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Physiology of the Kidneys is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
Urine Formation is the liquid waste product of the human body. It contains urea, uric acid, salts, water and other waste products that are the result of various metabolic processes occurring in the body. It is formed in the primary excretory organs– the kidneys. The structural and functional unit of the kidneys is called the nephrons. Millions of nephrons are involved in the process of urine formation.
The kidneys function in a wide variety of ways necessary for health. They excrete metabolic waste, regulate fluid and electrolyte balance, promote bone integrity, and more. These two bean-shaped organs interact with the cardiovascular system to maintain hemodynamic stability. Renal blood flow (RBF) and glomerular filtration are important aspects of sustaining proper organ functions. A delicate balance exists between renal blood flow and the glomerular filtration rate as changes in one may affect the other.
Anatomy of the Nephron
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The anatomy of the nephron is important to understand the urine formation process. Each nephron is made up of two parts:
- Renal Corpuscle
- Renal Tubule
The renal corpuscle is divided into the glomerular capillaries or glomerulus and the Bowman’s capsule. It is in the renal corpuscle that the blood is filtered at high pressure. The arteriole that brings blood into the glomerulus is called the afferent arteriole whereas the artery that takes blood away from the glomerulus is known as the efferent arteriole.
Between these arterioles forms, a network of capillaries called the glomerular capillaries of the glomerulus. The Bowman’s capsule is a cup-shaped structure in which this glomerulus is located. The glomerulus along with the Bowman’s capsule achieve the filtration of blood to form urine. The renal tubule consists of :
- The proximal convoluted Tubule(PCT)
- The U-shaped Loop Of Henle
- The Distal Convoluted Tubule(DCT)
Once the blood is filtered in the renal corpuscle, the resultant fluid is called the glomerular filtrate. This glomerular filtrate now passes into the PCT. In the PCT, substances like NaCl, K+, water, glucose, and bicarbonate are reabsorbed into the filtrate whereas urea, creatinine, uric acid are added to the filtrate.
From the PCT, the filtrate enters the U-shaped Loop of Henle where reabsorption and secretion of water and various metabolites occurs. The filtrate then passes into the DCT. From the DCT, the filtrate passes into the collecting tubules, into the renal pelvis, and the ureters as urine to be stored int the urinary bladder.
Process of Urine Formation
Glomerular Filtration
This process occurs in the glomerular capillaries. The process of filtration leads to the formation of an ultrafiltrate. The blood gushes into these capillaries with high pressure and gets filtered across the thin capillary walls. Everything except the blood cells and proteins are pushed into the capsular space of the Bowman’s capsule to form the ultrafiltrate. The glomerular filtration rate (GFR) is 125ml/min or 180 Litres/day.
Tubular Reabsorption
During glomerular filtration, all substances except blood cells and proteins are pushed through the capillaries at high pressure. At the level of the Proximal Convoluted Tubule(PCT), some of the substances from the filtrate are reabsorbed. These include sodium chloride, potassium, glucose, amino acids, bicarbonate, and 75% of water.
Absorption of some substances is passive, some substances are actively transported while others are co-transported. The absorption depends upon the permeability of different parts of the nephron. The distal convoluted tubule shows selective absorption. The substances and water which is reabsorbed are taken up by the peritubular capillaries to be returned to the blood.
Tubular Secretion
The peritubular capillaries that help in transporting the reabsorbed substances into the bloodstream, also help in actively secreting substances like H+ ions, K+ ions. Whenever excess K+ is secreted into the filtrate, Na+ ions are actively reabsorbed to maintain the Na-K balance. Some drugs are not filtered in the glomerulus and so are actively secreted into the filtrate during the tubular secretion phase.
Composition of Urine
Physical characteristics: Urine is the waste product that is eliminated by the kidneys. Urine contains waste products like urea, salts, excess ions, water, and metabolized products of drugs.
Urine is often light or pale yellow in color and fresh urine has a slight ammoniacal smell. It is often clear in turbidity with a pH of around 4-8. These characteristics vary depending upon the nature of the disease in the body. Often a urine sample analysis helps to detect diseases like insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes, kidney failures, etc.
Chemical composition: Chemically, urine is composed mainly of urea, sodium chloride, potassium ions, creatinine, ammonia products, and some amount of protein, and other metabolites. Certain abnormalities in the urine composition occur in the following:
- Hematuria- When blood is found in the urine, the condition is called hematuria. This indicates some pathology either injury or infection-related.
- Pyuria- This condition is characterized by the presence of pus cells in the urine. This indicates the presence of infection somewhere in the body.
- Glycosuria- This is a condition characterized by the presence of glucose in the urine. This is indicative of insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes that is most likely uncontrolled.
- Proteinuria- This is a condition where protein molecules are found in the urine. This indicates some defect in the kidney’s filtration process.
Overview of Urine Formation
Urine is formed in three steps: filtration, reabsorption, and secretion.
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 filtrate 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 filter the blood to make urine.
Urine is a waste byproduct formed from excess water and metabolic waste molecules during the process of renal system filtration. 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:
- Filtration
- Reabsorption
- Secretion
Filtration
During filtration, blood enters the afferent arteriole and flows into the glomerulus where filterable blood components, such as water and nitrogenous waste, will move towards the inside of the glomerulus, and nonfilterable components, such as cells and serum albumins, will exit via the efferent arteriole. These filterable components accumulate in the glomerulus to form the glomerular filtrate.
Normally, about 20% of the total blood pumped by the heart each minute will enter the kidneys to undergo filtration; this is called the filtration fraction. The remaining 80% of the blood flows 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 fluid 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 fluid osmolarity (ion concentration) changes. In the collecting duct, secretion will occur before the fluid leaves the ureter in the form of urine.
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 filtration 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 insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।" data-rx-term="diabetes" data-rx-definition="Diabetes is a condition where blood sugar stays too high because insulin is low or not working well. সহজ বাংলা: রক্তে চিনি বেশি থাকার রোগ।">diabetes mellitus respectively.
Normal kidney physiology: This illustration demonstrates normal kidney physiology, showing where some types of diuretics act, and what they do.
Glomerular Filtration
Glomerular filtration is the renal process whereby fluid in the blood is filtered across the capillaries of the glomerulus.
Key Points
The formation of urine begins with the process of filtration. Fluid and small solutes are forced under pressure to flow from the glomerulus into the capsular space of the glomerular capsule.
The Bowman’s capsule is the filtration unit of the glomerulus and has tiny slits in which filtrate may pass through into the nephron. Blood entering the glomerulus has filterable and non-filterable components.
Filterable blood components include water, nitrogenous waste, and nutrients that will be transferred into the glomerulus to form the glomerular filtrate.
Non-filterable blood components include blood cells, albumins, and platelets, that will leave the glomerulus through the efferent arteriole.
Glomerular filtration is caused by the force of the difference between hydrostatic and osmotic pressure (though the glomerular filtration rate includes other variables as well).
Key Terms
- glomerulus: A small, intertwined group of capillaries within nephrons of the kidney that filter the blood to make urine.
- hydrostatic pressure: The pushing force exerted by the pressure in a blood vessel. It is the primary force that drives glomerular filtration.
Glomerular filtration is the first step in urine formation and constitutes the basic physiologic function of the kidneys. It describes the process of blood filtration in the kidney, in which fluid, ions, glucose, and waste products are removed from the glomerular capillaries.
Many of these materials are reabsorbed by the body as the fluid travels through the various parts of the nephron, but those that are not reabsorbed leave the body in the form of urine.
Glomerulus Structure
Glomerulus structure: A diagram showing the afferent and efferent 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.
Blood plasma enters the afferent arteriole and flows 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 fluid passes through into the nephron. The size of the filtration slits restricts the passage of large molecules (such as albumin) and cells (such as red blood cells and platelets) that are the non-filterable components of blood.
These then leave the glomerulus through the efferent arteriole, which becomes capillaries meant for kidney–oxygen exchange and reabsorption before becoming venous circulation. The positively charged podocytes will impede the filtration of negatively charged particles as well (such as albumins).
The Mechanisms of Filtration
The process by which glomerular filtration occurs is called renal ultrafiltration. 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 filtrate 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 difference between the two determines the effective pressure of the glomerulus that determines the force by which molecules are filtered. These factors will influence the glomeruluar filtration 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 effector mechanism that corrects it.
Key Points
Glomerular filtration is occurred due to the pressure gradient in the glomerulus.
Increased blood volume and increased blood pressure will increase GFR.
Constriction in the afferent arterioles going into the glomerulus and dilation of the efferent 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 filtration rate (GFR) is the measure that describes the total amount of filtrate formed by all the renal corpuscles in both kidneys per minute. The glomerular filtration rate is directly proportional to the 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 filtration constant is based on the surface area of the glomerular capillaries, and the hydrostatic pressure is a pushing force exerted from the flow of a fluid 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 flow of blood to the glomerulus. GFR is most sensitive to hydrostatic pressure changes within the glomerulus. A notable body-wide 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 afferent 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 afferent and efferent arterioles that go into and out of the glomerulus itself will also impact GFR. Vasodilation in the afferent arteriole and vasoconstriction in the efferent arteriole will increase blood flow (and hydrostatic pressure) in the glomerulus and will increase GFR. Conversely, vasoconstriction in the afferent arteriole and vasodilation in the efferent arteriole will decrease GFR.
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 flow of urine that gradually causes a fluid 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 filtration 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 filtered 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.
Glomeruluar filtration: The glomerulus (red) filters fluid into the Bowman’s capsule (blue) that sends fluid through the nephron (yellow). GFR is the rate at which is this filtration 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 fluid and transported into the blood.
Key Points
Proper function of the kidney requires that it receives and adequately filters blood.
Reabsorption includes passive diffusion, 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 filtrate are reabsorbed in the different 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 infiltrate of the nephron.
- peri-tubular capillaries: The capillaries through which components of filtrate are reabsorbed from the lumen of the nephron.
Filtrate
The fluid filtered from the blood, called filtrate, passes through the nephron, much of the filtrate and its contents are reabsorbed into the body. Reabsorption is a finely tuned process that is altered to maintain homeostasis of blood volume, blood pressure, plasma osmolarity, and blood pH. Reabsorbed fluids, ions, and molecules are returned to the bloodstream through the peritubular capillaries and are not excreted as urine.
Mechanisms of Reabsorption
Tubular secretion: Diagram showing the basic physiologic mechanisms of the kidney and the three steps involved in urine formation. Namely filtration, reabsorption, secretion, and excretion.
Reabsorption in the nephron may be either a passive or active process, and the specific permeability of each part of the nephron varies considerably in terms of the amount and type of substance reabsorbed. The mechanisms of reabsorption into the peritubular capillaries include:
- Passive diffusion—passing through plasma membranes of the kidney epithelial cells by concentration gradients.
- Active transport—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 through the luminal barrier and the basolateral membrane, two plasma membranes of the kidney epithelial cells, and into the peritubular capillaries on the other side. Some substances can also pass through tiny spaces in between the renal epithelial cells, called tight junctions.
Osmolarity Changes
As filtrate passes through the nephron, its osmolarity (ion concentration) changes as ions and water are reabsorbed. The filtrate 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 filtrate is reabsorbed, along with an equal concentration of ions and water (through cotransport), so that the filtrate is still 300 mOsm/L as it leaves the tubule. The filtrate 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 final osmolarity of urine is therefore dependent on whether or not the final collecting tubules and ducts are permeable to water or not, which is regulated by homeostasis.
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.
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 diffusion.
It is the tubular secretion of H+ and NH4+ from the blood into the tubular fluid that helps to keep blood pH at its normal level—this is also a respiratory process.
Urine leaves the kidney through the ureter following secretion.
Key Terms
- 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 diffusion.
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 diffusion—the movement of molecules from the peritubular capillaries to the interstitial fluid 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 different from reabsorption because it deals with filtering and cleaning substances from the blood, rather than retaining them. The substances that are secreted into the tubular fluid for removal from the body include:
- Potassium ions (K+)
- Hydrogen ions (H+)
- Ammonium ions (NH4+)
- Creatinine
- Urea
- Some hormones
- Some drugs (e.g., penicillin)
Tubular secretion: Diagram showing the basic physiologic mechanisms of the kidney and the three steps involved in urine formation.
Many pharmaceutical drugs are protein-bound molecules that diagram showing the basic physiologic mechanisms of the kidney and the three steps involved in urine formation. namely filtration, reabsorption, secretion, and excretion. are easily secreted, which is why urine testing can detect exposure to many types of drugs. Tubular secretion occurs throughout the different parts of the nephron, from the proximal convoluted tubule to the collecting duct at the end of the nephron.
Hydrogen Ion Secretion
The tubular secretion of H+ and NH4+ from the blood into the tubular fluid is involved in blood pH regulation. The movement of these ions also helps to conserve sodium bicarbonate (NaHCO3). The typical pH of urine is about 6.0, while it is ideally 7.35 to 7.45 for blood.
pH regulation is primarily a respiratory system process, due to the exchange of carbon dioxide (a component of carbonic acid in the blood), however tubular secretion assists in pH homeostasis as well.
Following Secretion
Urine that is formed via the three processes of filtration, reabsorption, and secretion leaves the kidney through the ureter and is stored in the bladder before being removed through the urethra. At this final stage, it is only approximately one percent of the originally filtered volume, consisting mostly of water with highly diluted amounts of urea, creatinine, and variable concentrations of ions.
References
- https://www.ncbi.nlm.nih.gov/books/NBK500032/
- https://www.ncbi.nlm.nih.gov/books/NBK554544/
- https://www.ncbi.nlm.nih.gov/books/NBK482248/
- https://www.ncbi.nlm.nih.gov/books/NBK442014/
- https://www.ncbi.nlm.nih.gov/books/NBK559101/
- https://www.ncbi.nlm.nih.gov/books/NBK482482/
- https://www.ncbi.nlm.nih.gov/books/NBK305/
- https://www.ncbi.nlm.nih.gov/books/NBK547747/
- https://www.ncbi.nlm.nih.gov/books/NBK560738/
- https://www.ncbi.nlm.nih.gov/books/NBK519537/
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- https://www.ncbi.nlm.nih.gov/books/NBK470410/
- https://www.ncbi.nlm.nih.gov/books/NBK559227/
- https://en.wikipedia.org/wiki/Renal_physiology
