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BMS3052 > WEEK 3 PULMONARY HYPERTENSION > Flashcards

WEEK 3 PULMONARY HYPERTENSION Flashcards

1
Q

What can pulmonary hypertension lead to?

A
  • Destructive vasculature changes, hypertrophy and plexiform lesions
  • Right ventricular strain and function
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2
Q

What three things regulate vascular tone?

A
  1. Endothelin (activates endothelin A and B Rs - vasocontriction, cell proliferation and hypertrophy)
  2. NO (inhibits platelet aggregation).
  3. Prostacyclin
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3
Q

What can lowe levels of NO lead to?

A
  • Vasoconstriction
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4
Q

What is PAH characterised by?

A
  • High blood pressure that affects the arteries in lungs and RHS of heart
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5
Q

What is the appearance of the arteries in the pulmonary circuit in someone with PAH?

A
  • They are more constricted

- Thus leads to an increase in pressure, increase in resistance, and the heart must work harder

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6
Q

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?

A
  • NO on the RHS of heart, the arteries will constrict
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7
Q

What is the normal mean Pulmonary pressure?

A
  • 14/15mHg
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8
Q

What is the mean pulmonary artery pressure in Pulmonary hypertension?

A
  • > 25 mmHg at rest
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9
Q

Why is the systemic circulation under much higher pressures than the pulmonary circulation?

A
  • Because it needs high pressures to pump and reach the capillaries (must travel further)
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10
Q

What are the symptoms of PAH?

A
  • 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)
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11
Q

What are the risk factors for pulmonary hypertension? (7 main factors)

A
  • 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
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12
Q

How is pulmonary hypertension diagnosed?

A
  • ECG
  • Echocardiogram
  • Right heart catheterization.
  • Pulmonary CT angiogram / chest x-ray.
  • Pulmonary function tests. (due to breathing difficulty)
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13
Q

How many types of PAH are there?

A
  • 5 main types
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14
Q

What is class 1 PAH characterised as (causes)?

A
  • PAH with no known cause (idiopathic), inherited PAH, PAH by congenital heart disease , thyroid disease, HIV, autoimm, certain drugs
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15
Q

What is type 2 PAH characterised as?

A
  • Caused by diseases that affect the left side of the heart (e.g. mitral valve prolapse.)
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16
Q

What is type 3 PAH characterized as?

A

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
17
Q

What is type 4 PAH characterized as?

A
  • Pulmonary hypertension caused by blood disorders, such as clotting disorders.
18
Q

What is type 5 PAH characterized as?

A
  • Pulmonary hypertension caused by other medical conditions (e.g. sarcoidosis)
  • Or by a tumour pressing on the pulmonary arteries.
19
Q

What does the thickening of blood lead to?

A
  • An increase in total peripheral resistance which means it is harder for the heart to pump blood to the pulmonary side.
20
Q

What are 7 medications that can be used to treat PAH?

A
  • O2
  • Anticoagulants or “blood thinners”
  • Diuretics or “water pills”
  • Vasodilators
  • Inotropic agents
  • Endothelin-1 antagonists (i.e,. Bosentan)
  • Sildenafil
21
Q

What function does oxygen have in the treatment of pulmonary hypertension?

A
  • It replaces the low oxygen in your blood
22
Q

What function do anticoagulants have in the treatment of pulmonary hypertension?

A
  • EG warfarin decreases blood clot formation so blood flows more freely through the blood vessels.
23
Q

What function do diuretics have in the treatment of pulmonary hypertension?

A
  • They remove extra fluid from the tissues and bloodstream, which reduces swelling and makes breathing easier (e.g. furosemide, spironolactone)
24
Q

What effects do on a Inotrophic agents such as Digoxin in have in the treatment of pulmonary hypertension?

A
  • Improve the hearts pumping ability
25
Q

What effects do vasodilators such as nifedipine or Diltiazem have in the treatment of pulmonary hypertension?

A
  • They lower the pulmonary blood pressure and may improve the pumping ability of the right side of the heart.
26
Q

What function does Endothelin-1 antagonists (i.e. Bosentan) have in the treatment of pulm onary hypertension?

A
  • 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.
27
Q

What is the function of Sildenafil in the treatment of pulonry hypertension?

A
  • Relaxes pulmonary smooth muscle cells, which leads dilation of the pulmonary arteries.
28
Q

What are the two types of surgical therapies in the treatment of PAH?

A
  • Pulmonary thromboendarterectomy

- Lung transplantation

29
Q

What effect does a pulmonary thromboendarterectomy have for the treatment of pah?

A
  • If present, blood clots in the pulmonary artery may be surgically removed to improve blood flow and lung function.
30
Q

What effects does a lung transplantation have for the treatment of pah?

A
  • 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.
31
Q

Which type of pH is associated with a high mortality, thus having a lethal and poor prognosis?

A
  • Type 1
32
Q

What are potent vasoconstricters in PAH (chronic) and what happens to the artieries?

A
  • Endothelin-1 (ET-1)
  • 5-HT
  • TXA2
  • The arteries decrease in R (radius)
  • Overtime, (chronic hypoxia), this leads to less elasticity of the artery
33
Q

What are the actual mechanisms in the chronic hypoxia induced PAH?

A
  • 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
34
Q

If you restore the oxygen levels in rats with chronic hypoxia, what occurs?

A
  • There is a lowering of the mean PAP (pulmonary arterial pressure)
35
Q

What is the evidence to indicate that vascular remodelling plays a role in pulmonary hypertension from chronic hypoxia?

A
  • In rats, when they go from a hypoxic environment to a normal environment they still have high blood pressure
36
Q

What does Y27632 AKA ‘ROK inhibitor’ do?

A
  • ## Lowers the man PAP and PVR (pulm vascular resistance) in Chronic hypoxic rats

BMS3052 (14 decks)

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