1. Circulatory Physiology AnS 536 Spring 2015

2. Development of the Circulatory System 1st functional organ system – heart is functional when embryo is 2 mm in size 1st functional organ system – heart is functional when embryo is 2 mm in size Heart rate peaks at 9 weeks, and slows to ~145 beats at term Heart rate peaks at 9 weeks, and slows to ~145 beats at term Huge increase in cardiac output postnatally but limited ability to increase further Huge increase in cardiac output postnatally but limited ability to increase further –Increase in thyroid hormone prenatally matures myocardium in preparation for increased postnatal requirements

3. Development of the Circulatory System The heart functions partly in parallel and dominated by right ventricular function The heart functions partly in parallel and dominated by right ventricular function Parallel function allows the shunts to be more effective and the foramen ovale to not compromise cardiac output Parallel function allows the shunts to be more effective and the foramen ovale to not compromise cardiac output Heart functions in series postnatally with equal ventricular function Heart functions in series postnatally with equal ventricular function Blood volume ~11% in fetus (7.5% in adults) because of amount of placental blood Blood volume ~11% in fetus (7.5% in adults) because of amount of placental blood

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5. The Fetal Circulatory System Pathways of the fetal heart and representative oxygen saturation values (in numbers). The via sinistra (red) directs well oxygenated blood from the umbilical vein (UV) through the ductus venosus (DV) (or left half of the liver) across the inferior vena cava (IVC), through the foramen ovale (FO), left atrium (LA) and ventricle (LV) and up the ascending aorta (AO) to join the via dextra (blue) in the descending AO. Deoxygenated blood from the superior vena cava (SVC) and IVC forms the via dextra through the right atrium (RA) and ventricle (RV), pulmonary trunk (PA) and ductus arteriosus (DA). The isthmus aortae (arrow) and the section of the left portal vein between the main stem (P) and the DV (striped area) represent watershed areas during hemodynamic compromise. CCA, common carotid arteries; FOV, foramen ovale valve; LHV, left hepatic vein; MHV, medial hepatic vein; PV, pulmonary vein; RHV, right hepatic vein

6. Fetal Circulatory Shunts Foramen ovale Foramen ovale –Shunts blood from the right atrium to the left atrium Ductus arteriosus Ductus arteriosus –Shunts blood from the pulmonary artery to the ascending aorta –Bypasses pulmonary circulation Ductus venosus Ductus venosus –Shunts blood from the umbilical vein to the inferior vena cava –Separates the hepatoportal and systemic circulation Physiology Physiology –Fetal blood passes from the placenta  umbilical vein  fetal heart –Left ventricle shunts blood to the cranium Advantages of shunts Advantages of shunts –Bypasses normal “flow patterns” to allow most oxygenated blood (left ventricle) to reach the fetal brain –Unsaturated blood (from the right ventricle) is diverted to the trunk and lower body of the fetus

7. Oxygen Tension Levels Blood coming from the placenta (umbilical veins) is 80% saturated with oxygen Blood coming from the placenta (umbilical veins) is 80% saturated with oxygen Enters right atrium via inferior vena cava Enters right atrium via inferior vena cava –Half of venous return bypasses portal circulation via ductus venosus –Because ductus venosus has small diameter, blood accelerates and is more likely to push though foramen ovale into left atrium and to “upper circulation” From right atrium to left atrium via foramen ovale (now 65% saturated) From right atrium to left atrium via foramen ovale (now 65% saturated) –Pumped to carotid artery and to brain (most oxygen rich blood)

8. Foramen Ovale Flow distribution at the foramen ovale. The edge of the atrial septum (crista dividens) divides the ascending flow in two arms, to the right and left atrium (RA and LA). The horizontal diameter between the foramen ovale valve and the atrium (broken line) represents the restricting area into the LA. Position, direction and kinetic energy of the flow from the ductus venosus makes it predominantly enter the left atrium (dark gray). Conversely, blood from the inferior vena cava (IVC) enters the RA (light gray). Ao, aorta; PA, pulmonary trunk; PV, stem of the portal vein (From Kiserud and Rasmussen, 2001)

9. Oxygen Tension Levels Blood coming from the superior vena cava is directed primarily through tricuspid valve into right ventricle (50% saturated with oxygen) Blood coming from the superior vena cava is directed primarily through tricuspid valve into right ventricle (50% saturated with oxygen) Enters aorta, provides lower levels of oxygen to caudal half of body and then enters the umbilical arteries to be re-oxygenated in the placenta Enters aorta, provides lower levels of oxygen to caudal half of body and then enters the umbilical arteries to be re-oxygenated in the placenta –Once oxygenated, returns to body as fully oxygenated blood via umbilical veins

10. Ductus Arteriosus Factors involved in closure Factors involved in closure –PGE 2 helps maintain patency and nitic oxide will cause relaxation (indomethacin will induce closure anytime during latter half of third trimester through postnatal life) –Increased PO 2 of arterial blood postnatally causes spasms of the ductus –Fetus has low-resistance circulation from the placenta during gestation  Parturition, umbilical cord rupture, and initiation of respiration increase resistance

11. Ductus Arteriosus Physiological changes Physiological changes –Lungs become the organ of respiration –Oxygen tension increases –Right ventricular outflow passes into the lungs instead of the ductus –Ductus constriction begins shortly after birth –Closure occurs 24-48 hours after birth

12. Ductus Venosus Factors involved in closure Factors involved in closure –Liver pressure and resistance –Gestational age and weight at birth  Premature neonates will have delayed closure –Drugs  Promote closure –Antenatal corticosteroids  Delay closure –Prostaglandins and nitroxide distend diameter of ductus

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14. Ductus Venosus Physiologic changes Physiologic changes –Functional closure initially after birth –Umbilical vein constricts reducing supply of shunted blood Ductus venosus becomes ligamentum venosum Ductus venosus becomes ligamentum venosum Blood enters liver through hepatic sinuoids Blood enters liver through hepatic sinuoids

15. Foramen Ovale Factors contributing to closure Factors contributing to closure –Pulmonary and vascular resistance increase Physiological changes Physiological changes –Increased quantity of blood into the left atrium –Causes left atrial pressure to rise above that in the right atrium –Closes the flap of this one-way valve preventing blood flow across the septum Anatomical closure takes months or years Anatomical closure takes months or years

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17. Persistent (Patent) Ductus Arteriosus Failure of closure of the vessel that joins the pulmonary artery to the aorta Failure of closure of the vessel that joins the pulmonary artery to the aorta Effects Effects –Depend on size of shunt and degree of pulmonary hypertension  Small to moderate shunts –Easy to fatigue, dyspnea on exertion and exercise intolerance later in life  Large shunts –Poor growth and development –Frequent episodes of pneumonitis and development of congestive heart failure –Life expectancy is markedly reduced – these individuals often die in their second or third decade

18. Persistent (Patent) Ductus Arteriosus Potential causes Potential causes –Hypoxia and acidosis will increase pulmonary vascular resistance and increase right-to-left shunting –Higher incidence when infants are born at high altitudes (>10,000 ft) –Twice as common in females vs. males –Frequency increased in preterm infants  Fail to close spontaneously  Closure induced with cyclooxygenase inhibiting drugs in premature babies ONLY –COX-1 and COX-2 are enzymes in arachidonic acid metabolism producing producing prostaglandins, prostacyclins and thromboxanes –COX inhibitors are NSAID S (ibuprofen or indomethacin)

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20. Persistent Pulmonary Hypertension Occurs when pulmonary vascular resistance fails to decrease Occurs when pulmonary vascular resistance fails to decrease Treatments Treatments –Mechanical hyperventilation –Inhaled nitric oxide –Ventilation –Extracorporeal membrane oxygenation (ECMO) –Free radical scavengers (SOD)

21. Persistent Pulmonary Hypertension Mechanical hyperventilation Mechanical hyperventilation –Results in alkalosis  Improves condition as systemic pH rises over 7.55 to 7.6 –Problems can occur if too vigorous or sustained too long Inhaled nitric oxide Inhaled nitric oxide –Mimics endothelium- derived relaxing factor  Promotes pulmonary vasodilatation  Poorly sustained response in most infants

22. Persistent Pulmonary Hypertension Ventilation Ventilation –High oscillatory –Effective with severe associated lung disease ECMO ECMO –Infants placed on blood bypass pump –Blood exits the right atrium passes through a membrane oxygenator and returns to the aortic arch –Lungs are essentially at rest –When hypertension improves – infants are weaned off Problems Problems –Used as a last resort –Neurodevelopmental disorders can occur

23. Umbilical Vessel Constriction Factors involved Factors involved –Chemical  Bradykinins  Epinephrine  Seratonin –Mechanical  Increase in PO 2 –Humoral  Thromboxane  Histamine If constriction does not occur If constriction does not occur –Persistent bleeding leading to hemorrhage and severe blood loss –Potential for infection – Surgical intervention may be needed

24. Placental Transfusion Transfer of blood from the placenta to the fetus at birth Transfer of blood from the placenta to the fetus at birth Dependent upon timing of umbilical clamping (1-5 minutes) after birth Dependent upon timing of umbilical clamping (1-5 minutes) after birth Late clamping Late clamping –Increases blood volume and RBC’s of neonate (20-50%) –Can increase bilirubin concentrations Early clamping Early clamping –Decreases blood volume  anemia Foals Foals –Early clamping leads to barker syndrome, temporary blindness, and dummy foal syndrome –Increased frequency of death