Special Circulations

Special CirculationsMark T Ziolo, PhD, FAHAAssociate Professor, Physiology & Cell Biology019 Hamilton Hall614-688-7905ziolo.1@osu.edu1ObjectivesDescribe the regulation of coronary, cerebral, and skeletal muscle blood flow

Differentiate flow regulation in cutaneous, splanchnic, renal and pulmonary circuits2Detailed ObjectivesUnderstand how coronary blood flow is regulatedKnow why coronary blood flow must be increased and the primary factor responsible for coronary blood flowUnderstand extravascular compression in the heartUnderstand how cerebral blood flow is regulatedKnow why cerebral blood flow is always maintainedKnow what is the purpose of Cushings PhenomenonKnow how skeletal muscle blood flow is regulatedUnderstand why skeletal muscle blood flow switches from neuronal to local (metabolic) regulationKnow the role of the muscle-pump mechanismKnow the purpose of blood flow to the following organs: cutaneous, splanchnic, renal, and pulmonaryUnderstand the major mechanisms of blood flow regulation in the following organs: cutaneous, splanchnic, renal, and pulmonary3Mohrman DE, Heller LJ. Cardiovascular Physiology Seventh Edition. Lange Medical Books/McGraw-Hill Publishers, 2010.Berne RM, Levy MN. Cardiovascular Physiology Sixth Edition. Mosby-Year Book, Inc., 2010.MediaPhys 3.0. An Introduction to Human Physiology. The McGraw-Hill Publishers, 2010.References

4Coronary Blood FlowMyocardium extracts ~75% of the oxygenIncrease in myocardial O2 consumption must be accompanied by an increase in blood flow1 factor responsible for perfusion is the aortic pressureLocal control (metabolic)5Coronary circulation.1 = in the blood. Hence venous blood from heart has the lowest oxy content in body. The heart is not able to increase oxy extraction above this level, so with an increase in myocardial oxy consumption, one must increase blood flow.Remember bbulk? Transport. Tranpsort rate = flow rate x concentration. Conc wil not be diff, so we have to change flow.

3 = perfusion of the heart (or coronary perfusion). Coronary perfusion is under local (metabolic) control

Flow directly related to O2 consumption

6There is a direct relationship between the level of metabolic activity of the heart and coronary blood flow. As the metabolic activity of the heart increases (measured as myocardial oxygen consumption), there is a corresponding increase in coronary blood flow (graph). This effect is through local (metabolic) control.

You can see a direct relationship as we increase myocardial oxy consumption, we increase coronary blood flow.

Extravascular Compression7The primary factor responsible for perfusion of the myocardium is the aortic pressure. Shown in the graph (large gray bar) is the drop in aortic pressure and the corresponding decrease in coronary blood flow during the cardiac cycle (larger gray box). However, the contraction of the heart results in squeezing of the blood vessels (i.e., extravascular compression, or systolic compression). During ventricular contraction, large forces or pressure is generated within the tissue. This pressure presses on the outside of the coronary vessels and causes them to collapse during systole. This force is (can be) high enough to actually reverse flow in that vessel (smaller blue box). After the occlusion of the vessel, blood flow is increased via reactive hyperemia.

The generated systolic forces are much greater in the endocardial layer than the epicardial layer. This graph shows left coronary flow. The same is true for the right side, just lower volumes.

MyocardialO2 demand:MyocardialO2 supplyMyocardialMetabolic rateVasodilatormetabolitesCoronaryblood flowArterial O2contentCoronary Blood Flow, cont8A decrease in the ratio of oxygen supply to oxygen demand (results in) releases vasodilatory metabolites from the myocardium into the interstitial fluid which leads to relaxation of the blood vessels. This ratio can be changed by a reduction in oxygen supply or an increase in oxygen demand. For example, a decrease in arterial blood oxygen content and/or coronary blood flow would decrease myocardial oxygen supply. This will decrease the ratio and cause the release of vasodilatory metabolites (shown in figure, left). An increase in the myocardial metabolic rate will increase oxygen demand and decrease the ratio and cause the release of vasodilatory metabolites (shown in figure, right).

Local ControlVasodilator metabolitesAdenosineActivates adenosine receptorO2, CO2, H+, K+

Neuronal ControlSympathetic activationVasodilation (increase myocardial contractility)9Coronary blood flow is under local/metabolic control. Reguatled by conc of 1. the effects of these metabolites are transient. Coronary blood flow is also indirectly regulated by neuronal control. Symp vasodilation, not constriction, cuz Increase oxy demand of heartLack of Blood FlowMyocardial IschemiaArrhythmiasEndocardial layer of left ventricle10Lack of coronary blood flow results in 1. can result in 1a. This is usually observed at the endocardial layer of the LV cuz blood flow here is impaired more since the larger systolic forces generated by the LV will result in greater vessel compression. Unless person has some coronary disease, this lack of flow is made up during diastole. If the person has coronary disease, difficulty in maintaining sufficient flow to meet the metabolic demands of the heart and an infarct will ensue. There can also be brief periods of ischemia which will result in ischemia reperfusion injury (or IR injury). This injury will result in decreased contractility, known as myocardial stunning, which is caused by calcium overload in the ventricular myocytes. The pt will be able to fully recover from IR injury within 2 weeks.Cerebral Blood FlowIn ALL situations, blood flow to the brain is preserved (55 ml/min/100g)Whole brain has a nearly constant metabolic rateBlood flow to discrete regions is not constantRegulated almost entirely by local mechanismsO2, H+ (PCO2), K+, adenosineExcellent autoregulationSome sympathetic vasoconstriction112, however 3. These metabolites of 3a include those listed. Not directly, but changes in pH. And thus partial pressure of co2.

Brain has 4, in range of 60-160 mmHg via the metabolic or local influence and myogenic factors. There is some symp vasoconstriction regulating cerebral blood flow. Very little, most likely to protect the brain from large abrupt increases in arterial pressure. HandReasoningProblem SolvingCerebral Blood Flow, cont12Total cerebral blood flow in constant, but regional blood flow is associated with regional brain function. For example, movement of the hand increased blood flow only in the hand area of the contralateral sensorimotor and premotor cortex (shown by red circles). Reasoning, problem solving and other stimuli lead to increased blood flow to the appropriate region of the brain.

Cerebral Blood Flow, contNo reserves- very intolerant to ischemia5 sec: faintingMinutes: death

13Brain is very intolerant to ischemia. In fact least tolerant of any organ in our body. With 5 sec of no cerebral blood flow, we will faint.Cushings PhenomenonTumor Intracranial pressure CBFMetabolicvasodilationIschemic stimulation of vasomotorregions in medulla systemic blood pressureMaintain CBF14Elevation of intracranial pressure results in an increase in systemic blood pressure. This response is called Cushings Phenomenon (right side of slide). For example, a tumor will increase intracranial pressure, which will decrease cerebral blood flow by collapsing blood vessels. By increasing metabolites leading to vasodilation, and increasing systemic blood pressure, to increase mean arterial pressure, cerebral blood flow will be maintained. This maintains cerebral blood flow in conditions such as intracranial tumors.

Skeletal MuscleRate of blood flow directly related to contractile state of muscleAt rest, large percentage of capillary bed is not perfusedRegulation of flowNeuronal and local influencesPhysical factor- squeezing effect of contracting muscle

15Skeletal m blood flow. Skeletal m accounts for 40-50% of our body weight. Thus, skeletal m blood flow is an important factor in overall cv hemodynamics. The rate of blood flow to skeletal m varies directly with the contractile state of the m.

2 = and skeletal m will receive 15% of cardiac output. With exercise, the body can increase skeletal m bloodflow 15 fold. And now skeletal m bloodflow can receive 80% of cardiac output. Regulation of skeletal m blood flow done via neuronal or local/metabolic influences. Neuronal predominates in resting m. while local influence predom in working m. physical factor where contracting m squeezes on vs to push blood back to heart. Vs have valves to to allow bloodflow only in one direction.Skeletal Muscle, contNeuronal InfluenceHigh basal toneSympathetic fibers elicits vasoconstrictionPredominates in resting muscle16Skeletal m is under neuronal influence. High basal tone. Stimulation of symp fibers will elicit vasoconstriction. This predoms in resting m. the neuronal influence also protects us from full m vasodilation by the metabolic pathway. This will prevent a decrease in total peripheral resistance (TPR) to maintain arterial pressure.Skeletal Muscle, contLocal InfluenceVery strong in working muscleMuscle O2 consumption, adenosine, H+, K+, lactic acidNeuronal and local influences oppose each other, in working muscle the local (metabolic) influence predominates17Skeletal m is also under local influence. This pathway is very strong in working m. vasodilatory factors are listed. Thus skeletal m bloodflow is regulated by 2. neuronal influence predoms in resting m. Skeletal Muscle, contmuscle-pump mechanismContracting muscles push blood in veins towards thorax18The physical factor of skeletal m regulating bloodflow is known as 1. this is a physical factor of the contracting m squeezing the vs to push blood back to the thorax. 10% of our total blood volume is contained within the vs of the skeletal m. this mech is very important in whole body exercise to enhance venous outflow. This mech can also be observed in soldiers standing at attention. Without this mech, the solider will eventually faint.Cutaneous Very low O2 and nutrient requirementsMaintain constant body temperatureArterioles and arteriovenous anastomosesAV anastomoses shunt blood from arterioles to venulesGoverned by nervous system in response to temperature receptorsNE and E elicit vasoconstrictionChiefly influenced by environmental temperature19Skin blood flow. 1 = only receives 6% of the total cardiac output. An important role of cutaneous bloodflow is 2, since it is the primary site of exchange with the external environment.

Skin BF (blood flow) can be reduced 1/20 to retain heat or increase 7 fold to lose heat. This is accomplished by the arterioles and the arteriole venous anastomoses.

4, bypassing the capillaries.4a, in a reflex mech. This releases ne and e to cause vasoconstrictionHence, cold temps outside will activate this reflex to cause vasoconstriction to save heat. This is why hands and feet get cold.Splanchnic GI tract, spleen, pancreas, and liver~25% of resting cardiac outputNeuronal and local influencesSympathetic causes vasoconstrictionShifts blood to central venous pool (liver important blood reserve) Gastrointestinal hormones- functional hyperemiaAutoregulation not well developed20Splanchnic circ includes 1. these organs are arranged in series. Under 2. some local influence known as functional hyperemia = gastrin will increase bf when food is ingested. However, 3c. Renal Blood Flow0.5% TBW but 20% of cardiac outputStrong autoregulationRegulate GFRMyogenic mechanism (stretch)Tubuloglomerular feedbackTubular flow sensed by macula densa sends signal via juxtaglomerular apparatus to afferent arteriolesJGA also releases renin (angiotensin II)Neuronal InfluenceSympathetic decreases RBF, but GFR only slightly21The kidneys, while only weight 0.5% of total body weight, receive 20% of cardiac output. High metabolic rate, this value still far exceeds what is needed. Reason for this high blood flow = filtration. The kidneys have strong autoreg to reg GFR or glomerular filtration rate. Occurs via 2 mechs = myogenic, or tubuloglomerular feedback.

Also neuronal influence which will decrease renal bloodflow. Extreme conditions such as shock, this decrease kidney blood flow can lead to kidney damage.Pulmonary Blood FlowVascular system is low-resistance and highly distensibleCapillaries aligned in thin sheets between adjacent alveoliGravitational effects (regional distribution)Hypoxia most important influence on toneLow alveolar PO2 leads to shunting of blood from poorly ventilated regions to better ventilated regions22Pulm vasc system has much lower resistance compared to other organs. This is cuz main arterial pressure for our systemic circ is 100mmHg. But pulm system has a mean arterial pressure of 13mmHg. The caps are aligned in thin sheets between alveoli. With these low pressures, the pulm circ is greatly affected by gravity leading to regional distribution. Bottom of lungs are better perfused than top. Like many other organs, hypoxia is important influence on vessel tone. However, this leads to vasoconstriction to shunt blood away from poorly ventilated regions. In addition, the pulm bvs are thin walled and less muscular to allow for better exchange. There is also low cap hydrostatic pressure to strongly favor reabsorption.SummaryCoronary blood flow is regulated by metabolic influences and the primary factor responsible is arterial pressureWith increased oxygen demand, coronary blood flow must be increased because of the bulk flow principle Extravascular compression occurs in the heart due to high systolic forcesCerebral blood flow in mostly under metabolic influenceCerebral blood flow is always maintained since it is the least tolerant organ to ischemia and there are no reservesCushings Phenomenon is elevation of intracranial pressure results in an increase in systemic blood pressure to maintain cerebral blood flowSkeletal muscle blood flow is regulated by the neuronal influence at rest, and by the metabolic influence in working muscleThe muscle pump mechanism pushes blood back towards the heart23Summary, contPurpose of cutaneous blood flow is temperature regulation and is under neuronal controlPurpose of splanchnic blood flow is nutrient reabsorption and is under neuronal control and functional hyperemiaPurpose of renal blood flow is filtration and has strong autoregulation and is under neuronal controlPurpose of pulmonary blood flow is gas exchange and has hypoxic vasoconstriction

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***2*** = Oxygen consumption is the correct answer since the heart is a metabolically controlled organ. Oxygen consumption is directly related to the metabolic activity.25

***4*** = Pushes blood is the correct answer since this mechanism is the physical factor of the muscle squeezing the veins. With the valves in the veins, this will force blood to move back towards the thorax.26

***3*** = Body temperature is the correct answer since the skin is the primary site of exchange with the external environment.27

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