PH Flashcards
Definition
↑ PA pressure
* Systolic >30mmHg
* Diastolic >19mmHg
* Mean >14mmHg
Mechanisms for pulmonary hypertension
- ↑ PVR
o ↑ resistance to pulmonary venous drainage
o ↓ CSA of pulmonary vascular bed
Loss of pulmonary vessels
Luminal narrowing
Pulmonary vasoconstriction - ↑pulmonary blood flow (RV CO)
o Persistent exposure to ↑ blood flow → pulmonary artery pathology
o Permanent ↑ PVR - ↑blood viscosity
Etiology/classification
- PAH
- PVH 2nd to L heart dz
- PH 2nd to pulmonary dz
- PH from PTE
- Misc
Precapillary PH causes
o Idiopathic
o Systemic to pulmonary shunt: VSD, ASD, PDA
o Collagen vascular dz
o Drugs/toxins
o Vasoactive substances: TXA2, histamine, serotonine, endothelin
o PTE
o Persistent PH of the newborn
o ↑ blood flow
o HW
Pathophys L to R shunt PH
↑ pulmonary blood flow
Shear stress on pulmonary endothelial lining → PH
Significant PH can result in sunt reversal → Eisenmenger physiology
Causes of PH from incr blood flow
anemia, thyrotoxicosis, exercise
Pathophys PH w/ HW
Physical presence of HW and by products
Potentially irreversible endothelial damage
Capillary PH causes
o Pulmonary diseases:
Asthma, bronchitis, bronchomalacia
Interstitial lung disease: pulmonary fibrosis
o PTE
o Lungworms
o Neoplasia
o Sleep disorder breathing
o Alveolar hypoventilation disorders
o Chronic exposure to high altitude
Post capillary PH causes
= pulmonary venous hypertension
o L sided heart disease and secondary LAE
From ↑LAP
CVD, MVS, CM
o Pulmonary venous obstruction
o Neoplasia
o Congenital abnormalities
Misc causes
o Compression of pulmonary vessels
o Lymphadenopathy
o Neoplasia
o Fibrosing mediastinitis
o Granulomatous dz
o Sarcoidosis, histiocytosis, lymphangiomatosis
Feline PH causes
few case reports associated with
* PTE, R to L shunting PDA, HW, chronic upper airway obstruction, Aelurostrongylus abstrutus
Pathologic features of PH
- Grade 1: medial hypertrophy
- Garde 2:
o Medial hypertrophy
o Cellular intimal proliferation - Grade 3: partially reversible
o Intimal hyperplasia → lumen occlusion
o Early arterial dilation - Grade 4: irreversible
o Advanced arterial dilation
o Plexiform lesions in muscular arteries and capillaries - Grade 5: angiomatoid formation (terminal) plexiform lesions
- Grade 6: fibrinoid acute necrotizing arteritis
Features of pulmonary vascular bed
low pressure, low resistance, high capacitance
o PAP determined by: RV CO (blood flow), PVR, PVP
Pathophys of primary PH
imbalance btw vasoconstriction and dilation
- RV systolic overload from PH
o Diastolic overload from TR
o ↓ RV systolic performance with exercise - LV diastolic UNDERload
o Reduced compliance
Vasoconstriction agents
Alveolar hypoxia
ET1
Serotonin
TxA2
PDGF
Alveolar hypoxia on PVR
physiologic response shunting blood from hypoventilated areas → better ventilated areas of the lungs
ET1 PVR
- Released from vascular endothelium in response to changes in
o Blood flow
o Vascular stretch
o [Thrombin] - Causes: vasoconstriction, SM growth, ↑collagen synthesis, promotes vascular remodelling
- ↑ [ET1] in Hu with PH, also reported in dogs
Serotonin effect on PVR
- Vasoconstrictor
- Promote SM cell hypertrophy and hyperplasia
TXA2 and PGI effect on PVR
- Arachidonic metabolite of PA vascular cells
- TXA2: vasoconstrictor
o Predominates in patients w PH - Prostacyclin: vasodilator, inhibitor of platelet activation, antiproliferative properties
Platelet derived GF effect on PVR
- Induce PA SM cell proliferation and migration
Vasodilator agents
NO
NO effect on PVR
- Potent vasodilator, inhibitor of platelet activation and SM cell proliferation
- Synthetized from arginine and O2 by NOS enzyme in endothelium
o Activate cGMP → vasodilation
o cGMP inactivated by PDE5 isoenzyme
Cardiac KT pressure study PH 2nd to HW
- PA: ↑systolic, mean, diastolic P
- PCWP: should be normal
- RV: ↑ systolic P
Cardiac KT pressure study PH 2nd to MVS
- PA: ↑
o Normal in early stage of dz
o ↑ as a reflect of ↑LAP
o Late stage can have marked ↑ - PCWP: should be elevated from ↑LAP
o ↑a and v wave
o Prolonged Y descent - RV: elevated if PH present
What are the levels of resistance to flow in terms of RV work and how does this differ relative to the systemic circulation?
- RV have thin walls and high compliance
o Can accommodate high volumes at physiologic pressures
o Marked preload dependence and RV-LV interdependence - RV performance depend on afterload
o Less tolerant to pressure overload
Unable to face acute ↑PVR
Inefficient against PH
o Preload reserve helps to preserve RV function with PH (Frank Starling mechanism)
Eccentric hypertrophy
o RVH will occur to ↓ wall stress: Laplace law
Concentric hypertrophy
Features of exercise induced pulmonary hemorrhage in horses
o Hemorrhage from pulmonary capillaries into alveolar space
o Predominant in caudodorsal lung fields
Exercise induced pulmonary hemorrhage in horses histo
o Edema
o Pulmonary capillary and alveolar hemorrhage
RBC in alveoli and interstitial space
o Disruption of capillary and alveolar endothelium
RBC, platelets and macrophages accumulation
o Venoocclusive remodelling of intralobar PVs → ↑ stiffness and ↓ vascular compliance
Collagen deposition
SM hypertrophy
Intimal hyperplasia w/I PV
Exercise induced pulmonary hemorrhage in horses is a consequence of
o ↑CO
o Lack of sufficient pulmonary vasodilation
o ↑ blood viscosity with exercise
Exercise induced pulmonary hemorrhage in horses pathophys
o Ventilation inhomogeneity caused by small airway dz
Poor collateral ventilation + small airway dz → underventilation of certain lung units
Extreme fluctuation in alveolar pressure of underventilated areas
* Parenchymal tearing
* Alveolar capillary rupture
o Mechanical constraint of abdominal viscera on dorsocaudal lungfield
Can lead to parenchymal tearing → alveolar capillary rupture
o Stress failure of pulmonary capillaries
High transmural pressures
* High pulmonary capillary P and low alveolar P
* Tissue failure → hemorrhage
PCP >70mmHg→ disrupt endothelial and alveolar epithelial tight jcts
* Hemorrhage in interstitium/alveoli
What is cattle brisket dz
- Bovine high mountain disease
o Non contagious swelling of edematous fluid in
Ventral parasternal muscles (brisket) region
Ventral aspect of body → abdomen, submandibular region
o Cattles raised at high altitude in West USA (Colorado, Wyoming, NM, Utah)
Etiology of brisket dz
- Hypoxic condition in high altitude
o Pulmonary arterial hypertension
Pulmonary vascular shunting is normal mechanism for ventilation-perfusion mismatch - Divert deO2 blood to better oxygenated regions of lungs = dorsal aspect
- Strong response in cattle, horses, pigs
Exaggerated shunting in response to hypoxia
o Bovine lungs: small size compared to BW, lobulated
o Severe ↓ pulmonary caoacity - Pulmonary hypertension → RVH and RVEH → R-CHF
Lung response to hypoxia: acute
pulmonary arteriole constriction
Lung response to hypoxia: chronic
(3wks):
Vascular hypertrophy
Medial hypertrophy
Adventitial proliferation
o Loss of peripheral PAs → ↑ PVR → PH
Causes brisket dz
o Inherited:
Genetic predisposition
Altered chemoR activity
Myocardial metabolism
o Acute viral/bacterial pulmonary disease can exacerbate hypoxia
o Plants associated with ↑ incidence
Locoweed shown to induce dz
* Oxytorpis and Astragalus spp with alkaloid swainsonine
Lesions brisket dz: general
- Generalized edema
o Most severe in ventral subQ tissues, skeletal musculature, perirenal tissues, mesentery, GI tract walls
o Ascites, hydrothorax, pericardial effusion
o Transudate fluid: low cellularity and low protein fluid → R-CHF
Lesions brisket dz: liver
early nutmeg appearance to severe lobular and vascular fibrosis
o Depend on chronicity of passive congestion
Lesions brisket dz: lungs
o Variable degree of atelectasis
o Interstitial emphysema
o Edema
o Pneumonia
o Pulmonary arterial thrombosis frequent
Lesions brisket dz: heart
RVH and dilation
o Cardiac apex displaced to L
o RA flaccid and enlarged
Lesions brisket dz: histo
o Hypertrophy of medial in small arteries
o PA rupture (aneurysm) can result in acute death
Lesions brisket dz: IHC
- Immunohistochemistry/electron microscopy studies
o Swelling + cytoplasmic vacuolization of pulmonary IV macrophages + endothelial cells
o Vacuolation of myocardial interstitial cells
Tx brisket dz
- Move to lower alititude
o Hyperbaric chambers at high elevations - Minimal restraint/stress/excitement
- Supportive care: diuretics, thoracocentesis
- Treat concurrent dz
How can genetic selection help brisket dz
- Genetic selection of individuals by PAP measurements → ↓ prevalence
o At 5000-7000ft (1500-2000m): normal PAP = 34-41mmmHg
PAP >48mmHg = at risk, potential genetic carrier
Grey zone: 41-48mmHg → breed with caution
Consider age of animal: if <1y/o → difficult to interpret
o If altitude <5000ft → sometimes hypoxic conditions not sufficient to induce ↑PAP
Not use for breeding selection
Identify animals susceptible at higher altitudes
Animals moved at higher altitude should remain 3wks before testing
