REGULATION OF THE HEART AND BLOOD PRESSURE Cardiovascular System

Introduction 1. Although the heart is autorhythmic, it must be able to adjust to changing demands within the body 2. At rest, body cells must receive oxygenated blood with nutrients to maintain a healthy status. 3. When cells are very active, as occurs with exercise, the demands on the cardiovascular system

increase dramatically. As a result, more blood must circulate through exercising skeletal muscle as compared to a resting state.

4. Example: Strenuous Exercise a. At rest, skeletal muscle receives about 1L/min of blood (this is about 20-25% of all the blood

pumped by the heart at rest) and about 25% of the capillary beds are open b. During exercise, skeletal muscle demands more oxygen and fuel substrates (e.g. fatty acids and

glucose) and generates more waste (e.g. lactic acid and carbon dioxide). 1. During heavy exercise blood flow through muscle increases 2. Exercise is one of the most physiologically stressful periods for the cardiovascular system 3. The body must supply this extra volume of blood or the muscle fatigues

Cardiac Output (resting) 1. Cardiac Output (CO) - amount of blood pumped by the left ventricle (or the right ventricle) into the

aorta (or pulmonary trunk) each minute. There are around 5-6 L of blood in human body 2. Cardiac output is determined by

a. Resting Stroke Volume (SV) - the volume of blood ejected by the ventricle per beat = 70 ml/beat b. Resting Heart Rate (HR) - number of heart beats per minute = 70-75 beats/minute (resting)

3. Resting CO (ml/min) = Stroke Volume (70 ml/beat) x Heart Rate (75 beats/minute) = 5.25 L/min (rough comparisons: 4L = 1 Gal, b/c 1L = 1qt, 1qt = 2 pints, 1 pint = ½ L). 5.25 L or 5250 ml (1.4 gal) is equivalent to all of the blood in the body

Exercising Cardiac Output = (150 beats/min) x (140 ml/beat) = 21 liters/min 4. Resting CO is close to the total amount of blood in the body (approx 5 liters), thus the entire blood

volume flows through the pulmonary and systemic circuits each minute. 5. Interestingly, blood flow to the brain stays relatively constant between rest and exercise. In fact,

blood flow to the brain fluctuates less than any other organ. This is so because even a several second disruption in the blood flow to the brain can cause unconsciousness and 4 or 5 minutes of anoxia can result in irreversible brain damage or death.

CO=HRxSV Blood Flow (ml/min)

Cardiac Output (L/min)

Heart Rate

(beats/min)

Stroke Volume (ml/beat)

Skeletal Muscle

Abdominal viscera

and kidney

Brain

Skin

Breathing Rate (Breaths/min)

Rest 5 70 70 1200 2500 750 500 12/min

Strenuous exercise

25 (trained athlete)

180 140 >=5000 up to

12,000)

1200 750 2000 (heat loss)

20/min

* A cardiac output of 35 L/min is associated with world-class athletes, whereas 25 L/min is that of a person who is in good physical condition (HR of 180 bpm x SV of 140 ml/beat = CO of 25.2 L/min). Blood flow into skeletal muscles increases significantly during exercise. Resting skeletal muscle receives around 1 liter of blood (about 25% of the CO) and during rest only about 25% of the capillary beds are open.

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Regulation of Stroke Volume 1. End-Systolic Volume (ESV), End Diastolic Volume (EDV), and Stroke Volume (SV)

a. Healthy resting heart pumps out 50 to 60% of blood in ventricles with each beat (this can be severely reduced in individuals with diseased hearts). During vigorous exercise the ejection fraction may be as high as 90%. The ejection fraction at rest drops below 50% in a diseased heart.

b. EDV – volume of blood in ventricle at end of diastole (when heart chamber fills with blood) c. ESV – residual amount of blood remaining in the ventricles after systole (ejection of blood). At

rest, around 60% gets pumped out with each beat. d. SV = EDV – ESV = amount of blood pumped out of a ventricle when the heart beats e. More forceful contractions pump more blood Typical Heart (resting conditions) EDV = 120 ml ESV = 50 ml (around 40% of total remains in ventricles after each resting beat) SV = EDV – ESV = 70 ml (only 60% pumped out with each resting beat)

2. Contractility - factor that influences SV is myocardial contractility a. Contractility refers to the strength of muscle contraction regardless of volume in heart b. Factors that increase contractility (positive inotropic agents) cause a decrease in ESV because

more blood is pumped by the heart. Within limits, the greater the Ca2+ availability, the stronger the heart contraction. 1. Sympathetic innervation (release of epi and norepinephrine from postganglionic fibers) 2. Catecholamines from adrenal medulla (epinephrine into the blood)

c. Factors that Decrease Contractility 1. Parasymphathetic effects via asetylcholine and certain general anesthetics (e.g. halothane) 2. Increases in K+ level in extracellular fluid (too much will cause cardiac arrest where heart

muscle stops beating); excess K+ leads to a decrease in the availability of Ca2+ into the sarcoplasm of cardiac muscle cells

3. Medications referred to as Ca2+ channel blockers decrease myocardial force generation. 3. Effect of Stretching on Cardiac Muscle Contractility: Frank-Starling law of the Heart

a. Definition: Increasing amounts of blood into the heart, such as occurs during exercise, results in stronger contractions to eject more blood than at rest

Increase vol of blood filling ventricles during exercise -> increase force of contraction to pump out the extra blood

b. Within physiological limits, the force of contraction of cardiac muscle is proportional to load

(amount of blood). If stretch heart muscle as occurs during exercise when it pumps more blood per minute, then heart muscle contracts more forcefully

c. Heart acts like rubber band that is stretched to varying lengths in that cardiac muscle contracts more forcefully when stretched. Within limits, the more the ventricles are stretched because of increasing volumes of blood to contract against, the harder they contract.

d. effect is important during exercise

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Factors that Affect Heart Rate and Contractility Decrease Increase

Heart Rate Acetylcholine (parasym) Hyperkalemia (high K+) Hypoxia

Epi, norepi (sympathetic) Digitalis

Contraction Strength

Acetylcholine (parasym) slight effect Hypocalcemia (low Ca2+)

Epi, norepi Hypercalcemia (high Ca2+)

Organization of the Nervous System 1. CNS – brain and spinal cord 2. PNS – cranial and spinal nerves and all of their branches; sensory receptors and motor neurons a. Sensory (afferent, “towards”) b. Motor (efferent, “away from”) 1. somatic NS – somatic motor neurons associated with motor units release acetylcholine (Ach)

that stimulates skeletal muscle cells to contract. Ach is a stimulatory neurotransmitter that triggers cholinergic effects; somatic effects are voluntary (under conscious control with a few exceptions)

2. autonomic NS – autonomic motor neurons effect the activity of cardiac muscle cells, smooth muscle cells and glandular epithelial cells; autonomic effects occur automatically (under unconscious control)

a. parasympathetic motor neurons 1. release the neurotransmitter Ach (cholinergic) 2. promote resting and digestive functions

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b. sympathetic motor neurons trigger adrenergic effects through the following 1. release the neurotransmitter norepinephrine (NEpi) 2. respond to stressors: psychological (fear, anxiety, guilt) and physiological (exercise,

low blood sugar levels, hypothermia) 3. stimulate the release of the neurohormone epinephrine (Epi, adrenaline) into the

blood from the medulla of the adrenal gland a. since Epi circulates in blood throughout the body always get all Epi effects b. bronchodilation, vasoconstriction of arterioles, dilation of pupils, lipolysis, hepatic

glycogenolysis, increase BP, increase HR, increase SV, inhibit digestive activities

Regulation of Heart Rate by ANS 3 Autonomic Centers in Medulla Oblongata of Brainstem (CIC, CAC, VMC) 1. Autonomic Regulatory Centers in Medulla a. centers are clusters of autonomic motor neurons located in medulla oblongata of the brainstem

b. Cardioinhibitory Center (CIC) – triggers parasym effects to slow HR and reduce SV (decrease contractility)

c. Cardioaccelerator Center (CAC) – triggers sym output to increase HR and increase SV d. Vasomotor Center (VMC) – sym output to smooth muscle in walls of arterioles to control PR,

hence BP 2. Cardioinhibitory Center (CIC)

a. cluster of neurons in the medulla oblongata of the brainstem with output via parasympathetic fibers that travel within a branch off the vagus nerve (cranial nerve X) called the parasympathetic cardiac nerve primarily to the SA node and AV node. The right vagus nerve innervates mostly the SA node, while the left vagus nerve innervates mostly the AV node.

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Extrinsic Innervation of the Heart

▪ Heart is stimulated

by the sympathetic

cardioacceleratory

center

▪ Heart is inhibited by

the parasympathetic

cardioinhibitory

center

Figure 18.15

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b. Neurotransmitter - Acetylcholine released from postganglionic fibers (cholinergic effect) c. Effects (decr HR, decr SV, decr CO)(CO = HR x SV)

1. SA node - Decreased firing rate activity results in decreased HR (hyperpolarizing influence opens K+ channels in the membranes)

2. AV node - Increase AV node delay time (decrease HR since the impulse spreads more slowly) 3. decrease SV a. decrease contractility of ventricular myocardium (decrease strength of contraction). b. The ventricular myocardium receives very little parasympathetic innervation and the

effect on contractility is not pronounced. c. Vagal stim has little to no effect on cardiac contraction strength

d. Tonic Vagal Discharge - the CIC is tonically active all the time and in general has a braking action on the heart to help maintain the resting heart rate of 75 beats/minute. If the vagus nerves were cut, the heart rate would increase to the SA nodal rhythm (sinus rhythm) of about 90 to 100 beats/min

e. Maximal Parasympathetic Output can slow the heart rate to about 20 to 30 beats/minute or even stop the heart for a beat or two.

f. Parasympathetic effect: Consistent with its role to promote resting functions. The parasympathetic effect predominates during resting periods, which is most of the time

g. Emotions that Stimulate CIC: sadness and depression. These emotions that one experiences in the cerebrum can send impulses to cardiac centers in medulla oblongata of brainstem to slow down the heart to the point where a person faints as a result of insufficient blood flow to the brain (sometimes folks who hear bad news respond physiologically by fainting)

h. Atropine - drug that blocks Ach receptors on SA nodal cells – speeds up the heart rate 2. Cardioaccelerator Center (CAC)

a. Interneurons from the CAC of the medulla oblongata extend to the lateral horns of the thoracolumbar region of the spinal cord (T1-T5 in the case of the heart) where they stimulate sympathetic output to the heart (SA node, AV node, and atrial and ventricular myocardium) via the sympathetic cardiac nerves and to the medulla of the adrenal gland to release epi into the bloodstream

b. Heart Effects (direct) – when activated, the sym effects on the heart are more powerful and overwhelm the tonic parasym effects (incr Hr, incr SV, incr CO) 1. Neurotransmitter - Norepinephrine from postganglionic sympathetic fibers 2. SA node - Increases rate of SA node discharge, which increases HR 3. AV node - increases rate of cardiac impulse conduction (decrease AV node delay time and

increase HR) 4. Increase SV - increases Ca2+ availability for muscle contraction which increases strength of

contraction (contractility), thus increases SV (decrease ESV) 5. sympathetic fibers to the smooth muscle in the walls of the coronary arteries cause

vasodilation c. Adrenal Medulla - CAC discharge stimulates the modified sympathetic postganglionic cells in the

adrenal gland to release Epi into the bloodstream. a. Epi acts throughout body as a neurohormone. The medulla of the adrenal gland releases

90% Epi and 10% NEpi. b. Epi’s actions are on the heart (increase HR, SV, and contractility), lungs (incr diameter of

respiratory bronchioles), blood vessels (blood distribution changes), liver (glycogenolysis to increase blood glucose), and adipocytes (lipolysis to increase blood fatty acids).

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c. Overall Sympathetic effects 1. 50% Nepi (neurotransmitter) 2. 50% Epi (neurohormone from adrenal gland)

d. Maximal Sympathetic Stimulation – 230-250 beats/minute e. Sympathetic Discharge occurs in response to stressors a. physiological: exercise, injury, cold temperatures b. psychological: fear, anxiety, anger

Heart Rhythms 1. Normal - 75 beats/minute (60-100 bpm is normal range according to American Heart Association) 2. Tachycardia a. fast resting heart rate, usually > 100 beats/minute b. it can be caused by stress, anxiety, drugs, heart disease, or fever 3. Bradycardia - abnormally slow resting heart rate, usually less than 60 beats/minute.

a. The heart rate of an endurance- trained athlete is about 40 to 60 beats/minute. The heart rate also lowers naturally when one sleeps.

b. Training causes hypertrophy of the heart muscle (i.e., increased muscle mass, increased mitochondria, etc.) that causes the cardiac muscle cells to enlarge.

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Cardiac Output (CO)

Figure 19.7

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1. A stronger heart can pump more volume per beat so fewer are needed. Even with fewer beats per minute, the resting CO for a trained athlete is about the same as a healthy untrained individual.

2. Lance Armstrong (champion cyclist) had a resting heart rate of 32-34 bpm. c. Cardiovascular Fitness: Exercise aerobically for about 20 minutes three to five times per week -

brisk walking, jogging, bicycling, and swimming. Exercise must raise heart rate and cardiac output to realize beneficial effects. Exercise can increase HR significantly to 150 to 200 beats/min.

4. Atrial Flutter - atria rapidly contract at rates around 300 beats/minute. Atria do not pump blood and the pumping effectiveness of the heart is reduced by 20 to 30%

5. Myocardial infarction (MI, myocardial infarction), commonly known as a heart attack Myocardium – cardiac muscle in the wall of the heart

Infarct – cluster of cardiac muscle cells that die due to ischemia Ischemia – lack of O2 to cells because of decreased blood supply

a. What is an MI? Heart attack occurs as the oxygen-rich blood flow to an area of the myocardium

is blocked. If blood flow isn’t quickly restored, then the heart muscle dies. That can cause cardiac arrest (fibrillation)

b. Most Common Cause: Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) 1. CAD (also called CHD) is a condition that results from atherosclerosis over many years. a. Atherosclerosis occurs when fatty deposits (fat molecules and cholesterol) called plaque

build-up in arteries like the coronary arteries. Cholesterol circulating in the blood can cross through damaged endothelium and build up as plaque in walls of arteries

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b. The plaque can significantly occlude the artery all by itself (80% occlusion or more) and create health problems.

c. Hypertension increases the risk of atherosclerosis because it damages the inner lining of blood vessels. The damaged area can serve as a focal point where plaque forms

d. Atherosclerosis begins with damage to the endothelium caused by high BP, carbon monoxide from cigarette smoke (CO is taken up by endothelial cells and is toxic to them) and other factors such as high cholesterol or alcoholism

2. Thrombosis: Abnormal blood clots form on the surface of the plaque 3. Pieces of plaque can break off as an embolus and float with blood until it lodges in small

artery 4. Shuts off blood flow to tissue downstream resulting in ischemia (lack of oxygen) 5. Heart muscle cells die from oxygen deprivation causing an infarct. a. If the area is small, then a person may not be aware it occurred (silent heart attack) b. If large, then it causes a heart attack that may lead to death. 6. Infarct: The patch of myocardial cells that die is called an infarct. Damaged cells are replaced

by scar tissue (scar tissue is dense CT where it is not normally found) 7. the damaged heart muscle may loses its ability to contract properly and this may cause

arrhythmias (abnormal heart beat patterns) that lead to fibrillation and death 8. Dead and dying cells in the heart release pain-stimulating chemicals 9. A less common cause of a heart attack is a severe spasm of a coronary artery that shuts off

blood flow within blood vessels c. Symptoms: chest pain and shortness of breath, squeezing pressure within the chest as if a band

was tightening around the chest, dizziness, nausea (feel sick to stomach), vomiting, sweating d. a heart attack is a medical emergency and hospitalization (Code Blue condition) is required

because life-threatening arrhythmias may develop that cause death within the first few hours e. Risk factors: smoking, high blood pressure, lack of exercise, high fat diets, obesity, diabetes,

male, over 60 in age, high cholesterol levels (especially high LDL cholesterol). Many risk factors are associated with overweight individuals

f. about one-third of heart attacks are fatal. If a person lives beyond the first 2 hours after an attack then the probable outcome is good, but may include complications. Uncomplicated cases may fully recover with individuals resuming a normal and active lifestyle

6. Ventricular Fibrillation (VF) (also called cardiac arrest) a. What is it? VF is a life-threatening arrhythmia that may occur in a heart with dead and dying

cardiac muscle cells that result from heart attacks b. occurs when the cardiac impulse from the SA node loses the ability to control the beating of the

ventricles. This results in asynchronous contractions of small pockets of ventricular myocardium so that the heart quivers. Myocardial cells of ventricles contract independently of the SA node.

c. ventricles do not pump blood during fibrillation d. Death usually results within minutes unless corrected (Code Blue). Even if corrected, victim may

suffer irreversible brain damage e. Defibrillation (depolarize all myocardial cells at once allowing SA node to regain control)

1. External defibrillator used to apply a strong electric shock (700 volts) with insulated paddle electrodes applied to skin of the chest above the heart

2. heart stops beating, then hopefully resumes beating with a more normal rhythm 3. AED (automated external defibrillator) – devices often found in public places (hotels, schools,

airports, public buildings)

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4. Implantable defibrillator – device that can be implanted in the chest of people who are at risk of VF

f. Conditions that Can Cause VF include 1. the most common cause is a heart attack that destabilizes cardiac muscle cells 2. electrocution accidents 3. traumatic injuries to the chest that damage the heart (chest hits steering wheel in a crash) g. symptoms associated with a heart attack that occur within minutes to 1 hour prior to VF: chest

pain, shortness of breath, nausea, dizziness Congestive Heart Failure (CHF) 1. occurs when the pumping action of the heart is so low that blood circulation is inadequate to mee

tissue needs. 2. Results from the failure of either ventricle to eject blood effectively caused by a. coronary atherosclerosis – clogged vessels with fatty build up decrease oxygen and nutrients to

tissues downstream resulting in hypoxia. Cardiac muscle contracts ineffectively as a result. b. hypertension increases the load on the heart and causes myocardial cells to become

progressively weaker c. multiple myocardial infarcts over time create dead spots that are replaced by noncontractile

fibrous or scar tissue 3. If the left ventricle fails (pulmonary congestion) , then the blood backs up into the lungs and causes

pulmonary edema (fluid in the lungs), shortness of breath, and a sense of suffocation 4. If the right ventricle fails (peripheral congestion), then blood backs up in the vena cavae and leads to

systemic edema which causes fluids to pool in the abdominal cavity (ascites) and swelling of the fingers, ankles, and feet.

Control of Blood Pressure - BP changes to meet the different demands of the body. Pressures must be higher during exercise as compared to resting conditions 1. Blood Pressure (BP) a. BP is the force that the blood exerts against a vessel wall b. Generally given as the systemic BP which looks at the pressure of blood associated with left

ventricle as it undergoes systole and diastole c. Resting Systemic Arterial BP = 120 mmHg/80 mmHg (diastolic pressure never falls to 0 because

the elasticity of large arteries provides a recoil pressure). The pulmonary arterial pressure when the right ventricle contracts is much lower at 25/8 than the systemic blood pressure.

d. BP = CO x PR, where CO = HR x SV (BP = [HR x SV] x PR) e. Peripheral Resistance (PR, systemic vascular resistance) - resistance that blood vessels give to

the free flow of blood; blood is slowed by friction against the walls of the vessels 1. the diameter of blood vessels is inversely proportional to the peripheral resistance a. blood rubs against the wall of the blood vessel causing friction which slows down the flow

of blood b. some of the energy of motion is dissipated as heat energy as a result of friction 2. Vasomotion a. the PR is controlled by vasomotion which refers to changes in the diameter of blood

vessels, primarily arterioles although it involves arteries and veins as well. 1. diameter of the blood vessels is inversely proportional to the peripheral resistance 2. increase the diameter and decrease the PR 3. decrease the diameter and increase the PR

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b. Vasoconstriction – occurs as a vessel narrows in response to the contraction of smooth muscle within the wall of the vessel. Vasoconstriction leads to an increase in PR

c. Vasodilation – occurs as a vessel widens in response to the relaxation of smooth muscle in the wall of the vessel. Vasodilation leads to an decrease in PR

d. small arteries and arterioles account for about 50% of the total PR. However, large arteries and veins are also capable of vasomotion and control of the PR.

2. Autonomic NS Effects on BP (Cardiovascular Center (CIC, CAC, and VMC) – clusters of neurons in the medulla of the brainstem). Exercise is the most common stimulus to the CAC and VMC a. Cardioinhibitory Center (CIC) – mediates parasym response to decrease HR, decr CO, decr BP b. Cardioaccelerator Center (CAC) – mediates sym response to incr HR and SV, incr CO, incr BP c. Vasomotor Center (VMC) – exercise is the major stimulus to the VMC 1. Controls BP and effects vasomotion a. Controls diameter of most small arteries and arterioles exclusively via sympathetic output

to smooth muscle cells. b. Vasomotor center interneurons project to the spinal cord where sympathetic fibers

originate. c. Vasomotor fibers extend out from T1-L2. Postganglionic sympathetic neurons release

norepinephrine and affect the activity of smooth muscle in blood vessel wall, mainly arterioles

2. Vasoconstriction controlled by Vasomotor Center via sym output a. NEpi from sym neurons causes vasoconstriction in walls of blood vessels (mostly

arterioles) of kidney and digestive organs. Vasoconstriction decreases the diameter of vessels and increases the Peripheral Resistance (incr BP)

b. Epi from the adrenal gland causes (1) vasoconstriction in kidney, and digestive organs and (2) autoregulation of blood vessels (local regulatory mechanisms) in exercising skeletal muscle causes vasodilation that overrides any vasoconstrictor effects of Epi.

c. Autoregulation of arteriole diameter in exercising skeletal muscle 1. the vasodilation that occurs in exercising skeletal muscle is due primarily to the

build-up of local chemical factors in the IF around blood vessels (increases in lactic acid, CO2, H+)

2. These local chemical factors will relax smooth muscle in the walls of arteries and arterioles and cause vasodilation and relax precapillary sphincter muscles

3. this local effect occurs automatically and only in the specific muscles that are exercising

4. Blood flow to exercising skeletal muscle can increase by up to 20 times more than at rest

5. the effect of Epi on vasoconstriction in skeletal muscle decreases with exercise d. Exercise is the primary stimulus to the release of Epi from adrenal gland. Epi will do the

following during exercise 1. increase lipolysis in fat cells to provide fatty acids for ATP synthesis 2. increase hepatic glycogenolysis to provide glucose for ATP synthesis 3. increase muscle glycogenolysis to provide glucose for ATP synthesis 4. relax smooth muscle around bronchioles to cause bronchiodilation to increase the

volume of O2-rich air coming in to the lungs 5. increase HR, SV, CO, and BP to move more blood through the lungs and skeletal

muscle

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6. stimulate sweat glands to secrete sweat to evaporatively cool the body since exercising skeletal muscle generates a lot of heat

e. during exercise, local controls (mostly increasing levels of carbon dioxide, lactic acid and hydrogen ions) relax the smooth muscle within arteriole walls (vasodilation) and relax precapillary sphincter muscles to increase blood flow to capillaries within contracting skeletal muscle. Autoregulation at the level of skeletal muscle opposes the vasoconstriction and increases blood flow to and into muscle capillaries.

f. the predominant effect is to increase PR and increase BP when norepi and epi are released during stress

d. VMC is activated by physiological and psychological stressors

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3. Baroceptor Reflex – homeostatic mechanism that helps to regulate the resting BP a. Stretch receptors in the aorta arch and carotid arteries help to regulate blood pressure (also

found in walls of nearly all major arteries in neck and thorax) b. increases in resting BP stretches these blood vessels and that sends impulse along the axons of

sensory neurons to the medulla of the brainstem 1. Stimulate the CIC 2. Inhibit the VMC and inhibit the CAC 3. Effect: decrease BP

c. Baroceptor discharge is proportional to BP 1. if incr BP, then incr baroceptor firing rate which will incr CIC, decr VMC, decr CAC

2. if decr BP, then decr baroceptor firing rate which will decr CIC, incr VMC and incr CAC 4. Chemoceptors (control BP and Breathing)

a. chemoceptors adjust the breathing rate and depth in response to changes to pH, CO2, and O2 in blood plasma. Chemoceptors are located on the dendritic ends of unipolar sensory neurons

b. located in walls of aorta and carotid arteries and sensitive to changes in blood chemistry; also located in the medulla and on the sides of the IV ventricle

c. if increase [CO2] or increase [H+] as in acidosis or severe decrease [O2] these chemoceptors discharge

CO2 + H2O H2CO3 H+ + HCO3-

H2CO3: carbonic acid HCO3

-: bicarbonate ions During exercise Incr CO2, then incr H+ - this will increase breathing rate and depth Incr CO2, then incr H+ - this will increase chemoceptor activity to incr CAC, incr VMC and incr BP

to incr blood flow to the lungs 1. sensory impulses into medulla oblongata to increase CAC and increase VMC – Increase BP 2. Effect: Increase sympathetic outflow to increase PR, SV, and HR all of which increase BP

e. CO2 is the most important regulator of respiratory rate 1. Increase breathing rate and depth of breathing (hyperventilation) to blow off excess CO2

(flush CO2 out of the tissue spaces) 2. chemoceptors are highly sensitive to changes in CO2

Autoregulation 1. Autoregulation is the most important reason that blood vessels in skeletal muscle vasodilate during

exercise. This increases blood flow through the muscles involved in the exercise. Blood supply to exercising skeletal muscle can increase by 15-20 fold.

2 Autoregulation is the ability of tissues to regulate their own blood supply 3. If a tissue is not adequately perfused then it becomes hypoxic and metabolic waste products

accumulate such as CO2, H+, and lactic acid. 4. These waste products stimulate vasodilation which increases blood flow into local capillaries and

they relax precapillary sphincters 5. As the O2 supply increases and the waste products are flushed out the vessels vasoconstrict 6. autoregulation in exercising skeletal muscle overrides the vasoconstrictor effects of sympathetic

compounds (Epi, NEpi)

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During exercise several changes occur to increase BP 1. sym neurons increase HR, SV, and CO to increase BP 2. sym neurons vasoconstrict to skin, digestive organs and kidney – increase PR to increase BP 3. epi from adrenal gland vasodilates in skeletal muscle to increase blood flow 4. autoregulation to vasodilate to increase blood flow to exercising skeletal muscle Angiogenesis 1. In some cases, hypoxic tissue (lack of O2) can increase its own blood supply by angiogenesis, which is

the growth of new blood vessels 2. Angiogenesis occurs each month with the regrowth of the uterine lining. It also occurs as capillary

density increases over time in the muscles of well-conditioned athletes. Cancer cells within a tumor secrete angiogenic chemicals that cause blood vessels to grow into and vascularize the mass.

Chemical Control of Blood Pressure 1. Angiotensin II (Ang II) a. Ang II a potent vasoconstrictor that raises the PR, thus increases BP b. angiotensinogen is an inactive protein made by the liver that circulates within plasma. When BP

drops, kidney cells release renin. Renin, in turn, converts angiotensinogen to Ang I. An enzyme called ACE (Angiotensin Converting Enzyme) associated with cells in the lung that line capillaries, then converts Ang I to Ang II.

c. ACE inhibitors are drugs that block ACE, thus prevent the formation of Ang II. This lowers BP. 2. Aldosterone a. Salt-and-water retaining hormone from the cortex of the adrenal gland to help prevent water

loss and to regulate Na+ and K+ levels in plasma. Aldosterone is a corticosteroid hormone. b. aldosterone increases salt reabsorption (NaCl) within the kidney nephron. This creates an

osmotic gradient that allows for water reabsorption. c. aldosterone acts to increase blood volume which leads to an increase in BP 3. Antidiuretic Hormone (ADH) a. Water-regulating peptide hormone secreted when the body is in a dehydrated state from the

posterior pituitary gland b. ADH increases the permeability of epithelial cells that line the collecting duct to water allowing

for the osmotic uptake of water c. ADH promotes water retention which leads to an increase in blood volume and an increase in BP 4. Epinephrine and norepinephrine a. catecholamines released from sympathetic neurons (neurotransmitters) and from the medullary

cells of the adrenal gland (neurohormone) in response to physiological and psychological stress b. they both promote vasoconstriction in most blood vessels, especially those of the kidneys and

digestive organs. As a result they increase the PR which raises the BP c. Epi has just the opposite effect with respect to the coronary blood vessels of the heart and the

arterioles that supply skeletal muscle. In these cases, epi causes vasodilation which allows for the increase in blood flow during exercise.

d. the net effect of epi and norepi within the body is vasoconstriction and an increase in PR and BP

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Blood Vessels - closed circuit of tubes; interior referred to as the lumen

Estimated Blood Vessels in the Body

Aorta...1 Large arteries...40

Smaller arteries...2400 Arterioles...40 million Capillaries...1.2 billion

Venules...80 million Small Veins...2400

Large Veins...40 Vena Cava (inferior and superior)...2

1. Arteries and arterioles a. Three-layered wall

1. tunica externa – mostly loose connective tissue with elastic and collagen fibers in matrix; the tunica externa often merges with the loose connective tissues of surrounding organs to stabilize and anchor blood vessels

2. tunica media - thickest layer made of smooth muscle arranged in a circular pattern and elastic fibers; highly vascular and well-innervated by sympathetic neurons that release NEpi to control vasomotion. The elast CT allows the walls of arteries and arterioles to expand and recoil like a rubber band as pulsing blood flows through them

3. tunica intima (endothelium) - inner lining consists of simple squamous epithelium; it normally repels blood cells and platelets to prevent them from sticking to the vessel wall and forming an abnormal clot (thrombus); tunica intima consists of the endothelial cells and the underlying CT containing elastic fibers

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b. Arteries have very thick muscular walls since they must withstand the highest BP’s; the systolic pressure that develops in large systemic arteries averages 90-120 mmHg

c. Arterioles are difficult to see with the naked eye and may be microscopic (< 1 mm in diameter) 1. arterioles play the largest role in maintaining blood pressure; arteriole vasomotion accounts

for about 50% of the peripheral resistance 2. smooth muscle of arterioles respond to catecholamines (epi and norepi) from sympathetic

neurons (vasomotor center discharge) and adrenal gland; arterioles vasoconstrict or vasodilate depending on where they are found

3. largest drop in blood pressure occurs as the blood goes through the arterioles 4. one arteriole may give rise to dozens of capillaries 5. arterioles are around 0.150 to 0.3 mm in diameter.

2. Metarterioles and thoroughfare channels a. metarterioles (or arterial capillary) are short blood vessels that link arterioles to capillaries b. one arteriole can sprout many metarterioles where each metarteriole opens up into a capillary

bed. c. capillaries drain into thoroughfare channels that drain into venules d. metarerioles and thoroughfare channels provide a shunt route for blood to bypass capillaries

when the precapillary sphincters are constricted 3. capillaries

a. microscopic vessels that are found close to almost every cell of the body (epidermis is nonvascular as is cartilage and the cornea and lens of the eye). RBC’s tend to go through capillaries in single file. It takes a RBC about 1 to 2 seconds to squeeze through a capillary bed.

b. Capillary Wall = endothelium (simple squamous epithelium) c. Capillaries generally form networks or beds (10-100 capillaries in a bed) d. Primary Function: Exchange between the blood and the tissue spaces. Exchange only occurs

across capillary walls (5% of total blood volume in capillaries at any given time) and some thin-walled venules as well.

e. there are an estimated 1 billion capillaries in the human body and no cell is more than 0.005 inches from a capillary (this is equivalent to the width of about 5 cells)

f. most capillaries are made up of cells that have many pores through the cell called fenestrations. Water, glucose, and other small nutrients can rapidly pass through these opening, but red cells

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Fenestrated Capillaries

Figure 19.3bCopyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Capillary Beds

Figure 19.4a

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and platelets cannot. There may also be clefts between the cells. White cells can move through the clefts by pseudopodial locomotion and changes in their shape.

g. Precapillary sphincter 1. precapillary sphincters are circular bands of smooth muscle at the entrance to a capillary bed 2. precapillary sphincters receive no innervation from the sympathetic fibers and respond only

to local control (autoregulation); they open in response to elevated levels of CO2 or H+ or decreases in O2

3. constriction of these sphincters decreases or shuts off blood flow into the capillaries and vasodilation increases blood flow

4. if precapillary sphincter is closed, then blood bypasses the capillary bed by flowing directly from a metarteriole and into a thoroughfare channel and from there into venules

5. there is not enough blood in the body to fill up all of the capillary beds. At rest, many capillaries receive very little blood as a result of clamping off by the precapillary sphincters. In skeletal muscle, for example, about 75% of the capillaries have very little blood flow through them at rest. During exercise, the capillary beds open up to provide oxygen and glucose to the contracting muscle, while capillaries in the intestines shut down to compensate.

4. Venules and Veins

a. Three-layered Wall (tunica media is thin compared to arteries since veins carry low pressure blood) that averages about 10 mmHg

b. One-way valves (not present in any other blood vessels); also found in lymph vessels 1. cup-like structures on the sides of the vein that only allow blood to flow towards heart 2. blood flow towards the heart causes them to collapse against the wall of the vein, but they fill

up with blood and close off the vein when blood attempts retrograde flow 3. same construction as semilunar valves in the heart

Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings

Figure 19.14.2

Capillary Exchange of Respiratory Gases and

Nutrients

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Blood Pressure Changes in the Vessels

LV (120/80) pumps blood into aorta

BP drops slightly in the major arteries but still get a pulse pressure

BP fades in smaller arteries within organs

Constant BP of 30-35 mmHg in arterioles

Leaky capillaries cause BP to drop significantly

16 mmHg in venules <5 mmHg in major veins

c. Factors that Affect Venous Return - blood pressure in the venous system is relatively low and not always sufficient to return blood to the heart, especially from the lower extremities. BP is around 15mmHg in venules and < 5 mmHg in major veins 1. Heart Contractions 2. Major Artery Pumps (e.g., aorta, carotids) – elastic

recoil puts pressure on the blood 3. Skeletal Muscle Pumps (mostly affects deep veins in

the legs) - contracting skeletal muscle moves venous blood by "milking" (press down on veins inside skeletal muscles); one-way valves prevent backflow; this occurs, for example, as one walks and shifts positions; massaging action on large veins; if stand still for a long time get swollen ankles

4. Respiratory Pump a. Diaphragm contracts and flattens during

inspiration. This results in a decrease in the volume of the abdominal cavity and a simultaneous increase in its air pressure. Boyle’s Law: P inversely proportional to V. An incr in air P within the abdominal cavity presses down on the IVC to move blood towards the heart

b. Causes pressure and volume changes in thoracic and abdominal cavities that helps to move venous blood towards heart (abdominal pressure increases as thoracic pressure decreases, thus generating a pressure gradient for blood to move along)

c. Only possible because of one-way valves that prevent retrograde flow

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d. Varicose Veins (15% of adults) 1. Varicose veins are dilated superficial veins that are visible at the skin surface. Occurs in

individuals with weak one-way valves that become leaky; due to incompetent valves. 2. Veins become distended or swollen and enlarge. Over time, fluid tends to pool in the legs

and feet as drainage decreases. 3. Superficial veins are most affected and they sometimes bulge out at the surface of the skin

and assume twisted pathways (“spider” veins) 4. usually develop in people who stand for a long period of time such as cashiers, especially if

they are obese; varicose veins can also occur as a result of pregnancy. Overweight people with a potbelly can create pressure on the groin region and exert increased resistance to venous flow back to heart. This tends to enlarge veins and weakens valves.

5. hemorrhoids are varicose veins of the anal canal Aneurysms and Strokes 1. Aneurysm (Gk: dilate) – thin and weak balloon-like bulge in vessel wall a. an aneurysm is a weak point in the wall of an artery or the heart. b. over time, an aneurysm forms a bulging sac that may rupture. This can result in internal

hemorrhaging (bleeding) that can damage the brain and cause death c. the most common sites of aneurysms are the abdominal aorta, renal arteries, and arteries within

the brain d. the most common cause of an aneurysm is a combination of atherosclerosis and hypertension 2. Stroke (CVA, cerebrovascular accident) a. a stroke occurs as the result of the sudden death (infarction) of brain tissue by ischemia (lack of

oxygen). Ischemia can be caused by atherosclerosis, thrombosis, or a ruptured aneurysm b. Effects of CVA depend on the extent and site of the damage c. A stroke that affects the brain may result in blindness, paralysis, loss of sensation, slurred speech,

cognitive deficits, etc. d. recovery depends on the ability of neighboring neurons to take over lost function (some of the

function generally returns within a year) Capillary Exchange - movement of materials across capillary walls 1. Most substances freely diffuse across capillary walls such as blood gases, glucose, ammonia, lactic

acid, hormones, vitamins, fatty acids, amino acids, and mineral salts like sodium and chloride ions. Substances may diffuse through the epithelial cells or move through clefts and fenestrations (openings or gaps) between them. Clefts are small openings between epithelial cells. They are smaller then fenestrations and more numerous.

2. RBCs and platelets do not cross, but WBCs do (diapedesis or emigration) 3. Plasma proteins - most remain in blood plasma, but some peptide hormones (e.g., GH, insulin, ADH)

get through capillary wall (role of lymphatic system) (i.e., albumin (60% of plasma proteins), fibrinogen, angiotensinogen, prothrombin, antibodies, lipoproteins like LDL and HDL, protein hormones like insulin, glucagon, and FSH). Small proteins that cross through most capillary walls include insulin, GH and FSH.

4. Osmosis a. diffusion of a solvent (e.g., water) from one solution to another through a semipermeable

membrane b. terms used to describe the two solutions

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1. hypertonic – solution with the higher solute concentration and the lower free water concentration

2. hypotonic – solution with the lower solute concentration and the higher water concentration 3. isotonic – term used to describe two solutions with the same solute and water

concentrations c. during osmosis, water diffuses from a hypotonic to a hypertonic solution 5. Osmotic Pressures a. the osmotic pressure of water = 0 mmHg b. the osmotic pressure is directly proportional to the solute concentration of a solution 1. as the solute concentration goes up so does the osmotic pressure. 2. Water diffuses into a solution with the higher osmotic pressure.

c. IFOP (1 mmHg) - Interstitial Fluid Osmotic Pressure (some protein in interstitial fluid that eventually enters lymphatic vessels. The IFOP tends to draw water out of capillaries and into the interstitial fluid

d. Oncotic Pressure (25 mmHg)(also called the colloid osmotic pressure) 1. osmotic pressure due to plasma proteins. a. the oncotic pressure is the osmotic pressure of plasma. b. The oncotic pressure tends to prevent water from leaving the capillaries. 2. the contribution of protein to the blood oncotic pressure is very important as evidenced from

the effects of protein-deficient diets. 3. albumin (585 aa), a protein made in the liver, is the major protein involved with the oncotic

pressure since it accounts for 50-60% of all plasma proteins 4. liver damage that results in decreasing levels of albumin in blood plasma can cause

osmoregulatory problems in the body that result in edema e. osmotic pressure is proportional to the solute concentration of a solution; f. osmotic pressure sometimes is conceptualized as a “pulling” pressure since solutions with high

osmotic pressures relative to another solution “pull” water into them by osmosis; when osmosis occurs, water always diffuses down a water concentration gradient

6. Blood Pressure a. hydrostatic or fluid pressure b. BP drops from around 35 mmHg to 17 mmHg across the length of most capillaries c. BP pushes water out of capillaries

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Dynamics of Capillary Exchange: Filtration and Reabsorption 1. Oncotic Pressure – osmotic pressure exerted by the plasma proteins; it doesn’t change within the

capillaries since the protein concentration stays relatively stable; this is the major force that prevents the movement of plasma and dissolved solute out of capillaries since it opposes filtration caused by the blood pressure

2. IFOP (interstitial fluid osmotic pressure) – the osmotic pressure exerted by solute in the interstitial fluid

3. Capillary Hydrostatic Pressure (or Blood pressure) – the pressure exerted by the blood against the capillary wall; this is the major force that drives H2O and dissolved solute out of capillaries

4. Filtration – net movement of plasma and dissolved solute out of the arteriole end of the capillary bed

5. Reabsorption – net movement of the interstitial fluid back into the capillaries at the venule end of the capillary bed; the major force that brings water back into the capillaries by reabsorption is the oncotic pressure

Outward Filtration at Arteriolar End of Capillary Arteriole End: fluid movement out of capillaries and into the interstitial fluid

Source of Pressure Arteriole End Pressure (mmHg)

Net Water Movement

Blood Pressure + IFOP 35 Out of Capillary

Oncotic Pressure (plasma proteins)

25 Into Capillary

Net Pressure Out 10 Out of Capillary

*BP is the fluid pressure or hydrostatic pressure of the blood against the capillary wall

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Inward Reabsorption at Venule End of Capillary

Venule End: fluid movement into capillaries and out of the interstitial fluid

Source of Pressure Venule End Pressure (mmHg) Water Movement

Blood Pressure + IFOP 17 Out of Capillary

Oncotic P (plasma proteins) 25 Into Capillary

Net Pressure In 8 Into Capillary

Arteriole Capillary Venule

10 8 Since 10 > 8, there is a net movement of water and dissolved solutes out of capillaries

6. Lymphatic System

a. 10-15% of fluid filtered does not return to venules. It remains in the interstitial spaces b. Some proteins escape from blood plasma and move into tissue spaces c. One Function of Lymph System: return excess IF and plasma proteins to blood vascular system of

system circuit d. without the lymphatic system a human would die in 24 hrs of heart and kidney problems as a

result of decreased blood volume (hypovolemic shock) 7. Kwashiorkor

a. Nutritional deficiency caused by diet that is severely deficient in protein b. Many African children in poor countries develop this type of nutritional dysfunction, since their

diet lacks animal products and depends heavily on cornmeal, cereal grains (wheat, corn, rice) c. Symptoms: Swollen abdomen, but emaciated arms and legs because of exceptionally thin and

nutrient-deprived skeletal muscle cells (“skin and bones”) 1. Deficiency of amino acids to liver cells decreases the production of several plasma proteins

(especially albumin since it accounts for about 60% of the plasma proteins) 2. If decrease Oncotic P, then more fluid out of capillary and into interstitial spaces within

abdomen (stomach swelling). Filtration overexceeds reabsorption 3. the bloated looking stomach along with the stick-like arms and legs is a sign of chronic

malnutrition 4. children with kwashiokor often die by the age of 5 from dehydration and malnutrition.

Edema 1. abnormal accumulation of excess interstitial fluid (mostly water) in tissue spaces (often loose

connective spaces) 2. it often results in the swelling of the face, fingers, abdomen, and ankles. But it also occurs in internal

organs that are hidden from view 3., edema occurs when more fluid moves out of capillaries then is reabsorbed 4. edema can occur under the following conditions a. kidney failure that leads to excess water retention in the body b. histamine released during an allergic reaction. Histamines are powerful vasodilators. They also

increase the permeability of capillaries c. people with a sedentary (inactive) lifestyle (wheelchair-bound or bed-ridden) with poor

circulation because of congestive heart failure

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d. cirrhosis of the liver (as a result of damage or disease) that leads to a decrease in albumin production in the blood. Albumin accounts for about 60% of the plasma protein content of blood and is important in maintaining plasma’s osmotic pressure which is the major force in capillaries that counteracts filtration

e. when capillaries are damaged, plasma proteins can cross the capillary wall and enter the interstitial fluid. The resulting elevation of the interstitial colloid osmotic pressure reduces the rate of capillary reabsorption and produces a localized edema seen at a bruise.

f. in starvation, the liver cannot synthesize enough plasma proteins to maintain normal concentrations in the blood. The blood colloid osmotic pressure declines and fluids begin moving from the blood to the peripheral tissues. This produces the kwashiorkor seen in the swollen bellies of starving kids.

g. heart problems can lead to increases in venous pressure which can lead to edema If capillary hydrostatic pressure goes up, then fluid moves into the tissues.

5. Problems with Edema a. pulmonary edema makes breathing so difficult that it can cause suffocation if fluid fills the air

sacs and prevents gas exchange b. edema can cause a severe drop in blood volume which can lead to a drop in blood pressure

which in turn causes circulatory shock in which the kidneys and the heart fail to work properly 1. Circulatory Shock is any condition in which blood vessels are inadequately filled with blood

and blood cannot circulate normally (e.g., loss of blood, chronic diarrhea, vomiting) 2. this results in inadequate flow to tissues and can result in death Cholesterol and Plasma Lipoproteins 1. Two Sources of Cholesterol

a. Animal-based Food (25%) - eggs, meat (beef, pork, chicken, lamb, turkey) and dairy products (milk, cheese, yogurt). High fat diets are rich in cholesterol and saturated fats. Some of the saturated fats are taken up by liver cells and converted to cholesterol. Fatty foods contribute to high cholesterol levels.

b. Liver (75%) 1. most cholesterol formed by liver cells; 2. the amount produced by the liver depends on the amount ingested with the diet 3. there is no dietary requirement for cholesterol. If no cholesterol is taken in with the diet, then

the liver makes all that the body needs 2. Why cholesterol?

a. necessary for formation and maintenance of all plasma membranes (all animal cells like our own need cholesterol); cholesterol is found between the phospholipids in the lipid bilayer part of the plasma membrane

b. precursor for formation of steroid hormones (testosterone, cortisol, estrogens, progesterone) in ovaries, testes, and adrenal gland

c. forms bile salts in liver (emulsifying agents that help in digestion of lipids) 3. Transport of Cholesterol in Blood Plasma

a. Lipid compounds, such as cholesterol, do not dissolve in water-based solutions like plasma b. Cholesterol and triglycerides must bind to water-soluble proteins before they can be transported

within the bloodstream c. lipoproteins – lipid and protein bonded together

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Plasma Lipoproteins (VLDL, LDL, HDL, chylomicrons) Lipoproteins that contribute to the formation of plaque are sometimes referred to as “bad” cholesterol 1. VLDL (very low density lipoprotein) – “bad” cholesterol since it contributes to plaque formation

a. made of protein, TG (triglycerides or fat molecules), and cholesterol 1. lipids are C-containing or organic compounds that are insoluble in water 2. cholesterol and triglycerides are lipids 3. the density of a lipoprotein is relative to the amount of lipid that it carries 4. lipids are less dense than water or proteins 5. lipids are not soluble in plasma, thus they must bind to soluble proteins in order to be

carried in the blood b. synthesized in the liver, then secreted into blood 1. Liver cells make trigylcerides and cholesterol. 2. Fat molecules are often made in the liver from nutrients that come in with the diet. c. function: carry TG to adipocytes (fat cells) where the TG’s are stored d. become LDLs as they lose their TG’s to adipocytes 1. lipoprotein lipase is an enzyme in the plasma membranes of capillaries in adipose tissue 2. lipoprotein lipase splits TGs away from VLDLs which converts VLDLs to LDLs 3. When the triglycerides are removed from VLDLs within blood capillaries, the lipid breakdown

products move into fat cells where they are resynthesized into storage trigylcerides VLDL (TG > cholesterol) → LDL (cholesterol > TG) + TG (go into fat cells)

4. VLDLs → IDLs → LDLs a. VLDL is a large, triglyceride-rich lipoprotein secreted by the liver that transports

triglyceride to adipose tissue and muscle. b. The triglycerides in VLDL are removed in capillaries by the enzyme lipoprotein lipase, and

the VLDL returns to the circulation as a smaller particle with a new name, intermediate-density lipoprotein (IDL). Although one might intuitively assume that "intermediate-density" refers to a density between that of high-density and low-density lipoproteins, it in fact refers to a density between that of low-density and very-low-density lipoproteins. Lipoproteins are classified as less dense when the fat to protein ratio is increased.

c. The IDL particles have lost most of their triglyceride, but they retain cholesteryl esters. d. Some of the IDL particles are rapidly taken up by the liver; others remain in circulation,

where they undergo further triglyceride hydrolysis and are converted to LDL. e. A distinguishing feature of the IDL particle is their content of multiple copies of the

receptor ligand ApoE in addition to a single copy of ApoB-100. The multiple copies of ApoE allow IDL to bind to the LDL receptor with a very high affinity. When IDL is converted to LDL, the ApoE leaves the particle and only the ApoB-100 remains. Thereafter, the affinity for the LDL receptor is much reduced.

f. In general, IDL, somewhat similar to low-density lipoprotein (LDL), transports a variety of triglyceride fats and cholesterol and, like LDL, can also promote the growth of atheroma.

2. LDL (low density lipoprotein) – “bad” cholesterol since it contributes to plaque formation a. made of protein, some TG and cholesterol b. derived from VLDLs c. function: carry cholesterol to the cells of the body d. cholesterol is used by cells 1. build and maintain plasma membrane 2. synthesize steroid hormones a. ovaries – estrogen and progesterone

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b. testes – testosterone c. adrenal gland – aldosterone and corticosteroids 3. make bile salts in the liver that emulsify fats during digestion e. LDLs move through capillary walls and into the tissue spaces where they are taken into cells by

receptor-mediated endocytosis f. LDLs broken down in cells by lysosomal enzymes to release cholesterol. The proteins are

broken down to amino acids and used by the cell as nutrients g. Atherosclerotic Plaque 1. LDLs pass through damaged endothelium (e.g., effects of hypertension) into tunica media and

deposit cholesterol and TG’s into walls of arteries as atherosclerotic plaque 2. affects major arteries like the carotid, coronary, aorta, and renal.

h. cholesterol that is not used by cells is secreted from the cell into the blood 3. HDL (high density lipoprotein) – “good” cholesterol since it helps to prevent plaque formation a. made and secreted by liver cells b. HDL’s are secreted by the liver as just protein with no lipid attached to them. Initially, HDLs are

empty collapsed protein shells that are released by liver cells into the blood. c. HDL’s attach to cholesterol that is secreted from cells and carry the cholesterol to the liver.

HDL’s also transport cholesterol to adrenal glands and gonads for steroid synthesis d. HDLs are ultimately made up of protein and cholesterol as they circulate in the blood e. HDL’s will attach to some of the cholesterol associated with plaque a. HDLs will strip cholesterol off the plaque b. this reduces the size of the plaque which is good f. HDLs carry the extra cholesterol in the body to the liver 1. liver cells take up the cholesterol from HDLs and incorporate the cholesterol into an

excretory product called bile 2. bile is secreted by the liver into the small intestine and eliminated with feces 3. this is the way that the body gets rid of excess cholesterol along with bilirubin from Hb

breakdown 4. as HDLs circulate through the liver, hepatocytes remove the cholesterol and eliminate it from

the body in the bile, either as free cholesterol or as bile salts that aid in the digestion of lipids 4. The elimination of cholesterol in the bile is the only means by which the body gets rid of excess

cholesterol. Bile is eventually eliminated with the feces. 5. Total Cholesterol = LDL, VLDL, and HDL cholesterol

a. want low LDL and VLDL levels (bad cholesterol) b. want high HDL levels (good cholesterol)

6. Factors that Lower Cholesterol a. Lifestyle: Exercise and Diet (lower fat) b. Drugs

1. Increase bile secretion by liver (get rid of cholesterol) 2. Block cholesterol synthesis by the liver

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Atherosclerosis (major contributor to the death of individuals) 1. What is atherosclerosis and why is it bad? a. Atherosclerosis is the formation of fat (lipid, mostly cholesterol and triglycerides) deposits called

plaque in the tunica intima of arteries (subendothelial space) and between the tunica intima and the underlying tunica media in areas that are associated with damage to the endothelium (usually from hypertension)

b. tunica intima consists of simple squamous epithelial cells (endothelium) on top of a base of elastic connective tissue. The tunica intima is next to the tunica media.

c. Atherosclerotic plaques (atheroma) block arteries and lead to ischemia d. ischemia is a decrease in blood flow. 1. Ischemia is caused by either blockage of a blood vessel via thrombosis or arterial embolism 2. ischemia decreases the delivery of O2 and nutrients to tissue cells that may suffer and die as

a result. 3. ischemia can result in the death of cardiac muscle cells (heart attack) or a stroke in the brain

(CVA, cerebrovascular accident) e. Atherosclerosis is the hardening and narrowing of the arteries, due to the formation of plaques

in the blood vessel. f. the plaque always forms in the tunica intima of arteries between the endothelial cells and the

tunica intima. Veins do not develop atherosclerotic plaque 2. Onset and stages a. damage to the tunica intima (endothelium) that can be caused by several factors to include 1. hypertension (high BP) causes the arteries to stretch and tear over time 2. chemicals in cigarette smoke (e.g., carbon monoxide) 3. bacterial and viral infections b. LDL’s (plasma proteins called low density lipoproteins) carrying cholesterol and TGs move

through the injured endothelium and into the tunic intima of the arterial wall. HDLs don’t completely remove the fatty compounds, hence they accumulate in the tunica intima.

c. Macrophages (WBCs, monocytes that move into tissue spaces) in the tunica intima “eat” the LDLs by receptor-mediated endocytosis and become known as foam cells.

1. The macrophages eat the fatty compounds in an attempt to remove them from the wall of the blood vessel.

2. The accumulation of fat-filled macrophages forms a “fatty streak” during the early stages of the atherosclerosis process.

3. The fatty streaks, that are not made of fat cells, eventually become part of the plaque 4. when the foam cells die, their fatty contents are released into the extracellular spaces and

become part of the plaque 3. Atherosclerotic plaque (atheroma) in the tunica intima of arteries a. cholesterol and trigylcerides in extracellular spaces b. macrophages (and neutrophils) c. macrophages that have become foam cells. Foam cells are fat-filled macrophages d. dead and dying macrophages (cell debris) release cholesterol and TGs into the extracellular

spaces g. fibrous connective tissue containing collagen fibers (scar tissue) forms in the damaged wall of

the artery. The exposure of collagen fibers to the blood can trigger abnormal blood clots (thrombus) on the edges of the plaque

g. crystals of calcium salts that will settle into the plaque from the bloodstream and cause it to harden (calcification)

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4. Harmful effects of plaque a. occludes or narrows the artery over time reducing blood flow downstream leading to ischemia

(e.g., coronary arteries in the heart, carotid arteries to the brain). 1. This can lead to a heart attack (myocardial infarction) or cerebrovascular accidents (CVA,

stroke). The heart attack can lead to arrhythmias like ventricular fibrillation (cardiac arrest) that causes one to die

2. Ischemia is caused by either blockage of a blood vessel via thrombosis or arterial embolism b. plaque serves as focal point for formation of an abnormal blood clot (thrombus). This can narrow

the artery leading to ischemia. c. if a part of the clot breaks off and floats downstream it becomes an embolus that can block

small arteries downstream. This can lead to strokes in the brain (CVA) that result in irreversible brain damage or death.

5. arteriosclerosis and atherosclerosis a. arteriosclerosis (sclerosis means to harden) – this is a general term that describes any condition

that causes the arterial wall to harden (stiffen) which decreases their elasticity 1. arteriosclerosis is usually referred to as “hardening of the arteries.” 2. arteriosclerosis can be caused by several factors to include plaque formation, hypertension,

calcium deposits in the artery wall, the formation of scar tissue as a result of injury to the artery.

b. atherosclerosis 1. type of arteriosclerosis in which the hardening to the arterial wall is specifically caused by

the formation of a fatty deposit in the arterial wall called plaque 2. atherosclerosis is sometimes called arteriosclerotic vascular disease (ASVD) 6. Major Risk Factors a. Unhealthy blood cholesterol levels. This includes high LDL cholesterol (sometimes called "bad"

cholesterol) and low HDL cholesterol (sometimes called "good" cholesterol). b. High blood pressure. Blood pressure is considered high if it stays at or above 140/90 mmHg over

time. If you have diabetes or chronic kidney disease, high blood pressure is defined as 130/80 mmHg or higher. (The mmHg is millimeters of mercury—the units used to measure blood pressure.)

c. Smoking. Smoking can damage and tighten blood vessels, raise cholesterol levels, and raise blood pressure. Smoking also doesn't allow enough oxygen to reach the body's tissues.

d. Insulin resistance. This condition occurs if the body can't use its insulin properly. Insulin is a hormone that helps move blood sugar into cells where it's used as an energy source. Insulin resistance may lead to diabetes.

e. Diabetes. With this disease, the body's blood sugar level is too high because the body doesn't make enough insulin or doesn't use its insulin properly.

f. Overweight or obesity. The terms "overweight" and "obesity" refer to body weight that's greater than what is considered healthy for a certain height.

g. Lack of physical activity. A lack of physical activity can worsen other risk factors for atherosclerosis, such as unhealthy blood cholesterol levels, high blood pressure, diabetes, and overweight and obesity.

h. Unhealthy diet. An unhealthy diet can raise your risk for atherosclerosis. Foods that are high in saturated and trans fats, cholesterol, sodium (salt), and sugar can worsen other atherosclerosis risk factors.

i. Older age. As you get older, your risk for atherosclerosis increases. Genetic or lifestyle factors cause plaque to build up in your arteries as you age. By the time you're middle-aged or older,

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enough plaque has built up to cause signs or symptoms. In men, the risk increases after age 45. In women, the risk increases after age 55.

j. Family history of early heart disease. Your risk for atherosclerosis increases if your father or a brother was diagnosed with heart disease before 55 years of age, or if your mother or a sister was diagnosed with heart disease before 65 years of age.

7. What to do to reduce risk of atherosclerosis? a. Don’t smoke b. Exercise c. eat a healthy diet that is relatively low in fat 8. Balloon Angioplasty and Stent a. insert a catheter with a deflated balloon on the end of it into the femoral or brachial arteries b. inflate the balloon with a stent around it to compress the fatty deposit against the blood vessel

wall c. the stent (metal mesh tube) remains in place against the compressed deposit as the catheter is

removed 9. Coronary Artery Bypass Surgery - sections of the great saphenous vein of the leg or small arteries

from the thoracic cavity are used to build a detour from the aorta to a point on the coronary artery down from the obstruction; angioplasty, which is discussed next is less expensive than a coronary bypass

10. Laser angioplasty: Laser angioplasty is similar to balloon angioplasty, but instead of a balloon-tipped catheter, one with a laser at the tip is used. The laser is guided to the blockage, then used to destroy the plaque, layer by layer, by vaporizing it into gaseous particles. The laser can be used alone, or in combination with balloon angioplasty. If it is teamed up with balloon angioplasty, with the balloon inserted first to attack the hard plaque. It is not used as frequently as other angioplasty procedures.

Circulatory Shock 1. Shock is an acute circulatory crisis marked by low blood pressure (hypotension) and inadequate

peripheral blood flow 2. Severe and potentially fatal signs and symptoms develop as vital organs become starved of oxygen

and nutrients. 3. Common causes of shock are a. a drop in cardiac output after hemorrhaging or other fluid losses b. damage to the heart c. extensive peripheral vasodilation

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4. Symptoms a. hypotension with systolic pressures below 90 mmHg b. pale, cool and moist (clammy) skin. The skin is pale and cool due to peripheral vasoconstriction;

the moisture reflects the sympathetic activation of sweat glands c. confusion and disorientation, due to drop in blood pressure to the brain d. a cessation of urination, because the reduced blood flow to the kidneys stops or slows urine

formation e. a drop in blood pH (acidosis(); due to lactic acid generation in oxygen-starved tissues 5. In mild forms of circulatory shock, homeostatic mechanisms compensate. In severe forms where

blood volume drops by more than 35%, the consequences are often fatal. Irreversible shock begins when oxygen starvation in the heart, liver, brain, and kidneys has caused such extensive damage that death will occur even with medical treatment.

Aneurism Bulge in the weakened wall of a blood vessel, generally an artery (like a bubble on a tire). May blow out and cause strokes in brain that lead to sensory, cognitive, and physical deficits. If aorta blows, may be fatal in minutes. The cause is usually traced back to atherosclerosis and high BP.