Renal Physiology Autoregulation PDF

Last edited: 3/7/2022 AUTOREGULATION Renal | Autoregulation (updated) Medical Editor: Gerard Jude Loyola OUTLINE I) RENAL AUTOREGULATION...

Last edited: 3/7/2022 AUTOREGULATION Renal | Autoregulation (updated) Medical Editor: Gerard Jude Loyola OUTLINE I) RENAL AUTOREGULATION IV) APPENDIX II) INTRINSIC MECHANISMS V) REVIEW QUESTIONS III) EXTRINSIC MECHANISMS VI) REFERENCES I) RENAL AUTOREGULATION Ability of the kidney to modify the blood flow and urine output How? o Intrinsic mechanisms: o Extrinsic mechanisms:  Myogenic mechanism  Sympathetic nervous system  Tubuloglomerular feedback  Renin-angiotensin-aldosterone-ADH system (RAAS) II) INTRINSIC MECHANISMS (A) MYOGENIC MECHANISM Myogenic = muscle of afferent arteriole Blood pressure is a surrogate of the glomerular hydrostatic pressure o Glomerular hydrostatic pressure (GHP): pressure inside the capillaries exerted to push substances out of the capillaries and into the Bowman’s capsule (1) ↑BP (2) ↓BP Figure 1. Myogenic mechanism during increased blood pressure. AA – afferent arteriole, EA – efferent arteriole, BC – Figure 2. Myogenic mechanism during decreased blood Bowman’s capsule, PCT – proximal convoluted tubule pressure. ↑BP → ↑GHP → ↑GFR ↓BP → ↓GHP → ↓GFR o Higher glomerular filtration rate (GFR), more urine o ↓BP = ↓urine = can cause kidney injury Kidneys modulate the GFR so that it is not too excessive o How does the kidney prevent it? making too much urine, or the blood pressure does not (i) Mechanism: remain too high causing injury on the glomerular capillaries ↓BP = ↓blood to the AA = ↓stretch on the AA ↓stretch → ↓Na+ enter in the smooth muscle cell → less (i) Mechanism: positive charge → ↓Ca2+ released by the sarcoplasmic Blood flows through the AA then to the EA reticulum → ↓contraction = relaxation ↑BP = more blood to the AA Summary: ↑BP = ↑GFR o Counteracted by vasoconstriction of AA → ↓GFR o Na channels in the smooth muscle is sensitive to ↓BP = ↓GFR stretch o Counteracted by vasodilation of AA → ↑GFR AA vasoconstricts → ↓glomerular blood flow (GBF) → ↓filtered plasma and other substance (↓GFR) AUTOREGULATION RENAL PHYSIOLOGY: Note #1. 1 of 5  (B) TUBULOGLOMERULAR FEEDBACK This mechanism is sensitive to NaCl o NaCl gets reabsorbed in the proximal convoluted tubule (PCT) (1) ↑BP (2) ↓BP Figure 3. Tubuloglomerular feedback mechanism on high blood Figure 4. Tuberoglomerular feedback mechanism on low blood pressures. MDC – Macula densa cells, DCT – distal convoluted pressures. tubule, LH – loop of Henley, JG cells – juxtoglomerular cells ↓BP = ↓GFR = ↓NaCl excretion into the kidney tubules When macula densa cells detect ↓NaCl in DCT, they ↑BP = ↑GFR = ↑NaCl excretion into the kidney tubules release PGI2 and nitric oxide (NO) When NaCl transporters in the PCT are saturated, NaCl PGI2 and NO function to: can escape and move to the LH and then to the DCT o (1) vasodilate the AA → ↑GBF → ↑GFR → ↑NaCl where macula densa cells are found filtered o Special NaCl sensors o Release adenosine when it detects ↑NaCl Adenosine functions to: o (1) vasoconstrict AA → ↓GBF → ↓GFR → ↓NaCl Summary: being filtered ↑BP = ↑GFR = ↑NaCl filtered o (2) inhibit juxtaglomerular (JG) cells → ↓renin → o ↑NaCl detected by MD cells → release adenosine → vasoconstricts AA and inhibits JG cells to ↓blood pressure release renin Remember: ↓BP = ↓GFR = ↓NaCl filtered Renin functions to increase blood pressure through a o ↓NaCl detected by MD cells → release PGI2 and NO complicated process. → vasodilates AA and stimulates JG cells to release renin 2 of 5 RENAL PHYSIOLOGY: Note #7. AUTOREGULATION  III) EXTRINSIC MECHANISMS Kicks in when blood pressure is relatively low o These mechanisms are more involved in these circumstances (A) SYMPATHETIC NERVOUS SYSTEM (1) Effects of the Sympathetic Nervous System ↓BP triggers baroreceptors → CN IX and CN X send ↓signals to the medulla Medulla activates sympathetic nerve fibers in the thoracic part causing release of NE and epinephrine (i) Heart NE and epinephrine act on the nodal system → ↑HR, ↑SV (due to ↑contractility) → ↑CO → ↑BP o To increase blood flow in the kidneys to avoid injury NE and epi stimulate the β1 receptors in the nodal system and contractile fibers → ↑HR and ↑SV, respectively o Chronotropic: change in heart rate o Ionotropic: change in contractility (ii) Afferent and Efferent Arterioles SNS release NE and EPI that act on the α1 receptors of the AA and EA → vasoconstriction → ↓GBF → ↓GFR YES, the goal is to increase the blood flow towards the kidney BUT in sympathetic crisis, the SNS does not respect the kidneys (iii) Systemic Vessels NE and EPI act on the α1 receptors on the systemic vessels → vasoconstriction of multiple vessels → ↑systemic vascular resistance (SVR) → ↑BP (iv) Juxtoglomerular Cells NE and EPI stimulate the β1 receptors on the JG cells → ↑renin → activates angiotensin II →→→ ↑BP Effects of the Sympathetic Nervous System: Increase HR and SV Vasoconstriction of the afferent and efferent arterioles Vasoconstriction of the systemic vessels → ↑SVR Triggers release of renin The effects are the exact opposite when the blood pressure is HIGH. Figure 5. Action of sympathetic nervous system in autoregulation. HR - heart rate, SV - stroke volume, CO - cardiac output, EPI - epinephrine, NE - norepinephrine, AT II - angiotensin II and SVR – systemic vascular resistance. Erratum: SUR* instead of SVR Stimulus: ↓↓↓SBP → MAP < 65 mmHg o MAP (mean arterial pressure): measure of perfusion o When MAP < 65 mmHg, kidney is not perfused; blood flow is redirected to other “more important” organs such as the heart, brain and muscles ↓BP → ↓GFR → ↓urine output o ↓blood flow can cause kidney injury o SNS do its best to increase blood flow AUTOREGULATION RENAL PHYSIOLOGY: Note #1. 3 of 5  (B) RENIN-ANGIOTENSIN-ALDOSTERONE-ADH AXIS Figure 6. The renin-angiotensin-aldosterone-ADH axis. ↓BP → ↓GFR Juxtoglomerular cells are sensitive to changes in blood pressure o When BP is low, JG cells release renin Renin cleaves angiotensinogen to produce angiotensin I Angiotensin I move to the capillaries in the lungs and get converted to angiotensin II by angiotensin converting enzyme (ACE) (1) Functions of Angiotensin II (i) ADH Release (iv) Vasoconstriction of EA and ↑GFR Angiotensin II stimulates the hypothalamus that trigger Angiotensin II binds on the receptor on the EA → release of ADH from the pituitary gland vasoconstriction of EA ADH o Less blood can escape from the glomerulus, more o Also called vasopressin or antidiuretic hormone blood stays in the glomerulus → more blood filtered o Acts on the aquaporin in the collecting duct to out → ↑GFR reabsorb water o NOTE: Some books say that it also affects the AA;  ↑H2O in blood → ↑blood volume → ↑BP but the effect is much greater in EA (EA >>> AA) (ii) ↑Thirst Angiotensin II act on the PCT to cause increased reabsorption of Na+ and H2O Makes you thirsty → ↑water intake → ↑blood volume → o ↑Na+ and H2O → ↑BV → ↑BP ↑BP (v) Vasoconstriction of Systemic Vessels (iii) Aldosterone Release Angiotensin II act on systemic vessels → potent Angiotensin II stimulates release of aldosterone from the vasoconstriction → ↑SVR → ↑BP → ↑GFR zona glomerulosa (ZG) in the adrenal gland Function: act on the DCT to make them permeable water In cases of ↑BP, JG cells do NOT release renin. and Na+ Therefore, this cascade does not occur. o ↑Na+ and H2O → ↑BV → ↑BP (2) Atrial Natriuretic Peptide (ANP) Released from the heart in cases of ↑BP (Figure 6) Function: can block any function of the angiotensin II a. Blocks ADH release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume c. Prevents vasoconstriction of EA = ↓GFR b. Blocks aldosterone release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume e. Vasodilation of blood vessels = ↓SVR = ↓BP 4 of 5 RENAL PHYSIOLOGY: Note #7. AUTOREGULATION  IV) APPENDIX Table 1. Summary of autoregulatory mechanisms of the kidneys. INTRINSIC EXTRINSIC Renin-Angiotensin-Aldosterone- Myogenic Mechanism Tubuloglomerular Feedback Sympathetic Nervous System ADH Axis ↑BP = ↑GFR ↑BP = ↑GFR = ↑NaCl filtered ↓BP stimulates release of NE Renin cleaves angiotensinogen to Counteracted by ↑NaCl detected by MD cells → and EPI from medulla angiotensin I → angiotensin II vasoconstriction of AA → release adenosine → Actions: (lungs) ↓GFR vasoconstricts AA and ↑HR, ↑SV = ↑CO = ↑BP Functions of Ang II ↓BP = ↓GFR inhibits JG cells to release o Through the stimulation of Release of ADH = ↑H2O Counteracted by vasodilation renin the nodal system and reabsorption = ↑BP of AA → ↑GFR ↓BP = ↓GFR = ↓NaCl filtered through β1 receptors Thirst = ↑water intake = ↑BP ↓NaCl detected by MD cells → Release of aldosterone = ↑H2O release PGI2 and NO → Vasoconstriction of AE and EE through stimulation of α1 and Na+ reabsorption = ↑BP vasodilates AA and stimulates Vasoconstriction of efferent JG cells to release renin receptors = ↓GFR Vasoconstriction of systemic arterioles = ↑GFR vessels = ↑SVR = ↑BP ↑Reabsorption of water and Na+ Stimulates renin release from (PCT) JG cells Vasoconstriction of systemic vessels V) REVIEW QUESTIONS VI) REFERENCES 1) All of the following functions of angiotensin II increase the blood pressure EXCEPT: a) Stimulation of the hypothalamus b) Stimulation of the zona glomerulosa c) Vasoconstriction of the efferent arterioles d) Vasoconstriction of the systemic vessels 2) Which of the following is NOT an effect of the sympathetic nervous system in increasing blood pressure? a) Stimulates β1 receptors in the nodal system and contractile fibers b) Stimulates the α1 receptors on the afferent and efferent arterioles c) Stimulates release of renin d) Stimulates the α1 receptors on the general vascular system 3) What stimulus is important in the tubuloglomerular feedback? a) O2 b) Stretch c) NaCl d) Baroreceptors 4) At low blood pressures, the macula densa cells release what substances to counteract the change in blood pressure? a) Adenosine b) NO2 c) PGI2 d) B & C 5) Myogenic mechanism takes advantage of what stimulus? a) Stretch of the afferent arteriole b) Stretch of the efferent arteriole c) Change in osmolarity d) Change in osmolality AUTOREGULATION RENAL PHYSIOLOGY: Note #1. 5 of 5