ANALYSIS OF URINE AND OTHER BODY FLUIDS RENAL FUNCTION OUTLINE • Stages of Urine Formation • Glomerular Filtration o Factors influencing Actual Filtration • Tubular Reabsorption • Tubular Secretion • Urine Formation (Video) RENAL FUNCTION STAGES OF URINE FORMATION • Glomerular filtration (blood plasma spills out) • Tubular reabsorption (some items are selectively reabsorbed into the blood) • Tubular secretion (some blood plasma items are selectively sent out into the tubules) GLOMERULAR FILTRATION • Glomerulus – primary site of urine formation • Glomerulus has approximately 8 capillary lobes referred as Capillary tuft • Bowman’s capsule – forms the beginning of renal tubule • Non-selective filter of plasma substance with molecule weights of less than 70,000 molecular weight FACTORS INFLUENCING ACTUAL FILTRATION • Cellular structure o 3 Cellular Layers: ▪ Capillary wall Membrane ▪ Endothelial cells – contains pores and referred as fenestrated , Increased capillary permeability but don’t allow passage of large molecules. ▪ Basement Membrane o Bowman’s capsule – podocytes – intertwining functional processes • Glomerular Pressure o Hydrostatic pressure - increased or enhance filtration o Afferent arteriole : variation in size – Auto regulatory mechanism w/in juxtaglomerular apparatus maintains Glomerular blood pressure at a relative constant rate. o Dilation (Afferent Arteriole) & Constriction (Efferent Arteriole) when Blood Pressure drops - prevents marked down blood flowing through kidney therefore, prevents increase in blood level toxic waste product. o Increased blood pressure will result in constriction of Afferent arteriole to prevent overfiltration that Can cause damage to the Glomerulus. • Renin-Angiotensin-Aldosterone o Controls the regulation of blood filtration within Glomerulus o The system Responds to: ▪ Changes in blood pressure ▪ Plasma sodium content – by means of Juxtaglomerular apparatus (JGA) o Juxtaglomerular apparatus (JGA): ▪ JG cells + macula densa (inside the distal convoluted Tubule) ▪ Low plasma Na content – low H 2 O retention within the circulation; low blood volume and low blood pressure. ▪ Macula densa – senses this changes o Renin - an enzyme that reacts with angiotensinogen (Blood borne substrate) produce angiotensin 1 (inert hormone) o Action Of RAAS : ▪ Lungs (has Angiotensin1 converting enzyme) angiotensin II (active form) corrects renal blood filtration by: • Dilation of afferent arteriole and constriction of efferent arteriole. • Stimulation of sodium reabsorption in proximal convoluted tubule. • Triggers Adrenal Cortex to release aldosterone to cause reabsorption of sodium and excretion of potassium in the distal convoluted tubule and collecting duct. • Triggers the release of anti-diuretic hormone (ADH) (hypothalamus) to stimulate H2O reabsorption in collecting duct ▪ High BP and High Plasma Solution = Low Renin ▪ 120mL of H2O containing low molecular weight substances. ▪ Specific gravity: 1.010 – confirm: ultra filtrate plasma – useful for evaluating renal mechanism in convert plasma ultra filtrate into final urinary filtrate. TUBULAR REABSORPTION • Proximal Convoluted Tubule – reabsorption o Reabsorption Mechanism • Active transport – must combine w/ carrier protein • Electrochemical energy • When the glomerular filtrate exits the Bowman's Capsule, it enters the proximal convoluted tubule. Passive and active reabsorption occur here. This tubule contains many microvilli which increase the surface area for the reabsorption. • The cells surrounding this tubule contain numerous mitochondria for the active reabsorption. It's called selective reabsorption because only substances which are recognized by carrier proteins are actively reabsorbed into the peritubular capillaries • In passive reabsorption, the nutrients diffuse back into the blood. Also, some of the sodium ions are passively and actively transported into the blood; therefore, some of the chlorine ions passively follow. Because these ions cause a greater solute concentration, most of the water will go back into the blood stream by osmosis. Since the peritubular capillaries surround the nephron, this process occurs throughout the entire nephron.
TUBULAR SECRETION • occurs at the distal convoluted tubule. • Involves the passage of substances from the blood in the peritubular capillaries to the tubular filtrate. • Functions : o Elimination of waste products. o Regulation of Acid-Base balance in body through H+ secretions. o Proximal Convoluted Tubule: major site of removal of non-filtered waste products. ▪ Acid-Base Balance o Normal blood pH: 7.4 o Bicarbonate (HCO 3 ): buffer capacity of blood depends in it. o Secretion of H+ at renal tubular cells – prevents HCO3 excretion – reabsorption occurs at proximal convoluted tubules. • Secretory Functions : o H2PO4 excretion o NH4 excretion o Reabsorb HCO 3 s o Disruption of secretory functions will cause: Metabolic / Renal Tubular ACIDOSIS URINE FORMATION (VIDEO) • Kidneys o Filter blood plasma, removing metabolic wastes, toxins from the body and excrete them in the form of urine. o Maintain constant volume and composition of the blood, or homeostasis. • Blood enters the kidney via the renal artery, which divides to smaller arteries and finally arterioles. The arterioles get into contact with functional units of the kidney called nephrons . This is where blood filtration and urine formation take place. • The filtered blood is then collected in to a series of larger veins and exits the kidney through the renal vein. • The urine is collected in collecting ducts and leaves the kidney via the ureters. • Each kidney contains over a million nephrons. A nephron consists of 2 major parts: a capsule known as glomerular capsule, or Bowman’s capsule; and a long renal tubule. • Renal tubules of several nephrons connect to a common collecting duct. • There are 3 steps in the formation of urine: o glomerular filtration takes place in the Bowman’s capsule o tubular reabsorption and secretion occur in the renal tubule • Water conservation happens in the collecting duct Blood enters the Bowman’s capsule via the afferent arteriole, passes through a ball of capillaries called the glomerulus, and leaves via the efferent arteriole. • The afferent arteriole is significantly larger than the efferent arteriole, creating a blood flow with a large inlet and small outlet. As a result, the blood hydrostatic pressure in these capillaries is much higher than normal. • Hydrostatic and osmotic pressures drive water and solutes from blood plasma through a filtration membrane into the capsular space of nephron. • The filtration membrane acts like a sieve allowing only small molecules to pass through. o These include water, inorganic ions, glucose, amino acids and various metabolic wastes such as urea and creatinine. o This fluid is called glomerular filtrate. o The amount of filtrate produced per minute is called glomerular filtration rate, or GFR. • The GFR is kept at a stable value by several feedback mechanisms within the kidneys. This is known as renal autoregulation. o The GFR is also under sympathetic and hormonal control. o GFR control is generally achieved by constriction or dilation of the afferent arteriole, which causes the glomerular blood pressure to fall or rise, respectively. o In a healthy person, the total filtrate volume amounts between 150 and 180 litters a day. o However, only about 1% of this is excreted as urine, the rest 99% is re-absorbed back to the blood as the filtrate flows through the long renal tubule. • This is possible because the efferent arteriole, after exiting the Bowman’s capsule, branches out to form a network of capillaries, known as peri-tubular capillaries , which surround the renal tubule. • The first part of the renal tubule – the proximal convoluted tubule , re-absorbs about two thirds of the filtrate. o In this process, water and solutes are driven through the epithelial cells that line the tubule into the extracellular space. o They are then taken up by the peritubular capillaries. • Sodium reabsorption is most important, as it creates osmotic pressure that drives water and electrical gradient that drives negatively charged ions. o Sodium level inside the epithelial cells is kept low thanks to the sodium-potassium pumps that constantly pump sodium ions out into the extracellular space. o This creates a concentration gradient that favors sodium diffusion from tubular fluid into the cells. o Sodium is absorbed by symport proteins that also bind glucose and some other solutes. o Nearly all glucose and amino acids are re-absorbed back to the blood at this stage.
o About half of nitrogenous wastes also re-absorbs back to the bloodstream. • The kidneys reduce the blood levels of metabolic wastes to a safe amount, but do not completely eliminate them. • Some of the re-absorption also occurs by the paracellular route through tight junctions between the epithelial cells. • At the same time, tubular secretion , where additional wastes, drugs and other solutes leave the bloodstream to join the tubular fluid, also takes place. • The processes of re-absorption and secretion continue in the nephron loop – the loop of Henle, and the distal convoluted tubule. • The main function of the loop of Henle is to create and maintain an osmolarity gradient in the medulla that enables the collecting ducts to concentrate urine at a later stage. o The ascending limb of the loop actively pumps sodium out making the medulla “salty”. o The descending limb of the loop is permeable to water but much less to sodium. • As the water exits the tubule by osmosis, the filtrate gets more and more concentrated as it reaches the bottom. • The ascending limb , on the other hand, is permeable to ions but not water. As a result, the filtrate loses sodium as it goes up and becomes more diluted at the top of the loop. • The medulla is in equilibrium with the loop and hence has the same salinity gradient - saltier at the bottom. • Re-absorption and secretion in the distal convoluted tubule are under control of various hormones. o This is how the kidney respond to the body’s needs and adjust the composition of urine accordingly. • The collecting duct receives tubular fluid from several nephrons. o The main function of the collecting duct is to concentrate urine and therefore conserve water. o This is made possible by the osmolarity gradient generated by the loop of Henle. o As it gets saltier deep in the medulla, the filtrate loses more and more water as it flows down the collecting duct. o The collecting duct is also under hormonal control so it can adjust the amount of re-absorbed water accordingly to the body’s state of hydration. o For example, when the body is dehydrated, more water is re-absorbed back to the blood and the small volume of excreted urine is more concentrated.