Pulmonary Hypertension (General) Flashcards
What is Pulmonary Hypertension
Elevated Pulmonary Pressure
Pulmonary Arterial Hypertension
Specific type of PH
–> Elevated Pulmonary Artery Pressure
What does persistent elevated pulmonary vascular resistance cause
High Right Ventricular Systolic Pressure
–> Right Ventricular Growth/Remodeling
*Right ventricle must pump harder against the elevated pulmonary vascular resistance
Idiopathic PAH
Unknown Cause of PAH
Rare and Severe
Familial PAH
PAH is caused by Mutations in Bmpr2 Gene
Secondary PAH
PAH is associated with other medical conditions
Endothelial Cell Explanation of PAH
Endothelial Cell damaged
–> Endothelial Cell undergoes Apoptosis
–> Imbalance in Endothelial Cell Function
–> Imbalance in Vasodilating and Vasoconstricting Endothelial Cells
–> Increase in Vasoconstriction
–> Increases Pulmonary Vascular Resistance
–> Pulmonary Arterial Hypertension
Gene Explanation of PAH
Bmpr2 (Bone Morphogenic Protein 2) Mutation
–> Smooth Muscle Cell Overgrowth
(Hyperplasia of SMC)
–> Increased Pulmonary Vascular Resistance
–> Pulmonary Arterial Hypertension
Endothelin Receptor Antagonists (Mechanism)
Block Smooth Muscle Cell’s ET(A) Receptors
–> Vasodilation
Endothelin Receptor Antagonists (Adverse Effects)
Headache
Flushing
Edema
Birth Defect (Don’t take if pregnant)
Endothelin-1 (ET-1) Effects
Binds to ET(A) receptors leading to an increase of calcium
–> Vasoconstriction
Prostacyclin (Mechanism)
Binds to smooth muscle cells IP receptors
–> Increase G-protein activity
–> Increase Adenylate Cyclase
–> Increase cAMP signaling
–> Vasodilation
Prostacyclin (Adverse Effects)
Headache
Diarrhea
Birth Defect: Beraprost (Do not use if pregnant)
What causes the Largest Reduction in Pulmonary Artery Pressure
Prostacyclin (Ex. Epoprostenol)
What PAH Treatments are contraindicated in pregnancy
Endothelin Receptor Antagonists
–> Bosentan
Prostacyclin
–> Epoprostenol
sGC Activator (Mechanism)
Potentiate action of Nitric Oxide by:
Activates sGC (More sGC converts GTP into cGMP)
–> Vasodilation
sGC Activator (Adverse Effects)
Hypotension
PDE5i (Mechanism)
Phosphodiesterase 5 usually breakdown cGMP
PDE5i inhibits this breakdown of cGMP
–> Increases cGMP signaling
–> Vasodilation
PDE5i (Adverse Effect)
Headache
Do not use with nitrovasodilators
–> Will cause severe hypotension if used together
Calcium Channel Antagonists (Mechanism)
Reduces entry of calcium into smooth muscle cells
–> Generalized arterial/arteriolar dilation
–> Reduces Blood Pressure
Calcium Channel Antagonists (Adverse Effects)
Flushing
Headache
Swelling
Inhaled NO (Uses)
Used as acute vasodilator testing of PAH
No therapeutic uses except:
–> Intensive care for PH crisis in newborn babies
–> All other use if for diagnosis and testing
PH in Newborn (What Fails?)
Normally:
–> Pulmonary Vasculature goes from HIGH resistance state to a LOW resistance state at birth
Failure:
–> Disease in fetal development can cause HIGH resistance state to persist
–> Inhaled NO is used to treat this and cause a transition into a LOW resistance state
What is Shock
Inappropriate Vasodilation that can lead to very low arterial blood pressure
What kind of metabolism does Shock cause
Anaerobic Metabolism within Vital Organs
Where does Shock commonly occur
In intensive care settings
What can cause Shock
Hemorrhage (Loss of Circulating Volume)
Burns
Bacterial Infections (Septic Shock)
Anaphylaxis (Histamine Release)
Myocardial Infarction (Lowers Cardiac Output)
Epidural
Local Anesthesia, can produce a state of low blood pressure leading to shock
How is Shock Treated
Fluid Replacement
Adrenergic Vasopressors
Vasopressin
Shock (Fluid Replacement)
Transfusion is used to treat Hemorrhage
–> Increases Circulating Volume to replace volume lost
–> Increases Cardiac Output
–> Increases Blood Pressure to normal
Shock (Adrenergic Vasopressors)
Either causes vasoconstriction (alpha 1)
or increases cardiac output (beta 1)
–> Increases Blood Pressure back to normal
Shock (Vasopressin)
Vasopressin (ADH) is used along with noradrenaline to treat septic shock
–> Promotes water reabsorption
–> Increases Blood Pressure
How does Shock Kill a person
Not enough arterial pressure leads to a decrease in renal blood flow
–> Renal Failure –> Death
Group 1 PAH
PAH caused by Pulmonary Arterial Hypertension
Group 2 PAH
PAH caused by Left Heart Disease
Group 3 PAH
PAH caused by Lung Disease
Group 4 PAH
PAH caused by Chronic Blood Clots in Lungs
Group 5 PAH
Unknown Cause
