Pulmonary blood flow and gas exchange

Question 1

Distinguish pulmonary from systemic circulation

Answer 1

• Pulmonary Circulation vs Systemic Circulation
  
  • Main role: Receive cardiac output, deliver across small distances to pulmonary capillaries for gas exchange within alveolus
    
    • Thin-walled, distensible vessels, less smooth muscle ^[major anatomic diffs vs systemic]
    • Lower pressures than systemic circulation
      - Systolic 25mmHg, diastolic 8mmHg, MPAP = 15mmHg
    • Vessels influenced by surrounding tissue pressure (e.g., alveolus)

Question 2

List and describe the determinants of pulmonary blood flow

Answer 2

• F = P/R
  - PBF = (MPAP – LAP)/PVR
  - MPAP = Mean pulmonary artery pressure
  - LAP = Left atrial pressure
  - PVR = Pulmonary vascular resistance
  - PVR main determinant of PBF (other variables fairly stable)
  - R = 8nl/πr4 (vessel radius major determinant in PVR, thus PBF) ^[seen prev]

Question 3

Describe passive and active factors that contribute to pulmonary vascular resistance

Answer 3

• Passive Factors
  
  • Pulmonary Blood Flow: Adapts to large changes in cardiac output with small increases in pulmonary arterial pressure; PVR decreases as flow increases
    
    • Distension: Thin-walled vessels distend easily with increased flow
    • Recruitment: Increased flow opens previously closed pulmonary vessels
  • Lung Volume:
    
    • Optimal PVR at FRC
    • low lung vols = compression of extra-alveolar vessels
    • high lung vols = compression of alveolar vessels
  • Gravity: Lung and pulmonary vessels act as starling resistor: flow through tube is influenced by driving pressure (coming through) and pressure around tube
    - divides lung into 3 zones (West’s zones)
    - 1:alveolar pressure>arterial>venous -
    - no flow
    - effectively dead space
    - not really seen in absence of pathology ^[or can make one]
    - 2:arterial>alveolar>venous
    - flow dependent on alveolar volume
    - 3:arterial>venous>alveolar
    - flow occurs independently of alveolar volume, an effective shunt
• Active Factors
  
  • Hypoxic Pulmonary Vasoconstriction:
    
    • most important factor
    • key difference between systemic and pulmonary vasculature
    • protective: to optimise VQ matching across lung - away from ‘hypoxic’ areas e.g. pus filled infected areas
    • **Primarily mediated by alveolar PO2, arterial plays small role ^[like metabolic regulation of systemic vessels]
    • Mechanism: ^[debated]
      
      • Hypoxia inhibits K+ channels, opens VGCa channels (L-type), leads to Ca influx, smooth muscle contraction
      • Biphasic response: Rapid decrease then slower increase; PBF halves in first 5 min then plateaus, second slower increase around 40 min
    • Modulated by various factors: Inhibition (alkalosis, nitric oxide - dilator, prostacyclins, volatile anaesthetics) and enhancement (acidosis, hypercapnoea, hypothermia, endothelin): increases vascular tone
  • Neural Control:
  • Sympathetic (mixed effects): alpha 1 and vasoconstriction (NA response), beta 2 and vasodilation (Ad response)
  • para-sympathetic (vasodilation, via M3 receptor)
  • Humoral Control: Vasoconstriction (noradrenaline, adrenaline, thromboxane, serotonin, histamine) and vasodilation (prostacyclins)

Question 4

Describe hypoxic pulmonary vasoconstriction

Answer 4

• Hypoxic Pulmonary Vasoconstriction:
  
  • most important factor
  • key difference between systemic and pulmonary vasculature
  • protective: to optimise VQ matching across lung - away from ‘hypoxic’ areas e.g. pus filled infected areas
  • Primarily mediated by alveolar PO2, arterial plays small role ^[like metabolic regulation of systemic vessels]
  • Mechanism: ^[debated]
    
    • Hypoxia inhibits K+ channels, opens VGCa channels (L-type), leads to Ca influx, smooth muscle contraction
    • Biphasic response: Rapid decrease then slower increase; PBF halves in first 5 min then plateaus, second slower increase around 40 min
  • Modulated by various factors: Inhibition (alkalosis, nitric oxide - dilator, prostacyclins, volatile anaesthetics) and enhancement (acidosis, hypercapnoea, hypothermia, endothelin): increases vascular tone

Question 5

Describe how gravity affects blood flow in lung

aka zones

Answer 5

Lung and pulmonary vessels act as starling resistor: flow through tube is influenced by driving pressure (coming through) and pressure around tube
- divides lung into 3 zones (West’s zones)
- 1:alveolar pressure>arterial>venous -
- no flow
- effectively dead space
- not really seen in absence of pathology ^[or can make one]
- 2:arterial>alveolar>venous
- flow dependent on alveolar volume
- 3:arterial>venous>alveolar
- flow occurs independently of alveolar volume, an effective shunt

Question 6

Define pulmonary hypertension and list the five types

Answer 6

mPAP >20mmHg: Pulmonary Hypertension
- Causes:
- type 1:Idiopathic
- type 2: left heart disease (driving pressure higher)
- type 3: chronic hypoxia (protective pulmonary vasoconstriction)
- type 4: thromboembolic disease
- type 5:multifactorial mechanisms

Question 7

Describe forms of oxygen carriage

Answer 7

• Forms of Oxygen Carriage
  
  • Dissolved in Solution: Limited due to low solubility (per Henry’s L); 15ml of O2 dissolved in 5L blood
  • Bound to Haemoglobin: O2 binds to iron in haem; 1.39ml ^[calcd with Huffner’s c] of O2 per g of Hb (in vivo ~1.34ml due to Hb types e.g metHb)
• Haemoglobin States:
  
  • Relaxed (binds O2 easily): R state - favoured in alkalosis, hypocapnoea, hypothermia, decreased 23DPG
  • Tense (unloads O2 easily): T state – inverse ^[e.g. fetal, no beta subunit]
  • PHENOMENON = Bohr effect: alteration in O2 binding capacity of Hb depends on surrounding environment ^[a.k.a how readily]
  • Binding of one O2 favours Hb R state–‘more can bind more easily’: sigmoid shape ^[mind ICU point - 60 mmHg]
• Oxygen Delivery (DO2):
• CO x Arterial oxygen carrying capacity
  
  • DO2 = (HR x SV) x ((1.34 x Hb x SaO2) + (PaO2 x 0.0?3)) ^[how much bound, how much dissolved]
  • DO2 = 1000ml/min (rest) (e.g. - assuming all good)
• Oxygen Consumption: Rest ~250ml/min; mixed venous oxygen saturation 75%
  
  • changes with metabolic demand

Question 8

Describe forms of CO2 carriage

Answer 8

• Forms of CO2 Carriage
  
  • Dissolved in Solution: More soluble than O2; 5% of CO2 carriage, 10% of AV difference
  • Bicarbonate: CO2 + H2O → H2CO3 → H+ + HCO3- ^[CA influence]; 90% of CO2 carriage, 60% of AV difference
    
    • H+ - buffered by Hb
    • HCO3 swapped Cl (Chloride shift)
  • Carbamino Compounds: CO2 combines with terminal amino groups on proteins, Hb most important here (most abundant protein in red cell); **5% of CO2 carriage, 30% of AV difference
• Haldane Effect:
  
  • Deoxygenated blood transports CO2 more effectively (70% via carbamino compounds, 30% via buffering H+ - Hb free to buffer)

Question 9

Describe how tissues, lungs and expiration are involved in gas transport and exchange

Answer 9

• Tissues: Environment favors O2 unloading, due to byproducts of metabolism, leading to increased deoxygenated Hb and higher CO2 carrying capacity - as explained by Bohr
• Lungs: Reverse process; increased O2 concentration leads to HbO2 formation, **promoting CO2 unloading (dissociation from carbamino compounds and H+) ^[H+ buffered by Hco3, forms H2CO3 (c/b)]
• Expiration: Passive process due to lung elasticity, potential energy from inspiration to overcome elastic work (usually); becomes active with increased resistance