PULMONARY CIRCULATION AND CLINICAL ASPECTS

1. INTRODUCTION

2. ANATOMY

• Pulmonary artery enters each lung at the hilum alongside the main bronchus in a loose connective tissue sheath
• Branches accompany each airway generation down to the respiratory bronchiole - ensuring V/Q matching at every level
• Pulmonary veins follow Miller's dictum: they lie as far from airways as possible, occupying the peripheral connective tissue envelope
• Quantitative data (Murray & Nadel, Table 1.3):

3. NORMAL PRESSURES (Fishman's, Table 13-1)

4. PULMONARY VASCULAR RESISTANCE (PVR)

PVR = (mPAP - LAP) / CO

• LAP is estimated as PAWP (balloon-occluded PAP)
• CO measured by thermodilution (cooled saline, 5-10 mL into RA) or direct Fick method: CO = VO₂ / (CaO₂ - CvO₂)
• PVR is not constant - unlike electrical resistance. Increasing PAP or PAWP decreases PVR by two mechanisms:
  • Recruitment - opening of previously closed vessels
  • Distension - increase in caliber of open vessels
• During exercise, both mechanisms reduce PVR, limiting RV work
• Hematocrit effect: PVR rises exponentially with rising hematocrit. Polycythemia (e.g., COPD, altitude) significantly increases PVR. (Murray & Nadel, Ch. 10; Fishman's, Ch. 13)

5. DISTRIBUTION OF BLOOD FLOW - WEST ZONES

6. HYPOXIC PULMONARY VASOCONSTRICTION (HPV)

• Unique feature of pulmonary circulation: systemic vessels dilate in hypoxia; pulmonary vessels constrict
• Response triggered when alveolar PO₂ falls below 60 mmHg; response scales with degree of hypoxia
• Driven by alveolar PO₂, not blood PO₂ (proven by perfusing lung with high-PO₂ blood under hypoxic alveolar conditions - vasoconstriction still occurs)
• Site: predominantly small pulmonary arteries and arterioles
• Persists in transplanted lungs (no autonomic input needed) - intrinsic smooth muscle response

1. Redox hypothesis: Hypoxia → decreased mitochondrial ROS → reduced intracellular redox state → K⁺ channels (Kv1.5) close → membrane depolarisation → voltage-gated Ca²⁺ entry → vasoconstriction
2. ROS hypothesis: Hypoxia → complex III generates ROS → Ca²⁺ influx + sarcoplasmic reticulum Ca²⁺ release → Rho kinase (ROCK) activation → myofilament sensitisation → vasoconstriction

• NO (endothelium-derived relaxing factor): inhibits HPV; inhaled NO (20 ppm) reduces HPV
• Endothelins (vasoconstrictor peptides from endothelial cells): augment HPV; endothelin antagonists are key PAH therapies
• Metabolic acidosis: enhances HPV; metabolic alkalosis: attenuates HPV

• Locally: diverts blood from hypoventilated to well-ventilated areas → improves V/Q matching
• Fetal period: maintains high PVR when lungs don't exchange gas; only 15% of CO goes to fetal lungs

• Bronchodilators in asthma can inhibit HPV → worsen V/Q → drop arterial PO₂
• At high altitude (global hypoxia): generalized HPV → pulmonary hypertension → high-altitude pulmonary edema (HAPE)
• With sustained hypoxia: structural remodelling of arterioles, RV hypertrophy

7. DEFINITION OF PULMONARY HYPERTENSION (Current Consensus)

• Upper limit of normal: ~5-7 mmHg
• DPG >7 mmHg in heart failure = worse survival (precapillary component)
• DPG is preferable to Transpulmonary Gradient (TPG) for diagnosing pulmonary vascular disease in left heart failure, as TPG is sensitive to changes in stroke volume and PAC

• mPAP-CO slope limits of normal: 0.5-3 mmHg/L/min (average ~1.5 mmHg/L/min)
• mPAP >30 mmHg at CO <10 L/min = abnormal exercise response

8. RIGHT VENTRICULAR-PULMONARY ARTERIAL COUPLING

• Optimal RV-PA coupling: Ees/Ea = 1.5-2 (ratio of RV end-systolic elastance to arterial elastance)
• EF = 1 - mPAP/Pmax
• As PH progresses: Ees/Ea falls; EF decreases below 35% → RV dilation, systemic congestion
• Noninvasive surrogate: TAPSE/sPAP ratio (echocardiographic) - validated prognostic marker in PAH, heart failure, and chronic lung disease

9. CLINICAL ASPECTS

A. Pulmonary Arterial Hypertension (PAH)

• Precapillary PH with PVR ≥3 WU, PAWP ≤15 mmHg
• Initial evaluation: ECG, ABG, CXR, PFTs, 6-minute walk test, BNP/NT-proBNP, echocardiography
• Right heart catheterisation required to confirm diagnosis and assess severity
• Acute vasoreactivity testing: inhaled NO, epoprostenol, adenosine - guides use of calcium channel blockers
• Chronic thromboembolic PH: V/Q scan + CT pulmonary angiography (Murray & Nadel, Ch. 9)

B. Pulmonary Embolism (PE)

• Most frequently arises from DVT in lower extremities
• Elevated troponin = high short-term mortality risk
• Diagnosis:
  • CT pulmonary angiography (CTPA): current gold standard; high negative predictive value; limited for subsegmental clots; breast radiation concern in young women
  • D-dimer: high NPV for PE; poor specificity in pregnancy/surgery; negative D-dimer + low/intermediate clinical suspicion avoids CT in ~50% outpatients
  • V/Q scan (SPECT preferred): lower breast dose; better in young patients with normal CXR; PIOPED study showed high non-diagnostic rate with planar V/Q
  • Wells score, Simplified Geneva score, PERC score: pretest probability assessment (often underutilised)
  • Doppler US: if clinical DVT signs present - first test
  • MRI: not first-line; emerging alternative in renal impairment/pregnancy
• Haemodynamic impact: >50% obstruction required to raise mPAP >25 mmHg; severe PH (mPAP ~50 mmHg) = ~80% obstruction (Fishman's, Ch. 28)

C. Pulmonary Edema

• Results from imbalance of Starling forces across capillary membrane
• Hydrostatic (cardiogenic): raised PAWP → fluid filtration exceeds lymphatic clearance
• High-altitude pulmonary edema (HAPE): uneven HPV → high shear stress + vascular injury → edema; treated by descent/supplemental O₂/nifedipine
• Peribronchovascular cuffing on CXR: fluid accumulates first in the loose peribronchovascular connective tissue sheaths before filling alveoli (Murray & Nadel, Ch. 1; Fishman's, Ch. 91)

D. Effects of Lung Disease on Pulmonary Circulation

• COPD: patchy V/Q mismatch → regional HPV → if global hypoxia → sustained PH → cor pulmonale
• Fibrosis/cysts: local reduction in blood flow
• Left-to-right shunts (ASD, VSD): increased flow → cephalization → eventually irreversible pulmonary vascular remodelling (Eisenmenger syndrome)

10. SUMMARY (Fishman's Ch. 13 - direct)

"The pulmonary circulation is a high-flow and low-pressure circuit, with an average resistance of 1 mmHg·min·L⁻¹ in young adults that increases to 2.5 mmHg·min·L⁻¹ over 4-6 decades of life. Pulmonary vascular mechanics are best described by pressure-flow relationships conforming to distensible vessel models with a correction for hematocrit. The distribution of pulmonary perfusion is mainly determined by the effects of gravity and corrected to some extent by hypoxia-induced vasoconstriction to preserve matching to regional decrease in ventilation. Exercise is associated with a decrease in PVR. RV function is coupled to the pulmonary circulation, with an optimal Ees/Ea of 1.5-2."

• Fishman's Pulmonary Diseases and Disorders, 2-Vol Set - Ch. 13 (Naeije, Pulmonary Circulation), Ch. 28 (Imaging of PE), Ch. 91 (High-Altitude Disease)
• Murray & Nadel's Textbook of Respiratory Medicine, 2-Vol Set - Ch. 1 (Anatomy), Ch. 10 (Pulmonary Circulation, V/Q, HPV)This answer covers all high-yield MD exam points directly from Fishman and Murray. Quick orientation of what's inside:

PULMONARY CIRCULATION AND CLINICAL ASPECTS

1. INTRODUCTION

2. ANATOMY

• Pulmonary artery enters each lung at the hilum alongside the bronchus in a loose peribronchovascular connective tissue sheath
• Artery branches with each airway generation down to the respiratory bronchiole - ensuring V/Q matching at every level
• Pulmonary veins lie as far from airways as possible (Miller's dictum) - peripherally in connective tissue septa
• Total capillary surface area = 50-70 m² (key to efficient gas exchange)
• Capillary volume = 60-200 mL; serves as a reservoir that can be recruited

3. NORMAL PRESSURES

4. PULMONARY VASCULAR RESISTANCE (PVR)

• Measured via Swan-Ganz catheter (triple-lumen balloon-tipped, introduced by Swan, Ganz & Forrester, 1970s)
• PAWP estimates LAP (left atrial pressure)
• CO by thermodilution (5-10 mL cold saline into RA) or direct Fick (CO = VO₂ / CaO₂ - CvO₂)

1. Recruitment - previously closed capillaries open
2. Distension - increase in caliber of open vessels

5. DISTRIBUTION OF BLOOD FLOW - WEST ZONES

• Pulmonary embolism → perfusion defect with normal ventilation (V/Q mismatch)
• Left heart failure → cephalization (upper zone diversion) from raised PAWP
• COPD, fibrosis → patchy reduction in regional flow

6. HYPOXIC PULMONARY VASOCONSTRICTION (HPV)

• NO (endothelium-derived): vasodilator; inhibits HPV; inhaled NO (~20 ppm) reverses HPV
• Endothelins (endothelium-derived): vasoconstrictor; augment HPV → endothelin receptor antagonists are key PAH drugs
• Metabolic acidosis: enhances HPV; metabolic alkalosis: attenuates HPV

• Improves V/Q matching in localised lung disease
• Fetal circulation: HPV keeps PVR high → only 15% CO to fetal lungs
• Bronchodilators (β-agonists) inhibit HPV → V/Q worsens → ↓ PaO₂ (clinical trap in asthma)

7. DEFINITION OF PULMONARY HYPERTENSION

• Upper limit of normal: ~5-7 mmHg
• DPG >7 mmHg in heart failure = poor survival (precapillary component added)
• DPG is superior to TPG (mPAP−PAWP) for diagnosing pulmonary vascular disease in left heart failure

• 50% obstruction needed to raise mPAP >25 mmHg

• Severe PH (mPAP ~50 mmHg) = ~80% obstruction

8. RV-PULMONARY ARTERIAL COUPLING

• Optimal coupling: Ees/Ea = 1.5-2 (RV end-systolic elastance / arterial elastance)
• EF = 1 - mPAP/Pmax
• When EF falls <35% or SV/ESV <52% → RV dilates → systemic congestion
• Noninvasive surrogate: TAPSE/sPAP ratio (echocardiography) - validated in PAH, HF, chronic lung disease

9. CLINICAL ASPECTS

A. Pulmonary Arterial Hypertension (PAH)

• Workup: ECG, ABG, CXR, PFTs, 6-min walk test, BNP, echo
• Right heart catheterisation - mandatory to confirm diagnosis and severity
• Acute vasoreactivity test: inhaled NO / epoprostenol / adenosine → guides calcium channel blocker use
• Chronic thromboembolic PH: V/Q scan + CT pulmonary angiography

B. Pulmonary Embolism

• Arises from lower extremity DVT; elevated troponin = high short-term mortality
• CTPA - current gold standard; high NPV; limited for subsegmental clots
• D-dimer - high NPV; poor specificity in pregnancy/surgery; negative D-dimer + low pretest probability avoids CT in ~50% outpatients
• V/Q scan (SPECT) - preferred in young women and pregnancy (lower breast dose); limited by poor specificity (PIOPED study)
• Wells, Geneva, PERC scores - pretest probability assessment (frequently underused)
• Leg Doppler US - first test if clinical DVT signs present

C. Pulmonary Edema

• Fluid first accumulates in peribronchovascular connective tissue sheaths (seen as cuffing on CXR/CT)
• HAPE (High-Altitude Pulmonary Edema): global HPV → uneven vasoconstriction → high shear stress + vascular injury → edema
  • Treatment: immediate descent, supplemental O₂, nifedipine

D. Effects of Lung/Heart Disease

• COPD → patchy HPV → if global hypoxia sustained → PH → cor pulmonale (RV hypertrophy/failure)
• Left-to-right shunts → increased flow → vascular remodelling → Eisenmenger syndrome (irreversible precapillary PH)
• Altitude: acute HPV → reversible; weeks-months exposure → structural arteriolar remodelling → RV hypertrophy

10. SUMMARY

"The pulmonary circulation is a high-flow, low-pressure circuit with average PVR of 1 Wood unit in young adults rising to 2.5 Wood units over 4-6 decades. PVR falls with exercise. Distribution of perfusion is gravity-dependent, corrected by HPV. Optimal RV-PA coupling ratio is 1.5-2."