Physiology Renal System PDF

Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed Renal System Lec 8 Learning Objectives • Students will learn: 1. 2. 3. 4. Describe the morphology of a typical nephron and its blood supply. Basic Renal...

Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed Renal System Lec 8 Learning Objectives • Students will learn: 1. 2. 3. 4. Describe the morphology of a typical nephron and its blood supply. Basic Renal Processes. Define glomerular filtration rate (GFR). Describe the physiologic anatomy of the kidney.  Renal System:- (Urinary System) • The urinary system is composed of: 1. Two Kidneys. 2. Two Ureters. 3. Urinary Bladder. 4. Urethra. • The kidneys are located in the retroperitoneal space in the posterior abdomen. • The kidney plays a major role in controlling the volume of blood (water) and controlling ion concentration and acid-base balance (pH). • The kidney is a major excretory organ, responsible for the removal of metabolic waste products from the blood. • The kidney act on the plasma first converting it to ultrafiltrate to which it later add and remove substances so that the final product is urine. • Renal hilum (hilus) is the entry and exit site for structures servicing the kidneys: vessels, nerves, lymphatics, and ureters. Emerging from the hilum is the renal pelvis, which is formed from the major and minor calyxes in the kidney. • Hilum acts as a gateway for entry and exit of blood (by blood vessels), urine (by ureters), and nerves. 1 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed  Basic Renal Processes Urine formation begins with the filtration of plasma from the glomerular capillaries into Bowman's space. This process is termed glomerular filtration, and the filtrate is called the glomerular filtrate (ultrafiltrate). Glomerular filtrate is cell-free and, except for larger proteins, contains all the substances in virtually/almost the same concentrations as in plasma. The filtrate's composition is altered by:  When the direction of movement is from kidney tubular lumen to peritubular capillary plasma, the process is called tubular reabsorption or, simply, reabsorption.  When movement in the opposite direction-that is, from peritubular capillary plasma to kidney tubular lumen is called tubular secretion or, simply, secretion. Tubular secretion is also used to denote the movement of a solute from the cell interior to the lumen in the cases in which the kidney tubular cells themselves generate the substance.  The amount of any substance excreted in the urine is equal to the amount filtered plus the amount secreted minus the amount reabsorbed. Amount excreted =amount filtrate + amount secreted - amount reabsorbed  Forces Involved in Filtration • Filtration across capillaries is determined by opposing Starling forces. To review, Starling forces are: 1. The blood pressure in the glomerular capillaries- the glomerular capillary hydrostatic pressure (P GC ) (60 mmHg) - is a force favoring filtration. 2. The fluid in Bowman's space exerts a hydrostatic pressure (P Bs ) (15 mmHg) that opposes this filtration. 3. Opposing force is the osmotic force (π Gc ) (29 mmHg) that results from the presence of protein in the glomerular capillary plasma. 2 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed  Renal Functions: 1. Regulation of body water, inorganic ion balance, acid-base balance and electrolytes. 2. Excretion of metabolic waste products/foreign chemicals from the blood and their excretion in the urine. 3. Regulation of blood pressure (long and short term). 4. Regulation of vitamin D3 production by conversion of 25-hydroxyvitamin D (inactive) to 1,25-dihydroxyvitamin D (active), which influence calcium and phosphorus balance in the body. 5. Gluconeogenesis (is a process that transforms non-carbohydrate substrates (e.g. lactate, amino acids, and glycerol) into glucose. 6. Production of hormones/enzymes: A. Production of Erythropoietin hormones (controls erythrocyte production). B. Production of Renin enzyme that controls the formation of angiotensin, which influences blood pressure and sodium balance. 7. Other endocrine functions of the kidney include the secretion of prostaglandins (PGs) (there are secretary cells called Type I medullary interstitial cells present in the interstitial tissue e.g. PGI2 & PGE2). Note: PGE2 function to regulate salt & water homeostasis (vasodilation of renal arterioles). PGI2 secreted by the arterioles & glomeruli also causes vasodilation.  Physiologic anatomy of the kidney:- (Cortex & Medulla) • Medulla: this tissue appears as pyramids their apex is towards the renal pelvis and it appears striated because of the collecting ducts and loops of Henle. • Cortex: this tissue appears granulated because of the large number of glomeruli, the cortex is surrounded by a connective tissue called Renal Capsule. • Outside the renal capsule there is a thick layer of fat called Renal Fat Pad which protects the kidney from mechanical shocks.  Functional Anatomy:• The kidney is a complex structure consisting of one million or more, structural and functional unites called Nephrons, separated by connective tissue (interstitial tissue). • The Nephron is the functional unit because it accomplishes the entire complex of processes that result in the formation of urine. • Each individual renal tubule and its glomerulus is a nephron. 3 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) • Assist.Prof. Dr. Shaymaa Abdalwahed The size of the kidney in various species is determined largely by the number of nephrons they contain. • Each human kidney has approximately 1.3 million nephrons (the human needs 1/3 of the 1.3 million nephrons in order to survive). • The total length of the nephrons, including the collecting ducts, ranges from 45 to 65 mm. The Nephron consists of: A. Glomerulus 200µm in diameter is formed by the invagination of a tuft of capillaries inside Bowman's Capsule (dilated blind end of the nephron like a funnel). • The capillaries are supplied by an afferent arteriole and drained/leave by an efferent arteriole. Bowman's capsule: the invaginated end of the tubule surrounding the glomerular tuft. Two cellular layers separate the blood from the glomerular filtrate in Bowman's capsule, the capillary endothelium and specialized epithelium of the capsule made up of podocytes (Podocytes play an important role in glomerular function). • The layers are separated by a basal lamina (basement membrane), in addition to the Mesangial cells located between the basal lamina and endothelium (they are contractile and play a role in regulation of glomerular filtration). • • The endothelium of glomerular capillaries is fenestrated with pores that are 50-100 nm in diameter. The epithelium (podocytes) form filtration slits approximately ~ 5-9 nm in diameter. 4 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed B. Renal Tubule starts with:1. Proximal Convoluted Tubule (PCT): it contains cuboidal cells that are linked tightly at the apex but contain large lateral intracellular space. Its rich with mitochondria & the surface are covered with microvilli (brush border). Around 65% of filtrated fluid is reabsorbed in the PCT. 2. Loops of Henle (LH): thin descending loop with high permeability to water & thick ascending loop which is impermeable to water, but permit Cl- active reabsorption followed by Na+ movement, with many mitochondria. P P 3. Distal Convoluted Tubule (DCT): the first part (diluting segment) continues from the thick ascending loop, then the distal segment which are both under the control effect of hormone Aldosteron for Na+/K+ exchange reabsorption.  Macula densa is collection of specialized epithelial cell of DCT.  DCT starts at the macula densa, is about 5 mm long. 4. Collecting Duct (CD): The distal tubules coalesce/join to form collecting ducts that are about 20 mm long and pass through cortex and medulla and emptying into the renal pelvis at the apex of the medullary pyramids. CD form the medullary pyramids, which empty into the minor calix through the renal papilla. Cortical and medullary parts both are under effect of Anti Diuretic Hormone (ADH). • The epithelial cells of CD are of two types: A. Principle cells (P-cells): Predominant –involved in active Na+ reabsorption and vasopressin action (water reabsorption). P-cells that responds to ADH. B. Intercalated cells (I-cells): Few in number, concerned with acid (H+) secretion & HCO3- transport. I-cells participate in acid-base balance by regulating the secretion of acid. 5 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed Cortical nephron: is the nephron in the outer portion of the cortex have short loops of Henle and they are 85% of all nephrons. It is mainly perform excretory and regulatory functions. Juxtamedullary Nephrons: The nephrons in the inner portion of the cortex have long loops of Henle extending down into medullary pyramids and they form 15% of nephrons. It is concentrate and dilute urine. C. Juxta glomerular apparatus (JGA): • The thick ascending limb of the loop of Henle (LH) reaches the glomerulus of the same nephron which the tubule arose & passes close to its afferent arteriole (AA), the wall of the afferent arteriole contain Renin-secreting Juxta Glomerular cells. At this point, the epithelium of the distal tubule is modified histologically to form Macula Densa. • Macula Densa is group of modified epithelial cells in the distal convoluted tubule of the kidney that lie adjacent to the afferent arteriole just before it enters the glomerulus and control renin release by relaying information about the sodium concentration in the fluid passing through the convoluted tubule to the renin-producing juxtaglomerular cells of the afferent arteriole) • The juxta glomerular cells of AA & the macula densa of DCT form the Juxta Glomerular Apparatus (JGA) which is a secretary structure secreting renin & erythropoietin.  The JGA achieves a regulatory process for Na+ ions by secreting renin enzyme, the renin secretion is stimulated by the sympathetic nerves when sodium is decreased in the blood.  Renin is an enzyme released by JGA in the kidney when glomerular BP drops and osmolarity of the tubular fluid at the DCT decrease.  The renin enzyme converts the inactive form of Angiotensinogen (a plasma protein synthesized in liver) to Angiotensin I hormone (inactive peptide) in 6 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed which is converted to Angiotensin II by angiotensin-converting enzyme (ACE) in the blood.  Angiotensin II exerts many effects, but the most important are the stimulation of the secretion of aldosterone and the constriction of arterioles.  Angiotensin II stimulate thirst center resulting in increased ↑ fluid consumption → elevation ↑ of blood volume and it stimulate the contraction of arterioles → elevates ↑ systemic BP.  Functions of Angiotensin II are: A. Short term effect of Angiotensin II: 1. Its a potent vasoconstrictive agent due to increasing Blood Pressure (BP). 2. It also activate the heart which results in increasing the Cardiac Output (CO). B. Long term effect of Angiotensin II: 1. Stimulate secretion of Antidiuretic Hormone (ADH) from the Pituitary gland to stimulate water reabsorbtion. 2. Stimulate secretion of Aldosteron from the Adrenal cortex which regulates the sodium level in the blood (i.e Aldosteron cause Na+ retention (reabsorption).  Plasma angiotensin II is high during salt depletion and low when salt intake is high. It is this change in angiotensin II that brings about the changes in aldosterone secretion. • Erythropoietin hormone is secreted by the kidney if either decreased BP or reduced O2 carried in blood. This hormone stimulates erythropoiesis which increases Blood volume.  Rate of Glomerular Filtration • The volume of fluid filtered from the glomeruli into Bowman's space per unit time is known as the glomerular filtration rate (GFR). • GFR is determined not only by the net filtration pressure but also by the permeability of the renal corpuscular membranes and the surface area available for filtration. • In other words, at any given net filtration pressure, the GFR will be directly proportional to the membrane permeability and the surface area. The glomerular capillaries are much more permeable to fluid than most other capillaries. 7 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) • Assist.Prof. Dr. Shaymaa Abdalwahed Therefore, the net glomerular filtration pressure causes massive filtration of fluid into Bowman's space. In a 70 kg person, the GFR averages 180 L/day (125 mL/min)! This is much higher than the combined net filtration of 4 L/day of fluid across all the other capillaries in the body.  Rate of Glomerular Filtration • The total volume of plasma in the cardiovascular system is ~3 L, it follows that the kidneys filter the entire plasma volume about 60 times a day. This opportunity to process such huge volumes of plasma enables the kidneys to regulate the constituents of the internal environment rapidly and to excrete large quantities of waste products. • GFR is not a fixed value but is subject to physiological regulation. This is achieved mainly by neural and hormonal input to the afferent arterioles (AA) and efferent arterioles (EA), which causes changes in net glomerular filtration pressure. • The glomerular capillaries are unique in that they are situated between two set of arterioles (AA and EA).  Constriction of the afferent arterioles (AA) decrease hydrostatic pressure in the glomerular capillaries (P GC ) and decrease GFR.  Dilatation of efferent arterioles (EA) decrease hydrostatic pressure in the glomerular capillaries (P GC ) and decrease GFR.  Constriction of the EA and Dilatation of AA lead to increase GRF. 8 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed  The blood supply to the kidneys: The kidneys receive 20-25% of your total CO (98% which goes to the cortex & only 2% to medulla), in normal individuals about 1200 ml of blood flows through the kidneys each minute. Each kidney receives blood from a Renal Artery. As it enters the renal sinus, the renal artery provides blood to the Segmental Arteries. Segmental arteries further divides into a series of Interlobar Arteries that radiate outward between the renal pyramids. • The Interlobar arteries supply blood to the Arcuate Arteries, which arch along the boundary between the cortex & medulla of the kidney. • Each Arcuate artery gives rise to a number of Interlobular Arteries, and branching from each interlobular artery are Afferent Arterioles (blood reaches the vascular pole of each Glomerulus through an afferent arteriole & leaves in an efferent Arteriole). • Blood travels from the efferent arteriole to form a capillary plexus, a net-work of Peritubular Capillaries (that supplies the PCT & DCT). • The Peritubular capillaries provide a route for the pick-up or delivery of substances that are reabsorbed or secreted by these portions of nephrons. • In juxtamedullary nephrons, the efferent arteriole & peritubular capillaries are connected to a series of long slender capillary that accompany the loops of Henle into the medulla, these capillaries are known as the Vasa Recta, which absorb & transport solutes and water reabsorbed into the medulla from tubular fluid in the loops of Henle & collecting ducts (in the normal conditions the removal of solutes and water by the Vasa Recta balances the rate of solutes and water reabsorbed in the medulla). • From the peritubular capillaries & vasa recta, blood enters a network of venules and small veins that converge/meet on the Interlobular Veins (in mirror image of the arterial distribution). 9 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed  Innervation of the Kidneys:• The kidney and ureters are innervated by the renal nerves. Most of the nerve fibers involved are sympathetic postganglionic fibers, the sympathetic innervation targets: Juxta glomerular apparatus (JGA).  The smooth muscles in the walls of the afferent & efferent arterioles.  Mesangial cells (function to control glomerular filtration and involved in the response to local injury, including cell proliferation and basement membrane remodeling). Mesangial cells can generate interleukin 1 and platelet-derived growth factor and respond to these in an autocrine manner.  Functions of the sympathetic innervation: 1. Regulation of glomerular blood flow & pressure through control of the diameters of the afferent & efferent arterioles and glomerular capillaries. 2. Stimulation of renin release from JGA. 3. Direct stimulation of water and sodium reabsorption.  Micturition (is the action of urination) • Urine flow through the ureters to the bladder is propelled/push by contractions of the ureter wall smooth muscle. The urine is stored in the bladder and intermittently ejected during urination, or micturition. • The bladder is a balloon like chamber with walls of smooth muscle collectively termed the detrusor muscle. When the bladder is empty, the mucosa has numerous folds called rugae. • The contraction of the detrusor muscle squeezes on the urine in the bladder lumen to produce urination. That part of the detrusor muscle at the base (or "neck") of the bladder where the urethra begins functions as the internal urethral sphincter. Just 10 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed below the internal urethral sphincter, a ring of skeletal muscle surrounds the urethra is called external urethral sphincter, the contraction of which can prevent urination even when the detrusor muscle contracts strongly.  Regulation of Ion and Water Balance Total-Body Balance of Sodium and Water • Water composes about 55% to 60% of the normal body weight, and that water is distributed throughout different compartments of the body. • Since water is of such obvious/clear importance to homeostasis, the regulation of total body-water balance is critical to survival. This highlights two (2) important general principles of physiology: 1. Homeostasis is essential for health and survival; 2. Controlled exchange of materials-in this case, water- occurs between compartments and across cellular membranes. There are two (2) sources of body water gain: 1. Water produced from the oxidation of organic nutrients, 2. Water ingested in liquids and food (a rare steak is approximately~ 70% water). • Four (4) sites lose water to the external environment: skin, respiratory airways, gastrointestinal tract, and urinary tract. Menstrual flow constitutes a fifth potential source of water loss in women. • The loss of water by evaporation from the skin and the lining of the respiratory passage ways is a continuous process. It is called insensible water loss because the person is unaware of its occurrence. 11 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) • Assist.Prof. Dr. Shaymaa Abdalwahed Additional water can be made available for evaporation from the skin by the production of sweat. Normal gastrointestinal loss of water in feces is generally quite small, but it can be significant with diarrhea and vomiting. • Under normal conditions salt and water losses equal salt and water gains, and no net change in body salt and water occurs. This matching of losses and gains is primarily the result of the regulation of urinary loss, which can be varied over an extremely wide range. For example, urinary water excretion can vary from approximately 0.4 L/day to 25 L/day, depending upon whether one is lost in the desert or drinking too much water. • Similarly, some individuals ingest 20 to 25 g of sodium chloride per day, whereas a person on a low-salt diet may ingest only 0.05g. Healthy kidneys can readily alter the excretion of salt over this range to balance loss with gain. • The adrenal cortex produces a steroid hormone, aldosterone, which stimulates Na+ reabsorption by the distal convoluted tubule (DCT) and the cortical collecting ducts. • Aldosterone is a steroid and acts more slowly because it induces changes in gene expression and protein synthesis. In the case of the nephron, the proteins participate in sodium Na+ transport. • Aldosterone induces the synthesis of all the channels and pumps in the cortical collecting duct. • When a person eats a diet high in sodium, aldosterone secretion i s low, whereas it is high when the person ingests a low-sodium diet or becomes sodium-depleted. • The secretion of aldosterone is under control of hormone angiotensin II, which acts directly on the adrenal cortex to stimulate the secretion of aldosterone.  Renal Water Regulation: Water excretion is the difference between the volume of water filtered (GFR) and the volume reabsorbed. Thus, the changes in GFR initiated by baroreceptor afferent input that tends to have the same effects on water excretion as on Na+ excretion. The function of the baroreceptors is to maintain systemic blood pressure (BP) at a relatively constant level, especially during a change in body position • As is true for Na+, however, the rate of water reabsorption is the most important factor for determining how much water is excreted. As we have seen, this is determined 12 Al-Turath University College/Pharmacy Department st Physiology I-1 semester/2nd year students (2023/2024) Assist.Prof. Dr. Shaymaa Abdalwahed by vasopressin or antidiuretic hormone (ADH); therefore, total-body water is regulated mainly by reflexes that alter the secretion of this vasopressin hormone. • Vasopressin is produced by a discrete group of hypothalamic neurons whose axons terminate in the posterior pituitary gland, which releases vasopressin into the blood. The most important of the inputs to these neurons come from osmoreceptors and baroreceptors. • Baroreceptors, in the cardiovascular system, decrease their rate of firing when cardiovascular pressures decrease, as occurs when blood volume decreases. Therefore, the baroreceptors transmit fewer impulses via afferent neurons and ascending pathways to the hypothalamus, and the result is increased vasopressin secretion. • Conversely, increased cardiovascular pressures cause more firing by the baroreceptors, resulting in a decrease in vasopressin secretion. The mechanism of this inverse relationship is an inhibitory neurotransmitter released by neurons in the afferent pathway. • Vasopressin effect on water excretion, and vasopressin, like angiotensin II, causes widespread arteriolar constriction. This helps restore arterial blood pressure toward normal. Reference/ Further reading: Review of Medical Physiology by Ganong W.F. Text book of Medical Physiology by Guyton AC. Thank You Presented by Assist. Prof. Dr. Shaymaa Abdalwahed 13