Cardiovascular and Respiratory Medicine

What are the 6 main components of the heart?

1. Atria

2. Ventricles

3. Aorta

4. Vena cava

5. Pulmonary artery

6. Pulmonary vein

ventricles have a _______ capacity than atria

bigger

right ventricle has a _______ capacity than the left

larger

which part of the heart has the highest pressure?

aorta

Describe the flow of blood through the heart

Vena cava → right atrium → (tricuspid) right ventricle → (pulmonary valve) pulmonary artery → lungs

Lungs → pulmonary veins → left atrium → (mitral) left ventricle → (aortic valve) aorta → body

where is the tricuspid valve?

between right atria and right ventricle

where is the mitral valve?

between left atria and left ventricle

where is aortic valve?

between left ventricle and aorta

where is pulmonary valve?

between right ventricle and pulmonary artery

Where is the primary pacemaker signal generated?

at the sinoatrial node (SA node) - muscle cells

Which tract connects the SA node to the AV node?

internodal tract - electrical signals transmitted across it through myocardium of atrium

What causes contraction of the ventricles?

transmission of the electrical signal along the purkinje fibres

Where is the SA node located?

junction of crista terminalis; in the upper wall of the right atrium and opening of superior vena cava

What does the AV node do?

has pacemaker activity - slow calcium mediated action potential

Where is the AV node located?

in the triangle of Koch at the base of the Right Atrium

Which 2 tracts are involved in transmitting the electrical activity?

1. Bundle of His and bundle branches

2. Purkinje fibres

where does Bundle of His branch?

at the interventricular septum

Where does Bundle of His transmit the electrical signal?

apex of heart

Summary of how the cardiac cycle is controlled by the SAN and AVN

• SAN acts as pacemaker and initiates heartbeat

• SAN sends wave of electrical impulses across the atria causing them to contract

• Non-conducting tissue between atria and ventricles prevent impulse from reaching ventricles

• Short delay at AVN allowing the atria to empty and ventricles fill before they contract

• AVN sends wave of electrical activity down bundle of his and up purkinje fibres

• Causes ventricles to contract from apex upwards

What are the coronary arteries that supply blood to the heart?

1. right coronary artery

2. left coronary artery (splits into two)

   1. circumflex artery (fuses with left atria and ventricle)

   2. left anterior descending artery (LAD - fuses with left ventricle)

What is the role of the cardiac veins?

to return deoxygenated blood from the myocardium into the right atrium

What are the 3 cardiac veins?

1. coronary sinus (drains into right atrium)

2. great cardiac vein (drains left side into coronary sinus)

3. middle cardiac vein (drains RV into coronary sinus)

What is excitation-contraction (EC) coupling?

Excitatory event (AP) at myocyte leads to influx of Ca2+ and then Ca2+ release which causes contraction

What are T-tubules

• finger-like invaginations (folded back to form a cavity) of cell membrane

• lie alongside each Z line of every myofibril (spaced 2um apart, openings up to 200nm in diameter)

• overlies actin & myosin

what is the role of T-tubules?

carry surface depolarisation (arrival of AP) deep into muscle cell

What is the role of the sarcoplasmic reticulum?

stores the Ca2+ and supplies it to the myofilaments

How are the T-tubules and sarcoplasmic reticulum linked?

• sarcoplasmic reticulum wound around the T-tubule

• T-tubule has L type calcium channel (LTCC) on surface of cell

• NCX channel - sodium calcium exchanger on surface

• LTCC overlies RyR (ryanodine receptor - SR calcium release channel)

How does the cardiac muscle contract (excitation-contraction coupling in heart)?

1. arrival of action potential from SAN to AVN to muscle cell

2. LTCC in cardiomyocyte opens due to conformational change due to action potential

3. extracellular calcium goes into cell

4. Majority of Ca2+ bind to Ryanodine receptor on SR = open RyR triggers big release of Ca2+ - calcium induced calcium release

5. Ca2+ bind to Troponin C on actin which shortens sarcomere

6. Ca2+ actively pumped into SR by Ca2+ ATPase channel on SR - causes muscle to relax - lusitropy

7. all Ca2+ that came in through L-type Ca2+ channel funnelled back out through Na+/Ca2+ exchanger

8. Ca2+ influx = Ca2+ efflux

What is the difference between a nerve AP and a cardiac AP?

cardiac AP is long and sustained

How does AP induce cardiac muscle contraction?

1. AP produced along cell surface

2. depolarisation carried down T-tubule and sensed by LTCC

3. LTCC conformational change and open to allow Ca2+ from outside the cell → cytosol down its conc. gradient

4. Ca2+ binds to SR calcium release channel (RyR) on sarcoplasmic reticulum

5. Ca2+ stored in SR released into cytosol and binds to troponin C on actin which shortens sarcomere

What is the relationship between force production and Ca2+ delivered to myofilaments?

more Ca2+ = more forceful contraction

How does skeletal muscle contraction differ from cardiac muscle contraction?

• skeletal muscle doesn’t need extracellular Ca2+ entry to produce contraction

• in skeletal muscle the LTCC mechanically linked to ryanodine receptor on SR which triggers calcium release

How does force produced by the muscle change with muscle length?

higher muscle length → increased force production

What contributes to the passive force produced by the cardiac cells when stimulated?

cardiac cells also have some elasticity so have a tendency to recoil as they are stretched- meaning as you increase muscle length, base force (baseline tension) produced increases too

What is length-tension relation in cardiac vs skeletal muscle?

cardiac muscle produces more passive force than skeletal muscle because cardiac muscle more resistant to stretch

What is isometric contraction?

muscle fibres don't shorten but exert force

What stage of the cardiac cycle does isometric contraction occur?

when ventricles fill with blood and valves are closed so blood doesn't go anywhere- builds up ventricular pressure

What is isotonic (concentric) contraction?

shortening of fibres

What stage of the cardiac cycle does isotonic contraction occur?

when pressure in ventricles from isometric contraction overcomes backpressure in aorta, blood is expelled from ventricle, ventricular cells shorten and blood pushed out

What is preload?

weight that stretches muscle before it is stimulated to contract (no shortening = isometric contraction)

What happens to contractile force as preload increases?

As preload (stretch) increases, contractile force increases up to a point then decreases

What is afterload?

weight not apparent to muscle in resting state- only encountered when muscle has started to contract

What happens to shortening of muscle as afterload increases?

• as afterload increases, amount of shortening of muscle reduces

• the larger the weight, the more difficult it is to shorten the muscle

• amount and velocity of shortening decreases

how does preload affect the shortening of the muscle?

• smaller preload (shorter initial muscle length) → less stretch → less powerful contraction

• larger preload (longer initial muscle length) → more stretch → more powerful contraction

How does preload apply to heart?

ventricular filling: preload is amount of blood coming back to the heart

• during diastole, as blood fills heart it stretches the resting ventricular walls

• this determines the preload on the ventricles before ejection

How can we measure preload? (3)

• end-diastolic volume: the more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are.

• end-diastolic pressure (pressure just before contracting)

• right atrial pressure

How does afterload apply to the heart?

• afterload is the load against which the left ventricle ejects after opening of aortic valve

• any increase in afterload decreases the amount of isotonic (concentric) shortening that occurs and decreases the velocity of shortening

How can we measure afterload?

diastolic blood pressure (minimum pressure ventricle must overcome to eject)

What is the Frank-Starling relationship (Starling law)?

Law: increase diastolic fibre length increases ventricular contraction

What are the 2 factors that cause this relationship?

changes in the number of myofilament cross-bridges that interact as length increases

changes in the Ca2+ sensitivity of the myofilaments

explain changes in Ca2+ sensitivity for myofilaments:

1. Ca2+ required for myofilament activation

2. Troponin C is thin filament protein that binds Ca2+

3. TnC regulates formation of actin-myosin cross-bridges

4. at longer sarcomere lengths, affinity of TnC for Ca2+ increases due to conformational change in TnC

5. less Ca2+ required for same amount of force

explain changes in the number of myofilament cross-bridges that interact as length increases

• blood filling

• stretch muscles

• decrease in overlapping between actin filaments

• increased number of binding heads/ myofilament cross bridges

• more myosin and actin interactions = increased contraction

What is Stroke work?

Work done by heart to eject blood under pressure into aorta and pulmonary artery

How do you calculate stroke volume?

End diastolic - end systolic

What is the law of LaPlace?

when the pressure in a cylinder is held constant, the tension on its walls increases with increasing radius

What is the main function of the respiratory airways?

conduct oxygen to the alveoli and carbon dioxide out of the lungs

How are the respiratory airways facilitated? (3)

1. cartilage → mechanical stability

2. smooth muscle → controls of calibre (how open/closed airways are)

3. protection and cleansing

What is the role of the pharynx?

passageway for food, liquids and air

What is the role of the conchae?

highly vascular: warm and humidify the intra-nasally-inhaled air

What is the role of nasal hairs?

filter out large particles

What happens to inhaled particles?

trapped in mucous layer and get wafted by cilia and swallowed

What kind of branching does the lung have?

dichotomous (every branch splits into 2)

What does the cartilage do?

provides mechanical stability to help hold airways open

Why are the cartilage rings in the trachea C-shaped?

to allow food down the oesophagus unimpeded

Which cells make up an alveolar unit? (4)

1. Type I (cover 95% of alveolar surface) more flat, incredibly thin

2. Type II (most abundant but only cover 5% of alveolar surface) more chunky

3. macrophages

4. fibroblasts

5. capillary endothelium

What is the role of Type I cells?

form a very thin and delicate barrier to facilitate gas exchange

What is the role of Type II cells? (3)

1. replicate to replace Type I cells

2. secrete surfactant (reduce surface tension) and antiproteases

3. xenobiotic metabolism (break down harmful chemicals)

What is the role of macrophages?

destroy debris and microbes that we inhale

What do the fibroblasts do?

produce ECM matrix that holds the alveolar unit together

What are the 7 types of cells present in the airways?

1. lining cells

2. contractory cells

3. secretory cells

4. connective tissue

5. neuroendocrine

6. vascular cells

7. immune cells

Where are mucin granules found?

highly condensed in goblet cells

role of mucin granules:

• move to the apical surface of the goblet cell

• airway liquid enters the granules and is taken up by mucin

• mucin is released

What are acini?

mucus producing units

Where are acini found?

in airway submucosal glands

What do mucous acini secrete?

mucus

What do serous acini secrete?

anti-bacterial enzymes

What do submucosal glands also secrete?

water and salts

What is the role of cilia microtubules?

slide over one another in cilium to move mucus one way or another

What is the rhythm of ciliary beating?

metachronal rhythm- different lines of ciliary hair move at different times to waft mucous down to back of throat

What are the functions of airway epithelium? (4)

• secretions of mucine, water and electrolytes (components of mucus + plasma, mediators etc)

• movement of mucus by cilia - mucociliary clearance

• act as a physical barrier

• produce regulatory and inflammatory mediators

Examples of inflammatory mediators:

1. Nitric oxide (NO - via nitric oxide synthase, NOS)

2. Carbon monoxide (CO - via hemeoxygenase, HO)

3. Arachidonic acid metabolites (e.g. prostaglandins - via COX)

4. Chemokines (e.g. interleukin (IL)-8)

5. Cytokines (e.g. GM-CSF)

6. Proteases

What is the role of nitric oxide in the human airway epithelium?

speed up cilia

What colour does NOS stain?

nitric oxide synthase stains brown, as NO produced

What are the main roles of airway smooth muscle? (3)

1. structure

2. tone - contract & relax (airway caliber)

3. secrete mediators, cytokines and chemokines

What happens when the airway smooth muscles become inflamed?

• hypertrophy and proliferation → impacts tone and secretion

• secrete more mediators, cytokines and chemokines

• recruit inflammatory cells

Where do bronchial arteries arise from?

from proximal descending thoracic aorta, intercostal arteries and others

Where does blood from tracheal circulation return via?

systemic veins

Where does blood from bronchial circulation return via?

bronchial and pulmonary veins to both sides of the heart

What are the functions of the trachea-bronchial circulation?

1. good gas exchange

2. warms and humidifies inspired air

3. clears inflammatory mediators

4. clears inhaled drugs

5. supplies airway tissue and lumen with inflammatory cells and plasma exudation

What is the nervous response to detection of a foreign object in the airway?

1. sensory nerve detects a foreign object in the airway

2. signal sent to the brain via the vagus nerve and nodose ganglion (inferior ganglion of vagus nerve)

3. parasympathetic cholinergic nerves activated

4. ACh released and act on the smooth muscle causing it to contract and submucosal glands to contract

5. foreign object prevented from going further down the airway

6. once foreign object is coughed out muscles must be relaxed

7. so adrenal gland secretes adrenaline which causes bronchodilation (minor contribution)

8. nitric oxide secreting nerves can also induce bronchodilation as it relaxes airway smooth muscle

Can sympathetic nerves open up our airways directly?

No, as they don’t innervate our airway smooth muscle - instead nitric oxide secreting nerves are what induce bronchodilation (smooth muscle relaxant)

Give 3 examples of respiratory diseases that are associated with loss of airway control.

1. asthma

2. COPD

3. cystic fibrosis

What are the 2 main phases of a heart beat?

1. diastole - 2/3 of each beat

2. systole - 1/3 of each beat

What happens in diastole?

ventricular relaxation (fill with blood)

what happens in systole?

ventricular contraction

What are the 4 phases of diastole?

1. isovolumetric relaxation

2. rapid passive filling

3. slow passive filling

4. atrial systole

What are the 3 phases of systole?

1. isovolumetric contraction

2. rapid ejection

3. slow ejection

What is end diastolic volume (EDV)?

• max volume of blood in the heart just before the ventricles start to contract

• at isovolumetric contraction phase

What is end systolic volume (ESV)?

• amount of blood in the heart after contraction (residual)

• at slow ejection phase

What is stroke volume (SV)?

volume of blood expelled by heart in one cardiac cycle