Filtration Pressure is a calculation for fluid transfer into and out of capillaries
Figure 19.16

• NFP – all the forces acting on a capillary bed
• NFP = Force out of capillary – force into capillary
• NFP = (Hp blood
+ OP if
) – (Op blood
+ HP if
)
• Hp is hydrostatic pressure of the blood (which is really the mean pressure at the start of the capillary), OP if is the osmotic pressure of the interstitial fluid, Op blood is the osmotic pressure of the blood (higher because of plasma proteins),
• Hp if is the hydrostatic pressure of the interstitial fluids
• NFP (arterial end) = (35 mm Hg + 1mm Hg) - (26 mmHg + 0) = 10 out
• NFP (venous end) = (17 mmHg + 1 mmHg) – (26 mm Hg + 0) = 8 in
• At the arterial end of a bed, hydrostatic forces dominate (fluids flow out) and at the venous end forces dominate back into blood vessel – however more fluid does exit than comes back in – the role of the lymphatics to correct .

The lymphatics return the excess fluid to the circulation.

• Vein (capacitance vessels) – a blood vessel that returns blood back to the heart.
As with arteries – there are different types of veins.
• By the time the blood has reached the veins it is fairly devoid of pressure – so the dependent veins (veins below the heart) need external comprssion to bring blood back to heart – they also need valves.

Figure 19.5

Figure 19.6

C = ∆V/∆P
Veins are our capacitance vessels – they contain most of the blood in the body at any given time.

• The pulse rate generally is the same as the heart rate – thus normal resting pulse rate is between 60 and 100.
• The pulse pressure is the difference between the systolic blood pressure and the diastolic pressure – generally equal to slightly greater than 40 mmHg. Various conditions can lower or elevate the pulse pressure. Low blood volume can decrease pulse pressure, exercise may temporarily elevate pulse pressure and stiffness of major arteries may consistently elevate the pulse pressure.

• 0 = Absent
• 1 = Barely palpable
• 2 = Easily palpable
• 3 = Full
• 4 = Aneurysmal or Bounding pulse

• The pulse represents the tactile arterial palpation of the heartbeat (whether normal or abnormal)
• The pulse may be palpated in any place that allows an artery to be compressed against a bone such as at the neck
( carotid artery ), at the wrist ( radial artery ), behind the knee ( popliteal artery ), on the inside of the elbow
( brachial artery ), and near the ankle joint
( posterior tibial artery ).

Figure 19.11

• Pressure waves generated by cardiac systole move the artery walls, which are pliable and compliant. These properties form enough to create a palpable pressure wave.
• The Heart Rate may be greater or lesser than the
Pulse Rate depending upon physiologic demand.
In this case, the heart rate are determined by auscultation or audible sounds at the heart apex, in which case it is not the pulse. The pulse deficit
(difference between heart beats and pulsations at the periphery) is determined by simultaneous palpation at the radial artery and auscultation at the heart apex.

The alternating expansion (ejection
contraction) and contraction
(diastole) of the arteries during a heart beat causes the pulse.
The pulse pressure is the difference between the systolic blood pressure and the diastolic blood pressure
The further an artery is away from the heart – the less the alternating
Expansion and contraction – due to resistance – the magnitude of the pulse will not be as great.

1. Pulsus alternans - a physical finding with arterial pulse waveform showing alternating strong and weak beats. It is almost always indicative of left ventricular systolic impairment, and carries a poor prognosis.
2. Pulsus bigeminus a cardiovascular phenomenon characterized by groups of two heartbeats close together followed by a longer pause. The second pulse is weaker than the first. It is caused by premature contractions ventricular contractions (PVCs).

3. Pulsus bisferiens , a sign where, on palpation of the pulse, a double peak per cardiac cycle can be appreciated. Bisferious means striking twice. Classically, it is detected when aortic prolapse with regurgitation exists in association with aortic stenosis, but may also be found in isolated but severe aortic regurgitation , and hypertrophic obstructive cardiomyopathy
(idiopathic hypertrophy of heart muscle).
4. Pulsus tardus et parvus , ( slow-rising pulse) a sign where, upon palpation, the pulse is weak/small (parvus), and late
(tardus) relative to its usually expected character. It is seen in aortic valve stenosis.

5. Pulsus paradoxus is an exaggeration of the normal variation during the inspiratory phase of respiration, in which the blood pressure declines as one inhales and increases as one exhales. It is a sign that is indicative of several conditions including cardiac tamponade, pericarditis, chronic sleep apnea, and obstructive lung disease (e.g. asthma, COPD).

TAKING A BLOOD PRESSURE
See the PowerPoint
Blood Pressure Determination

Figure 19.18a

Figure 19.18b

Figure 19.19

Figure 19.20a

Figure 19.20b

Figure 19.21a

Figure 19.21b

Figure 19.21c, d

Figure 19.21d

Figure 19.22a

Figure 19.22b

Figure 19.23a

Figure 19.23b

Figure 19.23c

Figure 19.23d

Figure 19.24a

Figure 19.24b, c

Figure 19.25a

Figure 19.25b

Figure 19.26a

Figure 19.26b, c

Figure 19.26b

Figure 19.26c

Figure 19.27a

Figure 19.27b

Figure 19.28a

Figure 19.28b

Figure 19.28c

Figure 19.29a

Figure 19.29b, c