12.1 Control of blood flow

Question 1

What drives blood flow?

Answer 1

• Blood flow is driven by PRESSURE GRADIENTS
  
  • Thanks to the pumping of the heart
• Arterial Pressure usually held constant by baroreflex
  
  • ​Thus if we want to alter the rate of flow of blood to downstream tissues we need to alter the resistance to blood flow

Question 2

What is the definition of perfusion pressure?

Answer 2

The arterial minus the venous pressure in that organ

Question 3

What is Darcy’s Law of flow?

Answer 3

Δ Blood Pressure = Blood Flow x Resistance to blood flow

Question 4

What is Poiseuille’s Law?

Answer 4

• Small changes in the radius of the lumen of blood vessels can have significant effects on the resistance of the vessels

Question 5

What are the mechanisms of controlling blood flow?

Answer 5

1. LOCAL
   
   • Metabolic, myogenic
   • Used to autoregulate blood flow in the face of changing perfusion pressure
   • Or to increase blood flow in response to increase demand (eg exercise); active hyperaemia
2. ENDOTHELIAL
   
   • Nitric oxide, prostaglandins etc.
3. HORMONAL (endocrine)
   
   • ADH, adrenaline, Ang II etc.
4. CENTRAL (neural)
   
   • Sympathetic nerves

Question 6

Briefly explain the myogenic theory

Answer 6

Myogenic theory

Increase BP will increase flow to the tissue and stretches smooth muscle around arteriole, this activates stretch-activated Ca2+ channels in the arteriolar smooth muscle and leads to increased contraction/constriction, increase resistance and decrease flow back down

Question 7

Briefly explain the metabolic theory

Answer 7

Metabolic theory

Increased pressure* will increase *flow and washes away vasodilatory metabolites faster than they are produced – arteriole constricts and reduces flow back to where it was before the increase in BP

Question 8

What does increases in sympathetic outflow to the arterioles do?

Answer 8

Increases in the sympathetic outflow to the arterioles causes vasoconstriction

1. Post-ganglionic sympathetic neurones release noradrenaline onto arteriolar smooth muscle cells
2. Stimulation of α-adrenoreceptors causes a rapid rise in [Ca2+]cyt in the arteriolar smooth muscle cells
3. This stimulates the contraction of the arteriolar smooth muscle cells, and therefore vasoconstriction of these arterioles

Question 9

What happens in skeletal muscles when there is a low concentration of adrenaline?

Answer 9

Low concentrations of adrenaline = VASODILATION (act on Beta adrenoreceptors)

Question 10

What is the difference between noradrenaline & adrenaline?

Answer 10

NORADRENALINE

• Noradrenaline is the main neurotransmitter of the sympathetic nerves in the cardiovascular system
• ALWAYS causes vasoconstriction
• Acts on on alpha adrenergic receptors

ADRENALINE

• Adrenaline is the main hormone secreted by the adrenal medulla
• Can cause vasoconstriction & vasodilation (in low concentrations)
• Acts on on beta adrenoreceptors at LOW concentrations for vasodilation
• Acts on alpha adrenoreceptors at HIGH concentrations for vasoconstriction

Question 11

What does intrinsic factors of control of blood flow mean?

Answer 11

INTRINSIC FACTORS

• Regulation of blood flow to an organ by factors originating from within the organ
• e.g. PARACRINE
  
  • • Autoregulation by (pathways)
  • Metabolic
    
    • ​e.g. CO2, H+, K+, adenosine, O2
  • Myogenic (vasoconstricting)
  • Endothelial
    
    • ​NO (vasodilating)
    • Endothelin (vasoconstricting)

Question 12

What does the extrinsic factors of control of blood flow mean & what are the types & give examples?

Answer 12

• Regulation of blood flow to an organ by factors originating OUTSIDE the organ
• NEURAL
  
  • Sympathetic vasoconstrictor fibres
  • Parasympathetic vasodilator fibres (penis, salivary glands, pancreas)
  • Sympathetic vasodilator Fibres (sweat glands, cutaneous)
  • Nociceptive C-fibres
  • Noradrenaline (vasoconstriction)
  • Adrenaline (vasoconstriction/vasodilating)
• ENDOCRINE
  
  • Catecholamines
  • Anti-diuretic hormone (vasoconstrictor)
  • Angiotensin II (vasoconstrictor)
  • Insulin (vasodilator)
  • Oestrogen (vasodilator & hypotensive agent)
  • Relaxin (vasodilator)

Question 13

Equation to work out arterial blood pressure

Answer 13

ABP = CO x TPR

Arterial blood pressure = Cardiac output x Total peripheral resistance

Question 14

What happens in the cardiovascular system in response to exercise?

Answer 14

1. ↑Blood Flow to active muscles
2. ↑Blood Flow through pulmonary* *circulation
3. ↑heat loss via blood flow to skin
4. Maintain Arterial Blood Pressure
   
   • ​​Maintains O2 delivery to active tissues

Question 15

Explain what the central command does to control blood flow

Answer 15

• A feedforward response that triggers an increase in heart rate prior to exercise onset
• The motor cortex and other motor areas of the brain responsible for triggering skeletal muscle activation also trigger activation of the medullary cardiovascular control centres – leading to an increase in heart rate prior to exercise
• Cause:
  
  • ↑ Heart rate​
  • ↑ Cardiac output
  • ↑ Contractility
  • ↑ Arterial blood pressure
• Central Command also triggers a central resetting of the arterial baroreflex – allowing for GREATER HYPERTENSION during exercise
  
  • Increases in sympathetic nerve activity at the same arterial blood pressure – indicating a modulation of the normal arterial baroreflex.
    • allows us to temporarily increase the driving force (the pressure gradient) for blood flow during exercise

Question 16

How is the sympathetic nerve outflow to the cardiovascular system controlled?

Answer 16

• The sympathetic outflow is further controlled by feedbackmechanisms upon onset of exercise
  
  • Controlled by feedback activation of the medullary control centres by skeletal muscle mechanoreceptors and metaboreceptors, and arterial baroreceptors once exercise is underway

Question 17

What is a metaboreceptor?

Answer 17

A metaboreceptor is a type of chemoreceptor found in skeletal muscle that responds to an increase in production of metabolic products and stimulates an increase in blood flow in response to exercise

Question 18

List the mechanisms by which venous return is significantly increased during exercise

Answer 18

1. Sympathetic venoconstriction
2. Skeletal muscle pump
3. Respiratory muscle pump

Question 19

Explain how skeletal muscle pump mechanism inncreases venous return

Answer 19

• Muscle contraction compresses veins and increases blood pressure – increase rate of venous return
• Increases venous return in proportion to rate of activity

Question 20

Explain how the respiratory muscle pump mechanism leads to venous return

Answer 20

1. INSPIRATION triggers a drop in the intrapleural pressure in the thoracic cavity. This leads to a reduced venous pressure in the vena cava – creating an enhanced pressure gradient to drive venous return
2. EXPIRATION causes the converse changes – causing compression of the vena cava driving the enhanced blood flow back to the heart
3. As hyperventilation quickens, the faster blood is pumped back to the heart

Question 21

Explain the effect of blood flow in the body during exercise (areas of the body affected vs at rest) show as graph

Answer 21

Question 22

What is the definition of haemodynamics?

Answer 22

The distribution of blood flow

Question 23

Give an overview explanation of pulmonary circulation

Answer 23

• LOW pressure (25/8 mmHg)
  
  • Prevent oedema* and *limit afterload on right ventricle
• HIGH flow (entire cardiac output)
  
  • LOW resistance (5 fold less than systemic)
• Regional variation in blood flow
• Passive adaptation in pulmonary vascular resistance
  
  • To large changes in cardiac output
  • Changes in lung volume
• Active (local) control of blood vessel radius
  
  • In response to changes in PAO2

Question 24

How does the cardiovascular system respond to changes in flow?

Answer 24

• Large increases in pulmonary blood flow (eg during exercise) only give small increases in pulmonary blood pressure
• Thanks to:
  
  1. Recruitment
  2. Distention

P=FxR (R must fall)

Question 25

Explain the perfusion pressure in the lungs

Answer 25

* Due to the effects of **_gravity_**, perfusion is _greater_ to the ***base*** of the lung than the ***apex*** * Pulmonary artery pressure _decreases_ as we head from base to *apex* due to the effect of blood travelling against **GRAVITY** * Intrapleural pressure is _higher_ at the *_base_* of the lung due to the *weight* of the *lung* positioning it closer to the pleural membranes at the base of the lung compared to at the *apex* – *_decreasing_ intrapleural space* here and *_increasing_* it at the *apex*

Question 26

Explain the different zones of the lungs and how they function

Answer 26

**ZONE 1** Top of lung; arterial pressure (Pa) is below zero at the very apex due to the **height of the lung** and the **hydrostatic pressure effect**. Pv (pulmonary venous pressure) is _more negative_ than arterial Intra-alveolar (intrapulmonary) pressure zero everywhere (and is not influenced by height of the lung as it under the influence of atmospheric pressure) Thus, pressure is higher in the alveoli (zero) than in the capillaries (negative) and this will _collapse the capillaries_; **no flow will occur** (zone 1) The lung in this area is ventilated but _not_ *perfused* (called wasted ventilation) **ZONE 2** Middle of the lung; arterial pressure (Pa) is getting higher due the hydrostatic effect of the height of the lung (not as high up so higher pressure in capillaries), but Pv is still below zero Intra-alveolar (intrapulmonary) pressure still zero everywhere; hence it is lower than arterial but higher than venous; *_flow will occur in the first half_* of the capillary whilst **arterial pressure** (pressure in the vessel keeping it open) is _higher_ than **alveolar pressure** (pressure outside the vessel trying to collapse it). As Pa (BP) falls as blood is driven through the vessel, the pressure will eventually fall lower than alveolar pressure and the capillary will collapse. So some blood flow will occur but will cease at the venous end **ZONE 3/4** Bottom of the lung: **arterial pressure** (Pa) is **HIGHEST** due to the effect of gravity increasing hydrostatic pressure below the heart (this also increase Pv). This time **venous pressure** Pv is also _higher_ than **alveolar pressure** and thus flow will occur over the *full length of the capillary*

Question 27

What does **functional/metabolic _hyperaemia_** do to blood flow and how?

Answer 27

Functional (Metabolic) Hyperaemia **_INCREASES_** blood flow to *_active skeletal muscle_* during exercise A *_decrease_* in blood supply or an *increase* in *demand of oxygen* (eg in exercise) causes the *tissue* to **release** *vasodilator metabolites* such as: * Potassium ions * Hydrogen ions (lactic acid) * Phosphate ions * Carbon dioxide * Prostaglandins * Adenosine An *_increase_* in *blood pressure* can *_increase_* *blood flow*, which causes a ‘***_wash-out’ of vasodilator metabolites_***, leading to a loss of *vasodilator influence* and hence a **_vasoconstriction_**, *_reducing_ blood flow* back to the original level

Question 28

What are the types of hyperaemia and explain them

Answer 28

**ACTIVE hyperaemia** is the *_same_* as *metabolic hyperaemia* **REACTIVE hyperaemia** occurs *_after_* *vessel occlusion* such as during an operation to a limb where *blood flow is cut off* by using a pneumatic cuff *inflated above arterial pressure*, then releasing it after the operation, or following occlusion by a clot that then breaks down.

Question 29

Explain briefly coronary circulation (how it works --\> processes e.g. in exercise)

Answer 29

* *_Increased_* cardiac work due to exercise (inc. HR, force of contraction) = *increase* *_oxygen_* *_demand_* of the *myocardium* * *Perfusion pressures* determined by *_diastolic pressure_*, not MAP * Coronary circulation is *_autoregulated_* * Changes in blood flow mirror changes in cardiac demand (metabolism) * As cardiac work increases, coronary blood flow increases * Mainly by **metabolic mechanism**

Question 30

Explain how coronary perfusion works?

Answer 30

* Coronary arteries located in *_subendocardial region_* of the *myocardium* * *Flow* in *_diastole_* * Effected by: 1. Reduced diastolic time (tachycardia) * Increasing HR means the *whole cardiac cycle has shorten*, however, *diastole shortens more than systole.* This means at *high heart rates* *coronary perfusion* will be ***_reduced_*** – at a time when oxygen demand is high. 2. Elevated end-diastolic pressure * If ventricular EDP is raised then that is transmitted into the coronary vessels and pressure their will be higher during diastole when it normally receives its blood supply due to the pressure gradient between the aorta and the coronary vessel in diastole. *Thus the pressure gradient to drive blood through the coronary circulation will be reduced* and hence *blood flow to the myocardium will be **_reduced_**.* 3. Reduced arterial pressure * A reduced arterial BP in the aorta will have the same affect as in point 2; *it will **_reduce_** the pressure gradient driving blood flow through the coronary vessels during diastole*. * **_Metabolic methods_** *increase* flow * These problems magnified in **_coronary artery disease_** where there may be *_narrowing_* of the coronary vessels and thus *increased resistance*

Question 31

What happens to inactive muscle during exercise & how does this effect exercise?

Answer 31

* Inactive skeletal muscles undergo **SYMPATHETICALLY** mediated *vasoconstriction* during exercise * If all of the arterioles supplying the skeletal muscle of the leg vasodilates during exercise , *total peripheral resistance (TPR) would fall dramatically*, and thus so would **_ABP (ABP = CO x TPR)_** * Therefore *vasoconstriction* of arterioles supplying inactive skeletal muscle as well as *splanchnic and renal circulations* helps *_maintain TPR_* and thus *_ABP_* during exercise. * This allows the body to ***_increase_*** *blood supply* to the *active skeletal muscle* with minimal changes in the rate of blood flow to the other tissues. * Due to the central **resetting** of the **_baroreflex_**, the body also allows a *small rise in arterial pressure*, such that even though resistance to blood flow to the forearm is raised, *the blood flow* to the arm *isn’t compromised*.

Question 32

Explain the importance of the *battleground* of **cutaneous circulation**

Answer 32

* Initially cutaneous *sympathetic vasoconstrictor* activity kicks in to help maintain * ABP, by preventing TPR from decreasing too much in the face of skeletal muscle arteriolar vasodilatation. * However, as *core body temperature* starts to **_RISE_** cutaneous vasodilation kicks in, starting to allow greater blood flow to the skin. This however *_reduces_* *total peripheral resistance*, meaning that *cardiac output* has to increase (via increased HR mainly) to *_maintain arterial blood pressure_* * The cutaneous blood flow *increases* *linearly* with rising *core body temperature* until a certain point where it can increase no further – sacrificing thermoregulation for cardiovascular stability. * This critical temperature set is variable and depends on *_hydration_*, suggesting it may be set by *cardiopulmonary baroreceptors*

Question 33

How to work out mean blood pressure? (MBP equations)

Answer 33

**MBP = CO x TPR**

Question 34

What is the equation to work out cardiac output? (CO)

Answer 34

**CO = HR x SV**