GPS: CV Physiology (Wondisford) - 11/1/16

Question 1

What are the major changes that occur during the transition from fetal to adult circulation?

Answer 1

Before birth:

• Oxygenated blood travels from placenta via umbilical vein (single)
• Deoxygenated blood returns to placenta via umbilical arteries (paired)

At birth:

• 3 bypass channels close (ductus venosus, foramen ovale, ductus arteriosis)
• Removal of placenta

Question 2

Cardiac Muscle:

Involuntary / voluntary?

Striated / smooth?

Uninuclear cells / Multinuclear cells?

How are cells connected?

Answer 2

• Involuntary
• Striated tissue containing:
• Uninuclear cells

Cells are connected end to end by intercalated discs

• Gap junctions (ion channels to propagate depolarization signal)
• Desmosomes (“spot welds”)
• Tight junctions

Question 3

Myocardial/Ventricular Action Potential:

Main difference between cardiac myocyte and skeletal muscle AP

Steps in myocyte contraction

Answer 3

Main difference:

• cardiac myocyte AP has a plateau: due to Ca2+ influx and K+ efflux
• cardiac muscle contraction requires Ca2+ influx from ECF to induce Ca2+ release from SR (Ca2+-induced Ca2+ release)
• cardiac myocytes are electrically coupled to each other by gap junctions

Steps:

• Phase 0 = rapid upstroke, I_Na
• Phase 1 = initial repolarization
• Phase 2 = plateau, ICa + IK
• Phase 3 = rapid repolarization, IK
• Phase 4 = resting potential, IK

Question 4

Frank-Starling Curve

What does it measure?

How can you inc. contractility?

How can you dec. contractility?

Answer 4

Force of contraction (stroke volume) is proportional to ventricular EDV (preload)

Inc. contractility:

• Catecholeamines
• Positive inotropes (e.g. digoxin)

Dec. contractility:

• Beta-blockers (acutely)
• Loss of myocardium (MI)
• Non-dihydropyridine Ca2+ channel blockers
• Dilated cardiomyopathy

Question 5

Cardiac output = ?

SV = ?

Answer 5

CO = SV * HR

SV = EDV - ESV (all filled up - vol. after contraction)

Question 6

Factors that affect SV (3)

Answer 6

1. Inc. in preload inc. EDV and SV
2. Inc. in afterload on the heart inc. ESV → dec. SV
3. Inc. inotropy (contractility) dec. ESV → inc. SV

Question 7

Fick Principle

Answer 7

Another way to calculate CO =

rate of O2 consumption / (arterial O2 content - venous O2 content)

(ml/min)/(ml/L) = L/min

Question 8

Mean Arterial Pressure (MAP) =

Answer 8

CO * TPR

2/3 diastolic pressure + 1/3 systolic pressure

Question 9

Pulse Pressure =

What is pulse pressure proportional/inversely proportional to?

In what conditions do you see inc. pulse pressure (4)?

In what conditions do you see dec. pulse pressure (4)

Answer 9

Systolic pressure - diastolic pressure

PP is proportional to SV and inversely proportional to arterial compliance

Conditions with inc. pulse pressure:

1. Hyperthyroidism
2. Aortic regurg
3. Aortic stiffening (isolated systolic apnea) → inc. sympathetic tone ** not b/c diastolic goes down like in 1 & 2 but b/c systolic goes up
4. Exercise (transient)

Conditions with dec. pulse pressure:

1. Aortic stenosis
2. Cardiogenic shock
3. Cardiac tamponade
4. Advanced HF

Question 10

HR + contractility controlled by autonomic nervous system (PSNS + SNS).

Answer 10

PSNS

• via vagus nerve (cholinergic M2 receptors on SA and AV node) → REDUCE HR

SNS

• (adrenergic B1 receptors on SA and AV node, cardiac myocyte) → INC. HR + CONTRACTILITY

Question 11

Contractility (and SV) increase with:

Contractility (and SV) decrease with:

Answer 11

Contractility (and SV) increase with:

• Catecholamines (B1 receptor)
  
  1. Phosphorylation of Ca2+ channels cause Ca2+ channels to remain open longer
  2. Phosphorylation of proteins in SR enhances release of Ca2+
  3. Phosphorylation of myosin inc. myosin ATPase → inc. speed of cross-bridge cycling
  4. Phosphorylation of Ca2+ pumps in SR inc. speed of calcium re-uptake, and relaxation
• inc. intracellular Ca2+
• dec. extracellular Na+ (dec. activity of Na+/Ca2+ exchanger)
  
  • NCX removes calcium from cells (1 Ca2+ out for every 3 Na+ in) so if you dec. Na+ amt or if NCX works poorly, calcium accumulates in myocyte
• digitalis
  
  • (blocks Na+/K+ pump by competing with K+ for binding to Na+/K+ ATPase → inc. intracellular Na+ → dec. Na+/Ca2+ exchanger activity … no Na+ to come in for Ca2+ to go out → inc. intracellular Ca2+
  • hypokalemia increases risk of drug toxicity

Contractility (and SV) decrease with:

• Beta-blockade
• Heart failure
• Acidosis
• Hypoxia
• Ca2+ channel blockers

Question 12

Effect of SV on CO

Answer 12

Inc. SV with:

• Inc. contractility (e.g. anxiety, exercise)
• Inc. preload (e.g. early pregnancy)
• Dec. afterload

Question 13

Effect of Preload and Afterload on Cardiac Output

Answer 13

Preload: approximated by ventricular EDV; depends on venous tone and circulating blood volume

• vEnodilators (e.g. nitroglycerin) dec. prEload
• causes veins in leg to dilate –> all blood gets pooled down there –> result: dec. in preload

Afterload: afterload approximated by MAP

• vAsodilators (e.g. hydrAlAzine) dec. Afterload (Arterial)
• inc. afterload → inc. pressure → inc. wall tension per Laplace’s law
• LV compensates for inc. afterload by thickening (hypertrophy) in order to dec. wall tension
  
  • Inc. MAP → LV hypertrophy

Question 14

ACE inhibitors and ARBs _____ (inc/dec) both preload and afterload

Answer 14

decrease

Question 15

Laplace’s Law

Answer 15

Describes factors that affect wall tension

Wall tension = (Pressure x Radius)/2 * Thickness

MyoCARDial oxygen consumption (MVO2) = directly related to wall tension and inc. by inc.

• contractility,
• afterload,
• heart rate, and
• ventricular diameter

Question 16

Types of cardiac hypertrophy

Answer 16

1. Concentric → Pressure Overload (sarcomeres added in parallel)
   
   1. Inc. LV wall stress (T) → LV wall thickens (h) → LV chamber radius decreases to attempt to reduce wall stress
2. Eccentric → Volume Overload (sarcomeres added primarily in series)
   
   1. Inc. BV (i.e. mitral regurg) → inc. chamber radius → inc. wall thickness can reduce tension

Question 17

Cardiac hypertrophy can be physiologic or pathologic.

Answer 17

Physiologic:

• reversible
• pregnancy/endurance training → eccentric (cell predominately grows in length)
• Isometric exercise training (weight-lifting) → concentric

Pathologic:

• irreversible
• chronic HTN
• aortic stenosis

Question 18

BP, CO, Resistance, and Ohm’s Law

Answer 18

MAP = CO * TPR

• MAP = 2/3 diastolic pressure + 1/3 systolic pressure

V = IR

Question 19

O2 content

vs.

HbO2 saturation

Answer 19

O2 content determined by amount of hemoglobin

= (1.34 * Hb * SaO2) + (0.003 * PaO2)

Saturation determined by how much oxygen (% wise) is on hemoglobin

Example:

If you saturate one molecule of hemoglobin, that’s 100% saturation.

If you saturate 1000 molecules of hemoglobin, that’s 100% saturation. This one has more content b/c there’s more hemoglobin.

Question 20

21 y/o man has MAP = 89 mm Hg at rest. After running for 40 min, his MAP has risen only slightly to 99 mm Hg. A decrease in which of the following during exercise most likely accounts for the observed finding?

A. Systolic blood pressure

B. Renal blood flow

C. Cardiac stroke volume

D. Systemic vascular resistance

E. RAP

Answer 20

D. Systemic vascular resistance

During exercise, muscle receive up to 85% of blood flow due to vasodilation of muscle vascular beds. In most vascular beds, SNS causes vasoconstriction via alpha 1 adrenergic receptors.

Notable exception in muscles → beta 2 adrenergic receptors predominant → these receptors, when bound by catecholeamines → vasodilation

MAP = CO * TPR

• TPR drops
• CO increases to deliver more O2 to tissues that need it

Question 21

During early stages of exercise, CO maintined by inc. HR and SV.

During late stages of exercise?

Answer 21

CO maintained by increased HR only (SV plateaus)

SV taps out - only so much that the heart can pump

Very high HRs compromise diastolic filling → actually reduce SV (e.g. ventricular tachycardia)

Question 22

Normal adult cardiac pressures

Answer 22

RA → 5

RV → 25/5

PA → 25/10

LA → 10

LV → 125/10

Ao → 125/75

Question 23

Swan-Ganz Catheter

Answer 23

pulmonary artery catheter measures left atrial pressure (pulmonary capillary wedge pressure)

In mitral stenosis, PCWP > LV end diastolic pressure

Question 24

Poiseuille Equation

Answer 24

Resistance = 8n (viscosity) * length / (πr^4)

R (TPR) determined by arteriolar tone

Blood storage in large veins determined by venous tone

Resistance directly proportional to viscosity and vessel length and inversely proportional to radius^4

Question 25

Viscosity depends most on \_\_\_\_\_\_\_. Viscosity is increased in _______ and \_\_\_\_\_\_\_.

Answer 25

Hematocrit Viscosity is increased in **polycythemia (abnormally inc. hemoglobin amount in blood)** and **hyperproteinemic states.**

Question 26

Circulatory Resistance

Answer 26

Total resistance in series = sum of individual resistances Total resistance in parallel \< lowest individual resistance (liver gets largest share of systemic CO)

Question 27

Autoregulation * Organ (6) * Factors determining autoregulation * Why is the pulmonary vasculature unique?

Answer 27

how blood flow to an organ remains constant over a wide range of perfusion pressures or metabolic needs

Question 28

Capillary fluid exchange

Answer 28

Starling forces determine fluid movement through capillary membranes Filtration happening on arteriolar side Reabsorption happening on venous side

Question 29

What is edema? Common causes (4) All cause **pitting edema** unless edema is long-standing or highly inflammatory.

Answer 29

Excess fluid outflow into interstitium

Question 30

Cardiac Function Curves

Answer 30

As RAP increases, venous return decreases to a point (X-axis) called mean systemic pressure (arrow). If RAP = -4, venous return tapers off b/c at this point, RA has collapsed. Venous return sort of stabilizes as RAP becomes more negative.

Question 31

Curve: Effect: Examples:

Answer 31

Curve: **Inotropy** Effect: **Changes in contractility → altered CO for a given RAP (preload)** Examples: 1. **Digoxin (+ inotropy)** 2. **Uncompensated HF, narcotic overdose (- inotropy)**

Question 32

Curve: Effect: Examples:

Answer 32

Curve: **Venous return** Effect: * **Changes in circulating volume or venous tone → altered RAP for a given CO** * **Mean systemic pressure (x-intercept) changes with volume/venous tone** Examples: **3. Fluid infusion, sympathetic activity (+ venous tone)** * **this inc. systemic pressure b/c there is more pressure out in the periphery coming back to RA** → shifts venous curve to the right → get more preload → more CO **4. Acute hemorrhage, spinal anesthesia (- venous tone)**

Question 33

Curve: Effect: Examples:

Answer 33

Curve: **TPR** Effect: **At a given mean systemic pressure (x-intercept) and RA pressure, changes in TPR → altered CO** Examples: **5. Vasopressors** → insolated arteriolar constriction **(+ TPR)** * CO and venous return curves both go down b/c when you constrict your blood vessels, you keep more blood on arteriolar side of circuit and less on venous side → still same amt of blood but it is harder to get that blood to the heart so you shift the slope of the line down → not decreasing the entire amount of blood **6. Exercise, AV shunt (- TPR)**

Question 34

Answer 34

Contraction is green. Relaxation is red. All PV loops must lie between the end-systolic PV relationship and the end-diastolic PV relationship

Question 35

Cardiac cycle 1. Isovolumetric contraction 2. Systolic ejection 3. Isovolumetric relaxation 4. Diastolic Filling

Answer 35

1. **Isovolumetric contraction** - period between mitral valve closure (B) and aortic valve opening (C); period of highest O2 consumption 2. **Systolic ejection** - period between aortic valve opening (C) and closing (D) 3. **Isovolumetric relaxation** - period between aortic valve closing (D) and mitral valve opening (A) 4. **Diastolic filling** - period just after mitral valve opening (A) to mitral valve closing (B)

Question 36

What do the following situations do to EDV and ESV? A. Increased preload B. Increased afterload C. Increased contractility

Answer 36

A. Increased preload * Inc. EDV B. Increased afterload * Inc. ESV C. Increased contractility * Dec. ESV

Question 37

3 main types of **systolic heart failure** What does systolic HF reduce? **diastolic heart failure**

Answer 37

1. **MI,** where myocardial mass is lost 2. **Alcoholism,** which causes ventricular dilatation due to cardiomyopathy 3. **Pressure overload** **Systolic HF reduces _contractility and EF_** * Weakened heart muscle can't squeeze well * Less blood pumped out of ventricles (low EF) * Due to reduced contractility, SV first maintained by increased preload, resulting in increased end-diastolic pressure (EDP). * Increased EDP transmitted to lungs * Result: Dyspnea Diastolic Heart Failure * Stiff ventricle (concentric hypertrophy) inhibits ventricular filling (problem here is that you don't have enough volume to begin with) * EF is actually normal or elevated

Question 38

Answer 38

Systolic HF: Due to reduced contractility (solid line of ESPVR), stroke volume is at first maintained by increased preload, but end-diastolic pressure is increased as a result (arrow). This is transmitted to teh lungs resulting in dyspnea, etc. Diastolic HF: Due to concentric hypertrophy or other causes of a stiff LV, the EDPVR is shifted upward and to the left (solid line). This raises end-diastolic pressure (EDP), which also is transmitted to the lungs.

Question 39

Heart Sounds: S1 S2 S3 S4

Answer 39

S1: mitral and tricuspid valves close - loudest at mitral area S2: aortic and pulmonic valves close - loudest at upper sternal border S3: in early diastole during rapid ventricular filling phase * associated w increased filling pressures (e.g. mitral regurg, HF) * more common in dilated ventricles (but can be normal in children and young adults) S4: in late diastole ("atrial kick") * best heard at apex with patient in left lateral decubitus position * high atrial pressure * associated with ventricular noncompliance (e.g. hypertrophy) * LA must push against stiff LV wall * consider abnormal, regardless of patient age