Medical Physiology PDF - Kidney (Urinary) System I

Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Kidney (Urinary) System I Basic Kidney Anatomy: Kidneys are paired, about 150 gm each (0.2% of the body weight). The renal system consi...

Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Kidney (Urinary) System I Basic Kidney Anatomy: Kidneys are paired, about 150 gm each (0.2% of the body weight). The renal system consists of: Urine forming units: - 1. Cortex 2. Medulla (lobed: renal pyramids) Cortex and medulla composed chiefly of nephrons and blood vessels Urine collecting and expelling units –in sequence:- 1. Calyces 2. Renal pelvises 3.Ureters 4. Bladder 5. Urethra Urine flows from calyces, renal pelvises through ureters to the urinary bladder and then through urethra to out of body. The bladder is under both voluntary and autonomic control v The metabolic waste products excreted in the urine are: 1. Urea from protein. 2. Uric acid from nucleic acid. 3. Creatinine from muscle creatine. 4. Bilirubin end products of haemoglobin breakdown. 1 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Kidney Function: 1. Regulate volume of ECF (plasma and interstitial fluid) by maintaining a balance between intake and output of water in the body. 2. Regulate concentration of electrolytes (Na+, K+, and HC03- and other ions). 3. Playing a dominant role in the long-term and short-term regulation of arterial blood pressure. 4. Eliminate waste products such as the excretion of urea, creatinine and uric acids; as well as the excretion of various toxins such as drugs and food additives (i.e. detoxify drugs and toxins). 5. Regulate pH along with the respiratory system. 6. The kidneys act as endocrine glands producing hormones, by secreting erythropoietin, renin & production of calcitrol. Nephron Nephron is a structural and functional unit of the kidney. It is the fundamental urine-producing unit of the kidney. There are two types of nephrons: 1. Cortical nephrons. Glomeruli are present near the surface of the kidneys. These nephrons constitute about 86% of total nephrons. The main function of cortical nephrons is absorption of sodium. 2. Juxtamedullary nephrons. Glomeruli lie at the junction of cortex and medulla of the kidney. These constitute 14% of the nephrons. The main role of juxtamedullary nephron is to increase concentration of medullary interstitial fluid. 2 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Nephron consists of two major parts: 1. Glomerulus with surrounding Bowman’s capsule 2. A long renal tubule 1. Glomerulus: It is made up of tuft of capillaries which connect afferent arteriole with an efferent arteriole. Capillaries have single layer of endothelial cells attached to a basement membrane. Bowman’s capsule encloses the glomerulus and is formed of two layers: i. inner layer which covers the glomerular capillaries is called visceral layer, ii. outer layer is called parietal layer. Space between visceral and parietal layers is continued as the lumen of the tubular portion. 2. Renal tubule. It is mainly formed of three parts: a) Proximal convoluted tubule. b) Loop of Henle consisting of: Thin segment: walls of descending limb and lower end of ascending limb are very thin. Therefore, they are termed thin segment. Hair pin bend. Thick ascending limb or segment. c) Distal convoluted tubules. § open into initial arched collecting ducts called cortical collecting ducts present in renal cortex. Seven to ten such ducts form straight collecting duct which passes into medulla forming medullary collecting ducts. 3 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider ü So, the components of the nephron -in sequence- are: 1. Glomerulus - tuft of capillaries - for filtration 2. Bowman's capsule - surrounds glomerulus 3. Proximal convoluted tubule 4. Loop of Henle – for Na+ reabsorption 5. Distal convoluted tubule 6. Collecting duct - for concentration of urine by water reabsorption 7. Peritubular capillaries Glomerulus has large pores (larger than other capillaries in the body), allowing filtration of large volumes of fluid Young adult has a total of 1 million nephrons in each kidney. Number of nephrons declines with age, to about 50% at age 60; this causes the glomerular filtration rate (GFR) to drop to 50% of its value in a young person. Therefore, loss of nephrons can cause drug overdose in older persons. BLOOD FLOW TO KIDNEYS Although the kidneys are small organs, they receive ~ 25% of the cardiac output (This is quite high blood supply as compared to their size). This makes the rate of blood flow to kidneys ~ 1200 ml/min. This unique blood flow is extremely important for renal function to regulate the composition and volume of body fluids. Two sets of capillaries are peculiar for renal circulation: 1. Glomerular capillaries · These combine to form efferent arteriole which in turn breaks into peritubular capillary network around the tubules of cortical nephrons. 2. Vasa recta which are loop-shaped vessels in juxtamedullary nephrons. · the efferent arterioles continue as these loops dip into the medullary pyramids alongside the loops of Henle 4 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider ü Glomerular capillary bed has a high hydrostatic pressure because efferent arteriole is of a smaller diameter than afferent arteriole which offers considerable resistance to blood flow. ü Peritubular capillary bed is a low-pressure bed. ü Only 5% of blood flows through vasa recta. ü The flow is very sluggish. ü Renal blood flow shows remarkable constancy in face of blood pressure changes due to autoregulation ü The kidneys regulate the hydrostatic pressure in both capillary beds (glomerular & peritubular) by adjusting resistance of the afferent and efferent arterioles. ü High hydrostatic pressure in glomerulus (60 mmHg) causes rapid fluid filtration; whereas a much lower pressure in the peritubular capillaries (13 mmHg) permits rapid fluid reabsorption. ü The afferent arteriole is a short, straight branch of the interlobular artery. ü The efferent arteriole, that drains the glomerulus, has a relatively high resistance than the afferent arteriole. The Basic Processes of the Kidney are: : o Filtration takes place in the glomerulus. o Driven by the hydrostatic pressure of the blood (osmotic pressure opposes filtration, but the hydrostatic pressure is larger) o Water and small molecules (ions & glucose) are filtered; o blood cells and large molecules (most proteins) do not pass through the filter o Normal GFR = 125 ml/min (7.5 L/hr, 180 L/day) o As the filtrate (filtered fluid) passes down the nephron most of it is reabsorbed into the blood + e.g. 100% of glucose and HCO-3 reabsorbed & 99% of water and Na are reabsorbed. o Waste products such as urea, creatinine & uric acid are excreted >> reabsorbed. o Therefore, in renal failure or impairment urea and creatinine increased in blood 5 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider o A few substances are secreted from the blood (peritubular capillaries) to tubular cells; Primary functions of tubular secretion: 1. moving drugs into the urine 2. moving more urea & uric acid into urine 3. removing excess K+ from blood 4. regulating pH (H+ ion removal) ü Reabsorption and secretion are energy consuming; the kidney is one of the most metabolically active organs in the body The urinary excretion of substance depends on its filtration, reabsorption, and secretion 6 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Glomerular Filtration Rate (GFR): GFR can be defined as the volume of plasma that is filtered by the glomerulus in both kidneys per unit of time. The substance used for the measurement of GFR should be: 1) freely filtered 2) neither reabsorbed nor secreted by the renal tubules 3) it should be non-toxic 4) not metabolized by the body. The substance that has such criteria is inulin, a polymer of fructose. Inulin is not produced in the body and must be given by intravenous infusion to produce a constant plasma level (1mg/ml). Therefore, GFR can be calculated as the clearance of inulin as follows: U inulin × V GFR = = C inulin P inulin Where: U inulin = inulin concentration in urine = 35 mg/ ml. V = urine flow rate = 0.9 mL/ minute P inulin = plasma concentration of inulin = 0.25 mg/ ml. So GFR =~ 125 mL/ min. ü The clearance of creatinine (the byproduct of muscle metabolism) can also be used to assess GFR, because its measurement does not require i.v. (intravenous) infusion into the patient, it is more widely used clinically. However, creatinine clearance is not a perfect marker, because a small amount of it is secreted by the tubules, so that the amount excreted slightly exceeds the amount filtered. Nevertheless, there is normally an overestimation of the plasma creatinine; hence, both errors tend to cancel each other. From above, the GFR in an average-sized normal man approximately = 125 mL/minute, which equals to (180 L/day), whereas the normal urine volume is about (1-2 L/ day). Thus, 99% or more of the filtrate is normally reabsorbed, leaving 1-2 liters of urine/day. As the kidneys filter approximately 180 liters of plasma/day, the whole plasma [~ 3 liters] gets filtered about 60 times per day. It is remarkable that the kidney filter can be used continuously for 70 years or more without becoming clogged. Filtration Fraction: It represents the ratio of the GFR to the renal plasma flow (RPF) which is normally around (0.20 or 20%) 7 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Factors Affecting the GFR: 1. The Glomerular capillary membrane: The high permeability is due to the special structure of the glomerular membrane, these are the capillary endothelium and the specialized epithelium of the capsule made up of podocytes overlying the glomerulus: i. The presence of fenestrae in the endothelium of the glomerulus with pores that are “70 – 90 nm” in diameter are responsible for the high filtration rate across the glomerular capillary membrane. ii. The podocytes are not a continuous layer with numerous pseudopodia (foot-like processes) that interdigitate to form the filtration slits along the capillary wall. ü Those two layers are separated by a “basal lamina” consisting of a meshwork of glycoproteins that has strong negative electrical charges, giving the membrane its high selectivity. 2. Size of the capillary bed (Effective filtration surface area). 3. The Net Filtration Pressure: The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration : 1) Hydrostatic pressure inside glomerular capillaries, which promotes filtration; 2) Hydrostatic pressure in Bowman’s capsule, which opposes filtration; 3) Colloid osmotic pressure of the glomerular capillary plasma proteins, which opposes filtration; 4) Colloid osmotic pressure of the proteins in Bowman’s capsule, which promotes filtration (normally = 0). 8 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider ü It is important to know that filtration across the glomerulus is flow-limited, therefore, an increase in the renal plasma flow would à increase the filtration and GFR, because it would shift the point of equilibrium across the glomerular capillary bed toward the efferent arteriole; so, increases the surface area of filtration. ü Changes in Bowman’s capsule pressure normally does not serve as a primary means for regulating GFR. BUT precipitation of “stones” that lodge in the urinary tract, raises Bowman’s capsule pressure and reduces GFR and eventually can damage or even destroy the kidney. ü Changes in glomerular hydrostatic pressure serve as the primary means for physiologic regulation of GFR. Increases in it raise GFR, and vice versa. v Glomerular hydrostatic pressure is determined by three variables, under physiologic control: 1. Arterial pressure 2. Afferent arteriolar resistance 3. Efferent arteriolar resistance Increased arterial pressure tends to raise glomerular (PG) and, therefore, to increase GFR. However, this effect is buffered by autoregulatory mechanisms. Increased resistance of afferent arterioles (by vasoconstriction) reduces glomerular hydrostatic pressure and decreases GFR. Vasoconstriction of the efferent arterioles increases the resistance to outflow from the glomerulus: o This raises the glomerular hydrostatic pressure, as long as it does not reduce renal blood flow too much, GFR increases slightly. o Thus, efferent arteriolar constriction has a biphasic effect on GFR. ü At moderate levels of constriction, there is a slight increase in GFR, but with severe constriction (more than about a threefold increase in efferent arteriolar resistance, there is a decrease in GFR 9 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Physiologic Control of GFR & Renal Blood Flow 1. The Sympathetic Nervous System Activation: · Essentially all the blood vessels of the kidneys, including the afferent and the efferent arterioles, are richly innervated by sympathetic nerve fibers. · Strong sympathetic activation can constrict the renal arterioles and decrease renal blood flow and GFR, while, moderate or mild stimulation has little influence. · The renal sympathetic nerves are most important in reducing GFR during severe, acute disturbances lasting for few minutes - hours, e.g., brain ischemia, or severe hemorrhage. 2. Hormonal and Autacoid Control of GFR and Renal Circulation: Autacoid means any of a group of natural biochemicals, as serotonin, angiotensin, or histamine, that activate changes in the blood vessels, nerves, etc., similar to those caused by drugs 3. The Autoregulation of GFR and Renal Blood Flow (RBF): · Feedback mechanisms intrinsic to the kidneys normally keep the RBF and GFR relatively constant, despite marked changes in arterial blood pressure · This relative constancy of GFR and RBF is referred to autoregulation. · A decrease in arterial pressure to as low as 75 mmHg or an increase to as high as 160 mmHg changes GFR only a few percentage points. 10  Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Physiologic Control of GFR & RBF is done by the following Autoregulation Mechanisms: A. Tubuloglomerular Feedback Mechanism: Juxtaglomerular complex is a specialized organ situated near the glomerulus of nephron. Hence the name juxtaglomerular apparatus (juxta = near). It consists of the following: 1. Macula densa cells. Initial part of distal tubule. It passes in the angle between afferent and efferent arterioles of the glomerulus. · Epithelial cells of this part of distal tubule are specialized and termed macula densa cells. · They are not well adapted for reabsorption and do not show the signs of secretory activity. · Function of macula densa: it acts as a sensor of a tubular fluid flow and/or composition. This helps in local homeostatic response, which regulate renin secretion as well as helps in autoregulation of GFR. 2. Juxtaglomerular cells (Modified muscle cells in the wall of afferent arteriole) · They have well developed Golgi apparatus and endoplasmic reticulum, abundant mitochondria and ribosomes. · They contain secretory granules and therefore also called granular cells. · The granulation increases when there is sustained hypotension in afferent arteriole and sodium deficiency. · The granules contain renin. · Juxtaglomerular cells secrete two hormones renin and erythropoietin 11 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider v Secretion and functions of renin. Juxtaglomerular cells of the apparatus secrete renin into the blood when: i. blood pressure is decreased. ii. extracellular fluid volume is reduced. iii. sympathetic activity is increased. · Renin is a glycoprotein acts on alpha2-globulin called angiotensinogen in the liver and converts it into angiotensin I in the lungs. · Angiotensin I is converted to angiotensin II by an angiotensin converting enzyme (ACE) in the endothelium of blood vessels. · Angiotensin II has the following actions: i. It causes constriction of systemic arterioles causing elevation of systemic blood pressure. ii. It stimulates adrenal cortex to secrete aldosterone which in turn increases absorption of sodium and water by distal nephrons of kidney released K+ from body (excretion). It helps to maintain GFR and renal blood flow by the following scheme: 12 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider Renin-Angiotensin-Aldosterone Mechanism can be summarized as follows: 1) Low BP _ kidney secrete an enzyme called renin into the blood 2) Renin converts a protein called angiotensinogen (produced by the liver) into angiotensin I 3) Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE), which is found in capillary walls ACE inhibitors (e.g. capoten) are used to lower BP Angiotensin receptor blockers (ARBs), also known as angiotensin II receptor antagonists, are also used to treat high BP 4) Angiotensin II causes vasoconstriction of arterioles _ increased BP also it causes the adrenal cortex to secrete more aldosterone into the blood _ more Na retention & released K+ from body _ increased BP Summary of the Renin-Angiotensin-Aldosterone Mechanism: 13 Lec. 11 Medical Physiology Lec. Dr. Sarah Haider B. Myogenic autoregulation of the RBF and GFR: · It is an intrinsic feature of vascular smooth muscles that resist stretching during increased arterial wall tension by contraction of the vascular smooth muscles. · This would prevent over distention of the blood vessels and increase vascular resistance in afferent arterioles, inhibiting excessive increases in RBF and GFR. C. High Protein Intake and Increased Blood Glucose: · A high protein intake is known to increase both RBF and GFR. · GFR and RBF increase 20 to 30% within 1 or 2 hours after a person eats a high-protein meal. · A high-protein meal increases the release of amino acids into the blood, which are reabsorbed in the proximal tubule together with sodium. · This decreases sodium delivery to the macula densa, which elicits a tubuloglomerular feedback mechanism. · A similar mechanism may also explain the marked increases in RBF and GFR that occur with large increases in blood glucose levels in uncontrolled DM. 14