-LV Concentric Hypertrophy

-sarcomeres added in parallel

-in pressure overload patients
-thicker wall, smaller chamber volume (Law of Laplace)
-LV Eccentric Hypertrophy
-sarcomeres added in series
-in volume overloaded patients
-large, dilated ventricle

Regulation of Regional Circulations Thursday

List the specialized functions of each of the following circulations. For each of these circulations, explain the
structural and functional adaptations that underlie their specialized functions. Explain the special challenges faced
by each of these circulations.

Skeletal muscle
1. Specialized Functions
a. Blood pressure maintenance
i. Since skeletal muscle contributes to a large proportion of lean body mass (approximately 40%) its
circulation is critical to maintenance of arterial pressure.
ii. At rest, the skeletal muscle circulation has a significant amount of “vascular tone,”
1. at rest, the blood vessels in the skeletal muscle are partially constricted.

b. Oxygen/substrate delivery to exercising muscle, and waste removal

i. Blood flow to exercising muscle can increase up to 20 fold to meet the metabolic demands
(supplying nourishment and oxygen and removing waste) of exercising muscle.
2. Structural Adaptation
a. Slow twitch- Type 1- red
i. High cap density
ii. High mitochondrial content
iii. High myoglobin
iv. Marathoners
v. Tonically active, postural, muscles
vi. Almost constant metabolic demands
b. Fast Twitch- Type II- white
i. Sprinters
 3. Functional Adaptations
a. Vasoconstriction dominates at rest
i. Mediated by persistent SNS activation to blood vessels of skeletal muscles
ii. Sympathetic tone is controlled by arterial baroreceptors
iii. If you inhibit SNS activityà blood flow increase
iv. Activation of SNS helps maintain BP
v. How can increased oxygen demands be met if the SNS vasoconstricts?
1. Vasodilation occurs in exercising muscles
2. Mechanisms = Metabolic vasodilation and Skeletal muscle pump
3. Flow to exercising muscle can increase 20-fold
4. Metabolic Vasodilation
a. Ischemic metabolites generatedà act on arterioles locally to produce
vasodilation
b. Vasodilator substances = increased interstitial K, increased interstitial
osmolarity, inorganic phosphates, hypoxia and adenosine from the breakdown
of ATP
c. Lead to capillary recruitment by dilating terminal arterioles
5. Skeletal Muscle pump
a. Rhythmic muscle contraction during exercise messages venous blood from
capacitance vessels back to the heart
4. Special Challenges
a. Strong muscle contractions mechanically impede muscle blood flow
i. So heavy weight liftingà fatigue/pain/burning sooner than when jogging
ii. This isn’t a problem during rhythmic exercises (walking or jogging) b/c they are constantly relaxing
to allow flow again
iii. With weight lifting, we sustain the time spent in contraction
b. Increased capillary filtration during exercise leads to intravascular volume loss
i. Increased fluid movement out of capillaries
ii. Can lead to edema during exercise

Skin
1. Specialized Functions
a. Regulate internal temperature
i. Heat generated internally is lost at the surface
ii. 3 ways
1. radiation
2. Conduction-Convection
3. Evaporation of sweat
b. Protection
i. During trauma, from infection
ii. In response to traumaà increased blood flow in skin locallyà faster healing
2. Structural Adaptation
a. AVAs- arteriovenous anastomoses
i. Direct connections between arterioles and venules
ii. Large, coiled vessels concentrated in acral skin (hands, feet, lips, nose, ears)
iii. Normally constricted by SNS
iv. When core temp rises, sympathetic tone is removedà AVAs dilateà bring more blood to the skin
surface for heat loss
v. Controlled by hypothalamus
3. Functional Adaptation
a. Ambient temp directly influences skin blood flow
i. cold outsideà constrict AVAs
b. Ambient temp evokes weak spinal reflex
i. put on hand in iceà other hand will vasoconstrict too
c. Hypothalamus
i. senses core temp in anterior hypo.
ii. Controls brainstem neurons that govern sympathetic output to skin
 1. In acral skin- where AVAs are, withdrawing sympathetic vasoconstrictor activity causes
increased skin blood flow
2. In non-acral skin- no AVAs, dilation is due to active sympathetic vasodilater nerves
d. Supporting BP
i. Under extreme conditions, like hemorrhagic shock, skin blood flow helps to maintain BP
ii. During hemorrhagic shock, BP falls to low levelsà Vasoconstriction in skin supports BP and
Venoconstriction in skin helps increase preload
4. Special Challenges
a. Exercise on a hot day
i. Mandates increased blood flow to working muscle à results in increased core temp
ii. Skin blood flow must increase
iii. But there is decreased peripheral resistance due to vasodilation in exercising muscle
iv. Plasma volume is decreased due to transcapillary filtration
v. The capacity of the heart to meet cutaneous and muscle blood flow demands may be exceededà
causing hypotension and collapse
1. Heat Stressà Heat Exhaustionà Heat Stroke L

Brain
1. Specialized Functions
a. Needs a super secure blood supply.
i. It is very sensitive to hypoxia. LOC within seconds of hypoxia
b. Increased local perfusion to local activity.
i. Blood flow and metabolic rate increase in the visual cortex when the retina is illuminated
2. Structural Adaptation
a. Circle of Willis- all the main vessels that enter the cranium are connected at the circle
i. Basilar and Carotid arteries join to form complete arterial circle
ii. If one artery is obstructedà blood can still reach area through the circle
b. High Capillary Density
i. Large surface area for exchange and small diffusion distance
3. Functional Adaptation
a. High basal blood flow
b. Reflex control of body blood flow
i. Brain blood flow is maintained at the expense of perfusion to organs of the rest of the body
(except the heart)
c. Autoregulation
i. Brain can maintain the same level of blood flow despite systemic blood pressure changes
ii. Only when MAP is less than 50, the blood flow will declineà syncope
d. Cerebral vessels are super sensitive to arterial CO2 levels
i. Hypercapnia (high CO2)à Vasodilation
ii. Hypocapniaà Vasoconstriction
e. Cortical metabolic hyperemia
i. Blood flow increases to areas that are metabolically active
ii. Mediated by Increases in interstitial K, H+, adenosine that are made by metabolically active
neurons
f. Innervation of cerebral blood vessels
i. Flow is only minimally affected by changes in local sympathetic tone
g. BBB
i. Ensures tightly controlled cellular environment
ii. only lipid-soluble molecules can cross
4. Special Challenges
a. Postural Hypotension
i. Gravity can decrease our preloadà decrease COà decrease cerebral blood flow
b. Space-occupying lesions in a rigid box
i. No room for brain to swell
ii. Brain can herniate if swelling is bad enough

Lung
 1. Specialized Functions
a. Respiratory gas exchange
b. Metabolic conversion of vasoactive substances by endothelium
i. Ex: conversion of angiotensin I to angiotensin II carried out by lung endothelium
2. Structural Adaptations
a. Tons of capillaries
i. Huge surface area
ii. Tiny diffusion distances
iii. Flow limited exchange- greater oxygen uptake can be achieves if flow is increased
3. Functional Adaptation
a. Hypoxic Vasoconstriction
i. All other tissues vasodilate in response to hypoxia, but the lungs vasoCONSTRICT during local
hypoxia
ii. Helps optimize vent-to-perfusion ratio
iii. If oxygen supply to an area of lung is limitedà local pulmonary circulation constricts and directs
blood to working areas of the lung
iv. Endothelial mediated and may also be mediated by adenosine
4. Special Challenges
a. V/Q mismatch in vertical individual
i. Since pulmonary arterial pressure is low, the lung apices (tops) are poorly perfused in an upright
position
1. Creates a small vent-to-perfusion mismatch (well ventilated by poorly perfused)
2. During exercise, pulmonary artery pressure increasedà mismatch lessens

Cardiac Metabolism and Coronary Circulation Friday

List and define the different kinds of work performed by heart muscle.
1. Work (work, work, work, work, work) = Force applied over a distance
2. Different types of work that the heart does
a. Stroke Work = Stroke volume (the volume of blood ejected from the left ventricle with each beat) x Aortic
Pressure (the area inside the pressure- volume loop). Equivalent of Force x Distance.
i. Stroke volume is often abbreviated as SV. Aortic is often abbreviated as Ao.
b. Minute Work = Work per minute = Cardiac Output (CO) x Ao Pressure.
c. Volume work = Cardiac output (liters per minute of blood flow) ≈ External Work.
d. Pressure work ≈ Aortic Pressure ≈ Internal Work

List the principle substrates used by the myocardium for metabolism and discuss which is preferred and why.
1. Free fatty acids via β oxidationà into TCA Cycle
2. Glucose via aerobic Glycolysis
a. Also stored as glycogen
3. Heart prefers FA > glc and glycogen if FA and oxygen are available

Describe the changes in coronary flow during the cardiac cycle.

1. Coronary flow is regulated in large part through changes in coronary vascular resistance.
2. Local metabolites play the largest role, particularly hypoxia and the ATP breakdown product Adenosine.
a. Also acidosis, and hyperkalemia.
3. Reactive hyperemia occurs with each beat, as coronary arteries compressed during systole (causing reduced blood
flow)
a. so increased flow occurs during diastole to compensate (hyperemia).
b. Implications for tachycardia where diastole shortened.
c. 80% of coronary flow occurs during diastole
d. flow ceases, and can even reverse in systole
4. Endothelium-dependent relaxing factor (nitric oxide, NO) also critical in the regulation of coronary circulation.
a. NO vasodilates coronary arteries.
5. Autonomic nervous system and coronary flow:
a. parasympathetic à vasodilation
b. sympathetic à vasoconstriction
Explain the relationship of coronary blood flow to myocardial metabolism.
1. Energy requires oxygenà if need more oxygen, Increase the flow
2. Amount of O2 used by heart to generate energy is called Myocardial Oxygen Consumption (MVO2)
3. MVO2 correlates directly with cardiac minute work (MW= CO x Aortic Pressure)
4. Things that increase MVO2
a. Outflow obstruction- Aortic stenosis
b. Hypertension
c. Tachycardia

Explain the difference between the demands imposed by pressure work vs. volume work on the heart.
1. Pressure work is more costly than volume work!

Define coronary flow reserve, and describe the neural control of coronary vascular tone.
2. CFR= Increased potential flow through coronary arteries to meet demands of exercise
a. Normal coronary vessels can increase their flow 3-4 fold
b. Compromised CFR can limit supply to meet increased demands, leading to imbalance
3. Autonomic nervous system and coronary flow:
a. parasympathetic à vasodilation
b. sympathetic à vasoconstriction

Describe in detail the major determinants of O2 consumption (demand), including wall stress as defined by the
Law of LaPlace.
1. Wall tension in the heart is more commonly referred to as Wall Stress.
2. Wall stress (i.e. tension) is directly correlated with MvO2 along with:
a. Heart rate
b. Contractility (+dP/dt)

Explain why beta agonist drugs increase myocardial oxygen consumption and why beta antagonist (blockers) drugs
decrease myocardial oxygen consumption.
State the roles of adenosine and nitric oxide on coronary vascular tone and the relationship to cardiac work.

Define acute ischemia versus infarction

1. Ischemia- when O2 supply doesn’t meet demand
2. Infarction- area of necrosis caused by prolonged ischemia

List the sequence of functional failure during acute ischemia.

1. Impaired rate of relaxation
Immediate
2. Impaired force generation
3. Rapid K leak and Na gain

4. Onset of contracture (rigor)

After 15 minutes
5. Onset of Na-K pump failure

Case Studies: Chief Complaint: Fatigue Friday

Just study from the slides
 WEEK 3
Valvular Pathologies Monday
Understand concepts of preload and afterload in cardiac physiology. Understand and list factors that lead to
pressure and volume load, both physiologic and pathological
Already covered in previous lectures?

Understand role of Laplace’s law in demonstrating cardiac physiological remodeling responses to increased tension

𝑃𝑥𝑅
𝐴𝑓𝑡𝑒𝑟𝑙𝑜𝑎𝑑 = 𝑇𝑒𝑛𝑠𝑖𝑜𝑛 =
2ℎ
P= arterial pressure and/or OTHER OBSTRUCTION TO FLOW
R= Radius of the ventricle chamber
h- wall thickness of ventricle

1. Afterload is determined by the combination of the intrinsic wall stress during contraction and the forces that
oppose/resist LV contraction.
a. Like pushing against the door or blowing up the balloon

2. Increased LV wall thickness is in response to increased afterload and offsets wall stress

Identify factors that can lead to heart failure-like presentations, including valvular disease. Understand
mechanisms of volume and or pressure load that can be induced by valvular disease and identify shifts in pressure
volume curves for both significant aortic and mitral disease

1. Conditions that Increase Afterload

a. Hypertension
b. Aortic Stenosis
i. Increased afterloadà increased LV wall stressà increased work
ii. LV develops hypertrophy
iii. Incomplete emptying of the ventricleà increased end-systolic volume
iv. SV is decreasedà Heart Failure-like Symptoms

2. Conditions that Increase LV Preload

a. Aortic Regurgitation
b. Mitral Regurgitation
i. ↓ Afterload because blood goes forward to aorta AND back to left atrium
ii. ↑ Preload because the left atrial volume increasesà so left ventricle volume increased
iii. Stroke Volume is high but forward output is relatively decreased
iv. LV Dilates in responseà PV loop may shift right in severe cases
v. High left atrial pressure and pulmonary venous pressure causes Heart Failure-like Symptoms

Understand and identify clinical presentation of aortic stenosis and regurgitation, as well as basic physical exam
findings that demonstrate hemodynamic manifestations of this disease

1. Aortic stenosis is a condition of increased afterload caused by a restricted, thickened valve.

a. ↑ afterload = ↑ LV wall stress = ↑ work
b. Pressure in LV >> pressure in aorta
c. LV develops hypertrophy – ↓afterload per Laplace law
d. Incomplete emptying of the LV, thus ↑ in end systolic volume.
e. Stroke volume is ↓ => heart failure symptoms such as shortness of breath
2. EKG
a. Tall QRS complexes suggest LVH
3. Echo
a. Might have bicuspid valve
b. Valve will look thick
c. Doppler will show accelerating yellow flow because it is going through the smaller orifice
4. Murmur
 a. systolic crescendo-decrescendo murmur due to ↑ velocity of flow across the stenotic valve
5. Can occur at any age
6. Can fix with valve replacements

Understand and identify clinical presentation of mitral stenosis and regurgitation, as well as basic physical exam
findings that demonstrate hemodynamic manifestations of this disease

1. Mitral regurgitation: a condition of increased preload

a. ↓ afterload (blood from LV now has 2 exit routes: forward to aorta AND backwards to low pressure/ low
resistance left atrium
b. ↑ preload: ↑ left atrial volume, ↑ left ventricular diastolic filling and ↑end diastolic volume
c. Stroke volume is high but forward output is relatively decreased
d. Left ventricle DILATES in response – PV loop may shift rightward in chronic severe mitral regurgitation
e. High left atrial pressure and pulmonary venous pressure causes heart failure symptoms even though left
ventricular function is “normal”
2. EKG
a. Large negative P wave suggests left atrial enlargement
3. Mitral valve prolapse leading to regurgitation
4. Echo
a. Doppler will show blood backtracking back into the left atrium
5. Murmur
a. High pitched and blowing b/c the fast flow due to the big pressure difference between the LV and LA
b. Holosystolic murmur at the apex
6. LA pressure increases since it’s getting re-filledà Will have tall V-wave on the atrial pressure tracing on the Wiggers
Diagram
7. Can fix with new valves just like with aortic stenosis
8. Can occur at any age
 Cardiovascular Receptors Monday
Overview
1. 4 important groups of receptors
2. Each recognize different stimuli and will either inhibit or excite Sympathetic Outflow as a result
a. Inhibitory- inhibit Symp Outflow and decreases BP
b. Excitatory- increase Symp Outflow and increase BP

Arterial baroreceptors
1. Anatomy
a. Unencapsulated nerve endings in the adventitial walls of two major arteries:
i. Aortic Arch
ii. Carotid Sinus
b. Travel back to the brain via CN IX and X
c. Synapse in brain at Nucleus Tractus Solitaries (NTS)
2. Stimulus
a. Sense stretch which is mediated by changes in BP
b. They don’t sense absolute blood pressure, but CHANGES in BP
i. Change in pressureà change in amount of stretch
3. Action on NTS
a. Inhibitory on NTS
b. Increase in BPà Increase stretchà Increase Baroreceptor firingà Inhibits efferent Symp Outflow from CNS
c. Opposite effect for decrease in BP
4. Effect
5. Example: Hemorrhaging
a. Decrease in BPà decrease stretchà decrease in baroreceptor nerve firingà decrease I inhibition of the
central sympathetic outflow from the NTSà Efferent arm of sympathetic system increases and Vagal Tone
to heart decreasesà Increased HR, contractility and SV
b. SNS also increases to the kidneyà renal vasoconstriction and activation of renin-aldosterone-angiotension
system
c. SNS also increases to skeletal musclesà Vasoconstriction
d. SNS also increases to splanchnic circulationà Vasoconstriction and Venoconstriction in the gut
6. Q: Baroreceptors buffer ACUTE changes in blood pressure only. What would happen to blood pressure if the arterial
baroreceptors were surgically cut?
a. MAP doesn’t change, but fluctuations around the mean increase. Arterial baroreceptors are mainly
responsible for buffering ACUTE changes in BP