Pulmonary Circulation

Question 1

Ohm’s Law to describe pulmonary flow

Answer 1

PPA - PLA = CO x PVR

PPA = mean pulmonary artery pressure 
PLA = LA (wedge) pressure 
PVR = pulmonary vascular resistance

Question 2

Hypoxic pulmonary vasoconstriction

Answer 2

Alveolar hypoxia signals local arterioles to contract, directing blood flow away from hypoxic areas of the lung and optimizing V/Q matching

Question 3

Zone 1

Answer 3

The physiologic region of the lung where PA > Pa > PV

Pulmonary microvasculature is compressed by the positive pressure within the alveoli; blood flow is minimal

Zone 1 is found in the apices of an upright person but is very minimal under healthy lung conditions

Question 4

Zone 2

Answer 4

The physiological region of the lung where Pa > PA > PV

The driving pressure on the pulmonary circulation is the difference between arterial and alveolar pressure

Flow is greater than in Zone 1 but less than in Zone 3

Question 5

Zone 3

Answer 5

The physiological region of the lung in which Pa > PV > PA

The driving pressure on pulmonary circulation is the difference between arterial and venous pressure; blood flow is greatest in this region

Question 6

Equation to determine fluid movement across endothelium

Answer 6

Qf = Kf[(Pmv - Pi) - s(Pimv - Pii)

The difference between the hydrostatic pressure gradient and the oncotic pressure gradient

Question 7

Edema safety factors

Answer 7

Decreased interstitial oncotic pressure (Pii) - fluid that enters the interstitial space in edema dilutes the interstitial oncotic pressure, pulling fluid back into the vessels

Increased interstitial hydrostatic pressure (Pi) - fluid that accumulates in the interstitium surrounding the microcirculation increases the interstitial pressure, opposing further fluid movement out of vessels

Increased plasma oncotic pressure - sudden loss of fluid from microvasculature increases vessel oncotic pressure via concentration of albumin, opposing further fluid movement out of the vessel

Lymphatic reserve system - edema accumulates only when the reserve capacity of the lymphatics is overwhelmed

Question 8

2 types of pulmonary edema

Answer 8

Hydrostatic / Hemodynamic / Cardiogenic

Permeability

Question 9

Hydrostatic (Hemodynamic, Cardiogenic) Pulmonary Edema

Answer 9

Requires microvascular pressures exceeding 25-30 mmHg (normal is 5-10mmHg)

Most commonly caused by left heart failure, mitral valve disease, and congenital heart disease; may also be caused by renal failure

Treated with diuretics

Question 10

Permeability (non-cardiogenic) pulmonary edema

Answer 10

Caused by widespread injury to the pulmonary microvascular endothelium, altering the osmotic permeability coefficient from near 1 (total reflection) to near 0 (no reflection) of plasma protein; leads to edema formation even at normal microvascular hydrostatic pressures (Wedge pressure < 15 mmHg)

Caused by trauma, sepsis, inhalation of toxic gases, aspiration, amniotic fluid / fat embolism

Question 11

Adult Respiratory Distress Syndrome

Answer 11

Alveolar flooding caused by diffuse damage to microvascular endothelium, resulting in widespread permeability pulmonary edema

Causes decreased compliance, impaired gas exchange with resultant hypoxemia; requires high pressures to inflate the lung

Treatment is supportive - mechanical ventilation with high FIO2 and pressures

Question 12

Pulmonary Hypertension - Pressure Measurements

Answer 12

Defined as elevation of mean pulmonary arterial pressure above 25 mmHg

(Normal mean pulmonary arterial pressure is 15 mmHg)

Question 13

Factors that increase PPA

Answer 13

PPA = CO x PVR + PLA; therefore PPA can be increased by

Increased PLA (left heart failure, mitral stenosis) 
Increased PVR 
Increased CO (in theory; PPA does not increase linearly with increased CO)

Question 14

Classification of Pulmonary Hypertension - 5 main categories

Answer 14

1. Pulmonary arterial hypertension
2. Pulmonary hypertension due to left heart disease
3. Pulmonary hypertension due to lung diseases and/or hypoxia
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Miscellaneous (unclear, multifactorial mechanism)

Question 15

1. Pulmonary arterial hypertension - causes

Answer 15

Idiopathic
Heritable
Drug/toxin induced
Associated with: connective tissue disease, HIV, portal hypertension, congenital heart disease, schistosomiasis

Question 16

Idiopathic pulmonary arterial hypertension

Answer 16

Subset of Group 1 PH

Pre-capillary pulmonary hypertension due to unknown vascular causes

Characterized by sparing of the parenchyma; PFTs demonstrate normal lung physiology with selective decrease in DLCO

Primarily affects younger women; presents with RV hypertrophy and right sided heart failure

Treatment with vasodilators (CCBs, endothelin-1 blockers, phosphodiesterase inhibitors)

Question 17

3. Pulmonary hypertension due to lung disease / hypoxia

Answer 17

Caused by chronic hypoventilation, resulting in hypoxemic vasoconstriction; over time, chronic vasoconstriction leads to irreversible vessel wall remodeling with smooth muscle proliferation

Underlying causes of chronic hypoventilation: Emphysema, pulmonary fibrosis, sarcoid, asbestosis, silicosis

Question 18

Pre-capillary pulmonary hypertension

Answer 18

Pre-capillary causes of pulmonary hypertension do not increase pressure in the microcirculation and do not cause pulmonary edema

Group 1 - Primary vascular disorders
Group 3 - Lung disease / hypoxia
Group 4 - CTEPH

Question 19

Post-capillary pulmonary hypertension

Answer 19

Cardiac causes - left ventricular failure, mitral valve disease, atrial obstruction (i.e. Group 2 PH)

Pulmonary/venous causes - congenital stenosis of the pulmonary veins, pulmonary veno-occlusion

Increased resistance in the vessels distal to the capillaries causes microvascular hydrostatic pressure to increase, leading to pulmonary edema

Use of arterial vasodilators is contraindicated (increased pulmonary edema)

Question 20

Treatment of PAH

Answer 20

Vasodilators - decrease right ventricular afterload and improve right heart function

Endothelin antagonists
NO pathway (Guanylyl cyclas activators, PDE5 inhibitors)
Prostacyclin enhancers
Calcium Channel blockers (special indication)

Question 21

Indication for treatment of IPAH with CCBs

Answer 21

IPAH patients who have a significant pulmonary artery pressure decrease with administration of Ca2+ blockers are identified as having an “acute response” to administration of a pulmonary vasodilator (inhaled NO or IV prostacyclin) during right heart catheterization

To qualify as an “acute response”:

1. Mean PA pressure must drop below 40 mmHg
2. Mean PA pressure must drop by at least 10 mmHg
3. CO cannot decrease

5% of patients respond and will be put on oral CCB

Question 22

Visualization of PE on Chest X-Ray

Answer 22

Chest X-ray is most often normal; may observe a wedge-shaped infiltrate representing an area of infarct (Hampton’s Hump) or an area of decreased perfusion (Westermark Sign)

Question 23

Lab tests for PE

Answer 23

Increased A-a gradient - suggests V/Q alterations
Elevated D-dimer - useful for negative predictive value
Visualization of clot in lung by CT angiography or VQ scan

Question 24

Use of V/Q scan to diagnose PE

Answer 24

Patients are administered a radioactive tracer via IV which distributes to the perfused areas of the lung; they also inhale a radioactive gas, which distributes to ventilated regions of the lung

Areas with no perfusion but normal ventilation are suggestive of PE blocking circulation

Question 25

Treatment of PE

Answer 25

Heparin + Warfarin x 6 months
Thrombolytic therapy for patients with hemodynamic compromise or evidence of right heart strain
Inferior vena cava filter for high risk patients
Acute surgical thrombectomy - last resort

Question 26

Pulmonary Hypertension - Pathology

Answer 26

Muscular hypertrophy of pulmonary arteries
Muscularization of pulmonary arterioles
May involve plexiform lesions - replacement of central artery lumen by a proliferation of endothelial cells with multiple, “slit-like” lumens