• Autoregulation: “intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure“
• if perfusion pressure is decreased to an organ, blood flow initially falls, then returns toward normal levels over the next few minutes
• This autoregulatory response occurs in the absence of neural and hormonal influences and therefore is intrinsic to the organ, although these influences can modify the response

Mechanisms of Autoregulation

Local

• Myogenic
  • Stretch of vessel walls causes constriction due to stretch mediated Ca²⁺ release
    • Prominent in small arterioles throughout body
    • Prevents excessive increases in blood flow in response to pressure
  • Sheer stress on vessels due to increased flow causes release of Endothelial Derived Relaxing Factors such as Nitric Oxide which dilates the vessel, increasing vessel diameter and reducing sheer stress
• Metabolic
  • Increased concentration of metabolic byproducts such as CO₂, lactate, adenosine and H⁺, K⁺, cause upstream vasodilation
    • This diffuse through the interstitium to upstream pre-capillary sphincters, arterioles and meta-arterioles
    • Due to alteration of vessel radius, flow increases, according to the Poisuille-Hagen Equation
  • Conversely, presence of excess nutrients (and O₂) leads to vasoconstriction and decreased flow
• Reactive hyperaemia
  • During occlusion to blood flow to a tissue, metabolic products build-up
    • On restoration of flow to the tissue, flow can increase 4~7 fold due to buildup of metabolites and autoregulatory mechanisms
• Active hyperaemia
  • During periods of increased metabolic work, due to the consumption of nutrients and production of metabolites, blood flow increases due to autoregulation

Regional Circulations

Other Influences which modify Autoregulation

Neural factors

• Sympathetic
  • Sympathetic α adrenergic stimulation causes vasoconstriction (integral in baroreceptor response)
    • Resting sympathetic tone contributes significantly to peripheral vascular resistance
    • Most tissues except coronary and cerebral circulations
  • Sympathetic cholinergic vasodilator supply under cortical control to skeletal muscle

Hormonal factors

• β₂ mediated vasodilation in response to adrenaline in skeletal muscle
• α₁ mediated vasocontriction in response to circulating adrenaline

Long term

• Arterioles and vessels increase in size and number due to increased metabolic requirements of a tissue and chronic hypoxia
  • Important factors
    • VEGF
    • Angiogenin

Sakurai 2016

2014A 12: 8% of candidates passed this question.
Most candidates failed to fully comprehend the question. Candidates displayed some difficulty in differentiating regulation at a local level (which is what the question asked for) from that of central regulation (e.g. sympathetic nervous system activity, cardiac output, etc.), which was not what the question asked for. Other omissions were a failure to define and explain autoregulation. Most candidates mentioned the myogenic and the metabolic theories, but failed to provide sufficient details as to their mechanisms. It was expected candidates would provide some detail as to locally acting factors. Adenosine and nitric oxide were mentioned on occasions but others such as endothelin and prostacyclin were often omitted.

Portal System

• System where two separate capillary beds are supplied in consecutive series, before blood returns to the heart

Hepatic portal system

• Anatomy
  • Arterial blood perfuses the GI tract (from stomach to proximal rectum) via the Coeliac trunk, superior mesenteric arteries and inferior mesenteric arteries.
  • Capillary blood from GI tract drain to superior mesenteric and inferior mesenteric veins which converge to form the portal vein
  • Portal vein perfuses the liver as part of the portal triad
  • Hepatic venous blood drains into the inferior vena cava before returning to the heart
• Function
  • Protects systemic circulation from blood from portal venous blood
    • Toxins absorbed from GI tract (ammonia) metabolized by liver before reaching systemic circulation
    • Pathogens encounter leukocytes (e.g. macrophages) in space of Disse in liver
    • Fluctuation in blood constituents due to GI absorptions buffered by liver (e.g. glucose)

Renal portal system

• Anatomy
  • Renal arterial blood perfuses the renal cortex via afferent arterioles à glomeruli
  • Glomeruli drain blood into efferent arterioles
  • Efferent arteriolar vessels drain into peritubular capillary network
  • Proportion of efferent arteriolar vessels form vasa recta which supply blood to renal medullary interstitium via vasa recta à drains to renal venules and veins before returning to heart
• Function
  • As peritubular capillary network has lost Na and H₂O to glomerular filtrate à increases reabsorptive capacity of renal tubules due to concentration gradients

Hypothalamic-Pituitary Axis

• Anatomy
  • Arterioles from superior hypophysial artery (branch of circle of willis) supply hypothalamus via primary plexus à drains to portal hypophysial vessels
  • Portal veins supply anterior pituitary
  • Blood returns to heart via internal jugular vein
• Function
  • Delivery of tropic hormones to anterior pituitary for signalling
    • CRH
    • TRH
    • GnRH
    • GRH
    • PRH

Sakurai 2016

2011B 09: 8 (32%) of candidates passed this question.
A portal system is an arrangement by which blood collected from one set of capillaries passes through a large vessel or vessels, to another set of capillaries before returning to the systemic circulation. The three portal systems are the –
1) system of blood vessels that link the hypothalamus and the anterior pituitary in the brain, which allows endocrine communication between the two structures.
2) within the liver, whereby venous blood from the GI tract drains into the superior and inferior mesenteric veins; these two vessels are then joined by the splenic vein to form the portal vein which enters the liver, drains into the hepatic sinusoids and then eventually into the hepatic veins which join the inferior vena cava, with the purpose of defending against by breaking down and metabolising most of what has been absorbed from the gastrointestinal tract (including an immunoprotective action).
3) within the kidney, whereby blood from the afferent arterioles enters the glomerulus (first capillary network), followed by the efferent arterioles, then the peritubular network (second capillary network) and eventually the venous system, with the purpose of stronger re-absorptive capacity for water from within long Loops of Henle that go deep within the renal medulla.
Syllabus: N1 2c, I2d, D1 2a
Recommended sources: Ganong Review of Medical Physiology Chps 18, 38, 29

High Pressure Baroreceptor (HP BR)

• Carotid sinus and aortic arch receptors
  • Detects > 5-10 % change in plasma volume
  • ↓ Plasma volume → Increased central SNS tone and decreased PSNS tone
• Sensor:
  • Stretch receptor: ↑ distension of vessel → ↑ discharge rate
  • Threshold > 60mmHg → normally has baseline tone.
  • Located at Carotid Sinus and Aortic Arch
  • Spray like visceral nerve endings
  • Transmitted by:
    • Unmyelinated C-fibres (most receptors)
    • Myelinated A-fibres (↑ sensitivity at lower BP)
    • Individual fibres have narrow BP range
  • Increased reponsiveness to pulsitile rather than continuous flow
• Afferent signal:
  • Carotid sinus → Nerve of Hering → CN9
  • Aortic Arch → CN10 → NTS
  • Both then divide to:
    • Stimulatory afferents → ↑ Medullary vagal outflow
    • Inhibitory afferents → ↓ RVLM SNS outflow
• Outcome:
  • ↑’d distension → ↓’d HR/Contractility/SVR
  • Provides strict negative feedback to Δ’s in CO

Low Pressure Baroreceptors (LP BR)

• Location
  • Located at junction of return vessels and atria, vetricular walls, pulmonary vessles
  • Throughout the peripheral vasculature (esp kidney)
• Sensor:
  • Stretch receptor: ↑ distension of vessel → ↑ discharge rate
  • Detect > 10% decrease in plasma volume as decreased atrial stretch
  • ↓ Discharge rate with
    • Reduced ANP release
    • Increase SNS output
• 2 types
  • A receptors → fire at atrial contraction (a wave)
  • B type → fire at atrial filling (v wave)
• Outcome
  • ↓ PL → ↓ CO → ↓BR discharge rate
    • Medulla afferents cause
      • ↓ SNS (NA) and ↑PSNS (RVLM) outflow → peripheral vascular vaso and venodilation
      • ↓ SNS activity to kidney → ↓ Na/H2O conservation
      • ↑ SNS activity to sinus node
    • Hypothalamic afferents cause
      • → ↓ ADH release and ↓ Thirst
  • ↑ contractility/HR/SV/CO
  • ↑ SVR → autotransfusion and ↑ perfusing pressure (but ↑AL)

Gladwin 2016

2014B 16: 62% of candidates passed this question.
This is a core topic and a detailed knowledge was expected. Baroreceptors are stretch receptors located in the walls of the heart and blood vessels and are important in the short term control of blood pressure. Those in the carotid sinus and aortic arch monitor the arterial circulation. Others, the cardiopulmonary baroreceptors, are located in the walls of the right and left atria, the pulmonary veins and the pulmonary circulation. They are all stimulated by distention and discharge at an increased rate when the pressure in these structures rises. Better answers provided some detail on the innervation for these receptors. It was expected candidates would describe that increased baroreceptor discharge inhibits the tonic discharge of sympathetic nerves and excites the vagal innervation of the heart. This results in vasodilation, venodilation, a drop in blood pressure, bradycardia and a decreased cardiac output.
Some candidates had a major misunderstanding around the purpose of “low pressure baroreceptors” with many believing that these are the ones that respond to lower blood pressures, while the “high pressure baroreceptors” respond to higher blood pressures.

2007B 08: 5 candidates (71%) passed this question.
Good answers included the following

• description of, and types of, baroreceptors (e.g. stretch-receptors)
• their locations (e.g. walls of the aorta, carotid sinuses, the atria etc)
• the stimulus they respond to (e.g. pressure, volume)
• short term and long term responses, alteration to set points, impulse frequency / pressure
  curve
• a brief description of the afferent and efferent pathways and the resultant efferent effects
  (e.g. alterations to heart rate, blood pressure, etc)

Systemic Vascular Resistance
(Total Peripheral Resistance)

Systemic vascular resistance (peripheral vascular resistance, SVR) is the resistance in the circulatory system that is used to create blood pressure, the flow of blood and is also a component of cardiac function.

• Majority of resistance in systemic system results from arterioles – state of contraction and relaxation of smooth muscle cells of arterioles which determines distribution of blood to organs
• The % of each organ blood flow is dependent on the organ vascular resistance
• Systemic vascular resistance is the resistance of several circuits in parallel, which have both common and independent factors in their regulation.
  • As they are in parallel the sum of reciprocals is used to determine the overall value.

Control

• As per Hagen Poiseuille Equation:

where: η = blood viscosity
L = length of vessel
r = radius of vessel

• radius is the most important factor

Extrinsic Control

• Extrinsic SNS control
  • Arterioles have profuse SNS supply → NAd from nerve endings act on α1-adrenoceptors to cause vasoconstriction (and β2-adrenoceptors to cause vasodilation – but effect is weaker!)
  • Due to the tonic SNS outflow from medullary vasomotor centres, arterioles have a basal level of vasoconstriction → the degree of basal vasoconstriction (and arteriolar resistance) can be varied by altering SNS outflow
• Extrinsic PNS control
  • PNS control of arterioles is less important → vessels of external genitalia have dual ANS supply with PNS dilator nerves and SNS constrictor supply; PNS activation in heart, brain and lungs have an uncertain role
• Extrinsic hormonal control
  • Adrenaline (from adrenal medulla) → effect on organ blood flow depends on the relative % of α1- and β2-adrenoceptors present in the arteriole
  • AII (from RAAS) → vasoconstriction (via AT2R)
  • ADH (from posterior pituitary) → vasoconstriction (via V1R)
  • ANP (from RA) → vasodilation (via ANPR)

Intrinsic Control

• Autoregulation
  • Ability of an organ to maintain relatively constant blood flow across variations in perfusion pressure
  • flow = pressure/ resistance → as the P changes, the R also changes to maintain flow
  • Outside limits of autoregulation: flow = dependent on driving pressure
  • Kidneys, brain, heart
• Autoregulation is dependent on 2 mechanisms:
  • Pressure autoregulation: myogenic stretch response to ↑ and ↓ in pressure → vasoconstriction, and vasodilation
  • Metabolic or vasoactive autoregulation: direct action of locally derived metabolites and vasoactive substances e.g. platelets release thromboxane A2 → constriction in damage

Bianca / Kerr 2016

2022A 20: 22% of candidates passed this question.
A definition or description of SVR that recognised the importance of radius in small arteries/arterioles as the major determinant attracted marks. Resistance is ΔP/flow; where ΔP is not only MAP and flow is volume/time. The systemic vascular resistance is the resistance of several circuits in parallel, which have both common and independent factors in their regulation. As they are in parallel the sum of reciprocals is used, 1/SVR = 1/R1 + 1/R2 to determine the overall value. A detailed explanation of the Hagen-Pouiselle law was not required, attracted few marks and wasted writing time. The remainder of the answer focus was on the factors that control the radius of these vessels. As a question regarding control, an approach that included sensors, integrators and effectors tended to yield a more comprehensive answer with resultant higher marks. Other useful structures included divisions into intrinsic/local factors (including endothelial input and autoregulation), neural control (reflexes and central controller) and hormonal control. As the question was regarding physiological control, no marks were awarded to pharmacological manipulation of SVR. Given the potential scope of the question, detailed descriptions of how noradrenaline exerts its effect were not required beyond receptor level although stating ‘sympathetic nervous system activation results in vasoconstriction’ were too simplistic to attract full marks.

2020A 07: 21% of candidates passed this question.
This question invited a detailed discussion of the physiological control mechanisms in health, not pathophysiology nor drug-mediated effects. The central and reflex control mechanisms that regulate SVR over time are distinct from the local determinants of SVR. There was often confusion between dependent and independent variables. Cardiac output is generally depended upon SVR, not vice versa, even though SVR can be mathematically calculated from CO and driving pressures. The question asked about systemic vascular resistance and did not require a discussion of individual organs except for a general understanding that local autoregulation versus central neurogenic control predominates in different tissues. Emotional state, temperature, pain and pulmonary reflexes were frequently omitted. Peripheral and central chemoreceptors and low-pressure baroreceptors were relevant to include along with high pressure baroreceptors.