Learning objectives

1. Learning objectives • Explain for each of the circulations described, how n increase in blood flow is achieved; discuss the roles played by autoregulation, metabolic and reactive hyperemia and sympathetic activity in altering blood flow • Briefly describe the pathology and consequences of atheromatous plaques in the coronary circulation • Describe how angina pectoris arise • Describe the blood brain barrier and the advantages conferred by it • Describe the circumventricular organs and their functions • Briefly describe the major role of the cutaneous circulation

2. Most organs have their own special requirements in term of blood flow, related to their unique functions 1. Coronary Circulation Fig. 1. The coronary circulation

3. Fig. 2. Diagram of the coronary circulation

4. The heart receives ~ 5% of the resting cardiac output. At rest extracts 70-80% of the O2 from blood • The heart uses oxidative phosphorilation to generate adenosine triphosphate (ATP) required for pumping blood, demands being high • ~ 40% of the consumed O2 comes from oxidation of carbohydrate, and more than 60% is due to oxidation of fatty acids and ketone bodies • When O2 supply is adequate, the heart takes up and oxidizes both lactate and pyruvate.

5. -During resting conditions cardiac muscle uses as much oxygen as does an equal mass of skeletal muscle during vigorous exercise! During exercise the oxygen demands of the heart are increased. This increase is met by increasing coronary blood flow rather than by increasing oxygen extraction from blood. (At rest, the oxygen extraction from blood is already high at 70%; also the heart’s ability to use anaerobic metabolism is limited). Coronary blood flow can increase about four to five fold during heavy exercise. This increment in blood flow is termed the coronary reserve.

6. If hypoxia develops in the myocardium, nociceptive fibers trigger the sensation of referred pain, known as angina pectoris • When energetic demand for ATP exceeds the O2 supply, it can no longer take up lactate, but releases lactate by breaking down it own glycogen stores and can continue to function for a short time • More severe or prolonged insults damage the myocardial tissue, which become necrotic (myocardial infarction)

7. Pressure gradient and blood flow in coronary vessels • The pressure inside LV is slightly  than in aorta during systole flow occurs in subendocardial portion of LV only during diastole, and this region is prone to ischemic damage (myocardial infarction) • Since diastole is shorter at high heart rate, LF coronary flow is reduced during tachycardia • Coronary flow to LV is  in stenotic aortic valves, when aortic diastolic pressure is low (congestive heart failure) • In exercise O2 demands  and are met by  coronary blood flow (up to ~ 90%) • The mechanism responsible for  flow is metabolic (active) hyperemia (autoregulation), and the substances responsible for the arteriolar vasodilation are adenosine, K+, H+ nd NO

8. Pressure in aorta and left and right ventricles (V) in systole and diastole

9. In exercise O2 demands  and are met by  coronary blood flow (up to ~ 90%) . • The mechanism responsible for  flow is metabolic (active) hyperemia (autoregulation), and the substances responsible for the arteriolar vasodilation are adenosine, K+, H+ and NO Coronary vessels are sympathetically innervated and norepinephrine acting via 1 receptors cause vasoconstriction. During exercise SNS  heart rate and stroke volume, but the vasoconstriction of the coronaries is offset by the metabolic hyperemia . • 2 receptors are also found and when activated by circulating epinephrine cause vasodilation (minor effect)

10. Fig. 3. Coronary blood flow cycle. Note (second panel) that blood may actually reverse transiently in early systole, as the force of left ventricle isovolumetric contraction compresses left coronary artery (when aortic valve is still closed)

11. Ischemic Heart Disease (IHD): Insufficient coronary blood flow, which leads to ischemia of the cardiac muscle • Most common cause is deposition of atheromatous plaques (deposits of cholesterol found beneath the endothelium) in the coronary arteries. The plaques become invadedby fibrous material and become calcified, protrude into the lumen and partially or completely block blood flow • Common site of atheromatous plaque development is the first few cm of major coronary arteries. The plaque can promote formation of a blood clot (a thrombus) where the plaque has broken through the endothelium, coming into contact with the flowing blood platelets adhere deposition of fibrin and entrapped RBC (clot formation) • Activated platelets release 5-HT and thromboxanes vasospasm

12. Activated platelets 5-HT and thromboxanes vasospasm • The degree of coronary impairment of BF is determined by the degree of collateral circulation that can develop after occlusion • The collateral circulation is made up of anastomoses between the smaller arteries • After an occlusion BF can be restored by development of collaterals (especially if the atheromatous process is slow) • When eventually the collaterals become atherosclerotic, the heart muscle becomes severely limited in ability to pump blood cardiac failure

13. Angina Pectoris • Ischemic cardiac muscle can cause pain, triggered by various algogenic substances (kinins, histamine, lactic acid) released from the damaged cells • When progressive constriction of the coronary arteries develop, cardiac pain (angina pectoris) appear whenever the O2 supply (coronary BF) does not meet O2 demand • The pain may be referred to the left arm, neck, face • Angina is first felt during exercise, can be triggered by stress, cold (the last two  sympathetic activity vasoconstriction) • Exercise-induced angina is die to  O2 demand, and angina at rest due to vasospasm is due to  O2 supply

14. 2. Cerebral Circulation Fig. 4. Vascular anatomy of the brain; Major arterial supply and circle of Willis

15. Fig. 5. Vascular anatomy of the brain: with the temporal lobe pulled away, depicts the major branches of the middle cerebral artery, one of the distributing arteries

16. The metabolic activity of the brain is high; it consumes ~ 18% of resting O2 consumption and receives ~ 14% of cardiac output • Unlike other organs the brain must have a constant supply of blood since it relies solely on blood glucose for energy requirements. It has no glycogen stores • Disruption of BF for a few seconds van lead to unconsciousness, and for a few minutes – to irreversible neuronal damage • The overall BF to the brain is kept fairly constant by autoregulation which operates between ~ 60-160 mm Hg.

17. The autoregulation in the brain cerebral vessels is achieved by metabolic hyperemia due to alterations in PCO2 and H+. The ANS has minimal effect on the cerebral circulation • The CSF is in effect an ultrafiltrate of plasma, with its composition modified by transport processes in endothelial cells and choroid epithelium • There are some differences in transport between the endothelial cells and the choroid epithelium, but they do not produce persistent local differences in the composition of CSF • There is active transport and facilitated diffusion both into and out of the brain

18. Fig. 6. Top: Transport across cerebral capillaries; Bottom: Transport across cells of the choroid plexus

19. Protective function • The meninges and the CSF protect the brain Fig. 7. Investing membranes of the brain, showing their relation to the skull and to brain tissue

20. The Blood-brain Barrier • The special features associated with the cerebral circulation is the blood-brain barrier formed by tight junctions between capillary endothelial cells. • Only water, CO2 and O2 diffuse readily across. The other plasma electrolytes require 3-30 times as long to equilibrate with spinal fluid as they do with other portions of the interstitial fluid • Glucose crosses slowly via facilitated diffusion • The blood-brain barrier protects the brain from abrupt changes in the composition of arterial blood • Proteins cross to a very limited extend; the amines dopamine and serotonin penetrate to a very limited degree

21. The circumventricular organs, which include the chemoreceptor trigger zone (CTZ), are outside the blood-brain barrier. This means that CTZ is able to respond (by triggering vomiting) to toxic chemicals in the systemic blood Fig. 8. Circumventricular organs. The neurohypophysis (NH), organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP) are shown projected on a sagittal section of the human brain (SCO, subcomissural organ; Pl, pineal)

22. 3. Pulmonary circulation • It is a low pressure – low resistance circuit and receives ALL the cardiac output • Major factor that alters the resistance of pulmonary blood vessels is hypoxia • In contrast to other tissues, hypoxia results in vasoconstriction • The advantage is that pulmonary BF will be directed to areas of the lung which are well ventilated (not hypoxic) and this will help to optimize the ventilation – perfusion match

23. 4. Skeletal Muscle Circulation • ~ 45% of body mass is skeletal muscle and its blood vessels are richly supplied by SNS vasoconstrictor nerves (acting via 1 receptors) which provide a degree of intrinsic tone of resistance vessels (this is the major determinant of TPR) • Skeletal muscle circulation helps to regulate blood pressure. If BP suddenly falls on standingsympathetic tone (Baroreceptor reflex) peripheral resistance and returning BP to normal values • During vigorous exercise 80% of CO may be delivered to skeletal muscle BF (from ~ 1 L/min to ~ 20 L/min) • CVS responses to exercise are described in details later

24. Fig. 9. Microvascular units in skeletal muscle. A. a feed artery branches into primary arterioles, which undergo several more branching; B. The terminal arteriole supplies a “microvascular unit” (, 1 mm in length)

25. Fig. 10. The muscle pump

26. 5. The Splanchnic circulation • It includes the blood flow through the stomach, small & large intestine, pancreas, spleen and liver. The majority of flow to liver occurs through the portal vein, which carries the venous blood draining from all of these organs except the liver itself • The vascular supply to the gut is highly interconnected • The liver receives BF from both the systemic and portal circulation • BF to the GIT increases up to 8-fold following a meal – “postprandial hyperemia”

27. Sympathetic activity directly constricts splanchnic vessels, whereas parasympathetic activity indirectly dilates them - Preganglionic vagal nerves contact postganglionic parasympathetic neurons in intestinal wall - Parasympathetic activity stimulates intestinal motility and glandular secretion intestinal metabolism, thereby enhancing BF to the gut • Changes in the splanchnic circulation (SC) regulate TPR and the distribution of blood volume - SC contains ~ 15% of total BV, with the majority contained in the liver. Sympathetic constriction of capacitance vessels rapidly mobilizes ~ half of this BV. - Splanchnic arteriolar constriction  perfusion passive collapse of veins - Blood contained in these veins moves in inferior vena cava, thus increasing the circulating blood volume maintain arterial pressure

28. Exercise and hemorrhage can substantially reduce splanchnic blood flow • Portal hypertension - The cirrhotic liver is hard, shrunken, scarred, and laced with thick bands of fibrotic tissue - The scarring  resistance to BF and portal venous pressure  portal hypertension -  portal venous pressure pressure in splanchnic capillaries. The Starling forces promote the filtration and extravasation of fluid abdominal edema (ascites) - With progression, portal blood begins to flow and dilate the portal anastomoses with systemic veins (lower esophagus, umbilicus, rectum) dilation and development of esophageal varices which can burst and cause life-threatening hemorrhage

29. Fig. 11. Splanchnic circulation: major vessels and mesenteric arteries

30. Fig. 12. Splanchnic circulation: (C) Blood supply to layers of intestinal wall and (D) Microvasculature of the villus

31. 6. Cutaneous circulation • The skin has relatively constant metabolic rate, and its O2 needs are met by a relatively low blood flow, which is under the control of the sympathetic nervous system which causes vasoconstriction • The skin has many arterio-venous anastomoses and is an important site for temperature regulation. An increase in core t0 causes a reduction in sympathetic tone and cutaneous vasodilation, and vice versa • The epidermis does not have a blood supply. Venules near the epidermal border may contain a lot of blood (pinkish color of the skin). A fall in blood flow causes pallor

32. Fig. 13. Cutaneous blood vessels