Regional Circulation II Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology, Faculty of Medicine, Masaryk University (renal, fetal) •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. Renal Circulation Renal Circulation •main functions of kidneys – control of composition and volume of extracellular fluid, detoxification •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) -cortex: 5.3 ml/g/min -medulla - outer zone: 1.4 ml/g/min -medulla - inner zone: 0.4 ml/g/min - High blood flow in the renal cortex due to presence of glomeruli where plasma is filtered. Low blood flow in the inner medulla helps to prevent dilution of the hypertonic interstitium in this region. http://classes.midlandstech.edu/carterp/Courses/bio211/chap25/chap25.htm Renal Circulation Two capillary nets in series: 1.The glomerular capillaries – high pressure (60 mmHg – approx. doubled compared to the arterial end of a common tissue capillary) capillary net ensuring high filtration rate in the kidney; pressure not decreasing along the glomerular capillary (in contrast to a common tissue capillary) because the efferent arteriole follows (not a vein) 2.The peritubular capillaries – low pressure (12-15 mmHg) capillary net enabling high reabsorption rate of the tubular fluid http://classes.midlandstech.edu/carterp/Courses/bio211/chap25/chap25.htm Vasa recta only along the long loops of Henle of the juxtamedullary nephrons. Renal Circulation •v. aff., v. eff. •entry/exit of high pressure glomerular capillary system •regulate the glomerular filtration pressure: •glomerular blood flow = Pv.a. – Pv.e. Rv.a. + Rv.e. + Rg.k. • resistance in vas aff. or vas eff. ® ¯ the renal blood flow (if the arterial pressure is stable) constriction of vas aff. ® ¯ glomerular pressure ® ¯ filtration constriction of vas eff. ® glomerular pressure ® filtration Guyton & Hall. Textbook of Medical Physiology The resistance of the glomerular capillaries is negligible. The blood flow through the glomerulus is regulated in particular by changes in vas afferent and vas efferent resistance (diameter), which, like other arterioles, are characterized by a thick layer of the smooth muscle. The effect of changes of the diameter of vas afferens and vas efferens on the renal blood flow is the same, but on the filtration opposite! If both arterioles constrict at the same time, the flow will be reduced, but (unless it is extreme) without changing the filtration pressure - it is possible to regulate the flow in conjunction with the systemic blood circulation without changing the filtration! Behind the constriction in vas efferens, there is a pressure drop in the peritubular capillaries - the resorption of substances in the peritubular capillary network increases. 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 activity by maintaining stable blood flow at varying systemic pressure (stable glomerular pressure and, thus, also stable glomerular filtration rate) Ganong´s Review of Medical Physiology, 23rd edition Myogenic autoregulation (based on the Bayliss effect): When the blood pressure rises, tension in the vascular wall rises (the law of Laplace). It causes mechanical stimulation, depolarization and contraction of the vascular smooth muscles (due to activation of stretch-sensitive calcium channels). The resulting vasoconstriction shifts the blood flow back to the original level. The myogenic autoregulation asserts especially in tissues requiring stable blood flow, as in the brain and kidneys. Renal Circulation •Regulation of renal blood flow: 2)Neural regulation -conformed to demands of systemic circulation -renal blood flow forms 25% of the cardiac output, thus, it considerably influence BP -sympathetic system - norepinephrine light exertion (both emotional and physical) + upright body posture ® sympathetic tone ® tone of v. aff. and eff. ® ¯ renal blood flow but without ¯ GFR ( FF) higher of sympathetic tone - during anesthesia and pain - GFR may already ¯ The kidneys help to regulate the systemic blood pressure without impairing kidney function (filtration) under physiological consitions. Clinical comment: Decreased GFR (due to substantially increased sympathetic tonus, for example at extreme hypotension caused by bleeding, or during surgical stress) may result in uremia. 3)Humoral Regulation -contribute to regulation of systemic BP and regulation of body fluids -norepinephrine, epinephrine (from adrenal medulla) ® constriction of aff. and eff. arterioles ® ¯ renal blood flow and GFR in agreement with activity of sympathetic system (small impact with the exception of serious conditions, for example serious bleeding) Renal Circulation •Regulation of renal blood flow: -endothelin constriction of aff. and eff. arterioles ® ¯ 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) 3)Humoral Regulation -contribute to regulation of systemic BP and regulation of body fluids Renal Circulation •Regulation of renal blood flow: In the physiological state, endothelin (produced locally by the blood vessel endothelium) does not significantly contribute to regulation of the renal blood flow. -contribute to regulation of systemic BP and regulation of body fluids -NO (from the endothel) -prostanglandins (PGE2, PGI2), bradykinin continual basal production ® vasodilation in the kidney ® stable renal blood flow and GFR ® vasodilation – minor impact under physiol. cond. decrease the effect of vasoconstrictive substances which reduce marked ¯ of renal blood flow and GFR non-steroidal anti-inflammatory agents during stress (surgery, ¯ fluid volume) may ® notably ¯ GFR 3)Humoral Regulation Renal Circulation •Regulation of renal blood flow: Locally acting vasodilators counterbalance the continuous acting vasoconstrictive stimuli to stabilize the renal blood flow. Clinical comment: patients treated with inhibitors of NO synthesis or patients with impaired endothelial function (hypertension, atherosclerosis) – vasoconstriction in the kidneys, decrease of GFR and, thus, decrease of natriuresis – body fluid expansion – blood pressure increase Renal Circulation •Regulation of renal blood flow: -Renin-angiotensine system Ganong´s Review of Medical Physiology, 23rd edition -contribute to regulation of systemic BP and regulation of body fluids 3)Humoral Regulation Juxtaglomerular apparatus - renin-angiotensin-aldosterone system (RAAS) - see also other lectures (kidneys, hormones) Renal Circulation Renin-angiotensine system Ganong´s Review of Medical Physiology, 23rd edition vasoconstriction thirst, ADH ¯Na+ in plasma ¯BP sympathetic activity (b rec.) RAAS activation via angiotensin II, which acts in the kidney by vasoconstriction primarily in vas efferens, leads to normalization of GFR (which decreased due to hypotension that activated RAAS) and a decrease of the blood flow in the peritubular capillaries, thereby reducing hydrostatic pressure which increases reabsorption of tubular fluid. Reabsorption in tubules is further supported by the direct hormonal effect of angiotensin II and aldosterone on renal tubules (stimulating effect on Na+ and, thus, water reabsorption). Clearance of a substance which is fully cleared from plasma in glomerulotubular apparatus. Determination of renal plasma flow velocity (RPF) PAH (paraaminohippuric acid) cleared by 90% Guyton & Hall. Textbook of Medical Physiology RPF = 5.85 x 1 mg/min 0.01 mg/ml = 585 ml/min Renal Circulation (in juxtamedullar nephrons, vasa recta additionally originate from v. efferens – not in contact with proximal and distal tubuli ® no excretion of substances) Clearance was given in detail in lectures focused on kidney function. Guyton & Hall. Textbook of Medical Physiology RPF = 5.85 x 1 mg/min 0.01 mg/ml = 585 ml/min Correction to the extraction ratio of PAH (EPAH): RPF = 585 ml/min 0.9 = 650 ml/min EPAH = PPAH - VPAH PPAH = 0.9 Renal Circulation Clearance of a substance which is fully cleared from plasma in glomerulotubular apparatus. Determination of renal plasma flow velocity (RPF) PAH (paraaminohippuric acid) cleared by 90% The Renal blood flow: RPF / (1-hematocrit) = approx. 1200 ml/min Fetal Circulation Fetal Circulation •placenta, umbilical vein Ganong´s Review of Medical Physiology, 23rd edition •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 80% 67% 58% 62% 52% 62% The blood from the umbilical vein (saturation 80%) goes mainly to the liver, but part of the blood bypasses the liver through the ductus venosus. The blood from the liver and the ductus venosus flows through the vena cava inferior to the right atrium (separated by the crista dividens). The blood from the umbilical vein is directed to the foramen ovale in the atrial septum (right-to-left shunt) thanks to crista dividens and is driven by the left ventricle (along with the blood from the lungs) into the aorta and arteries of the head and upper limbs (still rather high O2). Only about 1/3 of the blood expelled from the right ventricle is delivered to the lungs (the lungs do not breathe, high resistance in the pulmonary circulation, pulmonary pressure slightly exceeds the aortic pressure), the rest flows via the second right-to-left shunt through the ductus arteriosus to the aorta. Blood continues to flow to the lower half of the body and to the placenta (60% of the fetal cardiac output goes to the placenta). The left ventricle pumps about 1/5 more blood than the right ventricle. The liver, heart, head and upper limbs are best supplied with oxygen. Fetal Circulation •fetal haemoglobin (higher affinity to oxygen) Ganong´s Review of Medical Physiology, 23rd edition •short-period hypoxia •longer hypoxia •thick muscle wall of umbilical vessels (sensitive contractile reaction to many stimuli – injury, hypoxia, sympathomimetics, etc.) Oxygen saturation of the fetal blood is possible due to the fetal hemoglobin, which has a higher affinity for oxygen than the adult hemoglobin (related to less effective 2,3-DPG binding) and can therefore bind oxygen from the maternal hemoglobin when flowing through the placenta. In addition, the fetus has a significantly higher number of red blood cells. After delivery, large quantities of red blood cells with the fetal hemoglobin disintegrate and gradually change into red blood cells with the adult hemoglobin. This condition, combined with immature liver enzymes, leads to the state called neonatal jaundice. Short-term hypoxia - tachycardia and increased umbilical vessel flow; longer hypoxia - bradycardia. The muscles of the umbilical veins respond sensitively to a number of stimuli by contractions (for example injury, tension, oxygen drop, sympathomimetics,…). In animals, it helps to stop bleeding from the umbilical stump after the birth. Fetal Circulation •Changes after birth •Closure of umbilical vein -sudden ↑ of peripheral resistance and blood pressure •The first inspiration (due to asphyxia and cooling of the body) Ganong´s Review of Medical Physiology, 23rd edition -contraction of musculature of ductus venosus and its closure -↓ resistance of the lung bloodstream -much more blood into lungs The first change after delivery - closure of the umbilical cord - leads to fetal asphyxia + to an increase in the total peripheral resistance of the systemic circulation and thus to an increase in the systemic blood pressure. This is followed by a reflex contraction of the ductus arteriosus and its closure. Asphyxia, along with cooling of the newborn's body due to changes in the temperature around - the first breath - decreases the resistance of the pulmonary circulation (up to 1/10 of the fetal) as well as its pressure (about 1/2 of the fetal). Placental transfusion - about 100 ml of placental blood is aspirated due to a sharp drop in the intrathoracic pressure during the first inspiration. 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 •Closure of formanen ovale Ganong´s Review of Medical Physiology, 23rd edition -↓ venous return to right atrium due to closure of umbilical vein -left ventricle works against ↑ pressure in aorta •Closure of ductus arteriosus Increase of the pressure in the left atrium (more blood coming from the lungs, higher pressure in the left ventricle due to increased afterload) and its decrease in the right atrium (lower venous return due to closure of the umbilicus) results in closure of the foramen ovale. Reversed pressure gradient between aorta and a. pulmonalis reverses flow in ductus arteriosus which results in constriction of its smooth muscle and closure (likely started by increased pO2 in the blood flowing through the ductus but other factors definitely contribute, for example decreased formation of vasoconstrictive prostaglandins after the birth – closure may be promoted by drugs inhibiting cyclooxygenase). Fetal Circulation Ganong´s Review of Medical Physiology, 23rd edition left and right heart work in parallel all connected in series The left and the right heart work in parallel in fetus due to presence of two shunts – ductus arteriosus and foramen ovale.