Dr. Tillie-Louise HackettDepartment of Anesthesiology, Pharmacology and Therapeutics

University of British Columbia

Associate Head, Centre of Heart Lung Innovation, St Paul’s HospitalTillie.hackett@hli.ubc.ca

Respiratory Pharmacology: Pulmonary vascular diseases

Aims of LectureDefine: Features of Pulmonary vasculature

Blood-Gas barrierCell structure functionPulmonary edemaMetabolism potential of the human lung

Pulmonary Vasculature

Weibel, 2009, Swiss Med Wkly

GAS EXCHANGE STRUCTURE

~ 300 alveoli units in a human lung

Pulmonary verses systemic circulation

Pressure difference: Pul: 15-5 = 10 Sys: 100-2 = 98 (10x that of pulmonary pressure)

Low PressureLow Resistance

Pressure of pulmonary capillaries

Pulmonary system can have extremely thin walls

Compression of capillaries with increased alveolar pressures

Small pulmonary vein

Effect of lung volume on resistance

Alveolar gas is very close to the wall of the artery

Smooth Muscle surroundingarteries maintains pressure

Less effect of radial traction

But is sensitive to nitric oxide produced by the oxidationstatus of the alveoli

Low alveolar PO2 causes vasoconstriction

Chronic bronchitus

Vasocontriction shuts of valves

Blood- Gas Barrier

Pulmonary capillary has a very thin wall

Pulmonary Blood-Gas Barrier & FunctionEPI: Epithelial Type I cellIN: InterstitiumEN: Endothelial Cell

Look similar but theirfunctions are Completely different!

Endothelium highly permeable to water, solutes, ions and some proteins (albumin)Alveolar impermeable!

Intracellular Junctions

Endothelium

Weak adhesions

Buffered together

Epithelium

Tight Junctions

Velcro

Pulmonary Edema

15Weibel, 2009, Swiss Med Wkly

Definition: An abnormal accumulation of fluid in the extravascular spaces and tissues of the lung

= means fluid should be within the capillariesAnd fluid has leaked out

Accompanies many lung and heart diseases and is often lethal

Electron Micrograph of Pulmonary capillary

Pulmonary Edema: Fluid leaks into interstitium or alveolar space

Two stages of Pulmonary Edema

Lymph

Lymph

LymphA. Normal

B. Interstitial Edema

B. Alveolar Edema

Peri vascularspace

Epithelial DamageResults in RBCs inAlveolar lining fluid

Interstitium of the lung

Perivascular andPeribronchiole spaces

Lymph nodes

Small pulmonary vein

Peri vascular cuff

Well developed pulmonary edema

Effect of Pulmonary edema Interstitial edema Generally little effect on lung function Some evidence that lung compliance is reduced

Alveolar Edema Lung compliance is reduced Airway compliance is reduced Seriously reduced O2 – CO2 transfer

Pathogenesis of Pulmonary Edema

1) Increased Capillary Hydrostatic Pressure

Caused by Myocardial Infarction Heart attack, left atrium fails, increase in pressure

2) Increased Capillary Permeability

Caused by capillary wall abnormalities Inhaled or circulating toxins (chlorine gas) Radiation (Breast cancer treatment)

Treatment for Pulmonary Edema

Oxygen Therapy: Most influential

Preload reducers: Use nitroglycerin and diuretics, such as furosemide (Lasix), to decrease the pressure caused by fluid going into your heart and lungs.

Afterload reducers: These drugs dilate your blood vessels and take a pressure load off your heart's left ventricle e.g. Nitropress, Vasotec.

Substances metabolized by the lung

Biological activation: Angiotensin I is converted to the vasoconstrictor, angiotensin II via ACE

ACE inhibitors (Ramipril) – Decrease tension on vessels, decreasing blood flow

Biological inactivation:. Examples include bradykinin, serotonin, prostaglandins E1, E2, and F2 alpha. Norepinephrine is also partially inactivated

Enterochromaffin cells in gut, secrete serotonin and in blood the platelets store it and release it when they bind clots – acts as vasconstrictor

Not affected: Examples include epinephrine, angiotensin II and vasopressin.

Metabolized and released: Examples include the arachidonic acid metabolites - the leukotrienes, and prostaglandins.

Questions