Respiratory Pharmacology: Pulmonary vascular...
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Dr. Tillie-Louise Hackett Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Associate Head, Centre of Heart Lung Innovation, St Paul’s Hospital [email protected] Respiratory Pharmacology: Pulmonary vascular diseases
Transcript of Respiratory Pharmacology: Pulmonary vascular...
Dr. Tillie-Louise HackettDepartment of Anesthesiology, Pharmacology and Therapeutics
University of British Columbia
Associate Head, Centre of Heart Lung Innovation, St Paul’s [email protected]
Respiratory Pharmacology:
Pulmonary vascular diseases
Aims of Lecture
Define the differences in the structure of alveolar epithelium and endothelium with regards to function
Describe the pathologies associated with pulmonary vascular disease
What are the treatment strategies used to treat pulmonary embolism and pulmonary hypertension
Pulmonary Vasculature
Weibel, 2009, Swiss Med Wkly
GAS EXCHANGE STRUCTURE
~ 300 million alveoli units in a human lung
Pulmonary Blood-Gas Barrier
Pulmonary Blood-Gas BarrierEPI: Type I alveolar
epithelial cell
IN: Interstitium (ECM)
EN: Endothelial Cell
Endothelium highly
permeable to water,
solutes, ions and some
proteins (albumin)
Alveolar impermeable!
EPI
IN
EN
Pulmonary Blood-Gas Barrier: cell Junctions
Endothelium
Gap junctions
Buffered together
Weak
Epithelium
Tight Junctions
Velcro
Strong
Pulmonary verses systemic circulation
Pressure difference: Pul: 15-5 = 10 Sys: 100-2 = 98
(10x that of pulmonary pressure)
High Flow, Low Pressure System
Enables extremely thin walls for gas exchange
Increased alveolar pressures at high altitudes leads
to compression of capillaries
Low Flow, High Pressure System
When the system is overloaded:
Pulmonary Edema
Definition:
An abnormal accumulation of fluid in the
extravascular spaces and tissues of the lung
= means fluid should be within the capillaries and fluid
has leaked out
Can accompany many pulmonary vascular
diseases and is often lethal
Two Types of Pulmonary Edema
Filling of peri vascular
space
Epithelial damage results
in RBCs in alveoli
Interstitial Edema
Pulmonary Edema
Conducting airways Alveoli
Peri vascular cuff
Pulmonary edema
Two Types of Pulmonary Edema
Interstitial edema
Two Types of Pulmonary Edema
White lines due to
interstitial edema
Increased opacity due
to pulmonary edema
Effect’s of Pulmonary edema
Interstitial edema
Generally little effect on lung function
Some evidence that lung compliance is reduced
Alveolar Edema
Lung compliance is reduced
Seriously reduced O2 – CO2 transfer
Pulmonary vascular diseaseAny condition that affects the vessels along the route between the heart and lungs
Pulmonary embolism
Common condition that results in the occlusion of the pulmonary arteries by thrombotic material (deep vein thrombosis, DVT).
Causes acute life threatening, but potentially reversible, right heart failure.
Incidence 6-20 cases per 100,000 people
Clinical manifestations
Breathlessness, chest pain, tachycardia, fainting, hypotension and shock, DVT.
Diagnosis
Electrocardiogram, arterial blood gases & chest radiograph
Treatment for Pulmonary embolism
Predisposing risk factors
High = lower limb fracture or trauma
Moderate = oral contraceptive, pregnancy, chronic heart problems
Low = bed rest >3 days, age, obesity, prolonged travel
Prevention
Anticoagulants (prevent further clots) – low-molecular weight heparin, warfarin
High risk – filter places in inferior vena cava
Management
Heparin, supplemental oxygen, warfarin, surgical pulmonary embolectomy
Thrombolytics (remove the blockage)
Alteplase – Converts trapped plasminogen
to plasmin, initiates local fibrinolysis
Prognosis
Fatality rate 7-11%
60% undergo a recurrent event
Pulmonary vascular disease
Pulmonary Arterial Hypertension
Progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death.
Defined as an increase in mean pulmonary arterial pressure to at least 25 mmHg at rest.
Common cause is left heart disease (congenital, connective tissue disorders, high altitude, COPD).
Causes chronic remodeling of the small pulmonary arteries leading to progressive vascular obstruction.
Incidence 1.5-5.2 cases per 100,000 people
Clinical manifestations
Breathlessness, fatigue, chest pain, haemoptysis.
Diagnosis
Notoriously difficult to detect early stages of disease, patients asymptomatic
Invasive right heart catheterization is mandatory to confirm PAH.
Treatment for Pulmonary arterial hypertension
Predisposing risk factors
Chronic cardiovascular and respiratory diseases
Prevention
Appropriate treatment of chronic heart diseases
Chronic respiratory diseases should be treated with O2 therapy to prevent hypoxaemia.
Management
Oral anticoagulation, diuretics and oxygen.
PAH results in elevated vascular resistance defective endothelium
secrete increased levels of endothelin-1 and decreased levels of prostacyclin.
Results in contraction of vascular smooth muscle and vasoconstriction remodeling
New drugs - Prostacyclin derivatives, endothelin receptors antagonists
Lung transplantation.
Prognosis
Mean survival 2.8 years in 1980’s now 67-87% survival rates.
60% undergo a recurrent event
