Exam 3 Pulmonary

pulmonary hypertension is on which side of the heart?

right side of the heart

direction of blood flow to the lungs is what

precapilary (arterial)

• right heart

direction of blood flow to the heart is what

post capillary (venous)

• left heart

the pulmonary circulation is low pressure, high compliance system → right side heart failure (t/f)

true

pulmonary arterial hypertension results from increased pulmonary vascular what?

resistance

pulmonary blood flow occurs in a low pressure, high compliance system (t/f)

true

• (PATHOPHYSIOLOGY) The increase in pulmonary vascular resistance:

• Restricts blood flow through the pulmonary arterial circulation

• Ultimately leads to right HF because the heart has to work harder to pump the blood to the lungs

• Normally, pulmonary blood flow occurs in a low pressure, high compliance system

• Endothelin

• Thromboxane A2 

• Angiotensin II 

• Norepinephrine

example of what?

vasoconstrictors

• Nitric oxide 

• Prostacyclin E

• DHF 

• Bradykinin

example of what?

vasodilators

• Endothelin

• Thrombin

• Norepinephrine

example of what?

stimuli

• Nicotine 

• Cytokines 

• Mechanical stress

example of what?

stimuli

endothelin is example of what?

vasoconstrictors

• Remodeling of the pulmonary vascular bed 

  • Intimal and medial hypertrophy with proliferation of smooth muscle cells and eventual obliteration 

  • Pulmonary arteries constrict → because hole is clogged aka pulmonary HTN

  • Right heart must pump against resistance 

  • Right heart becomes dilated and less efficient 

• Less blood gets out to the lungs and to the body 

• Adaptation to stress, increased activity or growth become impossible

why is it bad?

what drugs associated with PAH

fenfluramine

dexfenfluramine

methamphetamines

most common connective tissue disease associated with PAH

systemic sclerosis

for pathogenesis of PAH, what are the vasodilation

• nitric oxide

  • prostacyclin

for pathogenesis of PAH, what are the vasoconstrictors

endothelin

serotonin

thromboxane

Endothelin-1 (ET-1) pathway leads to what?

vasoconstriction

Nitric oxide (NO)-cGMP pathway leads to what?

vasodilation

Prostacyclin (PGI₂) pathway leads to what?

vasodilation

increase pressure, decrease flow is what pathway

endothelin

blood vessels become narrow is what

vasoconstriction

blood vessels become narrow is what

vasodilation

1. L-arginine in endothelial cells produces Nitric Oxide (NO).

2. NO activates soluble guanylate cyclase (sGC).

3. This converts GTP → cGMP.

4. cGMP relaxes smooth muscle.

nitric oxide

• Endothelium produces Endothelin-1 (ET-1).

• ET-1 binds to ETA and ETB receptors on vascular smooth muscle.

• This increases intracellular calcium (Ca²⁺).

• Smooth muscle contracts.

endothelin pathway

1. Arachidonic acid produces Prostacyclin (PGI₂).

2. PGI₂ binds to IP receptors on smooth muscle.

3. This increases cAMP.

4. Smooth muscle relaxes.

prostacyclin (PGI2) pathway

What is the function of pulmonary circulation?

To transport deoxygenated blood from the right heart to the lungs for oxygenation and return oxygenated blood to the left heart.

Describe the path of blood flow in pulmonary circulation.

Right atrium → Right ventricle → Pulmonary artery → Lungs → Pulmonary veins → Left atrium.

What type of system is pulmonary circulation?

Low pressure, high compliance system.

What causes pulmonary arterial hypertension (PAH)?

Increased pulmonary vascular resistance leading to elevated pulmonary artery pressure.

Mean pulmonary artery pressure is what

>20 mmHg

Pulmonary artery wedge pressure is what

<15 mmHg

Pulmonary vascular resistance is what

>3 wood units

What structural changes occur in pulmonary arteries in PAH

• Thickening of adventitia and media

• Smooth muscle proliferation

• Neointima formation

  • Inflammation and fibrosis.

Why is vascular remodeling harmful?

It narrows pulmonary arteries, increases resistance, and forces the right heart to work harder.

What is the main cardiac complication of PAH?

right heart failure

What is the main cardiac complication of PAH?

Because the right ventricle must pump against increased pulmonary vascular resistance.

Name major vasoconstrictors involved in PAH.

• Endothelin

• Thromboxane A₂

• Angiotensin II

• Norepinephrine.

Name major vasodilators in pulmonary circulation.

• Nitric oxide

• Prostacyclin

• EDHF

• Bradykinin.

hat are the three major pathways involved in PAH pathogenesis?

1. Endothelin pathway

2. Nitric oxide–cGMP pathway

3. Prostacyclin pathway.

What is the effect of endothelin-1?

Vasoconstriction and smooth muscle proliferation.

What is the effect of nitric oxide?

Vasodilation via the cGMP pathway.

What is the effect of prostacyclin (PGI₂)?

• Vasodilation

• Anti-platelet effect

• Anti-proliferative effects.

What imbalance occurs in PAH?

↑ Vasoconstrictors (Endothelin)
↓ Vasodilators (NO and Prostacyclin).

Name three connective tissue diseases associated with PAH.

• Systemic sclerosis

• Systemic lupus erythematosus

• Mixed connective tissue disease.

What happens to pulmonary vascular resistance during PAH progression

It increases progressively

What happens to cardiac output in advanced PAH?

Decreases due to right heart failure.

What does WHO functional classification measure

Severity of symptoms and limitation of physical activity.

WHO Class I PAH

No limitation of physical activity.

WHO Class II PAH

Slight limitation; symptoms with normal activity.

WHO Class III PAH

Marked limitation; symptoms with minimal activity.

WHO Class IV PAH?

Symptoms at rest and right heart failure.

is there a cure for PAH

no cure exists

no consensus on the incidence of PAH due to low number of cases non specific presentation and difficulty diagnosing (t/f)

true

What are the main goals of therapy in PAH?

• Improve exercise capacity

• Improve hemodynamics

• Prevent disease progression

• Improve quality of life

• Increase survival

What supportive therapies are used in PAH?

anticoagulation

oxygen

diuretics

low salt intake

What is the most common long-term outcome of PAH

slow progression to the right heart failure

Increased pulmonary vascular resistance → pulmonary artery pressure ↑ → right heart failure is what

PAH

what is the main mechanism of PAH

• Endothelin ↑

• Nitric oxide ↓

• Prostacyclin ↓

remodeling of the pulmonary vasculature leads to PAH

• Thickening of the adventitia and media 

• Proliferation of vascular smooth muscle cells and fibroblasts 

• Neointima formation

low levels of eNOS in vascular tissues lead to what?

vasoconstriction

Which statement best describes pulmonary circulation?

A. High pressure, low compliance system
B. Low pressure, high compliance system
C. High resistance system
D. High pressure systemic system

B

Which hemodynamic value defines pulmonary arterial hypertension?

A. mPAP ≥ 10 mmHg
B. mPAP ≥ 20 mmHg
C. mPAP ≥ 30 mmHg
D. mPAP ≥ 40 mmHg

B

Which of the following occurs in pulmonary arterial hypertension?

A. Decreased pulmonary vascular resistance
B. Increased pulmonary vascular resistance
C. Increased oxygen delivery
D. Decreased cardiac workload

B

Which cardiac chamber is most affected in pulmonary arterial hypertension?

A. Left atrium
B. Left ventricle
C. Right ventricle
D. Right atrium

C

Which pathway causes vasoconstriction in PAH?

A. Nitric oxide pathway
B. Prostacyclin pathway
C. Endothelin pathway
D. cAMP pathway

C

Nitric oxide causes vasodilation through which signaling molecule?

A. cAMP
B. cGMP
C. ATP
D. NADH

B

Prostacyclin causes vasodilation through which mechanism?

A. Increased Ca²⁺
B. Increased cAMP
C. Increased sodium influx
D. Increased potassium efflux

B

Which vasodilator is decreased in PAH?

A. Endothelin
B. Thromboxane
C. Nitric oxide
D. Angiotensin II

C

Which connective tissue disease is most commonly associated with PAH?

A. Rheumatoid arthritis
B. Systemic sclerosis
C. Psoriasis
D. Ankylosing spondylitis

B

Which drug has been associated with pulmonary arterial hypertension?

A. Methamphetamines
B. Ibuprofen
C. Acetaminophen
D. Amoxicillin

A

Define pulmonary arterial hypertension.

Pulmonary arterial hypertension is a condition characterized by increased pulmonary vascular resistance resulting in elevated pulmonary artery pressure and eventual right heart failure.

What are the three major pathways involved in PAH pathogenesis?

• Endothelin pathway

• Nitric oxide–cGMP pathway

• Prostacyclin pathway

What happens during vascular remodeling in PAH?

• Thickening of vessel walls

• Smooth muscle proliferation

• Neointima formation

• Narrowing of pulmonary arteries.

Why does right heart failure occur in PAH?

Because the right ventricle must pump against increased pulmonary vascular resistance.

Which WHO class includes symptoms at rest?

class IV

what are the drugs in PDE 5

sildenafil

tadalafil

what are the drugs for prostacyclins

epoprostenol

treprostinil

lloprost inh

selexipag

what are the drugs for endothelia receptor antagonists

bosentan

ambrisentan

macitentan

what is the drug for soluble guanylate cyclise stimulators

riociguat

NO diffuses to smooth muscles to increase cGMP → increase relaxation and decrease BP

true about cGMP pathway

inhibition of breakdown of cGMP

improved NO mediated vasodilation in pulmonary vasculature

true about cGMP

PDE breakdown cAMP and cGMP —> inhibitors prolong their actions as secondary messengers leading to what

relaxation of bronchial smooth muscles

anti-inflammatory role

major cAMP metabolizing enzyme found in inflammatory and immune cells is what?

PDE4

theophylline is sandwiched between what via hydrophobic bond

phenylalanine and valine

interaction is enforced by hydrogen bond between (tyrosine, N-7) and (glutamine, O-6)

true

causes blurred vision because of targeting blocking of PDE6 is what

PDE inhibitor

theophylline is non-selective PDE inhibitor metabolized by combination of C-8 oxidation and N-demethylation

true

Aminophylline is theophylline ethylenediamine which contains 79% theophylline

true

79mg of theophylline is equivalent to 100mg of aminophylline dehydrate

true.

dialkylphenyl oxygen forms

metabolized in the liver to its N-oxide derivation

used for COPD → PDE4

roflumilast (daliresp)

selectively inhibits PDE5

sildenafil & tadalafil

cGMP specific and responsible for the degradation of cGMP

PDE5

approved for treatment of PAH through inhibition of cGMP and smooth muscle relaxation of Pulmonary vasculature

sildenafil (revatio)

selective and potent inhibitor of cGMP-specific PDE5

sildenafil

approved in PAH at a dose of 20mg TID is what drug

sildenafil (revatio)

Indicated for treatment of PAH (WHO group 1) in adults to improve exercise ability and delay clinical worsening (no restriction) based on WHO FC; delay of clinical worsening demonstrated in combination with epoprostenol is what drug

sildenafil

sildenafil should not be prescribed for who in PAH

age 1-17

contraindicated for sildenafil

do not use with nitrates

epistaxis, headache, dyspepsia, flushing, insomnia, erythema, dyspnea, rhinitis, diarrhea, myalgia, pyrexia, gastritis, sinusitis, paresthesia are side effects of what

sildenafil