Kreislauf (4), full

Why is a circulatory system necessary for large multicellular organisms?

Simple diffusion (Diffusion) is not adequate because distances become too large to provide nutrients and eliminate waste products

What does circulation provide?

• A steep concentration gradient from the blood to the cells for nutrients, and from the tissues to the blood for waste products.

• These concentration gradients can be maintained as they are necessary for metabolism, only via means of a fast circulating fluid in the vascular system.

What are the main functions of the cardiovascular system?

• Transport of nutrients from the digestive tract to tissues and storage organs (e.g., adipose tissue, liver)

• Transport of metabolites between organs (e.g., lactic acid from muscle → liver), allowing metabolic specialization

• Transport of excretory products from tissues to excretory organs (e.g., urea produced in liver → kidney)

• Transport of respiratory gases:

  • O₂ from respiratory organs → tissues

  • CO₂ from tissues → respiratory organs

  • Includes oxygen storage

• Transport of hormones to target tissues

• Transport of non-respiratory cells, especially immune cells (e.g., leukocytes)

• Transport of heat from deeper organs to the body surface for dissipation (important in large animals with high metabolic rates)

• Transmission of force:

  • Locomotion in some animals (e.g., earthworms)

  • Generation of filtration pressure in kidney capillaries (ultrafiltration)

• Coagulation (blood clotting) to prevent blood loss after injury

• Maintenance of the internal environment (“milieu intérieur”), including stable:

  • pH

  • Ion concentrations

  • Nutrient levels

  • Other conditions required for normal cell function

How do blood vessels change as blood moves from the left ventricle toward the tissues?

• Blood flows: Left ventricle → aorta → arteries → arterioles → capillaries

• Vessels become progressively smaller in diameter

• Vessel walls become progressively thinner

• Histology changes:

  • Aorta: thick, elastic wall

  • Arteries: more smooth muscle

  • Arterioles: mainly smooth muscle for flow regulation

  • Capillaries: one-cell-thick endothelium for exchange of substances with tissues.

Where is the principal resistance to blood flow located?

• Until the beginning of the arterioles, the systemic resistance to blood flow is relatively small.

• The arterioles constitute the principal resistance to blood flow.

How does blood return to the heart from the capillaries?

• Blood passes from capillaries → venules → veins of increasing size → heart

• Most of the circulating blood volume is located in the veins

• The force for blood transport in veins is provided by the outside pressure of muscles.

• Blood then passes through the lung.

• After gas exchange, blood returns to the left atrium and left ventricle to complete the voyage.

Where is turbulence in the circulatory system found?

In very large vessels, such as the aorta, in conditions only of high cardiac output (during exercise).

What is a problem associated with artificial heart valves?

• Artificial valves can create turbulent blood flow.

• Turbulent flow increases the likelihood of thrombus (blood clot) formation.

What are the three types of pressure relevant to blood flow? (Blood flow is dependent on pressure)

• Driving pressure: exerted by the heart

• Tissue (transmural) pressure: because vessels are distensible rather than rigid, transmural pressure mainly governs vessel diameter and therefore the resistance of that vascular segment

• Hydrostatic pressure: due to the density of blood and gravitational forces

Resistance (blood flow is dependent on it)

The smaller the vessel the larger its resistance.

Why is blood considered a non-Newtonian fluid? (Blood flow is dependent on rheological properties of blood)

• Blood has anomalous viscosity properties and is therefore non-Newtonian.

• In a Newtonian fluid, relative viscosity (compared to water) is independent of tube size.

• In blood, relative viscosity decreases as vessel radius decreases, meaning blood flows more easily in smaller vessels.

• This is due to:

  • The non-uniform composition of blood (cells + fluid)

  • The rolling movement of red blood cells in very small capillaries.

Skeletal muscle.

• Formed during development by the fusion of myoblasts thereby creating a true syncytium.

• Innervated by motor neurons and thus is under voluntary control.

• Striated.

Heart muscle.

• Individual cardiomyocytes do not fuse but are connected to each other by gap junctions and desmosomes. Heart muscle is therefore not a true syncytium but functions like a syncytium.

• Myogenically activated and thus its contraction is not under voluntary control.

• Striated.

Smooth muscle.

• Individual smooth muscle cells are not fused but electrically coupled via gap junctions.

• Controlled by hormones and particularly by the autonomic nervous system. Thus, their contraction is not under voluntary control.

• Not striated.

What is the heart muscle characterized by?

• Semblance of a syncytium

• Abundance of mitochondria

• All-or-none reaction

Semblance of a syncytium of the heart muscle.

• Cardiac muscle functions as a syncytium, but it is not a true anatomical syncytium.

• Laterally, the fibers are separated by the sarcolemma.

• Longitudinally, the fibers are separated by intercalated discs.

• The intercalated discs contain high-conductivity gap junctions.

How do small animals achieve the higher oxygen supply required by their higher oxygen consumption per unit body weight?

• Small animals have a higher rate of oxygen consumption per unit body weight than large animals.

• Therefore, their hearts must supply oxygen at a higher rate.

• This increase is achieved primarily by a higher pulse rate (heart rate).

• It is not achieved by a larger heart (the heart remains a constant percentage of body mass) or by a larger stroke volume.

What demonstrates that the heart has inherent rhythmic contractility, and where does contraction normally begin?

• The heart can contract rhythmically without any external stimulus.

• Even when completely removed from the body, it may continue to beat for a considerable time.

• Evidence:

  • The heart of a developing chick embryo begins to beat before any nerves have reached it.

  • Heart muscle cells in tissue culture contract rhythmically without any external stimulus.

• Contraction normally begins in the sinus node (sinoatrial node, pacemaker).

• The sinus node is located where the vena cava enters the right atrium.

What happens when an action potential spreads through the heart?

• The spreading of the action potential within the heart creates changes in the membrane potential of the cardiomyocytes.

What is the role of the atrioventricular (AV) node?

• When the wave of contraction reaches the partition between the atria and ventricles, the atrioventricular (AV) node conducts the impulse to the ventricles.

• After a brief delay resulting from conduction, the ventricles contract simultaneously.

3 major controlling systems influencing cardiac output by affecting frequency, stroke volume or both.

1. Nervous system

2. Hormones

3. Venous return

What can an electrocardiogram provide insight into?

1. The anatomical orientation of the heart.

2. The relative size of its chambers.

3. Disturbances of rhythm and conduction (extrasystole and heart fibrillation).

4. Extent, location and ischemic damage of the myocardium (myocardial infarction).

5. The effects of altered electrolyte concentrations.

6. The influence of certain drugs, notably digitalis and its dertivatives.

How does thyroxin affect heart rate?

• Hypothyroidism (inadequate thyroid function): slow heart rate.

• Hyperthyroidism (overactive thyroid gland): increased heart rate.

Why is acetylcholine not transported in the blood to slow the heart?

• There is no corresponding release of the decelerating substance acetylcholine into the blood.

• Acetylcholine would not survive in the enzymic milieu of the blood.

• High doses of noradrenaline (norepinephrine) slow down the heartbeat, but such doses are never observed under physiological conditions.

What are the four major categories of blood function?

Mass transport of solutes and cells, transport of heat (Wärmetransport), transmission of force, and coagulation (Blutgerinnung)

Where are nutrients transported from and to in the cardiovascular system?

From the digestive tract (Verdauungstrakt) to tissues and storage organs like adipose tissue and the liver

Give an example of metabolite transport mentioned in the script.

Transport of lactic acid (Milchsäure) from muscle to the liver

How is heat dissipated in large animals with high metabolic rates?

By transport of heat from deeper organs to the surface for dissipation (Wärmeabfuhr)

What is the function of transmission of force in the human kidney?

It is used for ultrafiltration (Ultrafiltration) in the capillaries of the kidneys

What defines a closed circulatory system in vertebrates?

It is made up of a pump (the heart) and a series of distributing and collecting tubes (blood vessels)

What is the approximate weight of a human heart?

300 grams (300 Gramm)

Compare heart output at rest versus during exercise.

5 liters/min at rest and 25 liters/min or more during exercise (körperliche Anstrengung)

How much blood does a heart pump in a 70-year lifetime?

400 million liters (400 Millionen Liter)

Which heart chamber supplies the pulmonary circulation?

The right ventricle (rechter Ventrikel)

Which heart chamber supplies the systemic circulation?

The left ventricle (linker Ventrikel)

How is unidirectional flow through the heart achieved?

By the appropriate arrangement of flap valves (Herzklappen)

What allows for continuous blood flow to the periphery despite intermittent heart pumping?

The distension of the aorta and elastic recoil (elastische Rückstellung) of arterial walls during relaxation

What is the wall thickness and internal radius of the Aorta?

Wall thickness is 2.5 mm and internal radius is 12.5 mm

What is the wall thickness and internal radius of a typical Capillary?

Wall thickness is 1 μm and internal radius is 3 μm

Which vessel has the highest relative wall thickness (w/ri)?

The Arteriole (Arteriole) with a ratio of 1.0

Contrast the composition of the Aorta wall versus a Vena Cava wall.

The Aorta is rich in elastin and smooth muscle, whereas the Vena Cava has much less elastin and lower relative wall thickness

What are precapillary sphincters?

Smooth muscle segments (glatte Muskelzellen) that can narrow the vessel lumen to regulate local blood flow

Where is the principal resistance to blood flow located?

In the arterioles (Arteriolen), evidenced by a major pressure drop

By how much does the total cross-sectional area increase from aorta to capillaries?

It increases about 500-fold (500-fache Zunahme)

What is the relationship between blood velocity and total cross-sectional area?

They have an inverse relationship (umgekehrtes Verhältnis), velocity is slowest where cross-section is largest

Where is most of the circulating blood volume located?

In the veins (Venen)

What force provides blood transport in the veins?

Outside pressure from muscles (Muskelpumpe)

What prevents the back-flow of blood in veins?

Valves (Venenklappen)

What is the mean pressure in the pulmonary system compared to systemic arteries?

It is about 1/7 (ein Siebtel) of systemic arterial pressure

What determines if fluid flow is laminar or turbulent?

Velocity, flow becomes turbulent (turbulent) if velocity increases above a critical point

What are the clinical signs of turbulent flow?

Vortex formation sets up murmurs (Herzgeräusche) and increases the risk of blood clots (Thromben)

What three factors determine blood flow?

Pressure, Resistance, and rheological properties of blood (Fließeigenschaften)

What is a true syncytium in muscle types?

Skeletal muscle (Skelettmuskulatur), formed by the fusion of myoblasts

How are individual cardiomyocytes connected?

By gap junctions (elektrische Kopplung) and desmosomes, also called fascia adhaerens

Why is heart muscle considered a "pseudo-syncytium"?

Because individual cells do not fuse but function together electrically like a syncytium

What is the activation type of heart muscle contraction?

Myogenic (myogen), meaning it is not under voluntary control

How does the arrangement of heart muscle layers affect blood ejection?

Spiral bundles virtually wring (auswringen) the blood out of the heart during contraction

Why does cardiac muscle depend on abundant mitochondria?

Because it is incapable of developing a significant oxygen debt (Sauerstoffschuld) and needs constant ATP

What is the "all-or-none" reaction in heart muscle?

A stimulus leads to a reaction of all fibers or none at all (Alles-oder-Nichts-Gesetz)

How is heart rate related to body size in mammals?

• Inversely logarithmically (invers logarithmisch)

• small animals have much higher pulse rates

What is the resting pulse rate of an elephant versus a shrew?

• Elephant is 25/min

• Shrew (Spitzmaus) is over 600/min

Define Stroke Volume.

The volume of blood ejected by one heart stroke (Schlagvolumen)

Where is the sinus node located?

Where the vena cava enters the right atrium (rechter Vorhof)

What is the intrinsic frequency of the Sinus Node?

60 to 80 beats per minute (Schläge pro Minute)

Name the secondary and tertiary pacemakers and their frequencies.

AV node (~40/min) and His-bundle/Purkinje fibers (~20/min)

What is the "funny current" (Ih)?

A specific ion current through HCN channels activated by hyperpolarization that causes spontaneous depolarization in the sinus node

Describe the ion movement during the heart action potential phases.

Fast sodium influx (Natrium-Einstrom) for depolarization, calcium influx (Kalzium-Einstrom) for the plateau, and potassium efflux (Kalium-Ausstrom) for repolarization

How long does the cardiac action potential depolarization last?

Approximately 300 ms (300 Millisekunden)

Why can heart muscle not be "tetanized"?

• Because of the long plateau phase and long refractory period (Refraktärzeit)

• There is high permeability for calcium (calcium keeps the membrane potential depolarized)

What happens after a premature ventricular contraction (ventricular extrasystole)?

• The ventricle contracts prematurely.

• The next atrial contraction falls into the refractory period of that contraction.

• Therefore, the R–R interval is doubled after the extrasystolic event.

• REMEMBER: premature ventricular contraction ≠ premature ventricular contraction (superventricular extrasystole)

What does the vagus nerve release to slow the heart?

Acetylcholine (Azetylcholin)

How does the accelerans nerve speed up the heart?

By releasing noradrenaline (Noradrenalin)

Where are baroreceptors (pressoreceptors) located?

In the aortic arch (Aortenbogen) and carotid sinuses (Karotissinus)

What is the effect of Adrenaline on the heart?

It increases stroke volume and accelerates heart rate (Herzfrequenz)

What is Starling’s law of the heart?

The heart contracts with greater force if it is more distended (stretched) by venous return

What does an ECG measure?

The variations in electrical potential (elektrisches Potenzial) on the body surface, reflecting electrical activity, not contraction

What does the P-wave represent in an ECG?

Atrial depolarization (Depolarisation der Vorhöfe)

What does the QRS-complex represent?

Ventricular depolarization (Depolarisation der Ventrikel)

What does the T-wave represent?

Ventricular repolarization (Repolarisation der Ventrikel)

What are the normal durations for the PQ and QT intervals?

• PQ < 0.2s

• QT (at 70 bpm) 0.32-0.39s

How is an acute myocardial infarction visible on an ECG?

By an increase in the S-T interval (ST-Hebung) and potentially a deep Q wave

Define premature atrial contraction.

• A supraventricular extrasystole (supraventrikuläre Extrasystole) where the atrium contracts too early.

• Causes a shortening of the P-P interval followed by the lengthening of the P-P interval

What is a characteristic of a grade 3 AV block?

• Atria and ventricles beat independently

• A total block (totaler Block)

What causes atrial fibrillation?

• Multiple centers of initiation of action potentials within the atrium (Vorhofflimmern).

• As a consequence, the ventricles contract irregularly as the AV node is activated irregularly.

• Can result in a decrease in heartbet.

• Often results in exercise intolerance.

How does a defibrillator treat ventricular fibrillation?

It depolarizes the entire heart to allow the sinus node to take over a regular rhythm.

Ventricular fibrillation cause.

• Because of the uncontrolled contraction of the vetricles, only little or no blood is expelled from the heart.

• Can be induced by the touching of an electrical power.

• Treatment: defribillator (depolorizes the entire heart, allows the sinus node to take over again and initiate a regular heartbeat).

What is Long QT-syndrome?

• A genetic mutation in ion channels, often HERG channels, causing arrhythmias (Rhythmusstörungen).

• Mutation has high propensity to non-specifically bind to drugs.

• Thus, one of the important tests when new medications are developed is to test for interactions with HERG channels as drugs that do interact are prone to induce arrhytimias.

What happens during a cardiac cycle?

• The cycle starts with atrial systole, during which the atria propel additional blood into the ventricles (ventricular filling).

• This is followed by ventricular systole, during which blood is expelled from both ventricles into the periphery (lung and aorta).

Define Systolic Pressure.

The peak pressure reached during heart contraction (systolischer Blutdruck)

Define Diastolic Pressure.

The lowest pressure reached during heart relaxation (diastolischer Blutdruck)

What is the end-diastolic ventricular volume at rest?

About 130 ml

How much blood remains in the ventricle after systole?

About 50 ml

What is Ejection Fraction?

• The percentage of end-diastolic volume ejected per stroke, normally about 65% (Ejektionsfraktion).

• It’s an important index of ventricular function.

What happens during isovolumetric ventricular relaxation and ventricular filling?

• After the semilunar valves close, ventricular pressure continues to drop rapidly during isovolumetric ventricular relaxation.

• Isovolumetric relaxation ends when ventricular pressure falls below atrial pressure.

• The AV valves open, permitting the ventricles to be filled.

• Ventricular filling is rapid at first and then slows as the next cardiac contraction approaches.

• Atrial pressure continues to rise after the end of ventricular systole until the AV valves open, then drops and slowly rises again until the next atrial systole.

Why is arterial pressure in the head lower than at heart level when standing?

Due to the effect of gravity (Schwerkraft)

How are Korotkoff sounds used to measure BP?

The first sound marks systolic pressure, the disappearance of sound marks diastolic pressure (Korotkow-Geräusche)

What are the standard values defining Hypertension?

Levels above 140/90 mm Hg (Hypertonie)

What is "Nachtabsenkung"?

The circadian drop in blood pressure during sleep, which is often lost in hypertensive patients

What is hypertension and why is it important?

• Hypertension affects 15–20% of the adult population in industrial societies.

• It is a major risk factor for:

  • Stroke

  • Myocardial infarction

  • End-stage renal disease

• Elevated blood pressure is commonly defined as > 140/90 mm Hg in adults.

How do many rare mutations affect blood pressure?

• Most blood pressure–affecting mutations are rare mutations.

• They alter blood pressure through a common pathway:

  • Changing salt reabsorption in the kidney

  • Changing water reabsorption in the kidney.