What is Kidney Function and Physiology?

Kidneys are:

• Two bean-shaped organs of the renal system are responsible for blood filtration.
• Removing waste items and drugs.
• Balancing fluids.
• Releasing hormones that regulate blood pressure.
• Producing an active form of vitamin D for bones and controlling the production of red blood cells.

The kidneys lie below the rib cage on both sides of the spine. The left kidney sits slightly higher than the right kidney.

The weight of both kidneys slightly differs in males and females. The kidney of a newborn baby is approximately 50g in body weight. The weight of both kidneys reaches up to 270g in adults aged 22-25.

In males, the average weight of the right kidney is 129g, and that of the left kidney is 137 g. Similarly, in females, the average weight of the right kidney is 108g, while that of the left kidney is 116g. Both kidneys are 10-12 cm long, 5-7 cm wide, and 3-4 cm thick.

The amount of excretion depends on age because children produce less urine than adults. Approximately 20-25% of the cardiac output passes through the kidneys each minute. This high volume of blood flow allows the kidneys to filter out waste products from the bloodstream efficiently.

These kidneys filter approximately 180 litres of fluid (filtrate) from the blood plasma daily. In an average 24-hour period, this filtration process totals around 150 quarts (about 142 litres).

The glomeruli of nephrons filter water and other substances, and most of these substances return to the blood. The body excretes only 1 to 2 quarts of waste through urine from 150 quarts.

The kidneys secrete renin enzymes to regulate blood pressure and convert vitamin D to its active form. They also produce erythropoietin, which stimulates the production of red blood cells.

During excretion, the kidneys remove urea, creatinine, toxins, drugs, and other excess substances from urine. After filtration, the kidneys remove this excess waste from the body and release it outside through urine.

When the kidneys stop functioning, the waste products accumulate and do not excrete waste from the body. It is also important to note that kidneys only excrete excess wastes through urine in liquid form.

The gastrointestinal tract secretes undigested food particles and wastes as solid faeces. Negligence of improper functioning of the kidney may lead to kidney failure.

Kidney failure can be acute or chronic, depending on the situation and kidney function. The symptoms usually only appear once the kidneys retain only 15% of their total functioning.

It is necessary to understand the proper functioning of kidneys, with their detailed structure and functions. Let's discuss this in more detail.

What are Nephrons, Structure and Function

Nephrons are the basic functional unit of kidneys. Each kidney consists of more than a million nephrons in the renal cortex, which gives it a granular appearance.Nephrons are long tube-like structures varying from 35 to 55 mm.

Their primary function of nephrons is maintaining the plasma homeostasis and excreting waste. It accomplishes this function through filtration, reabsorption, and secretion. The construction of these nephrons involves linking numerous glomeruli with tubules.

Discover the detailed structure and anatomy of the kidney

The nephron tube closes at one end and forms a cup-like shape with two layers. We call this cup Bowman's capsule or the renal corpuscle capsule.

Bowman's capsule has three layers. The outer layer consists of epithelial cells with mini pores. We call this layer the parietal layer, and it has a diameter of 12 nm. The middle layer, the basement layer, has a selectively permeable membrane.

The visceral layer, the inner layer, consists of large nucleated cells called podocytes. These podocytes have finger-like projections known as podocel.

A glomerulus is a cluster of microscopic blood vessels in the Bowman's capsule, containing two portions. It fills large amounts of blood with a tubular system that filters waste products and turns them into urine.  

The proximal convoluted tubules (PCT) lead to the first portion of the glomerulus. The PCT consists of tubules and lies in the renal cortex. The second portion is similar to a hairpin structure called the loop of Henle. It penetrates the medulla and returns to the cortex via a distal convoluted tubule (DCT).

The Bowman's capsule and glomerulus form a renal corpuscle, and the rest of the nephrons become renal tubules. With this structure, the nephron drains into a collecting duct via connecting tubules. The renal tubule comprises a long, convoluted tube. This structure arises from the glomerulus and involves three parts based on their functions.

• The proximal convoluted tubule (PCT) links with Bowman's capsules. We name it due to its proximity to the glomerulus but remains in the renal cortex.
• The nephrons, after the PCT, feature the loop of Henle. We also call it the nephritic loop because its shape forms a loop. This loop surrounds the thin descending and ascending limbs. These limbs connect the proximal and distal convoluted tubules with the renal medulla.
• The distal convoluted tubule (DCT) forms the third part of the renal tubule. It attaches to a collecting duct and stays confined to the renal cortex.

Bowman's capsules, which are cup-shaped, enclose the glomerulus capillaries. This structure continues to form highly coiled proximal convoluted tubules and a loop of Henle with thin tubules. The loop continues to a distal convoluted tubule that leads to the collecting duct.

The tubules primarily reabsorb substances through either active or passive transport. The secretion by tubules of nephrons results in urine formation without affecting the human body's electrolyte balances.

Components of Nephron

The renal corpuscle or Malpighian body and renal tubules are the two parts of a nephron.

1. Renal Corpuscle
   
   
   The renal corpuscle consists of two main components: the Bowman's capsule and the glomerulus. The Bowman's capsule surrounds the glomerulus, which is a network of capillaries. An afferent arteriole supplies blood to the glomerulus, and an efferent arteriole drains blood from it. The smaller diameter of the efferent arteriole helps maintain high pressure in the glomerulus, which is crucial for the filtration process. This high pressure aids in filtering blood through the glomerulus, producing glomerular filtrate. This filtrate then passes into the renal tubules for further processing.
   
   
2. Renal Tubule
   
   
   The renal tubule is a long, coiled structure responsible for processing the filtrate received from the renal corpuscle. It comprises several segments, each with distinct functions: the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and the collecting duct. These segments work together to reabsorb essential substances and secrete waste products, ultimately forming urine.

Types of Nephron

Nephrons are of two kinds.

1. Juxtamedullary Nephrons:
   
   Juxtamedullary nephrons make up 15% of the total nephrons. This apparatus lies in the renal cortex, closer to the renal medulla of the kidney. 
   These nephrons consist of a longer loop of Henle that produces concentrated urine. This type of nephron also conserves water in the body's systems.
   
   
2. Cortical Nephrons:
   
   These are the abundant types of nephrons present within the cortex and comprise 85% of the total nephrons in the kidney. The outer part of the renal cortex mainly contains them, and they have the shorter loop of Henle. These nephrons are responsible for maintaining the overall body fluid balance.

The Filtration Process in Kidneys

Filtration is the mass transfer of water and other solutes from plasma to the renal tubule, which occurs within the renal corpuscle. 

At any point, the glomerulus filters around 20% of the plasma volume that passes through it. Filtration is a passive process, but it also has some disadvantages. It can filter important substances like glucose, vitamins, and amino acids. 

However, the renal tubules partially reabsorb substances filtered out of the blood into the bloodstream. After that, they secrete others into the tubules.

It indicates that the kidneys filter around 180 litres of fluid each day. The body filters the total plasma volume (about 3 litres) 60 times daily! The filtration process generally involves hydraulic pressure (blood pressure) in the glomerulus's capillaries.

Note that the kidneys filter far more fluid than the 1.5 litres of urine they expel daily. It is essential for the kidneys to effectively and quickly eliminate waste and toxins from the plasma.

The glomerulus' blood pressure is abnormally high in a capillary network. The rise in BP is because the efferent arteriole has a smaller diameter than the afferent arteriole. These capillaries are responsible for maintaining the high glomerular pressure.

The pressure in the glomerulus is comparatively high, usually 50 mm Hg. However, the other peripheral capillary beds have a pressure of 35 mm Hg. The filtration process involves the following layers.

Visceral Epithelium Layer: A visceral epithelium layer covers the glomerular capillaries inside the Bowman capsule.

Filtration Slits: For filtration, the substances need to be small enough to filter. The size of these particles should be smaller and sufficient to pass through the slits. The large molecules filter between pedicels to exit the glomerular capillaries. We call these gaps Filtration slits.

When we create the filtrate, it resembles the same serum but lacks proteins. Under normal circumstances, the body does not excrete protein and enters the filtrate. The body actively removes any large molecules through filtration. It must eliminate the unwanted substances from the circulation to move them farther down the tubule.

Filtrate Composition: The filtrate, which passes through the filtration barrier, primarily consists of water, glucose, ions, and small proteins. The filtration system's "gaps" differ in size. Plasma proteins can exit fenestrated capillaries but cannot pass through the gaps between pedicels in normal renal functioning. The reason is that the gaps in the capillaries are more comprehensive than the gaps between the pedicels.

Lamina Densa: The lamina densa is the basement membrane around the glomerular capillaries. This layer is unique because its cells can attach to multiple capillaries. The attachment allows them to regulate capillary diameter and blood flow more effectively.

The capillary endothelium contains holes and has fenestrations. The lamina densa, podocytes, and endothelium compose the filtration membrane.

Glomerular Filtration Rate (GFR):

The GFR is the volume of fluid that flows through all glomeruli within a single minute. Kidneys cleanse blood by eliminating waste and excess water to produce urine. The glomerular filtration rate (GFR) indicates the level of kidney filtration.

According to the National Kidney Foundation, around 37 million adults in the United States have chronic kidney disease (CKD). However, almost 90% of them must be aware of their condition. Individuals can implement safety measures to protect their kidneys if diagnosed in the early stages.

The normal GFR rate for healthy renal functioning is approximately 125ml/minute/1.73 m², where the value is adjusted for body surface area.eGFR refers to the 'estimated glomerular filtration rate.' It is a method of calculating GFR using a mathematical formula.

Serum creatinine, age, race, and sex are the necessary values for calculation. Doctors mainly refer to eGFR along with other blood tests. Doctors typically prescribe taking blood values for urea simultaneously with an eGFR. In healthy people, normal variations in blood pressure do not significantly alter the GFR.

For example, low blood pressure can cause

• Expansion of the afferent arteriole
• Narrowing of the efferent arteriole
• Dilation of the glomerular blood vessels and relaxation of the supporting cells.

Similarly, increasing BP levels has had opposite effects. Baroreceptors in the walls of afferent arterioles cause this effect. The increased Bp levels can cause these arterioles to constrict and cause the opposite changes.

Moreover, hormonal changes, specifically the renin-angiotensin system and natriuretic peptides, also play an essential role in regulating GFR. This table helps determine kidney health status based on GFR values.

Table 01: Stages of GFR

Diagnosis of GFR Test

GFR test is used to diagnose

• Kidney disease in people without any symptoms
• Help to diagnose kidney disease with physical symptoms
• Helps to identify the severity of kidney disease
• Monitor and keep a record of people who are suffering from chronic kidney disease (CKD)
• Checking the effect of medicines if they could harm their kidneys
• Check kidney health before starting any treatment for kidney failure

Factors Affecting Glomerular Filtration Rate (GFR)

GFR is a crucial indicator of kidney function, and it measures how much blood the kidneys filter per minute. The average value of GFR for adults is 90-120 mL/min/1.73 m². However, this average value may vary and depends on the following factors.

Table 02: Factors Affecting the Value of GFR

Creatinine Clearance:

Creatinine clearance is another method to assess GFR. The level of creatinine in the blood remains consistent. Creatinine also freely enters the filtrate and is secreted in minimal quantities. 

The physician also prefers creatinine clearance as an indicator of renal function to predict the values of estimated GFR. For example, it helps to compare the creatinine concentration in urine to the concentration in plasma. 

It can also determine the amount of creatinine a person eliminates during a specific timeframe (e.g., 84 mg/hour). It equals a rate of 1.4 milligrams per minute. Suppose the value of creatinine is 1.4 mg/100 ml. In that case, the kidneys filter 100 ml of blood per minute, producing a glomerular filtration rate (GFR) of 100 ml/min.

Calculate your creatinine clearance effortlessly—get started with our easy-to-use calculator!

Reabsorption and Secretion in the Nephron

After the filtration process, the filtered fluid from glomerular filtrate is similar to blood plasma without proteins. The fluid still contains other extracellular body substances. If the body excretes this fluid, a person will lose 10 times the entire plasma volume.

Reabsorption is necessary to absorb these nutrients. The tubular reabsorption system helps to reabsorb extracellular fluid and the circulatory system with the required water and solutes. 

Nephrons secrete additional compounds from the bloodstream to filtrate it. They also ensure the reabsorption of essential nutrients that the body requires. They work together to convert the glomerular filtrate into urine.

Nephrons play an essential role in hemostasis. They maintain extracellular fluids, including electrolytes, salt, and other minerals, which the tissues and organs need for normal functioning.

Tubular reabsorption is the process that returns water and solutes from the filtrate back to the bloodstream. This absorption occurs for the second time because the first absorption occurs when the food enters the bloodstream from the digestive tract.

The reabsorption process of kidneys occurs in two ways: renal tubules. The passive intake of substances takes place through diffusion. The active process involves pumping things out of the tubule against a concentration gradient.

The reabsorption includes the following three main sections:

Proximal Convoluted Tubule (PCT)

The renal artery brings blood to the glomerulus, which filters it, and then the PCT receives the filtered blood. The maximum reabsorption occurs in the proximal convoluted tubule of nephrons. It involves reabsorbing vital substances such as glucose, proteins and amino acids. 

PCT also includes significant portions of electrolytes and water in renal tubules. The lining of their simple cuboidal epithelium facilitates the surface area for reabsorption. 

Reabsorption is an active process for reabsorbing p]rimary substances our body requires. The proximal convoluted tubule absorbs bicarbonates (HCO3) from the filtrate by selectively secreting ions such as potassium, ammonia, and hydrogen. Therefore, PCT maintains body fluids' electrolytes and acid-base balance. 

About 70% of the reabsorption process occurs in proximal convoluted tubules. The kidney also secretes large molecules, usually strong acids and bases, which is why it secretes most drugs here.

Loop of Henle

Henle's loop consists of descending and ascending limbs, forming a loop connected to the proximal and distal convoluted tubules. The descending limb is highly permeable to water but impermeable to electrolytes. It reabsorbs water and concentrates it in the filtrate.

The ascending limb, consisting of thin and thick segments, is impervious to water. The thin ascending limb is permeable to some electrolytes, while the thick ascending limb actively reabsorbs electrolytes. It helps dilute the filtrate as it moves toward the distal convoluted tubule.

However, this section only limits the reabsorption.

The loop of Henle is responsible for concentrating the filtrate fluid by actively reabsorbing ions. It primarily includes sodium but also magnesium, potassium, and calcium. In response to a change in the concentration gradient, the body passively reabsorbs water.

Distal Convoluted Tubule (DCT)

The distal convoluted tubule is the final segment of the nephron. It connects and empties into the collecting ducts, interlinking with the medullary pyramids. 

As the collecting ducts approach the renal medulla's papilla, they gather content from several nephrons and fuse. The duct's primary function is to secrete ions into the filtrate, especially potassium. It can also reabsorb calcium.

The distal convoluted tubule reabsorbs HCO3 from the filtrate while secreting hydrogen, potassium, and NH3 ions. This process is similar to that of PCT. In DCT, the body reabsorbs water and sodium ions conditionally. Thus, it helps maintain the pH and sodium-potassium levels of blood cells. 

Secretion 

In general, secretion involves transferring active molecules from one place to another. If antidiuretic hormone (ADH) levels rise, the body returns more water from the urine to the bloodstream. It results in the production of highly concentrated urine due to increased ADH levels. 

During secretion, the kidneys eliminate waste products, including extra potassium or hydrogen ions, from the blood into the tubular fluid. The distal area mainly collects the nephron tubules for this procedure.

The Collecting System in the Kidney

The collecting duct is a long, straight tube that secretes H+ and K+ ions. These ions maintain the balance of electrolytes in the blood. The most water reabsorption occurs in this area, resulting in concentrated urine. 

After filtration, the collecting systems release hydrogen and bicarbonate ions to regulate blood pH. They are also responsible for the reuptake of bicarbonate, sodium, and urea in different quantities. This process is vital in the last step in urine concentration and volume determination. Two essential hormones, antidiuretic hormone (ADH) and aldosterone, significantly influence this process.

• Antidiuretic Hormone (ADH): ADH, also known as vasopressin, raises the porous nature of the collecting ducts to water. If ADH levels are high, the body returns extra water from the urine to the bloodstream. High levels of the ADH hormone result in a high concentration of urine. On the other hand, low levels of ADH result in hypoosmotic urine. It is due to the movement with high water permeability, which results in diluted urine.

• Aldosterone:  This hormone enhances sodium reabsorption in the distal tubules, the loop of Henle, and collecting ducts. The final segment of the nephron, the DCT, connects to and empties into the collecting ducts. The medullary pyramids are then linked to the collecting ducts.

Countercurrent Multiplication:

Countercurrent multiplication is a process in the kidneys that helps concentrate the urine in the renal medulla. Determining the gradient essential for water reabsorption in the collecting duct is necessary. Thus, it enables urine formation with varying concentrations according to the body's requirements.

Mechanism: Countercurrent multiplication involves the loop of Henle and the capillaries of the vasa recta. The vasa recta are blood vessels that surround the loop of Henle. As filtrate moves from the descending limb of the loop of Henle, the kidneys reabsorb more water from the filtrate. It makes the filtrate more concentrated. 

In the ascending limb, ions like sodium and chloride actively move out. Water does not follow this method of transport because this part of the nephron is impervious to water. This action increases the osmotic pressure in the surrounding interstitial fluid, helping maintain the renal medulla's concentration gradient. 

Facilitation of Water Reabsorption: Countercurrent multiplication creates an osmotic gradient. When antidiuretic hormone (ADH) is present, the collecting ducts actively reabsorb water. ADH increases the permeability of the collecting ducts to water, allowing the bloodstream to reabsorb more water.

In the vasa recta, countercurrent exchange maintains the gradient and prevents solutes from washing out of the medullary interstitium. This system allows the kidney to avoid waste and to maintain urine concentration in the tubules. It also helps to regulate the body's fluids and maintain electrolyte balance.

Juxtaglomerular Apparatus

The juxtaglomerular apparatus is essential for regulating blood pressure and kidney function. The cells in the distal convoluted tubules make up this apparatus.

The macula densa identifies the specialised cells in this area. The juxtaglomerular apparatus consists of the macula densa and unique cells of the afferent arteriole. These cells function as endocrine glands that secrete erythropoietin and renin hormones. They regulate blood pressure and GFR rate.

Waste Products in Urine

The kidneys efficiently excrete waste products from the body to maintain normal body temperature. They also ensure homeostasis by excreting harmful substances through urine. Urea, creatinine, and uric acid are the primary waste products in urine.

• Urea: The degradation of amino acids, ammonia, and CO2 produces urea. The liver carries out this process, and the kidneys filter the urea.
• Creatinine: Byproduct of creatinine phosphate and muscle metabolism entirely filtered by the kidneys.
• Uric Acid is a byproduct of recycled RNA molecules and purine metabolism. The kidneys filter and partially reabsorb uric acid.

It can only eliminate these items through water dissolution, which causes water loss during excretion. Thus, the kidneys can form a four times more concentrated liquid than plasma.

Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate

Understanding Renal threshold

The Renal Threshold is a point at which the body cannot reabsorb sufficient substances. Urea, glucose, or creatinine could start to appear in the urine because the body has exceeded its reabsorption capacity. 

For example, glucose exhibits a renal threshold. When the glucose concentration in the blood crosses this limit, it will start showing up in the urine. As a substance gets closer to the point where the kidneys begin to overflow, the urine rate also increases. The renal threshold of glucose is approximately 180 mg/dL. 

Therefore, if glucose levels exceed the threshold, the proximal convoluted tubule cannot eliminate all the glucose from the filtrate. It causes glucose and other substances to appear in the urine. Similarly, the renal threshold for water-soluble vitamins is shallow. 

A person taking any vitamin supplement excretes it through urination. The amino acids and phosphate threshold varies with the human body's metabolic demand.

Regulation and Homeostasis

The kidneys help regulate the body's internal environment, a process known as homeostasis. They also ensure the levels of water and electrolytes, blood pressure, and blood pH are maintained for optimum metabolism.

Fluid and Electrolyte Balance

The kidneys regulate the levels of various electrolytes, including sodium, potassium, calcium and phosphate, through reabsorption and secretion. 

• Sodium and Potassium: The body filters waste products and keeps sodium and potassium in the body by reabsorbing them. This regulation is essential for the proper functioning of nerves, plays a critical role in muscle contractions, and is responsible for maintaining the appropriate amount of fluids in the body.
• Calcium and Phosphate: The kidneys also regulate the level of minerals, including calcium and phosphate. These minerals are essential in the formation of bones and other metabolic roles. The kidneys regulate the secretion of these minerals or the amount of minerals reabsorbed back into the body.

Blood Pressure Regulation

The kidneys help to regulate blood pressure through several mechanisms:

• Renin-Angiotensin-Aldosterone System (RAAS):  In the kidneys, the juxtaglomerular apparatus observes changes in blood pressure and secretes renin. Renin performs several reactions to form the vasoconstrictor hormone angiotensin II. Angiotensin II is responsible for the release of aldosterone hormone. It helps the kidneys retain sodium and water, increasing blood volume and pressure.
• Antidiuretic Hormone (ADH):The hypothalamus synthesise vasopressin, also known as ADH. The posterior pituitary gland releases it upon receiving signals from the kidneys and other tissues. It works on the kidneys' collecting ducts to encourage water reabsorption. It is responsible for concentrating urine and raising the blood volume.

Acid-Base Balance

The blood pH must be regulated and maintained correctly to continue most bodily functions. The kidneys contribute to acid-base balance by The kidneys contribute to acid-base balance by:

• Excreting Hydrogen Ions: These organs filter out excessive hydrogen ions (H⁺) in the blood to avoid acidosis (high acidity).
• Reabsorbing Bicarbonate: The kidneys reabsorb bicarbonates from the waste. The reabsorption of HCO₃⁻ helps to maintain urea balance due to the action of the Renin-angiotensin-aldosterone system. This reabsorption helps maintain a blood pH of about 7.35 to 7.45, which is essential for the daily functioning of human cells. Through these processes, the kidneys regulate the body's internal environment to achieve homeostasis.

Secretion vs. Excretion in Kidney Function

Secretion and excretion are two different terms. Secretion involves the active transport of substances into the nephron. Excretion is opposite to secretion. It is the act of eliminating waste substances from the body. 

Therefore, the kidney actively eliminates waste through filtration, reabsorption, and secretion, which constitute excretion.