F5ii / 16B05: Describe the physiological factors that affect pulmonary arterial pressure

16B05: Exam Report

Describe the physiological factors that affect pulmonary arterial pressure (65% of marks). Write short notes on the use of inhaled nitric oxide as a pulmonary vasodilator (35% of marks).

51% of candidates passed this question.

Pressure in a system is generated by the interaction between flow and resistance. A structured approach to defining and describing the many factors that influence fluid flow and resistance was required to score well. Poiseuille’s law describes the determinants of resistance to laminar fluid flow and provides a useful answer structure. It is also necessary to describe factors that determine flow. This includes factors that determine venous return, as well right and left heart output.

A standard structured answer to the pharmacology of nitric oxide enabled concise and high scoring answering of this question.

F5ii / 16B05: Describe the physiological factors that affect pulmonary arterial pressure (65 marks). Write short notes on the use of inhaled nitric oxide as a pulmonary vasodilator (35 marks).

Definition/Values

Pulmonary Arterial Pressure = Pulmonary Blood Flow x Pulmonary Vascular Resistance

Pulmonary artery pressures: 25/8 (MAP 15mmHg)

Affected by:

  • Factors affecting PBF
  • Factors affecting PVR

Factors Affecting PVR:

  • System

1. Recruitment and Distention

Pulmonary vasculature is a high capacitance, low pressure

PBF can adapt to large changes in CO with only small increases in PVR, due to:

  • Recruitment of previously underperfused pulmonary vessels
  • Distension of the entire pulmonary vasculature

2. Lung Volumes

    • Low lung volumes → compression of the extra- alveolar vessels increases PVR;
    • High lung volumes → intra-aveolar vessels are compressed
    • Least resistance exists at FRC.

3. Gravity and West’s Zones of the Lung

    • In Zone 1 the PAP is just sufficient to raise blood to the apex of the lung. Any increase in alveolar pressure (eg; PEEP) or decrease in precapillary pressure (eg hypotension due to haemorrhage) will cause the alveolar pressure to exceed the precapillary pressure no flow. PA>Pa>Pv
    • In Zone 2, PAP increases because of the hydrostatic effect and now exceeds alveolar pressure. Blood flow is determined by arterial – alveolar pressure differences. Pa>PA>Pv
    • In Zone 3, venous pressure exceeds alveolar pressure. Pa>Pv>PA
    • A Zone 4 is sometimes referred to where an increase in extra alveolar vessel pressures due to gravity increases resistance. Hence at the very base there is a reduction in flow compared to zone 3.

4. Autonomic Influence

    • Alpha adrenergic stimulation vasoconstriction
    • Beta-adrenergic stimulation vasodilatation
    • Cholinergic stimulation vasodilatation

5. Metabolic Control + [CO2 + PH → vasoconstriction]

    • Local vasodilators (NO, prostacyclin)
    • Vasoconstrictors (serotonin, histamine, noradrenaline, hypercapnoea)

6. Hypoxic Pulmonary Vasoconstriction

    • Basal NO synthesis is inhibited in the presence of low PAO2 and results in vasoconstriction

Factors Affecting PBF

Venous Return (VR):

  • MSFP-RAP
  • Posture; upright posture reduces VR
  • Raised intrathoracic P reduces VR

RV Output & LV Output

  • HR
  • Contractility
  • preL
  • afterL
  • Intraventricular dependance

Nitric Oxide:

Inorganic gas. Also synthesised endogenously by endothelial cells by enzyme NO synthase

  • Use: ↑­V/Q ratio. ↓ PVR
  • Ceutics: In aluminium cylinders containing 100/800ppm of NO and N2. Inhaled dose of 5-20ppm
  • MoA: NO diffuses to vascular smooth muscle layer, stimulate guanylate cyclase →↑ ­cGMP → phosphorylation cascade. ↓ intracellular Ca → leading to smooth muscle relaxation and vasodilation
  • PK:
    • A – highly lipid soluble → freely diffuses across cell membranes
    • M – NO + OxyHb → MetHb + Nitrate. t1/2 5s
    • E – Nitrate – excreted by kidneys
  • PD
    • CVS: vasodilator, hypotension,
    • Haem: inhibits platelet aggregation and attenuates platelet and cell wall adhesion
    • Resp: inhibits pulmonary vasoconstriction. Improve V/Q matching and ratio
  • SE: NO reacts w superoxide ion to form free radical peroxynitrite, Methaemoglobinaemia, NO2 → pneumonitis, pulmonary oedema