Respiratory Pharmacology: Pulmonary vascular diseases€¦ · Department of Anesthesiology,...
Transcript of Respiratory Pharmacology: Pulmonary vascular diseases€¦ · Department of Anesthesiology,...
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 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
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