PDA - Buchanan Flashcards
Normal anatomy
From MPA bifurcation => ventral aspect of descending Ao, btwn L subclavian and intercostal arteries
Functional closure
Hours
Anatomic closure
2-4wks
Function in fetal circ
Carries O2 blood from R heart = bypass non-functioning lung
Angio
- Majority are funnel shaped, w maximal narrowing at PA orifice
- Categorized based on angio
o Most of ductus lies w/i walls of Ao
May appear as ventral and lateral bulge
o Dilated portion: diverticulum/ampulla
o Large PDAs w PH and R to L shunt
Rarely have aneurysm (narrowing)
Pulmonary vasculature almost normal or only mildy dilated and tortuous
Gross path
- External examination: not reveal true size of the defect
- Internal PDA diameter = varies with location
o Narrowest segment almost always PA orifice: intimal ridge/short tunnel
Rarely in the middle or towards Ao end => shift in the location of the hypoplastic ductus muscle mass - Surgery: 4th IC space = good exposure of external portion
o Length of PDA inversely proportional to size of aneurysm
Short PDA w large aneurysm = resemble aorta-pulmonary window
Shorter ductus then normal
Hypoplastic and eccentric smooth muscle
Aorta like elastic tissue present where should be muscular
* Inappropriate ductal elastic tissue
Histopath
- Hypoplastic ductal muscle: asymmetric
- ↑ # of elastic fibers proportional to muscle hypoplasia
Genetics
Hereditary => polygenic
2 dogs w/ PDA mated = 80% offspring
1 PDA dog w/ 1 offspring = 70% offspring
1 PDA dog w/ normal = 20%
Average litter abnormal ductus correlated w proportion of PDA genes
Ductus length inversely correlated w grade of abnormality
Grades on histo
- 6 grades
o 1 & 2: enough muscle to close PA end, lack at Ao end
Ductal aneurysm
o 3,4,5: partial closure at PA end = sm, med, lg PDA
o 6: no ductal constriction → lg L to R shunt
PE findings
continuous murmur at left base +/- precordial thrill
o Intensity, frequency, duration, radiation: determined by diameter/length + degree of PH
Peak intensity in systole
Small PDA = high pitched
Large PDA = diastolic component abbreviated/not present => diastolic BP Ao = PA
* Can only have systolic murmur
o Systolic murmur at left apex: MR 2nd to annular dilation
Water hammer pulses: incr systolic BP from incr SV
Decr diastolic from runoff
CTX findings
o Pathognomonic: leftward bulge of Ao at 1o clock in DV/VD
3 bulges: MPA, Ao, ductal bump
o Left heart enlargement
o Increased pulmonary vascular markings +/- CHF
ECg findings
high amplitude R waves => LVH
o Afib is most common arrhythmia
Echo findings
enlarged, hyperdynamic LV
o Doppler: continuous, turbulent, retrograde flow in MPA from Ao
KT findings
O2 step up in PA > 5% from RV
Epidemio
- Most frequent cardiovascular abnormality, small breed dogs
PDA closure phases
- Obliteration occurs through process of vasoconstriction and anatomic remodeling
- 2 phases
o Functional closure of the lumen w/i 1st hours after birth by smooth muscle constriction
o Anatomic occlusion over next several days: extensive neointimal thickening + loss of smooth muscle ¢ from the inner muscle media = fibrosis
Factors influencing intrinsic DA tone
Extra¢ Ca2+: more sensitive to the contractile effect of Ca2+ vs Ao or PA
- Increased Rho kinase activity
Endothelin-1: elevated basal tone in fetal DA
Factors that oppose DA constriction in utero
Incr vascular pressure in DA lumen 2nd to constricted pulmonary vascular bed
Vasodilators produced by DA
- Prostaglandins E2: most important/potent protanoid regulating DA patency
* DA +++ sensitive to PGE2: interact w several PGE R (EP2, EP3, EP4) => adenylate cyclase activation => cAMP => inhibit sensitivity of contractile protein to Ca2+
* EP3 also open K+-ATPase channel = hyperpolarize ¢
* Both COX-1 and 2 are expressed in fetal DA => constriction by COX inhibitors
* Also influenced by circulation PGE2 from placenta: incr [PGE2] because reduced clearance 2nd to low fetal pulmonary blood flow
- Phosphodiesterase inhibitor
- Nitric oxide
- Carbon monoxide: hemoxygenase 1 and 2 found in endothelial smooth muscle ¢ of DA (enzymes that produce carbon monoxide)
- If synthesis is upregulated (ex. Endotoxinemia)
Several events promotes DA constrictions after birth
o incr arterial partial O2 pressure
Mechanism involving smooth muscle depolarization: Inhibit K+ channels => depolarization => Ca2+ entry through L-type + T-type voltage dependent channels
Mechanism independent of membrane depol.
* Direct effect on Ca2+ channels
* Rho kinase mediated pathways activation => incr sensitivity to Ca2+
Decr blood pressure in the DA => 2nd to decr PVR
Decr circulating [PGE2] from loss of placental PGE2 + incr clearance by lungs
Decr in # of PGE2 R in DA wall => loose its ability to respond to PGE2 *continue to be sensitive to the effects of NO
Incr cortisol: decr sensitivity of DA to PGE2
Anatomic closure: histo changes
- Progressive intimal thickening
o Migration of smooth muscle ¢ from media to intima
o Proliferation of luminal endothelial ¢ - Cushion formation:
o Accumulation of hyaluronan below luminal endothelial ¢ => influx of water => widening of subendothelial space => good environment for ¢ migration
Faster migration of smooth muscle ¢
Mediated through hyaluronan mediated-motility R
o Loss of type 4 collagen from basement membrane of endothelial ¢ => separation from internal elastic lamina
o Secretion of fibronectin + chondroitin sulfate
Fibronectin facilitate smooth muscle ¢ migration
o Use integrins (¢ surface R) to help with migration - Alterations in elastin fibers assembly: thin + fragmented elastin fibers => not prevent from collapsing/closing when vasoconstriction
o PGE2 via EP4: inhibit thick elastin fiber formation
