PDA - Buchanan

Question 1

Normal anatomy

Answer 1

From MPA bifurcation => ventral aspect of descending Ao, btwn L subclavian and intercostal arteries

Question 2

Functional closure

Answer 2

Hours

Question 3

Anatomic closure

Answer 3

2-4wks

Question 4

Function in fetal circ

Answer 4

Carries O2 blood from R heart = bypass non-functioning lung

Question 5

Angio

Answer 5

• 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

Question 6

Gross path

Answer 6

• 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

Question 7

Histopath

Answer 7

• Hypoplastic ductal muscle: asymmetric
• ↑ # of elastic fibers proportional to muscle hypoplasia

Question 8

Genetics

Answer 8

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

Question 8

Grades on histo

Answer 8

• 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

Question 9

PE findings

Answer 9

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

Question 10

CTX findings

Answer 10

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

Question 11

ECg findings

Answer 11

high amplitude R waves => LVH
o Afib is most common arrhythmia

Question 12

Echo findings

Answer 12

enlarged, hyperdynamic LV
o Doppler: continuous, turbulent, retrograde flow in MPA from Ao

Question 13

KT findings

Answer 13

O2 step up in PA > 5% from RV

Question 14

Epidemio

Answer 14

• Most frequent cardiovascular abnormality, small breed dogs

Question 15

PDA closure phases

Answer 15

• 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

Question 16

Factors influencing intrinsic DA tone

Answer 16

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

Question 17

Factors that oppose DA constriction in utero

Answer 17

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)

Question 18

Several events promotes DA constrictions after birth

Answer 18

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

Question 19

Anatomic closure: histo changes

Answer 19

• 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