Circulatory Circulatory PhysiologyPhysiology

AnS 536AnS 536

Spring 2015Spring 2015

Development of the Development of the Circulatory SystemCirculatory System

1st functional organ system – heart is 1st functional organ system – heart is functional when embryo is 2 mm in sizefunctional when embryo is 2 mm in size

Heart rate peaks at 9 weeks, and slows Heart rate peaks at 9 weeks, and slows to ~145 beats at termto ~145 beats at term

Huge increase in cardiac output Huge increase in cardiac output postnatally but limited ability to postnatally but limited ability to increase further increase further – Increase in thyroid hormone prenatally Increase in thyroid hormone prenatally

matures myocardium in preparation for matures myocardium in preparation for increased postnatal requirementsincreased postnatal requirements

Development of the Development of the Circulatory SystemCirculatory System

The heart functions partly in parallel and The heart functions partly in parallel and dominated by right ventricular functiondominated by right ventricular function

Parallel function allows the shunts to be Parallel function allows the shunts to be more effective and the foramen ovale to more effective and the foramen ovale to not compromise cardiac outputnot compromise cardiac output

Heart functions in series postnatally with Heart functions in series postnatally with equal ventricular function equal ventricular function

Blood volume ~11% in fetus (7.5% in Blood volume ~11% in fetus (7.5% in adults) because of amount of placental adults) because of amount of placental bloodblood

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The Fetal Circulatory SystemThe 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

Fetal Circulatory ShuntsFetal Circulatory Shunts Foramen ovaleForamen ovale

– Shunts blood from the Shunts blood from the right atrium to the left right atrium to the left atriumatrium

Ductus arteriosusDuctus arteriosus– Shunts blood from the Shunts blood from the

pulmonary artery to the pulmonary artery to the ascending aortaascending aorta

– Bypasses pulmonary Bypasses pulmonary circulationcirculation

Ductus venosusDuctus venosus– Shunts blood from the Shunts blood from the

umbilical vein to the umbilical vein to the inferior vena cavainferior vena cava

– Separates the hepatoportal Separates the hepatoportal and systemic circulationand systemic circulation

PhysiologyPhysiology– Fetal blood passes from the Fetal blood passes from the

placenta placenta umbilical vein umbilical vein fetal heartfetal heart

– Left ventricle shunts blood to Left ventricle shunts blood to the craniumthe cranium

Advantages of shuntsAdvantages of shunts– Bypasses normal “flow Bypasses normal “flow

patterns” to allow most patterns” to allow most oxygenated blood (left oxygenated blood (left ventricle) to reach the fetal ventricle) to reach the fetal brainbrain

– Unsaturated blood (from the Unsaturated blood (from the right ventricle) is diverted to right ventricle) is diverted to the trunk and lower body of the trunk and lower body of the fetusthe fetus

Oxygen Tension LevelsOxygen Tension Levels

Blood coming from the placenta (umbilical veins) Blood coming from the placenta (umbilical veins) is 80% saturated with oxygenis 80% saturated with oxygen

Enters right atrium via inferior vena cavaEnters right atrium via inferior vena cava– Half of venous return bypasses portal circulation via Half of venous return bypasses portal circulation via

ductus venosusductus venosus– Because ductus venosus has small diameter, blood Because ductus venosus has small diameter, blood

accelerates and is more likely to push though foramen accelerates and is more likely to push though foramen ovale into left atrium and to “upper circulation”ovale into left atrium and to “upper circulation”

From right atrium to left atrium via foramen ovale From right atrium to left atrium via foramen ovale (now 65% saturated)(now 65% saturated)– Pumped to carotid artery and to brain (most oxygen Pumped to carotid artery and to brain (most oxygen

rich blood)rich blood)

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

Oxygen Tension LevelsOxygen Tension Levels

Blood coming from the superior vena cava Blood coming from the superior vena cava is directed primarily through tricuspid is directed primarily through tricuspid valve into right ventricle (50% saturated valve into right ventricle (50% saturated with oxygen)with oxygen)

Enters aorta, provides lower levels of Enters aorta, provides lower levels of oxygen to caudal half of body and then oxygen to caudal half of body and then enters the umbilical arteries to be re-enters the umbilical arteries to be re-oxygenated in the placentaoxygenated in the placenta– Once oxygenated, returns to body as fully Once oxygenated, returns to body as fully

oxygenated blood via umbilical veins oxygenated blood via umbilical veins

Ductus ArteriosusDuctus Arteriosus Factors involved in closureFactors involved in closure

– PGEPGE2 2 helps maintain patency and nitic oxide helps maintain patency and nitic oxide will cause relaxation (indomethacin will will cause relaxation (indomethacin will induce closure anytime during latter half of induce closure anytime during latter half of third trimester through postnatal life)third trimester through postnatal life)

– Increased POIncreased PO22 of arterial blood postnatally of arterial blood postnatally causes spasms of the ductuscauses spasms of the ductus

– Fetus has low-resistance circulation from the Fetus has low-resistance circulation from the placenta during gestationplacenta during gestation Parturition, umbilical cord rupture, and initiation of Parturition, umbilical cord rupture, and initiation of

respiration increase resistancerespiration increase resistance

Ductus ArteriosusDuctus Arteriosus

Physiological changesPhysiological changes– Lungs become the organ of respirationLungs become the organ of respiration– Oxygen tension increasesOxygen tension increases– Right ventricular outflow passes into the Right ventricular outflow passes into the

lungs instead of the ductus lungs instead of the ductus – Ductus constriction begins shortly after Ductus constriction begins shortly after

birthbirth– Closure occurs 24-48 hours after birthClosure occurs 24-48 hours after birth

Ductus VenosusDuctus Venosus Factors involved in closureFactors involved in closure

– Liver pressure and resistanceLiver pressure and resistance– Gestational age Gestational age

and weight at birthand weight at birth Premature neonates will have Premature neonates will have

delayed closuredelayed closure

– DrugsDrugs Promote closurePromote closure

– Antenatal corticosteroidsAntenatal corticosteroids Delay closureDelay closure

– Prostaglandins and nitroxide Prostaglandins and nitroxide distend diameter of ductusdistend diameter of ductus

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Ductus VenosusDuctus Venosus Physiologic changesPhysiologic changes

– Functional closure initially after Functional closure initially after birthbirth

– Umbilical vein constricts reducing Umbilical vein constricts reducing supply of shunted bloodsupply of shunted blood

Ductus venosus becomes Ductus venosus becomes ligamentum venosumligamentum venosum

Blood enters liver through Blood enters liver through hepatic sinuoidshepatic sinuoids

Foramen OvaleForamen Ovale Factors contributing to closureFactors contributing to closure

– Pulmonary and vascular Pulmonary and vascular resistance increaseresistance increase

Physiological changesPhysiological changes– Increased quantity of blood into the left Increased quantity of blood into the left

atriumatrium– Causes left atrial pressure to rise above that Causes left atrial pressure to rise above that

in the right atriumin the right atrium– Closes the flap of this one-way valve Closes the flap of this one-way valve

preventing blood flow across the septumpreventing blood flow across the septum Anatomical closure takes months or yearsAnatomical closure takes months or years

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Persistent (Patent) Persistent (Patent) Ductus ArteriosusDuctus Arteriosus

Failure of closure of the vessel that joins the Failure of closure of the vessel that joins the pulmonary artery to the aortapulmonary artery to the aorta

EffectsEffects– Depend on size of shunt and degree of Depend on size of shunt and degree of

pulmonary hypertensionpulmonary hypertension Small to moderate shuntsSmall to moderate shunts

– Easy to fatigue, dyspnea on exertion and exercise Easy to fatigue, dyspnea on exertion and exercise intolerance intolerance later in lifelater in life

Large shuntsLarge shunts– Poor growth and developmentPoor growth and development– Frequent episodes of pneumonitis and development of Frequent episodes of pneumonitis and development of

congestive heart failurecongestive heart failure– Life expectancy is markedly reduced – these individuals Life expectancy is markedly reduced – these individuals

often die in their second or third decadeoften die in their second or third decade

Persistent (Patent) Persistent (Patent) Ductus ArteriosusDuctus Arteriosus

Potential causesPotential causes– Hypoxia and acidosis will increase pulmonary vascular Hypoxia and acidosis will increase pulmonary vascular

resistance and increase right-to-left shuntingresistance and increase right-to-left shunting– Higher incidence when infants are born at high Higher incidence when infants are born at high

altitudes (>10,000 ft)altitudes (>10,000 ft)– Twice as common in females vs. malesTwice as common in females vs. males– Frequency increased in preterm infantsFrequency increased in preterm infants

Fail to close spontaneouslyFail to close spontaneously Closure induced with cyclooxygenase inhibiting drugs in Closure induced with cyclooxygenase inhibiting drugs in

premature babies ONLYpremature babies ONLY– COX-1 and COX-2 are enzymes in arachidonic acid metabolism COX-1 and COX-2 are enzymes in arachidonic acid metabolism

producing producing prostaglandins, prostacyclins and producing producing prostaglandins, prostacyclins and thromboxanesthromboxanes

– COX inhibitors are NSAIDCOX inhibitors are NSAIDSS (ibuprofen or indomethacin) (ibuprofen or indomethacin)

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Persistent Pulmonary Persistent Pulmonary HypertensionHypertension

Occurs when pulmonary vascular Occurs when pulmonary vascular resistance fails to decreaseresistance fails to decrease

TreatmentsTreatments– Mechanical hyperventilationMechanical hyperventilation– Inhaled nitric oxideInhaled nitric oxide– VentilationVentilation– Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation

(ECMO)(ECMO)– Free radical scavengers (SOD)Free radical scavengers (SOD)

Persistent Pulmonary Persistent Pulmonary HypertensionHypertension

Mechanical Mechanical hyperventilationhyperventilation– Results in alkalosisResults in alkalosis

Improves condition as Improves condition as systemic pH rises over systemic pH rises over 7.55 to 7.67.55 to 7.6

– Problems can occur if Problems can occur if too vigorous or too vigorous or sustained too long sustained too long

Inhaled nitric oxideInhaled nitric oxide– Mimics Mimics

endothelium-endothelium-derived relaxing derived relaxing factorfactor Promotes pulmonary Promotes pulmonary

vasodilatationvasodilatation Poorly sustained Poorly sustained

response in most response in most infantsinfants

Persistent Pulmonary Persistent Pulmonary HypertensionHypertension

VentilationVentilation– High oscillatory High oscillatory – Effective with severe Effective with severe

associated lung diseaseassociated lung disease

ECMOECMO– Infants placed on Infants placed on

blood bypass pumpblood bypass pump– Blood exits the right atrium Blood exits the right atrium

passes through a membrane passes through a membrane oxygenator and returns to oxygenator and returns to the aortic archthe aortic arch

– Lungs are essentially at restLungs are essentially at rest– When hypertension improves When hypertension improves

– infants are weaned off– infants are weaned off ProblemsProblems

– Used as a last resortUsed as a last resort– Neurodevelopmental Neurodevelopmental

disorders can occurdisorders can occur

Umbilical Vessel ConstrictionUmbilical Vessel Constriction

Factors involvedFactors involved– ChemicalChemical

BradykininsBradykinins EpinephrineEpinephrine SeratoninSeratonin

– MechanicalMechanical Increase in POIncrease in PO22

– HumoralHumoral ThromboxaneThromboxane HistamineHistamine

If constriction does If constriction does not occurnot occur– Persistent bleeding Persistent bleeding

leading to leading to hemorrhage and hemorrhage and severe blood losssevere blood loss

– Potential for Potential for infectioninfection

– Surgical Surgical intervention may be intervention may be neededneeded

Placental TransfusionPlacental Transfusion

Transfer of blood from Transfer of blood from the placenta to the the placenta to the fetus at birthfetus at birth

Dependent upon Dependent upon timing of umbilical timing of umbilical clamping clamping (1-5 minutes) after (1-5 minutes) after birthbirth

Late clampingLate clamping– Increases blood volume Increases blood volume

and RBC’s of neonate and RBC’s of neonate (20-50%)(20-50%)

– Can increase bilirubin Can increase bilirubin concentrationsconcentrations

Early clampingEarly clamping– Decreases blood volume Decreases blood volume

anemia anemia FoalsFoals

– Early clamping leads to Early clamping leads to barker syndrome, barker syndrome, temporary blindness, and temporary blindness, and dummy foal syndromedummy foal syndrome

– Increased frequency of Increased frequency of deathdeath