WEEK 3 PULMONARY HYPERTENSION Flashcards
What can pulmonary hypertension lead to?
- Destructive vasculature changes, hypertrophy and plexiform lesions
- Right ventricular strain and function
What three things regulate vascular tone?
- Endothelin (activates endothelin A and B Rs - vasocontriction, cell proliferation and hypertrophy)
- NO (inhibits platelet aggregation).
- Prostacyclin
What can lowe levels of NO lead to?
- Vasoconstriction
What is PAH characterised by?
- High blood pressure that affects the arteries in lungs and RHS of heart
What is the appearance of the arteries in the pulmonary circuit in someone with PAH?
- They are more constricted
- Thus leads to an increase in pressure, increase in resistance, and the heart must work harder
You would normally think that with low O2, the arteries would dilate in the systemic circulation, however is this the case in PAH for the pulmonary circvulation?
- NO on the RHS of heart, the arteries will constrict
What is the normal mean Pulmonary pressure?
- 14/15mHg
What is the mean pulmonary artery pressure in Pulmonary hypertension?
- > 25 mmHg at rest
Why is the systemic circulation under much higher pressures than the pulmonary circulation?
- Because it needs high pressures to pump and reach the capillaries (must travel further)
What are the symptoms of PAH?
- Shortness of breath
- Dificulty breathing with exertion
- DIzziness
- Rapid breathing
- Rapid HR
- Edema or swelling (in lungs but also hands and feet
- Chest pain (RV hypertropy and swelling)
What are the risk factors for pulmonary hypertension? (7 main factors)
- Family history (if two or more members in your faimly have it or there is mutation in PH-gene)
- Obesity and it’s obstructive sleep apnea (If obesity is COMBINED with sleep apnea)
- If you are female (at least 2.5x more likely) + childbearing age
- Pregnancy (risk of mortality)
- Altitude
- Other diseases (scleroderma, liver disease, lung disease, lupus)
- Drugs and toxins
How is pulmonary hypertension diagnosed?
- ECG
- Echocardiogram
- Right heart catheterization.
- Pulmonary CT angiogram / chest x-ray.
- Pulmonary function tests. (due to breathing difficulty)
How many types of PAH are there?
- 5 main types
What is class 1 PAH characterised as (causes)?
- PAH with no known cause (idiopathic), inherited PAH, PAH by congenital heart disease , thyroid disease, HIV, autoimm, certain drugs
What is type 2 PAH characterised as?
- Caused by diseases that affect the left side of the heart (e.g. mitral valve prolapse.)
What is type 3 PAH characterized as?
Results from breathing conditions such as:
- chronic obstructive pulmonary disease (COPD)
- Scarring in lung tissue (interstitial lung disease)
- Obstructive sleep apnea (OSA)
- This type is more common
What is type 4 PAH characterized as?
- Pulmonary hypertension caused by blood disorders, such as clotting disorders.
What is type 5 PAH characterized as?
- Pulmonary hypertension caused by other medical conditions (e.g. sarcoidosis)
- Or by a tumour pressing on the pulmonary arteries.
What does the thickening of blood lead to?
- An increase in total peripheral resistance which means it is harder for the heart to pump blood to the pulmonary side.
What are 7 medications that can be used to treat PAH?
- O2
- Anticoagulants or “blood thinners”
- Diuretics or “water pills”
- Vasodilators
- Inotropic agents
- Endothelin-1 antagonists (i.e,. Bosentan)
- Sildenafil
What function does oxygen have in the treatment of pulmonary hypertension?
- It replaces the low oxygen in your blood
What function do anticoagulants have in the treatment of pulmonary hypertension?
- EG warfarin decreases blood clot formation so blood flows more freely through the blood vessels.
What function do diuretics have in the treatment of pulmonary hypertension?
- They remove extra fluid from the tissues and bloodstream, which reduces swelling and makes breathing easier (e.g. furosemide, spironolactone)
What effects do on a Inotrophic agents such as Digoxin in have in the treatment of pulmonary hypertension?
- Improve the hearts pumping ability
What effects do vasodilators such as nifedipine or Diltiazem have in the treatment of pulmonary hypertension?
- They lower the pulmonary blood pressure and may improve the pumping ability of the right side of the heart.
What function does Endothelin-1 antagonists (i.e. Bosentan) have in the treatment of pulm onary hypertension?
- Helps block the action of endothelin, a substance that causes narrowing of lung blood vessels.
- These medications require monthly lab work to monitor liver function.
What is the function of Sildenafil in the treatment of pulonry hypertension?
- Relaxes pulmonary smooth muscle cells, which leads dilation of the pulmonary arteries.
What are the two types of surgical therapies in the treatment of PAH?
- Pulmonary thromboendarterectomy
- Lung transplantation
What effect does a pulmonary thromboendarterectomy have for the treatment of pah?
- If present, blood clots in the pulmonary artery may be surgically removed to improve blood flow and lung function.
What effects does a lung transplantation have for the treatment of pah?
- Currently, this is the only cure for pulmonary hypertension.
- Transplantation is reserved for advanced pulmonary hypertension that does not respond to medical therapy.
- Right side of the heart will generally return to normal after the lungs or lungs have been transplanted. This is quite rare procedure.
Which type of pH is associated with a high mortality, thus having a lethal and poor prognosis?
- Type 1
What are potent vasoconstricters in PAH (chronic) and what happens to the artieries?
- Endothelin-1 (ET-1)
- 5-HT
- TXA2
- The arteries decrease in R (radius)
- Overtime, (chronic hypoxia), this leads to less elasticity of the artery
What are the actual mechanisms in the chronic hypoxia induced PAH?
- TGF-b pathwsy activated
- INcreased survivin, Reduced K+ channel levels
- these are only a few examples and lead to pulmonary vascular proliferation
- This MAY occur via vascular remodelling, hypoxic vasoconstriction which increase vascular resistance thus leading to PAH
If you restore the oxygen levels in rats with chronic hypoxia, what occurs?
- There is a lowering of the mean PAP (pulmonary arterial pressure)
What is the evidence to indicate that vascular remodelling plays a role in pulmonary hypertension from chronic hypoxia?
- In rats, when they go from a hypoxic environment to a normal environment they still have high blood pressure
What does Y27632 AKA ‘ROK inhibitor’ do?
- ## Lowers the man PAP and PVR (pulm vascular resistance) in Chronic hypoxic rats
