Pulmonary Vascular Disease - Patho 1

What does this refer to

• Low-resistance, high-compliance system

• Pressure: 15 mmHg (mean); Flow: ~5L/min

• Thin-walled vessels accommodate entire cardiac output

Normal Pulmonary Circulation

What does this refer to

• : carry deoxygenated blood

Pulmonary arteries

What does this refer to

• : site of gas exchange

Capillaries

What does this refer to

• : return oxygenated blood to left atrium

Veins

What does this refer to

• : regulates tone, permeability, inflammation

Endothelium

What does this refer to

• Subjective sensation of uncomfortable breathing

• Severe _______

  • Flaring of the nostrils

  • Use of accessory muscles of respiration

  • Retraction of the intercostal spaces

• _______ on exertion

  • Shortness of breath with activity

• Orthopnea

  • _______ when lying down

Dyspnea

What does this refer to

• : Awaking at night and gasping for air; must sit up or stand up

Paroxysmal nocturnal dyspnea

What does this refer to

• Protective reflex that helps clear the airways by an explosive expiration

• Acute ______

  • Resolves within 2–3 weeks

• Chronic ______

  • Lasts longer than 3 weeks

Cough

What does this refer to

• Changes in amount, consistency, color, and odor provide information about the progression of disease and the effectiveness of therapy.

Abnormal sputum

What does this refer to

• Coughing up blood or bloody secretions

Hemoptysis

What does this refer to

• Normal breathing pattern

Eupnea

What does this refer to

• Adjustments made by the body to minimize the work of the respiratory muscles

• Kussmaul respirations (hyperpnea)

  • Slightly increased ventilatory rate, very large tidal volume, and no expiratory pause

• Labored breathing

  • Increased work of breathing

• Restricted breathing

  • Disorders that stiffen the lungs or chest wall and decrease compliance.

• Cheyne-Stokes respirations

  • Alternating periods of deep and shallow breathing; apnea lasting 15–60 seconds, followed by ventilations that increase in volume until a peak is reached, after which ventilation decreases again to apnea.

Abnormal breathing patterns

What does this refer to

• Alveolar ventilation is inadequate in relationship to metabolic demands.

• Leads to respiratory acidosis from hypercapnia.

• Is caused by alterations in pulmonary mechanics or in neurologic control of breathing.

Hypoventilation

What does this refer to

• Alveolar ventilation exceeds the metabolic demands.

• Leads to respiratory alkalosis from hypocapnia.

• Is caused by anxiety, head injury, or severe hypoxemia.

Hyperventilation

What does this refer to

• Bluish discoloration of the skin and mucous membranes

• Develops when having five grams of desaturated hemoglobin, regardless of concentration

• Peripheral ______

  • Most often caused by poor circulation.

  • Best observed in the nail beds

• Central _______

  • Caused by decreased arterial oxygenation (low partial pressure of oxygen [PaO2]).

  • Best observed in buccal mucous membranes and lips

Cyanosis

What does this refer to

• Is the most common pain caused by pulmonary diseases.

• Is usually sharp or stabbing in character.

• Infection and inflammation of the parietal pleura (pleuritis or pleurisy) can cause pain when the pleurae stretch during inspiration and are accompanied by a pleural friction rub

Pleural pain

What does this refer to

• May be from the airways.

• May be from muscle or rib pain.

Chest wall pain

What does this refer to

• Increased carbon dioxide (CO2) in the arterial blood

• Occurs from decreased drive to breathe or an inadequate ability to respond to ventilatory stimulation

Hypercapnia (Conditions Caused by Pulmonary Disease or Injury)

What does this refer to

• Hypoxemia vs. hypoxia

• Ventilation-perfusion abnormalities: Most common cause

  • Shunting

  • Alveolar dead space: Area where alveoli are ventilated but not perfused

Hypoxemia (Conditions Caused by Pulmonary Disease or Injury)

What does this refer to

• Gas exchange is inadequate (hypoxemia).

• PaO2 is ≤50 mmHg.

• Hypercapnia occurs, during which partial pressure of carbon dioxide (PaCO2) is ≥50 mmHg.

• pH is ≤7.25.

• Requires ventilatory support, oxygen, or both

Acute respiratory failure (Conditions Caused by Pulmonary Disease or Injury)

What does this refer to

• Mean Pulmonary Artery Pressure (mPAP) < 20 mmHg

• Pulmonary Vascular Resistance (PVR) < 3 Wood units

  • Wood unit - a unit of measurement for pulmonary vascular resistance (PVR). Specifically, one Wood unit (WU) is equal to 1 mmHg·min/L. This unit is derived from the relationship between pressure (measured in mmHg) and blood flow (measured in L/min) through the pulmonary circulation.

• mPAP ≥ 25 mmHg = Pulmonary Hypertension (PH)

Hemodynamic Parameters

What does this refer to

• Group of disorders affecting pulmonary arteries, veins, capillaries

• Characterized by elevated pressure, vascular remodeling, or obstruction

Overview of Pulmonary Vascular Disease

What does this refer to

• : triggered by hypoxia, endothelin-1

Vasoconstriction

What does this refer to

• : smooth muscle proliferation, fibrosis

Vascular remodeling

What does this refer to

• : localized coagulation in pulmonary vessels

In situ thrombosis

What does this refer to

• Loss of vasodilators (NO, prostacyclin)

• Excess vasoconstrictors (endothelin-1, thromboxane)

• Increased permeability and inflammation

Endothelial Dysfunction

What does this refer to

• Medial hypertrophy and intimal fibrosis

• Formation of plexiform lesions (in PAH)

• Reduced lumen diameter → ↑ resistance

Vascular remodeling

What does this refer to

• Infiltration by T cells, macrophages

• Cytokines (IL-6, TNF-α) contribute to vascular changes

• Autoimmune diseases may initiate injury (e.g., SLE, scleroderma)

Inflammation & Immunity

What does this refer to

• Chronic alveolar hypoxia → persistent vasoconstriction

• Common in COPD, ILD, high altitude exposure

• Reversible early, later leads to fixed changes

Hypoxic Vasoconstriction

What does this refer to

• Increased afterload → RV hypertrophy

• Chronic strain leads to RV dilation and failure

• Septal flattening on echo is an early sign

Right Ventricular Response

What does this refer to

Right heart insufficiency in pulmonary hypertension ——→

What does this refer to

• Mean pulmonary artery pressure above 25 mmHg at rest

• Idiopathic, familial, or associated

• Pathophysiology

  • Overproduction of vasoconstrictors and decreased production of vasodilators

  • Remodeling

  • Resistance to pulmonary artery blood flow, thus increasing the pressure in the pulmonary arteries

  • Workload of the right ventricle increases and subsequent right ventricular hypertrophy, may be followed by failure and eventually death

Pulmonary Hypertension

What does this refer to

• Group 1 PH: pre-capillary, idiopathic or associated

• Proliferation of endothelial and smooth muscle cells

• Often involves genetic mutation (e.g., BMPR2)

Pulmonary Arterial Hypertension (PAH)

What does this refer to

• Masked by primary pulmonary or cardiovascular disease

• First indication: Chest radiograph (enlarged pulmonary arteries and right heart border) or an electrocardiogram that shows right ventricular hypertrophy

Clinical manifestations of pulmonary hypertension

What does this refer to

• Loss of vascular tone regulation

• Smooth muscle proliferation and fibrosis

• Increased PVR → RV failure and hypoxia

Pathophysiology of pulmonary hypertension

What does this refer to

• ↓ Prostacyclin, ↓ NO → vasoconstriction

• ↑ Endothelin-1 → proliferation and fibrosis

• BMPR2 mutation → unchecked cellular growth

Molecular pathway of pulmonary hypertension

What does this refer to

• Oxygen, diuretics, anticoagulants

• Avoidance of contributing factors such as air travel, decongestant medications, nonsteroidal antiinflammatory medications, pregnancy, and tobacco use

• Prostacyclin analogs (epoprostenol, beraprost, iloprost)

• Endothelin receptor antagonists (bosentan, ambrisentan)

• Phosphodiesterase-5 inhibitors

• Calcium channel blockers

• Lung transplantation

• Secondary pulmonary artery hypertension

  • Treat the primary disorder.

  • Once pulmonary hypertension has persisted long enough for hypertrophy to develop, it is no longer reversible.

  • Supplemental oxygen reverses hypoxic vasoconstriction.

Treatment of Pulmonary Hypertension

What does this refer to

• Persistent obstruction after PE

• Fibrotic webs and bands in arteries

• Secondary arteriopathy develops over time

Chronic Thromboembolic PH (CTEPH)

What does this refer to

• Initial emboli cause mechanical obstruction

• Non-resolving thrombi stimulate remodeling

• ↓ perfusion → mismatch, RV overload

Pathogenesis Chronic Thromboembolic PH (CTEPH)

What does this refer to

• Persistent obstruction after PE

• Fibrotic webs and bands in arteries

• Secondary arteriopathy develops over time

Chronic Thromboembolic PH (CTEPH)

What does this refer to

• Back-pressure from LA → ↑ venous pressures

• Capillary stress → remodeling, rarefaction

• RV dysfunction due to chronic afterload

Pulmonary Hypertension (PH) Due to Left Heart Disease

What does this refer to

• Destruction of capillaries (e.g., emphysema)

• Alveolar hypoxia → vasoconstriction

• ILD and fibrosis cause obliteration of vessels

Pulmonary hypertension (PH) due to lung diseases

What does this refer to

• Chronic hypoxia → pulmonary vasoconstriction

• Loss of vessels in emphysema

• Low grade PH worsens prognosis

COPD & PH

What does this refer to

• Secondary to pulmonary hypertension

• Right ventricular enlargement

• Pulmonary hypertension, creating chronic pressure overload in the right ventricle

Cor Pulmonale

What does this refer to

• Heart appears normal at rest.

• With exercise: Decreased cardiac output, chest pain

Clinical manifestations of Cor Pulmonale

What does this refer to

• Decrease workload of the right ventricle by lowering pulmonary artery pressure.

• Same as for PAH

• Reversal of the underlying lung disease

Treatment of Cor Pulmonale

What does this refer to

• Is the occlusion of a portion of the pulmonary vascular bed by a thrombus, embolus, tissue fragment, lipids, foreign body, amniotic fluid, or air bubble.

• Commonly arise from the deep veins in the thigh.

• Virchow triad

  • Venous stasis, hypercoagulability, and injuries to the endothelial cells that line the vessels

Pulmonary Embolism

What does this refer to

• Release of neurohumoral substances

• Widespread vasoconstriction

• Atelectasis of the affected lung segments, further contributing to hypoxemia

• Pulmonary edema, pulmonary hypertension, shock, and even death

Pathophysiology of Pulmonary Embolism

What does this refer to

• Sudden onset of pleuritic chest pain, dyspnea, tachypnea, tachycardia, and unexplained anxiety

Clinical Manifestations of Pulmonary Embolism

What does this refer to

• Bed exercises, frequent position changes, early ambulation, and pneumatic calf compression

• Prophylactic anticoagulation with low–molecular-weight heparin, warfarin, or fondaparinux

• Filter in the inferior vena cava: To prevent emboli from reaching the lung

Prevention of venous stasis

What does this refer to

• Oxygen and hemodynamic stabilization with fluids

• Anticoagulation and/or fibrinolytic agent (streptokinase)

• Percutaneous or surgical embolectomy

Treatment of pulmonary embolism

What does this refer to

• Occlusion of post-capillary venules

• Leads to pulmonary edema, capillary congestion

• May mimic PAH but worsens with vasodilators

Pulmonary Veno-Occlusive Disease

What does this refer to

• Thickened venules, capillary proliferation

• Lymphatic dilation due to congestion

• Associated with EIF2AK4 gene mutation

PVOD Pathology

What does this refer to

• Inflammation of vessel wall (e.g., GPA, EGPA)

• Granulomatous changes and necrosis

• May cause aneurysms or hemorrhage

Pulmonary Arteritis

What does this refer to

• ↑ PVR → RV hypertrophy and failure

• Reduced cardiac output, increased venous pressure

• Systemic hypotension and exercise intolerance

Hemodynamic Consequences

What does this refer to

• Volume overload: tricuspid regurgitation

• Forward failure: hypotension, fatigue

• Backward failure: hepatomegaly, edema

RV Failure in Pulmonary Vascular Disease

What does this refer to

• : ventilation with poor perfusion

V/Q mismatch

What does this refer to

• V/Q mismatch: ventilation with poor perfusion

• Impaired diffusion due to thickened capillary membrane

• Right-to-left shunting in extreme cases

Gas Exchange Abnormalities

What does this refer to

• Hypoxemia leads to polycythemia

• Reduced oxygen delivery to organs

• Neurohormonal activation (RAAS, SNS)

Systemic Effects

What does this refer to

• Pathophysiology varies by disease but involves vascular remodeling, increased resistance, and RV strain

• Understanding mechanisms helps guide diagnosis and treatment

Summary (kind of silly but why not)