Human Physiology I - Lecture notes - Lec 8 PDF

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Lecture 8: Cardiac cycle and metabolism

BPK305

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Cardiac cycle and metabolism • Cardiac cycle -pressure-volume relationship -pressure and volume as a function of time -physiological variations -increased preload -increased afterload -increased contractility • Right ventricle • Cardiac work and metabolism

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Pressure-volume loop Aortic valve closes

140 120

100 Left ventricular Pressure (mmHg) 80 60

Slow ejection phase E F Isovolumetric relaxation

Rapid ejection phase Aortic valve opens D

40 Diastole

20

Mitral valve 0 opens Mitral valve: separates L. atrium and ventricle

A

B

C

Isovolumetric contraction Aortic valve closed

50 70 120 Left ventricular volume (ml)

Mitral valve closes

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Pressure-volume loop 140 120 100 Left ventricular Pressure (mmHg) 80

= SV EDV

E F D

60 EDV – ESV = SV

40 20 0 End systolic vol - ESV

A

B

C

End diastolic vol (EDV)

50 70 120 Left ventricular volume (ml)

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Pressure-volume loop pressure

140 120 Left ventricular Pressure (mmHg)

100

Systolic – Diastolic = ~40mmHg

E

pressure

F

Aortic valve opens

80

D

60 40 20

A

B

C

0 50 70 120 Left ventricular volume (ml)

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R

Pressure-volume loop

Left ventricular Pressure (mmHg)

140

T

120

E

100

P

T Q S

F

80

D

60 40 20 0

A

B

P C

QRS

50 70 120 Left ventricular volume (ml)

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Pressure-volume loop • Pressure versus time • Heart sounds indicate: • S1 = closure of mitral valve • S2 = closure of aortic valve • S3 & S4 hard to hear with stethoscope •

notch: • brief increase in Paorta • due to: • Closure of aortic valve • of aorta

Berne, Figure 16-40

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Cardiac cycle and metabolism • Cardiac cycle -pressure-volume relationship -pressure and volume as a function of time -physiological variations -increased preload -increased afterload -increased contractility • Right ventricle • Cardiac work and metabolism

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Increased preload ↑ vo ume ↓ ↑ stretch ↓ ↑ length ↓ ↑ tension ↓

Increased venous return

Boron, Figure 22-13

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Increased afterload ↑ pressure to open ↓ ↑ isovolumetric contraction time ↓ Early closing of aortic valve ↓ ↓ ↓SV

Increased arterial blood pressure

Boron, Figure 22-13

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Increased contractility ↑ contractility ↓ ↑ force contracon ↓ ↑ max systolic pressure & ↓ ESV ↓ ↑SV

Increased force of contraction

Boron, Figure 22-13

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Cardiac cycle and metabolism • Cardiac cycle -pressure-volume relationship -pressure and volume as a function of time -physiological variations -increased preload -increased afterload -increased contractility

• Right ventricle • pumps against lower pressure pulmonary circulation • Shorter isovolumetric contraction • Longer ejection phase • Cardiac work and metabolism

Cardiac work • The heart is an organ -metabolism is almost completely • Increased work requires increased -and this requires increased O2 -so we need to increase the coronary artery to increase ATP supply • So how is ATP produced?

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Cardiac work • The heart uses 70-90% • Skeletal muscle uses ~5% free fatty acids -glucose metabolism is dominant • Fat is a reliable fuel source -skeletal muscle can work anaerobically -cardiac muscle • The heart may use: -glucose -glycogen -even lactate -but are the primary source

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How is the heart designed for fat use? Albumin

FFA

Mito 18-C

9x 2-C Acetyl co-A CAT

TCA

Acyl chain + coA

18-C

FABP

β-oxidation Myocyte FABP - Fatty Acid Binding Protein CAT - Carnitene Acyl Transferase TCA cycle – The Citric Acid cycle

The heart has high: i) expression of ii) expression of iii) numbers of

BV

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β-oxidation 16-C TCA

12ATP

Acyl chain + Acetyl co-A

8x 18-C Acyl chain

2-C

3 NADH 1 FADH2 1 ATP

NADH (3ATP) FADH2 (2ATP)

e- transport chain

NAD FAD

5ATP ½ O2

( = 134 ATP)

Mitochondria

i) β-oxidation takes place in the mitochondria - more mitochondria facilitates β-oxidation ii) The whole process

(critically dependent on blood supply)

- without O2, β-oxidation does not take place - this is unlike glucose metabolism, which can occur in the absence of O2

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Glucose metabolism Glycolysis Mito

Glucose Acetyl co-A

GLUT4

Glucose-6-P

TCA NADH FADH2

Pyruvate dehydrogenase (PDH)

e- transport chain

5mM

2 Triose-P 2 Pyruvate

Lactate dehydrogenase (LDH)

½ O2

Glucose

BV

2ATP 36ATP (glucose oxidation)

Regulation of glucose metabolism: i) glucose uptake: conc gradient increases GLUT4

Lactate ii) enzymatically – PDH vs LDH choice is determined by the presence of iii) high β-oxidation of FFA suppresses

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Lactate metabolism 1-10mM Mito

Lactate

Lactate

Acetyl co-A H+

TCA NADH FADH2

e- transport chain

Pyruvate dehydrogenase (PDH)

Lactate dehydrogenase (LDH)

Pyruvate BV

½ O2 Lactate metabolism: i)

Lactate

ii)

Cardiac specific LDH that allows production of

Review Question 1: Which of the following is NOT a target of protein kinase A (PKA)? A. B. C. D.

RyR SERCA L-type Ca2+ channels Troponin I

Lecture 8 quiz

Concept Check 1: How much volume does the right ventricle pump per heart beat compared to the left ventricle? A. B. C. D.

Less than left ventricle Same as left ventricle More than left ventricle Cannot determine

Lecture 8 quiz

Concept Check 2: The heart’s preferred fuel source is? A. B. C. D.

glucose lactate free fatty acids Red Bull

Lecture 8 quiz

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Cardiac cycle and metabolism • Cardiac cycle -pressure-volume relationship -pressure and volume as a function of time -physiological variations -increased preload -increased afterload -increased contractility • Right ventricle • Cardiac work and metabolism

Review Question 1: Which of the following is a “beta blocker”? A. B. C. D.

pseudoephedrine cocaine nicotine propranolol

Lecture 8 quiz...