COR-PULMONALE

Presenter: Dr kimeu
Facilitator: Dr. Githanga
 Enlargement of the RV secondary to
abnormality in the lung, thorax, pulmonary
ventilation or circulation.

 There is RV failure with increased end

diastolic pressure
 pathophysiology
 Stoke volume of RV is regulated by:

 Preload
 Contractility stroke volume
 Afterload

 Pulmonary artery pressure

 The entire pulmonary vascular system is a distensible
low pressure sys. Pulmonary arterial pressure is 24/9
average 15 mmHg
 Capillary pressure ~10 mmHg. > 25 mmHg lead to
pulmonary congestion and oedema
RA LA

2 8

Aorta
25/0 120/0
24/9 120/80
PA
RV LV
 TheRV afterload is closely related to the
pulmonary artery pressure and is low

 The severity of RV enlargement in cor-

pulmonale is a function of the increase in
afterload.

 Increase in Pulmonary vascular resistance

which is relatively fixed causes an increase in
pulmonary artery pressure
 Causes of pulmonary resistance
 Severe Pulmonary parenchymal disease
 Hyperinflated lungs as in COLD-compression of
alveolar capillaries and lengthening of pulmonary
vessels
 Restrictive lung disease- pulmonary vessels are
compressed and distorted
 Decreased lung vol due to resection

 In parenchymal dse cor pulmonale is a marker of poor

prognosis since it reflects the seriousness of underlying
disease
 Pulmonary vascular disease
 vasoconstriction – hypoxia, acidosis, high altitude
 Pulmonary emboli
 Pulmonary vasculitis
 Veno-occlusive disease
 Elevated cardiac output-physical exercise
 Congenital heart dse with Left to right shunting
 Idiopathic pulmonary hypertension
 Pulmonary emboli
 Pulmonary hypertension
 Pulmonary emboli
Acute cor-pulmonale
 Acute RV failure secondary to a massive
pulmonary embolism or moderate PE in a
patient with previous compromise by
pulmonary vascular dse or parenchymal
dse
 A low output state
 Failing occurs when RV systolic pressure is
forced to double acutely to ~50 mmHg
 A sudden onset of severe dyspnea
 clinically
 Pallor, sweating, hypotension, rapid pulse
of small volume
 Increased JVP
 Prominent V waves
 Pulsatile hepatomegally
 TR murmur
 BGA- Decreased PaO2 due to V/Q
mismatch
 Chronic Cor pulmonale
 Increase in pulmonary vascular resistance and
RV hypertrophy is gradual
 Pulmonary vascular pressure may approach
systemic values
 Causes:
 Chronic medium PE that fail to lyse but organize
resulting to thrombo-embolic pulmonary hypertension
 Particles form IDU
 Tumour tissue embolisation
 Chronic widespread vasculitis in collagen vascular dse
 Idiopathic pulmonary hypertension
 clinically
 Tachypnea, dyspnea
 Unproductive cough
 Anterior chest pain
 Hepatomegally, pedal edema
 Left parasternal heave
 Audible P
2
 TR murmur
 Prominent a wave
 Pulmonary arterial hypertension
 Pulmonary arterial hypertension is defined
as a sustained elevation of pulmonary
arterial pressure to more than 25 mmHg
at rest or to more than 30 mmHg with
exercise
 The mean pulmonary-capillary wedge
pressure and left ventricular end-diastolic
pressure of less than 15 mm Hg.
 pathophysiology
 Imbalance in vascular effectors
 Vasoconstriction
 Endothelial cell proliferation
 Thrombosis

 Thesehave been attributed to pulmonary

endothelial cell dysfunction or injury
 Prostacyclin and thromboxane A2
 Prostacyclin-a potent vasodilator, inhibits platelet activation and
has antiproliferative properties;
 Thromboxane A2 is a potent vasoconstrictor and platelet
agonist.
 In pulmonary arterial hypertension, the imbalance between
these two molecules is shifted toward thromboxane A2
 Endothelin 1
 a potent vasoconstrictor
 Stimulates the proliferation of pulmonary-artery smooth-muscle
cells.
 The plasma levels of endothelin-1 are increased in pulmonary
arterial hypertension, and the level of endothelin-1 is inversely
proportional to the magnitude of the pulmonary blood flow and
cardiac output,
 Nitric oxide
 a potent vasodilator and inhibitor of platelet activation
 Inhibits vascular smooth-muscle cell proliferation.
 synthesis is catalyzed by the family of nitric oxide synthase
enzymes.
 Decreased levels of nitric oxide synthase have been observed in
the pulmonary vascular tissue of patients with pulmonary
hypertension
 Serotonin
 a vasoconstrictor
 promotes smooth-muscle cell hypertrophy and hyperplasia.
 Elevated levels in plasma in idiopathic pulmonary arterial
hypertension
 and persist even after the normalization of pulmonary-artery
pressures following lung transplantation.
  vascular endothelial growth factor (VEGF)
 increased In acute and chronic hypoxia
 Vasoactive intestinal peptide
 a potent systemic vasodilator,
 decreases pulmonary-artery pressure and pulmonary
vascular resistance
 Inhibits platelet activation and vascular smooth-
muscle cell proliferation
 levels are decreased in the serum and the lungs in
patients with pulmonary arterial hypertension
 Adrenomedullin
 dilates pulmonary vessels,
 increases the pulmonary blood flow
 synthesized by several cell populations in the normal
lung
 Increased in both pulmonary arterial hypertension
and pulmonary hypertension associated with
hypoxemia,
 elevation correlates with increases in the mean right atrial
pressure, pulmonary vascular resistance, and the mean
pulmonary arterial pressure.
 adrenomedullin is a marker of pulmonary hypertension,
 Environmental factors
 Hypoxia
 induces vasoconstriction in the pulmonary vasculature
 Acute hypoxia inhibits the function of voltage-gated
potassium channels in these smooth muscle cells,
resulting in membrane depolarization, an increase in
the concentration of cytoplasmic calcium, and
vasoconstriction.
 Acute hypoxia-reversible changes in vascular tone
 chronic hypoxia -structural remodeling the
proliferation and migration of vascular smooth
muscle, and an increase in the deposition of vascular
matrix.
 Central nervous system stimulants
 The use methamphetamine and cocaine has been
associated with an increased risk of pulmonary
arterial hypertension.

 Anorexigens:aminorex fumarate.
 An association was initially observed in the 1960s,
 Incidence increases with the duration of use, though
an elevation in pulmonary pressure can occur after as
little as three to four weeks of exposure to these
agents.
 Other associated conditions
 HIV
 An association between HIV infection and pulmonary
arterial hypertension was first reported in 1991
 Scleroderma
 A pulmonary arteriopathy occurs in limited systemic
sclerosis especially in the CREST variant.
 At autopsy, up to 80 % of patients histopathological
changes consistent with pulmonary arterial
hypertension
 10 to 15% percent have clinically significant
pulmonary hypertension.
 Portal hypertension
 uncommon association between portal hypertension
and pulmonary arterial hypertension.

 human herpes virus

 HHV-8 is the causative agent of Kaposi’s sarcoma.
 similarities between the plexiform lesions in
pulmonary arterial hypertension and endothelial
abnormalities in Kaposi’s sarcoma
 evidence of HHV-8 infection in specimens of lung
tissue obtained from 10 of 16 patients with
pulmonary arterial hypertension.
 Hemoglobinopathies
 pulmonary hypertension and right ventricular
dysfunction in patients
 thalassemia, particularly homozygous b-thalassemia.
 In sickle cell anemia
 The destruction of bioactive nitric oxide by free
Hemoglobin and an increase in the production of
reactive oxygen species play a role
 Thrombocytosis
 In chronic myelodysplastic syndromes with
thrombocytosis.
 the pulmonary parenchyma however, a correlation
between the platelet count and the level of
pulmonary hypertension has been found, and in two
cases, there was evidence of pulmonary-artery
hypertension
 Hereditary hemorrhagic telengiectasia
 Causes idiopathic pulmonary arterial
hypertension in ~ 15 % of patients
 autosomal dominant vascular dysplasia
 Mutations in two genes encoding the TGF-b
receptors
 Genetic Abnormalities
 The familial form accounts for ~ 6 % of all
cases of pulmonary arterial hypertension
 an autosomal dominant inheritance,
 in each successive generation in which the
disease develops, it occurs at younger age
and with greater severity than in the
preceding generation.
 histology
 Similarity in the above cases
 Intimal fibrosis
 Increased medial thickness
 Pulmonary arteriolar occlusion
 Plexiform lesions predominate
 Molecular basis for treatment
 There is no cure for pulmonary arterial
hypertension.
 The mainstays of current medical therapy
fall into several classes:
 vasodilators
 anticoagulants
 anti-platelet agents
 anti-inflammatory
 vascular-remodeling therapies
Sidenafil
 Therapeutic agents
 Many of the most effective agents have
pleiotropic effects.
 Epoprostenol (IV prostacycline)- a
vasodilator, a platelet inhibitor,and an anti-
inflammatory agent,

 Bosentan (endothelin-receptor antagonist)

vasodilator,an anti-inflammatory agent, and a
remodeling mediator.