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Unformatted text preview: 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Boundless Anatomy and Physiology Urinary System Physiology of the Kidneys 1/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Overview of Urine Formation Urine is formed in three steps: ltration, reabsorption, and secretion. LEARNING OBJECTIVES Summarize the steps in urine formation KEY TAKEAWAYS Key Points Filtration involves the transfer of soluble components, such as water and waste, from the blood into the glomerulus. Reabsorption involves the absorption of molecules, ions, and water that are necessary for the body to maintain homeostasis from the glomerular ltrate back into the blood. Secretion involves the transfer of hydrogen ions, creatinine, drugs, and urea from the blood into the collecting duct, and is primarily made of water. Blood and glucose are not normally found in urine. Key Terms urine: A liquid excrement consisting of water, salts, and urea, which is made in the kidneys then released through the urethra. glomerulus: A small, intertwined group of capillaries within nephrons of the kidney that lter the blood to make urine. 2/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system ltration. The primary function of the renal system is to regulate blood volume and plasma osmolarity, and waste removal via urine is essentially a convenient way that the body performs many functions using one process. Urine formation occurs during three processes: 1. Filtration 2. Reabsorption 3. Secretion Filtration During ltration, blood enters the a erent arteriole and ows into the glomerulus where lterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and non lterable components, such as cells and serum albumins, will exit via the e erent arteriole. These lterable components accumulate in the glomerulus to form the glomerular ltrate. Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo ltration; this is called the ltration fraction. The remaining 80% of the blood ows through the rest of the body to facilitate tissue perfusion and gas exchange. Reabsorption The next step is reabsorption, during which molecules and ions will be reabsorbed into the circulatory system. The uid passes through the components of the nephron (the proximal/distal convoluted tubules, loop of Henle, the collecting duct) as water and ions are removed as the uid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the uid leaves the ureter in the form of urine. 3/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Secretion During secretion some substances±such as hydrogen ions, creatinine, and drugs—will be removed from the blood through the peritubular capillary network into the collecting duct. The end product of all these processes is urine, which is essentially a collection of substances that has not been reabsorbed during glomerular ltration or tubular reabsorbtion. Urine is mainly composed of water that has not been reabsorbed, which is the way in which the body lowers blood volume, by increasing the amount of water that becomes urine instead of becoming reabsorbed. The other main component of urine is urea, a highly soluble molecule composed of ammonia and carbon dioxide, and provides a way for nitrogen (found in ammonia) to be removed from the body. Urine also contains many salts and other waste components. Red blood cells and sugar are not normally found in urine but may indicate glomerulus injury and diabetes mellitus respectively. Normal kidney physiology: This illustration demonstrates the normal kidney physiology, showing where some types of diuretics act, and what they do. Glomerular Filtration Glomerular ltration is the renal process whereby uid in the blood is 4/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology ltered across the capillaries of the glomerulus. LEARNING OBJECTIVES Explain the process of glomerular ltration in the kidneys KEY TAKEAWAYS Key Points The formation of urine begins with the process of ltration. Fluid and small solutes are forced under pressure to ow from the glomerulus into the capsular space of the glomerular capsule. The Bowman’s capsule is the ltration unit of the glomerulus and has tiny slits in which ltrate may pass through into the nephron. Blood entering the glomerulus has lterable and non- lterable components. Filterable blood components include water, nitrogenous waste, and nutrients that will be transferred into the glomerulus to form the glomerular ltrate. Non- lterable blood components include blood cells, albumins, and platelets, that will leave the glomerulus through the e erent arteriole. Glomerular ltration is caused by the force of the di erence between hydrostatic and osmotic pressure (though the glomerular ltration rate includes other variables as well). Key Terms glomerulus: A small, intertwined group of capillaries within nephrons of the kidney that lter the blood to 5/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology make urine. hydrostatic pressure: The pushing force exerted by the pressure in a blood vessel. It is the primary force that drives glomerular ltration. Glomerular ltration is the rst step in urine formation and constitutes the basic physiologic function of the kidneys. It describes the process of blood ltration in the kidney, in which uid, ions, glucose, and waste products are removed from the glomerular capillaries. Many of these materials are reabsorbed by the body as the uid travels through the various parts of the nephron, but those that are not reabsorbed leave the body in the form of urine. Glomerulus Structure Blood plasma enters the a erent arteriole and ows into the glomerulus, a cluster of intertwined capillaries. The Bowman’s capsule (also called the glomerular capsule) surrounds the glomerulus and is composed of visceral (simple squamous epithelial cells—inner) and parietal (simple squamous epithelial cells—outer) layers. The visceral layer lies just beneath the thickened glomerular basement membrane and is made of podocytes that form small slits in which the uid passes through into the nephron. The size of the ltration slits restricts the passage of large Glomerulus structure: A diagram showing the a erent and e erent arterioles bringing blood in and out of the Bowman’s capsule, a cup-like sac at the beginning of the tubular component of a nephron. molecules (such as albumin) and 6/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology cells (such as red blood cells and platelets) that are the non- lterable components of blood. These then leave the glomerulus through the e erent arteriole, which becomes capillaries meant for kidney–oxygen exchange and reabsorption before becoming venous circulation. The positively charged podocytes will impede the ltration of negatively charged particles as well (such as albumins). The Mechanisms of Filtration The process by which glomerular ltration occurs is called renal ultra ltration. The force of hydrostatic pressure in the glomerulus (the force of pressure exerted from the pressure of the blood vessel itself) is the driving force that pushes ltrate out of the capillaries and into the slits in the nephron. Osmotic pressure (the pulling force exerted by the albumins) works against the greater force of hydrostatic pressure, and the di erence between the two determines the e ective pressure of the glomerulus that determines the force by which molecules are ltered. These factors will in uence the glomeruluar ltration rate, along with a few other factors. Regulation of Glomerular Filtration Rate Regulation of GFR requires both a mechanism of detecting an inappropriate GFR as well as an e ector mechanism that corrects it. LEARNING OBJECTIVES List the conditions that can a ect the glomerular ltration rate (GFR) in kidneys and the manner of its regulation 7/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology KEY TAKEAWAYS Key Points Glomerular ltration is occurs due to the pressure gradient in the glomerulus. Increased blood volume and increased blood pressure will increase GFR. Constriction in the a erent arterioles going into the glomerulus and dilation of the e erent arterioles coming out of the glomerulus will decrease GFR. Hydrostatic pressure in the Bowman’s capsule will work to decrease GFR. Normally, the osmotic pressure in the Bowman’s space is zero, but it will become present and decrease GFR if the glomerulus becomes leaky. Low GFR will activate the renin–angiotensin feedback system that will address the low GFR by increasing blood volume. Key Terms Bowman’s capsule: A cup-like sac at the beginning of the tubular component of a nephron in the mammalian kidney. osmotic pressure: The pressure exerted by proteins that attracts water. Water tends to follow proteins based on an osmotic pressure gradient. Glomerular Filtration Rate Glomerular ltration rate (GFR) is the measure that describes the total amount of ltrate formed by all the renal corpuscles in both kidneys per minute. The glomerular ltration rate is directly proportional to the 8/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology pressure gradient in the glomerulus, so changes in pressure will change GFR. GFR is also an indicator of urine production, increased GFR will increase urine production, and vice versa. The Starling equation for GFR is: GFR=Filtration Constant × (Hydrostatic Glomerulus Pressure–Hydrostatic Bowman’s Capsule Pressure)–(Osmotic Glomerulus Pressure+Osmotic Bowman’s Capsule Pressure) The ltration constant is based on the surface area of the glomerular capillaries, and the hydrostatic pressure is a pushing force exerted from the ow of a uid itself; osmotic pressure is the pulling force exerted by proteins. Changes in either the hydrostatic or osmotic pressure in the glomerulus or Bowman’s capsule will change GFR. Hydrostatic Pressure Changes Many factors can change GFR through changes in hydrostatic pressure, in terms of the ow of blood to the glomerulus. GFR is most sensitive to hydrostatic pressure changes within the glomerulus. A notable bodywide example is blood volume. Due to Starling’s law of the heart, increased blood volume will increase blood pressure throughout the body. The increased blood volume with its higher blood pressure will go into the a erent arteriole and into the glomerulus, resulting in increased GFR. Conversely, those with low blood volume due to dehydration will have a decreased GFR. Pressure changes within the a erent and e erent arterioles that go into and out of the glomerulus itself will also impact GFR. Vasodilation in the a erent arteriole and vasconstriction in the e erent arteriole will increase blood ow (and hydrostatic pressure) in the glomerulus and will increase GFR. Conversely, vasoconstriction in the a erent arteriole and vasodilation in the e erent arteriole will decrease GFR. 9/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology The Bowman’s capsule space exerts hydrostatic pressure of its own that pushes against the glomerulus. Increased Bowman’s capsule hydrostatic pressure will decrease GFR, while decreased Bowman’s capsule hydrostatic pressure will increase GFR. An example of this is a ureter obstruction to the ow of urine that gradually causes a uid buildup within the nephrons. An obstruction will increase the Bowman’s capsule hydrostatic pressure and will consequently decrease GFR. Osmotic Pressure Changes Osmotic pressure is the force exerted by proteins and works against ltration because the proteins draw water in. Increased osmotic pressure in the glomerulus is due to increased serum albumin in the bloodstream and decreases GFR, and vice versa. Under normal conditions, albumins cannot be ltered into the Bowman’s capsule, so the osmotic pressure in the Bowman’s space is generally not present, and is removed from the GFR equation. In certain kidney diseases, the basement membrane may be damaged (becoming leaky to proteins), which results in decreased GFR due to the increased Bowman’s capsule osmotic pressure. 10/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Glomeruluar ltration: The glomerulus (red) lters uid into the Bowman’s capsule (blue) that sends uid through the nephron (yellow). GFR is the rate at which is this ltration occurs. GFR Feedback GFR is one of the many ways in which homeostasis of blood volume and blood pressure may occur. In particular, low GFR is one of the variables that will activate the renin–angiotensin feedback system, a complex process that will increase blood volume, blood pressure, and GFR. This system is also activated by low blood pressure itself, and sympathetic nervous stimulation, in addition to low GFR. Tubular Reabsorption Tubular reabsorption is the process by which solutes and water are removed from the tubular uid and transported into the blood. LEARNING OBJECTIVES Describe the process of tubular reabsorption in kidney 11/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology physiology KEY TAKEAWAYS Key Points Proper function of the kidney requires that it receives and adequately lters blood. Reabsorption includes passive di usion, active transport, and cotransport. Water is mostly reabsorbed by the cotransport of glucose and sodium. Filtrate osmolarity changes drastically throughout the nephron as varying amounts of the components of ltrate are reabsorbed in the di erent parts of the nephron. The normal osmolarity of plasma is 300 mOsm/L, which is the same osmolarity within the proximal convoluted tubule. Key Terms NA+/K+ ATPase: An ATPase pump that consumes ATP to facilitate the active transport of ions in ltrate of the nephron. peri-tubular capillaries: The capillaries through which components of ltrate are reabsorbed from the lumen of the nephron. Filtrate The uid ltered from blood, called ltrate, passes through the nephron, much of the ltrate and its contents are reabsorbed into the body. Reabsorption is a nely tuned process that is altered to maintain 12/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology homeostasis of blood volume, blood pressure, plasma osmolarity, and blood pH. Reabsorbed uids, ions, and molecules are returned to the bloodstream through the peri-tubular capillaries, and are not excreted as urine. Mechanisms of Reabsorption Reabsorption in the nephron may be either a passive or active process, and the speci c permeability of the each part of the nephron varies considerably in terms of the amount and type of substance reabsorbed. The mechanisms of reabsorption into the peri-tubular capillaries include: Passive di usion—passing through plasma membranes of the kidney epithelial cells by concentration gradients. Active transport— Tubular secretion: Diagram showing the basic physiologic mechanisms of the kidney and the three steps involved in urine formation. Namely ltration, reabsorption, secretion, and excretion. membrane-bound ATPase pumps (such as NA+/K+ ATPase pumps) with carrier proteins that carry substances across the plasma membranes of the kidney epithelial cells by consuming ATP. Cotransport—this process is particularly important for the reabsorption of water. Water can follow other molecules that are actively transported, particularly glucose and sodium ions in the nephron. These processes involve the substance passing though the luminal barrier and the basolateral membrane, two plasma membranes of the kidney epithelial cells, and into the peri-tubular capillaries on the other 13/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology side. Some substances can also pass through tiny spaces in between the renal epithelial cells, called tight junctions. Osmolarity Changes As ltrate passes through the nephron, its osmolarity (ion concentration) changes as ions and water are reabsorbed. The ltrate entering the proximal convoluted tubule is 300 mOsm/L, which is the same osmolarity as normal plasma osmolarity. In the proximal convoluted tubules, all the glucose in the ltrate is reabsorbed, along with an equal concentration of ions and water (through cotransport), so that the ltrate is still 300 mOsm/L as it leaves the tubule. The ltrate osmolarity drops to 1200 mOsm/L as water leaves through the descending loop of Henle, which is impermeable to ions. In the ascending loop of Henle, which is permeable to ions but not water, osmolarity falls to 100–200 mOsm/L. Finally, in the distal convoluted tubule and collecting duct, a variable amount of ions and water are reabsorbed depending on hormonal stimulus. The nal osmolarity of urine is therefore dependent on whether or not the nal collecting tubules and ducts are permeable to water or not, which is regulated by homeostasis. 14/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Reabsorption throughout the nephron: A diagram of the nephron that shows the mechanisms of reabsorption. Tubular Secretion Hydrogen, creatinine, and drugs are removed from the blood and into the collecting duct through the peritubular capillary network. LEARNING OBJECTIVES Describe the purpose of tubular secretion in kidney physiology KEY TAKEAWAYS Key Points The substance that remains in the collecting duct of the kidneys following reabsorption is better known as urine. Secreted substances largely include hydrogen, creatinine, ions, and other types of waste products, such as drugs. Tubular secretion is the transfer of materials from peritubular capillaries to the renal tubular lumen and occurs mainly by active transport and passive di usion. It is the tubular secretion of H+ and NH4+ from the blood into the tubular uid that helps to keep blood pH at its normal level—this is also a respiratory process. Urine leaves the kidney though the ureter following secretion. Key Terms 15/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology collecting duct: A system of the kidneys that consists of a series of tubules and ducts that connect the nephrons to the ureter. peritubular capillaries: Tiny blood vessels that travel alongside nephrons, allowing reabsorption and secretion between blood and the inner lumen of the nephron. lumen: The inside space of a tubular structure, such as an artery or intestine. Tubular secretion is the transfer of materials from peritubular capillaries to the renal tubular lumen; it is the opposite process of reabsorption. This secretion is caused mainly by active transport and passive di usion. Usually only a few substances are secreted, and are typically waste products. Urine is the substance leftover in the collecting duct following reabsorption and secretion. Mechanisms of Secretion The mechanisms by which secretion occurs are similar to those of reabsorption, however these processes occur in the opposite direction. Passive di usion—the movement of molecules from the peritubular capillaries to the intersitial uid within the nephron. Active transport—the movement of molecules via ATPase pumps that transport the substance through the renal epithelial cell into the lumen of the nephron. Renal secretion is di erent from reabsorption because it deals with ltering and cleaning substances from the blood, rather than retaining them. The substances that are secreted into the tubular uid for removal from the body include: Potassium ions (K+) 16/18 8/7/2019 Physiology of the Kidneys | Boundless Anatomy and Physiology Hydrogen ions (H+) Ammonium ions (NH4+) Creatinine Urea Some hormones Some drugs (e.g., penicillin) Many pharmaceutical drugs are protein-bound molecules thatDiagram showing the basic physiologic mechanisms of the kidney an...
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