Regional Circulations (pulmonary, skin, muscle, cerebral, splanchnic, renal, fetal, coronary) Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology, Faculty of Medicine, Masaryk University This presentation includes only the most important terms and facts. Its content by itself is not a sufficient source of information required to pass the Physiology exam. Regional 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 organs ^ Pulmonary Circulation Pulmonary 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 Pulmonary 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 - high compliance Capillaries - wide, abundant anastomoses form a net surrounding alveoles - time of passage, area of perfused capillaries at rest and intensive exertion Veins - high compliance (blood reservoir, ortopnoe) Blood pressure in pulmonary circulation Pulmonary Circulation Nutrient circulation - physiological arteriovenous shunt Pulmonary artery Pulmonary vein Bronchial artery Bronchial vein Azygos vein 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 No filtration in pulmonary capillaries physiologically! 1. pressures in intersticium and pulmonary capillaries 2. permeability of pulmonary capillaries 'fir/15 Pulmonary Circulation Regulation of blood flow in lungs A. Systemic mechanisms 1) Neural regulation (sympathicus, parasympathicus) 2) Humoral regulation (circulating substances) B. Local mechanisms - chemical (metabolic) autoregulation opposite reaction compared to systemic circulation (vasoconstriction) C. Passive factors - cardiac output ^ - gravity (blood distribution in lungs) Pulmonary Circulation Ratio of ventilation and perfusion - kept constant (local metabolic autoregulation) non-ventilated alveolus - vasoconstriction non-perfused alveolus - bronchoconstriction decreased ratio -most often cause of hypoxic hypoxia in clinical practise fright-left shunt) -» I arterial blood saturation with On X E 50 E CM O Ü A V Ganong's Review of Medical Physiology, 23rd edition Decreasing VA/Q Norma, Increasing VA/Q 50 100 Po2 (mm Hg) 150 content of C02 usually not changed (compensatory hyperventilation in other alveoles) Mr Skin Circulation Skin Circulation • Skin blood flow considerably varies (0.02-5 l/min). Function: • Metabolic demands of skin - small (decubitus) Maintenance of body temperature Poikilothermie tissue Arteriovenous anastomoses Protection against environment Maintenance of mean blood pressure Skin Circulation Arteriovenous anastomoses - convoluted muscle vessels directly connecting arteriols and venules (low-resistance shunt) Honzíkova N - Poznámky k přednáškám z fysiologie (1992) - regulated by sympathetic vasoconstrictive nerve fibers Skin Circulation Regulation of skin blood flow: - Sympathetic nerve fibers - Humoral - local factors (histamine, Serotonine) . **** it. • 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 Skin Circulation reflex near arteriole Ganong's Review of Medical Physiology, 23rd edition. Muscle Circulation Muscle Circulation Function: 1) Blood supply of muscles the resting blood flow - 18% of the cardiac output vs. even 90% at intensive exertion (the local blood flow f even 20times) 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 The blood flow during muscle activity is intermittent, during the tetanic contraction even zero (oxygen debt). Muscle Circulation Regulation of the muscle blood flow: 1) Neural regulation dominates at rest (vasocontriction through sympathicus big dilation reserve) 2) Local chemical regulation dominates at physical exertion (metabolic vasodilation) almost linear increase of the flow with increasing metabolic activity increased blood flow + increased 02 extraction t capillary pressure + t osmolarity -> t filtration edema in active muscles Cerebral Circulation Cerebral 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)4 Percentage of Total Region Mass (kg) mL/min mL/100 g/min uxygen Difference (mL/L) mL/100 mL/min 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 3R units are pressure (mm Hg) divided by blood flow (mL/s). Reproduced with permission from Bard P (editor): Medical Physiology, 1 Ith ed. Mosby, 1961. Ganong's Review of Medical Physiology, 23rd edition Cerebral Circulation provides: 1) constant sufficient blood supply (black-out during several seconds of the brain ischemia, irreversible damage during several minutes) 2) dynamic blood redistribution (metabolic hyperaemia) Cerebral Circulation Anatomical specialities of cerebral circulation: 1) 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) Cerebral Circulation • Functional adaptation of cerebral circulation: 1) high and stable blood flow 2) high 02 extraction 3) well developed autoregulation (myogenic and metabolic) 4) high reactivity on changes of C02 concentration 5) local vs. total hypoxia 6) innervation Cerebral Circulation sympathetic system 70 140 Arterial pressure (mm Hg) Ganong's Review of Medical Physiology, 23rd edition. Cerebral Circulation Special physical conditions of cerebral circulation: 1) solid cover of brain by skull Monro-Kelli theory -» flow may be increased only by acceleration of the blood flow, not by an increase of capacity of the bloodstream -» Cushing reflex 2) gravity orthostatic reaction (postural syncope) Cerebral Circulation Blood-brain barrier cerebral capillaries - tight inter-endothelial connections Nucleus v Mitochondrion Glucose, etc Tight junction Ganong's Review of Medical Physiology, 23rd edition • 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, ... Cerebral Circulation Blood-brain barrier 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 Cerebral Circulation Cerebrospinal fluid - localization - composition - volume-150 ml, rate of production -550 ml/d (exchange 3.7times/day) 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 PC02 (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 Cerebral Circulation Cerebrospinal fluid Function: - protection of brain (together with menanges) 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 Ganong's Review of Medical Physiology, 23rd edition Cerebral Circulation Cerebrospinal fluid 1.6 _ 1.2 c 'E E, 0.8 o 0.4 0 0 68 100 112 200 Outflow pressure (mm CSF) Ganong's Review of Medical Physiology, 23rd edition Cerebral Circulation Paraventricular organs - brain regions where the blood-brain barrier is missing (fenestrated capillaries) - secretion of polypeptides (oxytocin, vasopressin, ...), - chemoreceptive zones (AP) - osmoreceptive zones (OVLT) Ganong's Review of Medical Physiology, 23rd edition Cerebral Circulation Measurement of cerebral blood flow Kety method - Fick principle, method of indicatory gas nitrous oxide N20 N20 concentration in the venous blood r cerebral blood flow = N20 removed from blood by brain / time average arteriovenous difference of N20 -> average blood flow through all perfused regions! Cerebral Circulation Measurement of cerebral blood flow - regional PET (positron emission tomography) fMRI (functional magnetic resonance) Splanchnic Circulation Splanchnic Circulation blood flow through GIT including liver and pancreas blood flow through spleen Main functional roles: - metabolic function of GIT - blood reservoir - special (e.g. spleen - removal and degradation of old/altered erythrocytes) y Splanchnic Circulation Blood reservoir at rest -20% of the total blood volume rich innervation with sympathetic vasoconstrictive fibers - a rec. (even 350 ml of the blood emptied into the systemic circulation during several minutes!) Splanchnic Circulation Intestinal circulation (a. coeliaca, a. mesenterica superior and inferior) submucous plexus, branches enter musculature and intestinal villi countercurrent exchange of substances Villus Simple columnar epithelium Lacteal Capillary network Goblet cells Venule Ganong's Review of Medical Physiology, 23rd edition Splanchnic Circulation • Intestinal circulation (a. coeliaca, a. mesenterica superior and inferior) • Regulation of blood flow: - metabolic vasodilation (mediators: adenosine, j [K+]e and | osmolarity) - neural regulation - almost exclusively sympathicus, a > ß rec. vasoconstriction Splanchnic Circulation Hepatic circulation (v. portae, a. hepatica) 25% of the cardiac output (-1.5 l/min) - 3A v. portae, % a. hepatica Regarding 02 supply, the ratio is opposite! portal circulation - 2 capillary bloodstreams in series (intestinal villi, liver sinusoids) - I 02 content -> a. hepatica represents the nutritive hepatic circulation Splanchnic Circulation Hepatic circulation (v. portae, a. hepatica) Sinusoids Branch of the portal vein Ganong's Review of Medical Physiology, 23rd edition Splanchnic Circulation Hepatic circulation (v. portae, a. hepatica) Sinusoids pressures: - a. hepatica: - v. hepatica: - v. portae: - sinusoids: Bile canaliculi 90 mmHg 5 mmHg 10 mmHg 2.25 mmHg Bile duct Branch of the hepatic artery Branch of the portal vein Ganong's Review of Medical Physiology, 23rd edition Splanchnic Circulation Hepatic circulation (v. portae, 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 |, adenosine washed faster -» constriction of hepatic arterioles, higher flow in v. portae opens so far collapsed sinusoids increased hepatic pressure (cirhosis) -> ascites Splanchnic Circulation Hepatic circulation (v. portae, a. hepatica) Regulation of blood flow: - neural: symp. vasoconstrictive fibers - a rec. - metabolic: adenosine -> vasodilation - passive: | BP -» passive dilation of portal vein radicles -> | liver blood amount congestive heart failure diffuse noradrenergic discharge due to I BP sufficient 02 supply is essential for liver function! -1 flow -> t 02 extraction Splanchnic Circulation • Hepatic circulation (v. portae, a. hepatica) • hepatic lymphatic circulation - formation of almost 3A 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) Renal Circulation Renal Circulation main functions of kidneys High filtration rate requires an adequate blood supply! - kidneys form only -0.4 % of the body weight - blood flow 1.2 l/min, -25% of cardiac output distribution of blood flow is irregular, the most flows through cortex (glomeruli - filtration) Renal Circulation Cortical radiate vein Cortical radiate artery Arcuate vein Arcuate artery Interlobar vein Interlobar artery Segmental arteries Renal vein Renal artery Renal pelvis Ureter Renal medulla Renal cortex Aorta i Renal artery Segmental artery Interlobar artery I Arcuate artery I Cortical radiate artery I Afferent arteriole L Inferior vena cava í Renal vein í Interlobar vein -*■ Arcuate vein Cortical radiate vein 4- Peritubular capillaries i ■or vasa recta í Efferent arteriole Glomerulus (capillaries) J (a) Frontal section illustrating major blood vessels O2013 Rtwion Eduutan. me. Nephron-associated blood vessels (see Figure 25.7) (b) Path of blood flow through renal blood vessels http://classes.midlandstech.edu/carterp/Courses/bio211/chap25/chap25.htm © 2013 Pearson Education, lne http://classes.midlandstech.edu/carterp/Courses/bio211/chap25/chap25.htm r v. aff., v. eff. glomerular blood flow = P - P 1 v.a. 1 v.e. Guyton & Hall. Textbook of Medical Physiology Rv.a. + Rv.e. + t resistance in vas aff. or vas eff. I the renal blood flow (if the arterial pressure is stable) regulate the glomerular filtration pressure:_ constriction of vas aff. i glomerular pressure i filtration constriction of vas eff. t glomerular pressure -» t filtration Renal Circulation • Regulation of renal blood flow: 1) Myogenic autoregulation 2) Neural regulation 3) Humoral regulation Renal Circulation Regulation of renal blood flow: 1) Myogenic autoregulation - dominates - provides stable renal filtration activity by maintaining stable blood flow at varying systemic blood pressure Renal Circulation • Regulation of renal blood flow: 2) Neural regulation - conformed to demands of systemic circulation - sympathetic system - norepinephrine light exertion/upright body posture ->• t sympathetic tone -> t tone of v. aff. and eff. ->■ I renal blood flow but without 4 GFR (t FF) higher t of sympathetic tone - during anesthesia and pain - GFR may already i Renal Circulation • Regulation of renal blood flow: 3) Humoral Regulation - contribute to regulation of systemic BP and regulation of body fluids - NE, E (from the adrenal medulla) constriction of aff. and eff. arterioles -» i renal blood flow and GFR (small impact with the exception of serious conditions, for example serious bleeding) Renal Circulation • Regulation of renal blood flow: 3) Humoral Regulation - contribute to regulation of systemic BP and regulation of body fluids - endothelin constriction of aff. and eff. arterioles -» i renal blood flow and GFR released locally from the impaired endothel (physiological impact - hemostasis; pathologically increased levels at the toxemia of pregnancy, acute renal failure, chronic uremia) Renal Circulation * Regulation of renal blood flow: 3) Humoral Regulation - contribute to regulation of systemic BP and regulation of body fluids - NO continual basal production vasodilation stable renal blood flow and GFR - prostanglandins (PGE2, PGI2), bradykinin -» vasodilation minor impact under physiological conditions non-steroidal anti-inflammatory agents during stress! Renal Circulation Regulation of renal blood flow: 3) Humoral regulation - contribute to regulation of systemic BP and regulation of body fluids - Renin-angiotensine <*»»«*■ system Ganong's Review of Medical Physiology, 23rd edition Juxtaglomerular cells Afferent arteriole Renal Circulation Renin-angiotensine system l Na+ in plasma Juxtaglomerular apparatus I BP ^ t sympathetic activity ((3 rec.)' Angiotensinogen <- I- Renin Angiotensin I I- Angiotensin II Angiotensin- Increased renal arterial mean pressure, decreased discharge of renal nerves Increased extracellular fluid volume converting enzyme Aldosterone vasoconstriction thirst, ADH Adrenal cortex Decreased Na+ (and water) excretion Ganong's Review of Medical Physiology, 23rd edition Renal Circulation Determination of renal plasma flow velocity (RPF) Clearance of a substance which pPAH=oo1mg/m, * is fully cleared from plasma in glomerulotubular apparatus. PAH (paraaminohippuric acid) cleared by 90% Renal plasma flow RPF = 5.85 x 1 mg/min 0.01 mg/ml = 585 ml/min ^ Renal venous PAH = 0.001 mg/ml UPAH = 5.85 mg/ml V = 1 ml/min Guyton & Hall. Textbook of Medical Physiology Correction to the extraction ratio of PAH (EPAH): 585 ml/min ■PAH PpAH " VpAH _ Q g PpAH + RPF = = 650 ml/min 0.9 Fetal Circulation Fetal Circulation Left atriu Superior vena cava 62% Ductus arteriosus Foramen ovale placenta, umbilical vein liver, ductus venosus crista dividens, foramen ovale blood supply of the head and upper limbs v cava superior and inferior the right ventricle ductus arteriosus aorta - the blood supply of the lower part of body + 60% of the cardiac output is directed to placenta Ganong's Review of Medical Physiology, 23rd edition Pulmonary artery Left ventricle Fetal Circulation fetal haemoglobin short-period hypoxia longer hypoxia thick muscle wall of umbilical vessels 10 20 30 40 50 60 70 80 90 100 P02 (mm Hg) Ganong's Review of Medical Physiology, 23rd edition Fetal Circulation Left atrium Superior vena cava Ductus arteriosus Foramen ovale Changes after birth Closure of umbilical vein - sudden f of peripheral resistance and blood pressure - contraction of musculature of ductus venosus and its closure The first inspiration (due to asphyxia and cooling of the body) - i resistance of the lung bloodstream - much more blood into lungs Ganong's Review of Medical Physiology, 23rd edition Portal vein Umbilical vein From placenta\ Pulmonary artery Left ventricle Fetal Circulation Changes after birth Decrease of pressure in right atrium and its increase in left atrium due to: - | filling of left atrium by the blood from lungs - I venous return to right atrium due to closure of umbilical vein - left ventricle works against | pressure in aorta Closure of formanen ovale Closure of ductus arteriosus Ganong's Review of Medical Physiology, 23rd edition Coronary Circulation Coronary Circulation a. cor sinistra a. cor dextra 02 diffusion directly from the blood situated in the cardiac cavities placing of coronary arteries and capillaries in the cardiac walls; consequences! Epicardial coronary arteries Right coronary artery Left coronary artery Subendocardial arterial plexus Circumflex branch Anterior descending branch Septal branches Marginal branch Marginal branch Posterior descending branch Ganong's Review od Medical Physiology, 23rd edition Guyton and Hall. Textbook of Medical Physiology, 11th edition Coronary Circulation http://pochp.mp.pl/aktualnosci/show.html?id=55102 Coronary Circulation TABLE 34-4 Pressure in aorta and left and right ventricles (vent) in systole and diastole. Pressure (mm Hg) in Pressure Differential (mm Hg) between Aorta and Aorta Left Vent Right Vent Left Vent Right Vent Systole 120 121 25 -1 95 Diastole 80 0 0 80 80 intramural vessels left vs. right ventricle high heart rate 120 if) _2> 8? x 100 a- E I E o < 0.4 0.6 Time (s) 1.0 Ganong's Review od Medical Physiology, 23rd edition Coronary Circulation 02 extraction is almost maximal already at rest, capillaries are open The only possibility how to increase 02 supply (for example during exercise) is the coronary vasodilation! Coronary Circulation Control of coronary blood flow 1) reduction/interruption of the blood flow or increased demands hyperaemia (reactive or active) based on the metabolic vasodilation Coronary Circulation Control of coronary blood flow 2) the neural regulation of the vessel diameter-secondary impact a) indirect effects w Y (mostly opposite) b) direct effects Coronary Circulation Control of coronary blood flow 2) the neural regulation of the vessel diameter-secondary impact a) indirect effects sympathetic system (NE, E) f HR + contractility ->■ rate of cardiac metabolism -> increased 02 consumption ->• activation of local vasodilating mechanisms parasympathetic system (ACH) opposite changes —> vasoconstriction „^ Coronary Circulation Control of coronary blood flow 2) the neural regulation of the vessel diameter-secondary impact a) indirect effects b) direct effects vasospastic sympathetic system (NE, E) myocardial ischemia epicardial vessels - mostly a-rec. -> vasoconstriction intramural vessels - mostly |3-rec. -> vasodilation parasympathetic system (ACH) vasodilation, but not significant (only few fibers) Coronary Circulation Control of coronary blood flow 2) the neural regulation of the vessel diameter secondary impact a) indirect effects b) direct effects Whenever the direct effects alter the coronary blood flow in the wrong direction the metabolic control overrides them within seconds! Coronary Reserve • ability of coronary vessels to adapt blood flow to the actual cardiac work (ergometry) • the maximal blood flow / the resting blood flow • reduction of the coronary reserve: - relative coronary insufficiency - absolute coronary insufficiency (~ coronary heart disease) Reduced coronary reserve is a limiting factor of the cardiac output, thus, also of the effort of organism!