Renal Physiology PDF

Renal Physiology By: Yemisrach Tekle December, 2023 1  Introduction Over view of renal function – Excretion of metabolic waste products and foreign chemicals – Regulation of water and electrolyte balances – Reg...

Renal Physiology By: Yemisrach Tekle December, 2023 1  Introduction Over view of renal function – Excretion of metabolic waste products and foreign chemicals – Regulation of water and electrolyte balances – Regulation of body fluid osmolality and electrolyte concentrations – Regulation of arterial pressure – Regulation of acid-base balance – Secretion and excretion of hormones – Gluconeogenesis 2  Specific functions of the kidney Excretion - excess water, excess electrolytes, urea, uric acid, creatinine, toxins, drugs… Retention - glucose, amino acids, electrolytes… Synthesis - ammonia, bicarbonate, prostaglandins – Prostaglandins minimize degree of renal ischemia (by vasodilatation) in volume depletion. 3  Activation of vitamin-D - mitochondrial 1-α hydroxylase of PCT Endocrine function - erythropoietin Regulation of arterial blood pressure - Renin-angiotensin-aldosterone (RAS) system. 4  Effects of Malfunctioning Kidneys 1. Alteration in water and electrolyte balance 2. Accumulation of nitrogenous waste products. 3. Alteration in acid-base balance 4. Mineral and skeletal disorder 5. Anemia 6. Uremia 5 1. Alteration water and electrolyte balance Chronic renal failure can produce: Fluid overload Hypertension Increased vascular volume Heart failure Edema Inability to concentrate urine Electrolyte imbalance 6  2. Accumulation of nitrogenous waste Abnormally high level of nitrogen containing compounds in blood. – Urea - is the first nitrogenous waste that accumulate.  Normal concentration in plasma is 20mg/dl. Could rises to 800mg/dl in renal failure. – Creatinine - is a by product of muscle metabolism freely filtered but not reabsorbed.  Normal value is about 1mg/dl.  It is an indicator of altered filtration and extent of renal damage. 7 3. Alteration in acid-base balance Renal failure triggers metabolic acidosis due to – Failure to secrete hydrogen – Failure to reclaim bicarbonate – Failure to synthesize bicarbonate 8 4. Mineral and skeletal disorder – Impaired phosphate excretion with corresponding rise in calcium loss in its inverse relation to phosphate. – This stimulate PTH then increase calcium reabsorption from bone. – And low level of active Vitamin D resulting reduced calcium absorption from GIT. 5. Anemia – Kidney disease result in low erythropoietin 9 6. Uremia (urine in blood) – Uremia is clinical syndrome associated with fluid, electrolyte and hormone imbalance which develops as signs and symptoms of renal failure. 10 Kidneys and accessory structures – Located in abdominal cavity. – Attached to posterior abdominal wall. – Found at the level of T12-L3 vertebrae. – Weighs about 160gm, 11cm long and 5 - 7cm wide. 11 12 Cortex and inner medulla parts – There are 7-15 conical divisions of the medulla known as renal pyramids. – The tip of this pyramid forms renal papilla. – The upper expanded portion of the ureter is called renal pelvis. – There are 2-3 divisions of renal pelvis known as major calyces. – The divisions of each major calyces are called minor calyces. – Totally there are about 250 collecting ducts that drain urine into the renal papilla. – Each collecting duct receives urine from 4000 nephrons 13 Two types of nephrons The nephron is the functional unit of the kidney. 1.Cortical nephron Glomeruli in outer cortex & short loops of Henle that extend only short distance into medulla. 2. Juxtamedullary nephron Glomeruli in inner part of cortex & long loops of Henle which extend deeply into medulla. Important in the ability to produce a concentrated urine. 14 Nephron: types – Cortical nephron (85%) - has peritubular capillaries – Juxtamedullary nephron (15%) - has vasa recta – 2.6 million nephrons 15 16  Each nephron contains a. Glomerular capillaries - called the glomerulus, through which large amounts of fluid are filtered from the blood. b. A long tubule - in which the filtered fluid is converted into urine on its way to the pelvis of the kidney. 17 Nephron: Components – Types: Cortical, Juxta- medullary – Abundance of nephrons - (2 - 2.6 millions) – Components: – Glomerulus – Renal tubules 18  Glomerulus: Glomerulus – a capillary supplied and drained by afferent and efferent arterioles. The glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman's capsule. Fluid filtered from the glomerular capillaries flows into Bowman's capsule and then into the proximal tubule, which lies in the cortex of the kidney. 19 The Renal Corpuscle –Composed of Glomerulus and Bowman’s capsule 20  Glomerular capillary membrane The glomerular capillary membrane has three major layers: 1. The endothelium of the capillary 2. A basement membrane, and 3. A layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane. Together, these layers make up the filtration barrier. 21 Fig. Basic ultrastructure of the glomerular capillaries. 22  Renal tubules Proximal convoluted tubules (PCT) Loop of Henle (LH) – Thin descending (tDLH) – Thin ascending (tALH) – Thick ascending segments (TALH) Distal convoluted tubules (DCT) Collecting ducts (CD) 23 The tubules: structure Proximal convoluted tubules Have brush boarder Abundant mitochondria Invaginated basolateral wall Thick ascending limb and DCT Have abundant mitochondria Invaginated basolateral wall Thin limb Poorly developed apical basolateral wall Late DCT and cortical collecting duct Have intercalated cells Concerned with acid secretion and bicarbonate reabsorption Principal cells Involved in Na+ reabsorption and vasopressin induced water reabsorption 24  Renal Circulation Vascular arrangement 25 26 Renal fraction: fraction of cardiac out put that goes to the kidneys (20-25 %) 27 Characteristics of renal circulation Renal fraction: fraction of cardiac out put that goes to the kidneys (20-25% COP). High flow rate to: Ensures (determines) high GFR. Modify rate of solute and water reabsorption by Proximal convoluted tubule. Participate in concentrating and diluting urine. Deliver gases and nutrients. 28 Characteristics of renal circulation (continued) – High permeability (50x skeletal muscle) – Portal circulation (two capillary system) – High pressure (60 mmHg vs. 25 mmHg) – High degree of Autoregulation (90-180mmHg) through neural, humoral and autoregulatory feedback to keep renal blood flow and GFR constant 29  Regulation of renal blood flow Sympathetic nervous system -increase vascular resistance in afferent arterioles and reduce GFR and renal blood flow. Angiotensin II- Constriction of efferent arterioles at low level; constriction of afferent and efferent arterioles at higher level. Atrial natriuretic peptide (ANP) cause afferent arteriolar dilatation and increase GFR. 30  Autoregulation of renal blood flow Renal autoregulation is an intrinsic phenomenon observed in the renal blood vessels to keep GFR and renal blood flow relatively constant despite wide change in arterial blood pressure. 31  Autoregulation of renal blood flow(continued) Intrarenal autoregulation is mediated by changes in preglomerular afferent arteriolar resistance. Renal blood flow (Q) = Aortic pressure – Renal venous pressure ------------------------------------------ Renal vascular resistance 32  Relationship between arterial blood pressure and RBF and between arterial blood pressure and GFR. Autoregulation maintains GFR and RBF relatively constant as blood pressure changes from 90 to 180 mm Hg. 33  Autoregulation of renal blood flow(continued) The intrarenal resistance vessels respond to arterial blood pressure changes by: 1. Myogenic mechanism Feedback mechanism in smooth muscle that sense change in arterial blood pressure. Elevated arterial blood pressure induces myogenic contraction that increase intrarenal vascular resistance, consequently reducing renal blood flow. 34  Autoregulation of renal blood flow(continued) Effect on Regulation Major stimulus Mechanism GFR Stretching of afferent Contraction of arterioles wall smooth muscles in Decrease Myogenic due to increased afferent arterioles GFR systemic blood wall pressure 35  Autoregulation of renal blood flow(continued) 2. Tubuloglomerular feedback- – Feedback mechanism in which rate of flow of tubular fluid and rate of NaCl reabsorption is sensed by the macula densa of Jaxtaglomerular apparatus. The feedback adjust the resistance in renal vessels, thus idealizing renal blood flow 36  Fig. Structure of the juxtaglomerular apparatus, demonstrating its possible feedback role in the control of nephron function. 37 Juxtaglomerular apparatus: 38 39 40 41  Three points concerning autoregulation should be noted: 1. Autoregulation is absent when arterial pressure is less than 90 mm Hg. 2. Autoregulation is not perfect; RBF and GFR do change slightly as arterial blood pressure varies. 3. Despite autoregulation, RBF and GFR can be changed by certain hormones and by changes in sympathetic nerve activity 42  Physiology of nephrons: urine formation Processes of urine formation involves – The three steps Filtration Reabsorption Secretion 43 1. Filtration – First step in urine formation. – Bulk transport of fluid from blood into a bowman’s capsule and kidney tubules. – Blood cells and proteins do not filter. 44 2. Tubular reabsorption: – A process of returning filtered material from the renal tubules into the blood. – 99% of what is filtered will be reabsorbed. – Normally glucose is totally reabsorbed. 3. Tubular secretion: – Secretion of substances from the blood into the renal tubules. 45 Fig. Basic kidney processes that determine the composition of the 46 urine. Renal handling of four hypothetical substances. 47  Physiology of glomerulus Ultrafiltration (filtration under high pressure) creates glomerular filtrate. The rate of formation of glomerular filtrate is called Glomerular Filtration Rate (GFR). 48  Glomerular filtration A passive process occurs as fluid move across the glomerular capillary in response to glomerular hydrostatic pressure. Large proteins and cells stay behind Everything else is filtered into nephron. 49  Glomerular filtration rate  Amount of filtrate produced in the kidneys each minute.  GFR = 125ml/min or 180L/day  Urine output is about 1- 2 L /day. – About 99% of filtrate is reabsorbed. – The normal filtrate is devoid of cells and proteins. 50  Pressures that determine GFR 1.An increase in Glomerular capillary hydrostatic pressure cause increases in net Ultrafiltration pressure and GFR. It is increased by dilation of afferent arterioles or constriction of efferent arterioles. 2.Bowman's space hydrostatic pressure (PBS). – Increase in PBS cause decreased net ultrafiltration pressure and GFR. 51 52 53 54  The filtration rate of the kidneys depend on the difference between blood pressure in the glomerular capillary and the hydrostatic pressure in the lumen of the nephron. 55 Regulation of GFR : Adjusting blood flow GFR is regulated using three mechanisms. 1. Renal Autoregulation 2. Neural regulation 3. Hormonal regulation 56 1. Renal Autoregulation  Is accomplished by changing renal vascular resistance.  If arterial pressure changes, a proportional changes occurs in renal vascular resistance to maintain a constant RBF. 57 2. Neural regulation of GFR Sympathetic nerve fibers innervate afferent and efferent arteriole. Normally sympathetic stimulation is low but can increase during hemorrhage and exercise. Activation of SNS causes vasoconstriction, which leads to decrease RBF. 58 3. Hormonal regulation of GFR  Angiotensin II  ANP  Prostaglandin :improves renal perfusion , reduce total peripheral resistance (TPR) and increase renin release. 59 –Pathway by which hemorrhage activates renal sympathetic nerve activity and stimulates the production of angiotensin II. 60 61  Tubular reabsorption The water and solutes reabsorbed from the nephron enter the peritubular capillaries. The cells of the nephron are highly selective and absorb most efficiently. Tubular reabsorption occurs throughout the renal tubule, but most of it takes place in proximal convoluted tubule. 62 –Filtration, reabsorption, and excretion rates of substances by the kidneys Filtered Reabsorbed Excreted Reabsorbed (%) –Glucose (g/day) 180 180 0 100 –Bicarbonate (meq/day) 4,320 4,318 2 > 99 –Sodium (meq/day) 25,560 25,410 150 99 –Chloride (meq/day) 19,440 19,260 180 99 –Water (l/day) 169 167.5 1.5 99 –Urea(g/day) 48 24 24 50 –Creatinine(g/day) 1.8 0 1.8 0 63  Reabsorption at proximal tubule Reabsorption – 100 % of Glucose, amino acids, vitamins. – 85% of bicarbonate. – 70 % of water (obligatory water reabsorption). – 60-70 % of Na +. – Cl-(80%) passive follows Na + and K + reabsorption. – 65% K+ reabsorption. – 60-65% Ca2+ – 50 % urea. 64 65  Reabsorption across the tubular epithelium can be either through the cells (the transcellular route) or around the cells (the paracellular route).  Transcellular reabsorption is a two-step process.  Paracellular reabsorption is always a passive process through the 66 tight junctions. FIGURE: Mechanisms of transmembrane 67 solute transport. Reabsorption and secretion of substances at PCT68  Physiology of Loop of Henle 20-30% reabsorption of NaCl 27% reabsorption of K+ 10 % bicarbonate reabsorption 20% reabsorption of Ca2+ Creates osmotic stratification (300 - 1200 mOsm/l) initial step to form dilute or concentrated urine 69  Descending thin segment – Highly permeable to water (10 % obligatory water reabsorption) – Impermeable to solutes (concentrating segment) 70  Thick ascending segment – Active Na transport Using Na+ -K+- 2Cl- Co-transport – Impermeable to water – Diluting segment Thin ascending segment – Moderate permeability to Na, Cl, urea and water 71 72  Distal Convoluted Tubule (DCT) ADH-dependent water reabsorption 7% Na+ reabsorption by: – Na+- H+ antiport – Na+- K+ antiport – Na+- Cl- co-transport Aldosterone sensitive part – K+ - secretion – H+ - secretion Poor passive permeability to urea and NaCl. 73 74  Collecting Duct Primarily ADH-dependent water reabsorption (large) Urea reabsorption only in inner medullary collecting duct. 5% HCO-3 reabsorption 4% K+ secretion Aldosterone-dependent Na-reabsorption. Final adjustment of urine. 75 76  Final adjustment of urine volume, pH & composition Volume: 700 ml) 108  Nerve supply of the bladder – Sympathetic efferent Relax bladder Contract internal urethral sphincter (IUS) – Parasympathetic efferent Motor to Detrusor muscle Inhibitory to IUS – Somatic efferent Motor to external urethral sphincter 109 110 111