Regional Circulation (pulmonary, skin, muscle, cerebral, splanchnic) Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology, Faculty of Medicine, Masaryk University > 1 1/3 CT egional Circulation • an organ may be supplied by two blood inflows: - the nutrient circulation - the functional circulation • various ways of anatomical and functional adaptation of an organ-specific circulation to provide the optimal function of the organ • varying impact of particular ways of regulation of the blood flow (~ vasal tone) in various oraans ^ ulmonary Circulation /IV ulmonary Circulation • Blood flow through lungs is virtually equal to the blood flow through all other organs. • Functions: - provide the gas exchange - blood reservoir - mechanical, chemical and immunological filter ulmonary Circulation • Arteries (differences compared to the arteries in the systemic circulation) - bigger total cross-section of all pulmonary arteries - smaller thickness of the vessel walls - arterioles have a thin muscle layer lower resistance (1/10 of the resistance in systemic circulation; the smallest during a mild inspiration), lower decrease of blood pressure in this part of bloodstream - high compliance 0 12 3 4 Time (s) Ganong's Review of Medical Physiology, 23rd edition ulmonary Circulation Capillaries - wide, abundant anastomoses form a net surrounding alveoles - time Of passage -0.75 S (gas exchange) - area of perfused capillaries: at rest -60 m2 at intensive exertion -90 m2 Veins - high compliance (blood reservoir, autoregulatory mechanism at maintaining the blood pressure during orthostasis - in lying position, about 400 ml of blood moves to lungs -> i vital capacity) - failure of the left heart -» ortopnoe http://www.percussionaire.com/ historyreview.asp ulmonary Circulation Nutrient circulation - aa. bronchiales, vv. bronchiales, vv. pulmonales (physiological arteriovenous shunt + part of blood from coronary capillaries ->• saturation of blood with oxygen in Pulmonary artery Pulmonary vein the systemic circulation 98%, the stroke volume in the left ventricle by 1-2% bigger than in the right ventricle) Bronchopulmonary arterial anastomosis \ Bronchial artery Bronchopulmonary vein Bronchial vein xAzygosvein Ganong's Review of Medical Physiology, 23rd edition Lymphatic vessels - fast transport of proteins and various particles from the peribronchial and perivascular tissue -> I formation of the tissue fluid ~ prevention of the pulmonary edema ulmonary Circulation Blood pressure in the pulmonary bloodstream - pressure in a. pulmonalis (mmHg) 24 \ 0 (s) pressure in pulmonary capillaries - measured as the pulmonary artery wedge pressure (-7.5 mmHg) pressure in pulmonary veins pulsates between 1 and §, mmHg (as the pressure in left atrium) ^^^^ cT ulmonary Circulation • Factors affecting the fluid filtration into intersticium: Minimal filtration in pulmonary capillaries physiologically! 1. pressures in intersticium and pulmonary capillaries capillary pressure about 10 mmHg, oncotic pressure 13 mmHg 2. permeability of pulmonary capillaries • Pulmonary edema inhibits effective gas exchange. Regulation of blood flow in lungs A. Systemic mechanisms B. Local mechanisms ulmonary Circulation Regulation of blood flow in lungs A. Systemic mechanisms 1) Neural regulation - sympathetic nerve fibers through rec. - vasoconstriction (small impact on resistance, i.e. pressure, but decrease capacity of the lung bloodstream, -empty lung blood reservoir) through relaxation - no) 2) Humoral regulation (circulating substances) vasoconstriction: adenosine (A^, endothelin (ETA), angiotensine IJ vasodilation: adenosine (A2), endothelin (ETB), histamine (H^hj^ 7p, -^sr ^ ulmonary Circulation • Regulation of blood flow in lungs B. Local mechanisms - chemical (metabolic) autoregulation opposite reaction compared to systemic circulation (I p02 - also systemic hypoxia, t pC02,1 pH , histamine -> vasoconstriction -> deviation of perfusion from the non-ventilated alveoli within 5-10 min) unknown mechanism, key role likely playes surrounding lung tissue, maybe degranulation of basofile granulocytes releasing vasoactive substances (namely histamine) works also in opposite way: obstruction of perfusion in a part of lungs -> I pC02 -> constriction of influent bronchus to provide optimal ratio of ventilation/perfusion) ulmonary Circulation • Regulation of blood flow in lungs C. Passive factors - cardiac output physical exertion t cardiac output -> saturation of haemoglobin is stable, opening of so far non-perfused capillaries -» t blood flow through lungs and total amount of 02 delivered to body - gravity ulmonary Circulation Blood distribution in lungs - gravity - irregular due to action of the hydrostatic pressure - pulmonary apexes - about 15 cm above the orificium of a. pulmonalis, hydrostatic and arterial pressure is approx. equal -» minimal blood flow - blood flow increases from apex to base in a linear way - T total blood flow (e.g. physical exertion) ~ equivalent t flow through individual regions apex báze ulmonary Circulation Blood distribution in lungs - gravity - irregular due to action of the hydrostatic pressure - pulmonary apexes - about 15 cm above the orificium of a. pulmonalis, hydrostatic and arterial pressure is approx. equal -» minimal blood flow - blood flow increases from apex to base in a linear way - intensive physical exertion t cardiac output even 6times -> opening of so far unperfused capillaries -> pressure in a. pulmonalis increased only slightly (decreased work of the right heart + prevention of formation of the pulmonary edema due to increased capillary pressure) ulmonary Circulation At apex Intrapleural pressure more negative Greater transmural pressure Large alveoli Lower intravascular pressure Less blood flow So less ventilation and perfusion Ventilation / perfusion 50 V o o O- v ^— Decreasing VA./Q Normal Increasing VA/Q 50 100 Po2 (mm Hg) 150 Ganong's Review of Medical Physiology, 23rd edition Z ulmonary Circulation Defective ratio of ventilation and perfusion - most often cause of hypoxic hypoxia in clinical practise blood flow through non-ventilated alveoli ->• right-left shunt (deoxygenated blood directly to the left heart) ->• I arterial blood saturation with 02 Ventilation / perfusion Q3 I E E: 50 - A - lo V ^— Decreasing VA/Q Increasing VA/Q 0 50 100 Po2 (mm Hg) content of C02 usually not changed (compensatory hyperventilation in other alveoles) 150 z erebral Circulation erebral Circulation TABLE 34-1 Resting blood flow and 02 consumption of various organs in a 63-kg adult man with a mean arterial blood pressure of 90 mm Hg and an 02 consumption of 250 mL/min. Blood Flow Arteriovenous Oxygen Consumption Resistance (R units}3 Percentage of Total Region Mass (kg) mL/min mL/100 g/min uxygen Difference (mL/L) mL/min mL/100 g/min Absolute per kg Cardiac Output Oxygen Consumption Liver 2.6 1500 57.7 34 51 2.0 3.6 9.4 27.8 20.4 Kidneys 0.3 1260 420.0 14 18 6.0 4.3 1.3 23.3 7.2 Brain 1.4 750 54.0 62 46 3.3 7.2 10.1 13.9 18.4 Skin 3.6 462 12.8 25 12 0.3 11.7 42.1 8,6 4.8 Skeletal muscle 31.0 840 2.7 60 50 0.2 6.4 198.4 15.6 20.0 Heart muscle 0.3 250 84.0 114 29 9,7 21.4 6,4 4.7 11.6 Rest of body 23.8 336 1.4 129 44 0.2 16.1 383.2 6.2 17.6 Whole body 63.0 5400 8.6 46 250 0.4 1,0 63.0 100.0 100,0 aR units are pressure (mm Hg) divided by blood flow [mlVs). Reproduced with permission from Bard P (editor!: Medical Physiology, 11th ed. Mos by, 1961, Ganong's Review of Medical Physiology, 23rd edition erebral Circulation provides: 1) constant sufficient blood supply intensive oxidative metabolism of the grey matter (40% of the brain matter), is metabolically more active - the grey matter is very sensitive to hypoxia ! (black-out during several seconds of the brain ischemia, irreversible damage during several minutes) 2) dynamic blood redistribution neuronal activity and, thus, the rate of metabolism of particular regions of the grey matter notably varies (metabolic hyperaemia) http://observatory.cz/static/vystavy/castice/p2_PET-tomogram.jpg erebral Circulation • provides: 1) constant sufficient blood supply 2) dynamic blood redistribution Cover of these specific demands of brain, namely of its grey matter, requires both anatomical and functional adaptation of the cerebral circulation. Anatomical specialities of cerebral circulation: 7) circulus arteriosus cerebri (interconnection of main cerebral arteries by anastomoses) 2) very high density of capillaries (3000 - 4000 capillaries / mm2 od the grey matter) ~ minimalization of diffuse distance for gases and other substances 3) very short arteriols (almost 1/2 of the vasal resistance falls on arteries which are abundantly innervated) erebral Circulation Functional adaptation of cerebral circulation: 1) high and Stable blood flow (grey matter: 1 l/kg/min) 2) high 02 extraction (35%) 3) Well developed aUtOregulation (myogenic and metabolic) 100 o 50 I sympathetic system 70 140 Arterial pressure (mm Hg) Ganong's Review of Medical Physiology, 23rd edition z erebral Circulation Functional adaptation of cerebral circulation: 1 2 3 4 high and Stable blood flow (grey matter: 1 l/kg/min) high 02 extraction (35%) well developed autoregulation (myogenic and metabolic) high reactivity on changes of C02 concentration local vs. total hypoxia innervation sympathetic vasoconstr. fibers (norepinephrine, neuropeptide Y) parasympathetic cholinergic fibers (acetylcholine, VIP) sensoric fibers (substance P, CGRP; migraine headache) erebral Circulation • Special physical conditions of cerebral circulation: 1) solid cover of brain by skull Ultimate value of actual blood volume in brain, of cerebral tissue and liquor is constant (Monro-Keiii theory). ->• flow may be increased only by acceleration of the blood flow, not by an increase of capacity of the bloodstream ->• Cushing reflex (tumour, bleeding) 2) gravity orthostatic reaction (lower central venous pressure + decreased stroke volume -» hypotension -» postural^ syncope) fXf) erebral Circulation • Blood-brain barrier cerebral capillaries - tight inter-endothelial connections erebral Circulation • Blood-brain barrier By free diffusion: lipophilic substances (02, C02, xenon; unbound forms of steroid hormones) water (aquaporins; osmolality of blood and cerebrospinal fluid is identical!) -» glucose - the main source of energy for neurons (free diffusion would be slow - accelerated by GLUT) By transcellular transport (regulated): ->ions {e.g. H+, HCO3" vs. C02 !) -» transporters for thyroid hormones, some organic acids, choline, precursors of nucleic acids, aminoacids, ... Blood-brain barrier Many drugs and peptides pass the capillary wall as well but they are immediately transported back to the blood by a nonspecific transporter - glycoprotein P located in apical membranes of endothelial cells. Functions: - maintenance of constant composition of the neuron environment - protection of brain against endogenic and exogenic toxins - prevention of loss of neurotransmitters to the bloodstream d erebral Circulation Cerebrospinal fluid - fills the brain chambers and subarachnoidal space - volume -150 ml, rate of production -550 ml/d (exchange 3.7times/day) Cerebrospinal fluid is constantly of a composition different from plasma. Substance CSF Plasma Ratio CSF/Plasma Na+ (meq/kg H20) 147.0 150.0 0.98 K+ (meq/kg H20) 2.9 4.6 0.62 Mg2+ (meq/kg H20) 2.2 1.6 1.39 Ca2+ (meq/kg H20) 2.3 4.7 0.49 cr (meq/kg H20) 113.0 99,0 1.14 HCO3- (meq/L) 25.1 24.8 1.01 Pco2 (mm Hg) 50.2 39.5 1.28 pH 7.33 7.40 Osmolality (mosm/kg H20) 289.0 289.0 1.00 Protein (mg/dL) 20.0 6000.0 0.003 Glucose (mg/dL) 64.0 100.0 0.64 Inorganic P (mg/dL) 3.4 4.7 0.73 Urea (mg/dL) 12.0 15.0 0.80 Creatinine (mg/dL) 1.5 1.2 1.25 Uric acid (mg/dL) 1.5 5,0 0.30 Cholesterol (mg/dL) 0.2 175.0 0.001 Ganong's Review of Medical Physiology, 23rd edition erebral Circulation Cerebrospinal fluid Function: - protection of brain (together with menanges) Ganong's Review of Medical Physiology, 23rd edition Outer table of skull Trabecular bone Inner table of skull Dura mater Subdural (potential) space Arachnoid Subarachnoid space Arachnoid trabeculae Artery Pia mater Perivascular spaces Brain z erebral Circulation Cerebrospinal fluid 68 100 112 200 Outflow pressure (mm CSF) Ganong's Review of Medical Physiology, 23rd edition As/ z Paraventricular organs ~ brain regions where the blood-brain barrier is missing (fenestrated capillaries) - neurohypophysis + neighbouring ventral part of eminentia medialis - area postrema (AP) - organum vasculosum laminae termmahs (OVLT) Ganong's Review of Medical - subfornical organ (SFO) Physiology, 23rd edition Regions secreting polypeptides into the bloodstream (oxytocin, vasopressin, hypothalamic hormones), chemoreceptive zones (AP), osmoreceptive zones (OVLT). • Measurement of cerebral blood flow Kety method - Fick principle, method of indicatory gas - nitrous oxide N20 N20 concentration in the venous blood ( ^ ^ N20 removed from blood by brain / time cerebral blood flow =- average arteriovenous difference of N20 \_) average blood flow through all perfused regions! erebral Circulation • Measurement of cerebral blood flow - regional PET (positron emission tomography) - a substance labelled by radionuclides with a short half time - the substance is injected, the increase and following decrease of its concentration is evaluated by scintillation detectors placed around the head - e.g. labelled 2-deoxyglucose - its consumption is a good indicator of the flow erebral Circulation • Measurement of cerebral blood flow - regional PET (positron emission tomography) - a substance labelled by radionuclides with a short half time - the substance is injected, the increase and following decrease of its concentration is evaluated by scintillation detectors placed around the head - e.g. labelled 2-deoxyglucose - its consumption is a good indicator of the flow fMRI (functional magnetic resonance) - better resolution - reduced haemoglobin becomes paramagnetic, change the signal emitted by blood, we can measure the amount of oxy-and deoxyhaemoglobin as an indicator of the blood flow #\/|y\ Splanchnic Circulation InfflfKjf wna c«~iva THORACIC AORTA Cefcac Hepatic Jrtfrfy prcosr ._ CySttc Common rwpat>c Gnsfcxl ..«tor.il ROI a&ilnc Rigru gasiroeppioic Superior me-senteric Supenor paiťoaiiCi-3 /Korji Duixfeii.il Middle coin: ľ jtl Ii.n-1 ::- pancra^iiraduDdiKial R^t; cole iieocoic Inlotfirvil Right «xlernul i ß rec. ->• vasoconstriction (during defense reaction, blood diverted from GIT to ^ muscles and heart by vasoconstriction) fVf planchnic Circulation • Intestinal circulation (a. coeliaca, a. mesenterica superior and inferior) • Regulation of blood flow: - metabolic vasodilation (mediators: adenosine, j [K+]e and t osmolarity) - neural regulation - almost exclusively sympathicus, a > (3 rec. ->• vasoconstriction During ischemia, the metabolic vasodilation will be present regardless of vasoconstrictory action of sympathetic system (the so called autoregulatory escape). • Hepatic circulation (v. portae, a. hepatica) • 25% of the cardiac output (~1.5 l/min) - % v. portae, Va a. hepatica • portal circulation - 2 capillary bloodstreams in series: 1) in intestinal villi - resorption of water-soluble substances from the intestine 2) in liver sinusoids - high permeability (large gaps between endothelial cells), also for proteins synthesized in liver and released to circulationfyf^\ • Hepatic circulation (v. portae, a. hepatica) • 25% of the cardiac output (~1.5 l/min) - % v. portae, Va a. hepatica • portal circulation - 2 capillary bloodstreams in series: • the portal blood which has already passed the first capillary bloodstream in the intestine has I 02 content a. hepatica represents the nutrition hepatic circulation (interrupted blood flow lethal liver necrosis) Regarding 02 supply, the ratio is opposite! Sinusoids planchnic Circulation Hepatic circulation {v. portae, a. hepatica) terminal portal venules and hepatic arteriols empty into a net of sinusoids in liver lobuli, the mixed blood leaves lobuli through the central vein Bile canal iculi Biie duct Branch of the hepatic artery Branch of the portal vein functional unit - acinus Ganong's Review of Medical Physiology, 23rd edition Central vein ^r. ~\^- planchnic Circulation Hepatic circulation (v. portae, a. hepatica) pressures different from other tissues: - a. hepatica: 90 mmHg - v. hepatica: 5 mmHg - v. portae: 10 mmHg - sinusoids: 2.25 mmHg (big pressure reduction due to high resistance in branches of a. hepatica) Pressure in sinusoids below pressure in v. portae\ Sinusoids Bile canal iculi Biie duct Branch of the hepatic artery Branch of the portal vein Ganong's Review of Medical Physiology, 23rd edition Central vein z planchnic Circulation • Hepatic circulation (v. portae, a. hepatica) • due to sudden pressure I in a. hepatica -» inverse regulation of blood flow in v. portae and a. hepatica: - between meals: many sinusoids collapsed, flow in v. portae low, adenosine formed constantly and washed less -> dilation of terminal hepatic arterioles - after a meal: flow in v. portae t, adenosine washed faster -»• constriction of hepatic arterioles, higher flow in v. portae also opens so far collapsed sinusoids -> pressure in v. portae does not t too much (protection against fluid loss in highly permeable liver tissue) • increased hepatic pressure (cirhosis) -» ascites!X|aj • Hepatic circulation (v. portae, a. hepatica) • Regulation of blood flow: - neural: sympathetic vasoconstrictive fibers - a rec. -> vasoconstriction - metabolic: adenosine -» vasodilation - passive: t BP -» passive dilation of portal vein radicles -» t l'ver blood amount congestive heart failure -»• extreme venous congestion diffuse noradrenergic discharge due to [ BP -» constriction of portal vein radicles ->• t portal pressure -> blood flow bypasses most of liver and enters 4 systemic circulation planchnic Circulation • Hepatic circulation (v. portae, a. hepatica) • flow in a. hepatica and in v. portae are complementary - reciprocal compensation of changes but incomplete due to different way of autoregulation: - a. hepatica - ability of autoregulation - v. portae - not able to autoregulate • sufficient 02supply is essential for liver function! -1 flow -> | 02 extraction (reserve for \ 02 extraction - anatomical setting of hepatic circulation, arteries and veins distant no l of ^js\ arterial 02 by countercurrent exchange) planchnic Circulation • Hepatic circulation (v. portae, a. hepatica) • hepatic lymphatic circulation - formation of almost % of the body lymph - lymph rich on proteins (many plasmatic proteins are formed in hepatocytes + proteins from plasma due to the high permeability of sinusoids) in Circulation in Circulation • Skin blood flow considerably varies (0.02-5 l/min). • Regulation of skin blood flow: - Sympathetic nerve fibers - Humoral - local factors (histamine -> vasodilation, Serotonine -> vasoconstriction) Metabolie demands of skin - small (decubitus) - warm supply from the core (dependent on blood inflow) - warm loss (conduction, convection, radiation, evaporation) Poikilothermie tissue (toleration of strong warm fluctuation, 0 - 45°C) Arteriovenous anastomoses Protection against environment Maintenance of mean blood pressure Maintenance of body temperature Arteriovenous anastomoses - specific structural adaptation - convoluted muscle vessels directly connecting arteriols and venules (low-resistance shunt) capillaries Honzíkova N - Poznámky k přednáškám z fysiologie (1992) - regulated by sympathetic vasoconstrictive nerve fibers (their activity regulated by the centre for thermoregulation located in hypothalamus) (Vf • Reaction on a temperature change: 1) direct impact of a temperature change on the vessel tone 2) excitation of skin thermoreceptors 3) excitation of thermoreceptors in brain reflex modulation of sympathetic vasoconstrictive activity in Circulation Axon reflex Spinal cord Sensory neuron \ \ \ i-\ \ ■* Orthodromic conduction ■> Antidromic conduction ■*■ Direction taken by impulses Endings in skin Endings near arteriole Ganong's Review of Medical Physiology, 23rd edition, .ŕ z uscle Circulation unstimulated muscle regularly stimulated muscle Guyton and Hall. Textbook of Medical Physiology, 12th edition uscle Circulation • Function: 1) Blood supply of muscles 02 and nutrients supply, namely glucose wash of metabolites (C02) and metabolic heat the resting blood flow - 18% of the cardiac output vs. even 90% at intensive exertion (the local blood flow f even 20times; opening of capillaries closed at rest) 2) Regulation of blood pressure skeletal muscles - 40% of the body weight ->• resistance of the muscle bloodstream has a high impact on the total peripheral resistance uscle Circulation • The blood flow during muscle activity is intermittent. Minutes Guyton and Hall. Textbook of Medical Physiology, 11th edition fy?Sf\ uscle Circulation • The blood flow during muscle activity is intermittent. • During the tetanical contraction, the blood flow may be almost stopped. 02 content in myoglobin is sufficient for about 5-s to 10-s lasting ischemia. Anaerobic glycolysis follows, lactate is formed and cumulates (fatique, pain). • Muscle pump (massage of the deep veins during contractions, increase of the venous return) uscle Circulation • Regulation of the muscle blood flow: 1) Neural regulation dominates at rest 2) Local chemical regulation dominates at physical exertion uscle Circulation • Regulation of the muscle blood flow: 1) Neural regulation dominates at rest rich innervation by tonic active sympathetic vasoconstrictive fibers (norepinephrine) -> high tone of arteriols at rest ~ big dilation reserve activity regulated from baroreceptors (baroreflex) -noted impact on regulation of total peripheral resistance (orthostasis, hypovolaemia -> j flow even to only 1/5 of the resting norepinephrine - at low dose vasodilation (baroreceptors), at high doses vasoconstriction (a receptors) flow) epinephrine - vasodilation (more (3 receptors) uscle Circulation • Regulation of the muscle blood flow: 1) Neural regulation dominates at rest sympathetic cholinergic vasodilatory fibers (resistant vessels in muscles and skin) ->• f flow even before the start of muscle activity ~ anticipation of the muscle activity during the stress reaction (+ vasoconstriction in other locations - prevention of sudden drop of the blood pressure) uscle Circulation • Regulation of the muscle blood flow: 2) Local chemical regulation dominates at physical exertion release of K+ from contracting muscles ->• t concentration of K+ in intersticium + t osmolarity (also lactate) + i p02 (and nutrients) + t pC02 + l pH (also lactate) -> metabolic vasodilation almost linear increase of the flow with increasing metabolic activity uscle Circulation • Sufficient release of energy for the muscle activity is dependent on: 1) increased blood flow (-increased 02 supply) 2) increased 02 extraction (from 25 to 80%) uscle Circulation • Anaerobic glycolysis The amount of formed lactate is proportional to 02 deficiency (oxygen debt). lactate -» acidosis -» metabolic vasodilation + pain (nociceptive C fibers) - the pain terminates the intensive muscle load hyperaemia persists after the end of muscle work^ lactate washed and mostly metabolized in liver to glycogen + primary source of energy for the heart uscle Circulation • Local vasodilation in contracting muscles -> t blood flow -» t capillary pressure + t osmolarity (K+, lactate) -> t filtration ->• edema in contraction muscles