5 Easy Steps: Nephron Structure and Physiology
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Example Case
A female patient presents with palpitations, fatigue, and nausea. Symptoms began approximately 24 hours ago and were initially intermittent lasting for several minutes before resolving. However, over the past 8 hours her symptoms have become more persistent and have increased in severity.
You ask about recent medication changes, and she informs you that her dose of furosemide was doubled 3 days ago. You notice on her chart that she is also taking hydrochlorothiazide and spironolactone.
She is bradycardic on the monitor. As you try to recall the pharmacology of each drug, you are concerned that her recent medication change has impacted her renal function and is potentially causing an electrolyte disturbance.
Nephrons in the Kidney
Learning the nephron structure and physiology can be daunting at first.
Fortunately, you will learn an easy way to remember the nephron in 5 easy steps using the phrase “Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
As crazy as it sounds, memorizing this simple phrase will help you remember the nephron structure and physiology for practical use and on future tests. It’s much easier to commit this to memory than having to memorize each component individually. And let’s face it, we’ve had to memorize much worse.
We’ll walk through each step below.
There will be a future post on diuretics, and since most of them act on various parts of the nephron this article will serve as a good foundation to better understand the pharmacology in those posts.
Nephron Structure Overview
Before we dive into the 5 steps, let’s first discuss the overall structure of the nephron as this will make it easier when we walk through each component.
Each kidney comprises over 1 million nephrons, microscopic units that function to filter plasma and reabsorb or secrete substances to ultimately excrete the waste as urine.
Each nephron is composed of 2 parts, the renal corpuscle and the renal tubule.
The renal corpuscle is the filtration unit of the kidney. It is where the vascular system and urinary system meet. The renal corpuscle consists of networks of renal capillaries, called glomeruli, where plasma gets filtered into the renal tubule to start producing urine.
The renal tubule is a U-shaped structure where the filtrate from the renal corpuscle enters. The beginning and end of the U are the proximal and distal convoluted tubules, while the curved portion of the U is the loop of Henle.
As the filtrate travels through the renal tubule, some content is reabsorbed back into the vasculature while other substances are secreted into the tubule, and whatever remains in the tubule is eventually excreted as urine.
Let’s summarize the nephron overview quick and then dive right in. The renal corpuscle’s job is to filter the plasma. The filtrate then enters the renal tubule beginning at the proximal convoluted tubule, followed by the loop of Henle, then the distal convoluted tubule, and ultimately into the collecting duct to be excreted as urine.
As the filtrate travels through the renal tubule, some of it is reabsorbed back into the vasculature while other new content is secreted into the tubular system. What is left in the tubule at the end is excreted as urine.
The renal corpuscle (in blue) consists of the glomerulus and Bowman’s capsule. The renal corpuscle functions to filter plasma into the renal tubule to initiate urine production.
The renal tubule (in purple) consists of the proximal convoluted tubule, loop of Henle, distal convoluted tubule, and collecting duct. As filtered plasma content travels through the tubule some of it is reabsorbed back into the vasculature, while other content is secreted into the tubule, and what is left is excreted as urine through the collecting duct.
Terminology
You have heard several terms being used: filtration, reabsorption, secretion, and excretion.
These terms can be confusing at first, so I wanted to easily define them below.
Filtration - Refers to the plasma content that gets filtered from the glomerulus (vasculature) into Bowman’s capsule (urinary system) within the renal corpuscle.
Reabsorption - Refers to the filtered plasma content that gets reabsorbed from the renal tubule back into the vasculature.
Secretion - Refers to the intravascular content that gets secreted from the bloodstream into the renal tubule to be added to the already filtered content.
Excretion - Refers to the renal tubular content that gets excreted out of the kidney as urine. Therefore, excreted content is what is left in the renal tubule after filtration, reabsorption, and secretion occurs.
Renal Corpuscle
As mentioned above, the nephron consists of the renal corpuscle and renal tubule.
The renal corpuscle is the first part of the nephron and serves as the bridge that connects the vasculature to the urinary system. It filters blood to initiate urine production.
The 5 steps will be used to explain the renal tubule, the second part of the nephron, as this is more complex. The renal corpuscle is more straight forward and will be explained first.
The renal corpuscle consists of 2 structures, the glomerulus (vascular pole) and a capsule around the glomerulus referred to as Bowman’s capsule or glomerular capsule (urinary pole).
The renal corpuscle, the first part of the nephron, consists of the glomerulus and Bowman’s capsule. It serves as a bridge connecting the vasculature and the urinary system.
1. Glomerulus - Vascular Pole
The glomerulus is a network of capillaries where plasma is filtered into Bowman’s capsule, the second structure of the renal corpuscle.
Blood enters the glomerulus through the afferent arteriole and exits the glomerulus via the efferent arteriole.
As plasma is filtered from the glomerulus into Bowman’s capsule it travels through 3 layers, glomerular capillary endothelial layer, glomerular basement membrane, and Bowman’s capsule podocytes.
The endothelial layer of the capillaries have small pores, called fenestrae, that allow water and soluble substances to exit the capillary. The fenestrae are large enough to allow small substances to pass through, yet small enough to not allow larger important blood products such as red blood cells, white blood cells, or platelets to pass through.
Filtered content then travels through the glomerular basement membrane and ultimately enters the Bowman’s capsule through podocytes, foot processes extending off the capsule.
The rate in which filtration occurs from the glomerulus to Bowman’s capsule is called the glomerular filtration rate, or GFR, which is a clinically relevant blood test to assess overall renal function.
The renal corpuscle is the first part of the nephron and consists of the glomerulus and Bowman’s capsule. The content in blue is filtered out of the plasma into Bowman’s capsule to initiate urine production. The red content does not get filtered in a normal functioning kidney.
2. Bowman’s Capsule - Urinary Pole
Bowman’s capsule is the second structure of the renal corpuscle. It is ultimately the structure that connects the renal corpuscle to the renal tubule, the second part of the nephron.
Bowman’s capsule is a sac-like structure surrounding the glomerulus. Fluid and content filtered out of the plasma is collected into the Bowman’s capsule through foot like processes called podocytes and sent to the proximal convoluted tubule, the first part of the renal tubule.
Positively charged electrolytes, such as sodium and potassium, along with smaller molecules will enter Bowman’s capsule. This content includes sodium chloride, potassium, glucose, urea, and amino acids.
Larger content such as cells, protein, and platelets do not normally enter Bowman’s capsule, and if present in the urine could indicate some underlying renal pathology taking place that is allowing inappropriate glomerular filtration of these larger contents.
The renal corpuscle is the first part of the nephron and consists of the glomerulus and Bowman’s capsule. The content in blue is filtered out of the blood into Bowman’s capsule to initiate urine production. The red content does not get filtered in a normal functioning kidney.
The 5 Steps - Renal Tubule
Up to this point it has been fairly simple. The renal corpuscle is the first part of the nephron and serves as the bridge between the vasculature and urinary system.
It filters the blood and sends the filtrate to the renal tubule, the second part of the nephron.
The renal tubule is a U-shaped structure. As the filtrate travels through the renal tubule, some of it is reabsorbed back into the blood while other content is secreted from the blood and added to the filtrate already in the tubule. Whatever is left is ultimately excreted as urine.
The unfiltered plasma exits the glomerulus via the efferent arteriole which then turns into peritubular capillaries that surround the renal tubules. This will allow for reabsorption and/or secretion of content to occur between the renal tubule and vasculature.
The renal tubule consists of 5 components: the proximal convoluted tubule, descending loop of Henle, ascending loop of Henle, distal convoluted tubule, and collection duct.
The renal tubule will be broken down into 5 easy steps while using a phrase I came up with to help remember each part and the physiology that takes place. “Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The renal tubule, the second part of the nephron, consists of the proximal convoluted tubule, descending loop of Henle, ascending loop of Henle, distal convoluted tubule, and collecting system.
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”
Step 1: Proximal Tubule - “Every”
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The proximal convoluted tubule is the first component of the renal tubule.
“Every” is used to remember the physiology of the proximal tubule as nearly every substance that was filtered in the renal corpuscle has the potential to be reabsorbed here.
Water, sodium, potassium, chloride, urea, glucose, amino acids, bicarbonate, and phosphate all get reabsorbed in the proximal convoluted tubule.
H20, Sodium, and Potassium: Approximately two-thirds of the water, sodium, and potassium that was filtered in the renal corpuscle is reabsorbed back into the vasculature at the proximal tubule.
Urea: As water is reabsorbed from the renal tubule, the concentration of filtered urea increases and therefore some of it is subsequently reabsorbed back into the vasculature as well.
Glucose and Amino Acids: All of the filtered glucose and amino acids get reabsorbed back into the vasculature in a normal functioning state at the proximal tubule.
Phosphate and Citrate: Lastly, phosphate and citrate also get reabsorbed in the proximal tubule but are affected by parathyroid hormone (prevents phosphate reabsorption) and pH (acidosis increases citrate reabsorption whereas alkalosis decreases reabsorption).
Of note, the proximal tubule also regulates the pH of the filtrate in the tubule by the secretion of hydrogen ions from the peritubular capillaries and/or bicarbonate reabsorption from the tubule back into the vasculature. Other bases are also secreted into the filtrate at the proximal tubule.
“Every” = Proximal tubule, nearly everything filtered can be reabsorbed
Proximal Convoluted Tubule: Reabsorbs water, sodium, potassium, urea, glucose, amino acids. Secretes hydrogen ions and bases.
“Every” = Proximal tubule, nearly everything filtered can be reabsorbed
Step 2: Descending Loop - “Waterfall”
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The descending loop of Henle is the second part of the renal tubule after the proximal convoluted tubule.
“Waterfall” is used to remember the physiology of the descending loop of Henle. Water is reabsorbed as the descending loop falls deeper into the renal medulla.
The osmolarity of the interstitium, area outside of the renal tubule, increases as the U-shaped loop of Henle penetrates deeper into the renal medulla.
Since the osmolarity/concentration is greater outside of the tubule, water is easily reabsorbed from the descending loop into the more concentrated interstitium to balance it out.
Therefore, the tubular fluid is the most concentrated at the bottom of the loop of Henle, after all that water has been reabsorbed in the descending limb.
Waterfall = Descending loop, water reabsorption as descending loop falls
Descending Loop of Henle: Water reabsorption occurs. As the interstitium gets more concentrated the deeper into the renal medulla the loop goes, the more water that gets reabsorbed to balance out the osmolarity.
Waterfall = Descending loop, water reabsorption as descending loop falls
Step 3: Ascending Loop - “Raises Sodium”
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The ascending loop of Henle is the third component of the renal tubule after the descending loop.
“Raises sodium” is used to remember the physiology of the ascending loop of Henle. Sodium is reabsorbed as the ascending loop raises up higher.
As the concentrated tubular fluid travels back up through the ascending limb, the surrounding osmolarity outside the tubule begins to decrease again.
Now the tubular fluid is more concentrated than outside the tubule, and therefore sodium rather than water is reabsorbed to balance things out.
The ascending limb is occasionally referred to as the diluting portion of the nephron for this reason as it decreases the concentration of tubular solute.
Of note, potassium is also reabsorbed in the ascending limb mainly through potassium “leak” channels.
Raises Sodium = Ascending loop, sodium reabsorption as ascending loop rises
Ascending Loop of Henle: Sodium reabsorption occurs. As the interstitium concentration decreases the further up the renal medulla the ascending loop goes, the more sodium that gets reabsorbed to balance the osmolarity.
Raises Sodium = Ascending loop, sodium reabsorption as ascending loop rises
Step 4: Distal Tubule - “In Exchange For Potassium”
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The distal convoluted tubule is the fourth part of the renal tubule after the ascending loop.
“In exchange for potassium” is used to remember the physiology of the distal convoluted tubule. Sodium and potassium levels are regulated through sodium reabsorption and potassium secretion.
Sodium reabsorption and potassium secretion is further augmented by aldosterone, a hormone released by the adrenal cortex secondary to hypotension, hyponatremia, sympathetic activity, or renin-angiotensin-aldosterone system activation.
Blood pH is also regulated at the distal convoluted tubule. If blood pH is high indicating alkalosis, then renal compensation occurs via bicarbonate secretion and hydrogen reabsorption to correct the alkalosis.
Alternatively, if the blood pH is low indicating acidosis, then renal compensation occurs via hydrogen ion secretion in exchange for bicarbonate reabsorption to correct the acidosis.
This is why, for example, patient’s with chronic respiratory acidosis from COPD tend to have elevated bicarbonate levels at baseline. They have renal compensation to their acidosis via bicarbonate reabsorption.
Calcium is also regulated at the distal convoluted tubule through calcium reabsorption into the vasculature, primarily mediated by parathyroid hormone. Increased levels of parathyroid hormone augment calcium reabsorption and phosphate urinary excretion.
In Exchange for Potassium = distal tubule, sodium reabsorption in exchange for potassium secretion
Distal Convoluted Tubule: Sodium is reabsorbed and potassium is excreted, mediated by aldosterone. Calcium is reabsorbed and phosphate excreted, mediated by parathyroid hormone. The pH is also regulated through hydrogen and bicarbonate reabsorption/secretion.
In Exchange for Potassium = distal tubule, sodium reabsorption in exchange for potassium secretion
Step 5: Collecting Duct - “To Make Another Waterfall”
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
The collecting duct is the fifth and final part of the renal tubule after the distal convoluted tubule.
“To make another watefall” is used to remember the physiology of the collecting duct. Similar to the descending loop of Henle, water is reabsorbed here.
The distal convoluted tubules of all the nephrons converge onto the collecting duct system, which then delivers the filtrate to the renal calyces and pelvis for ultimate urinary excretion.
Water reabsorption in the collection duct is mediated by antidiuretic hormone (ADH). In the presence of ADH as seen in dehydration or hypotension, water reabsorption occurs. Alternatively, water reabsorption is negligible in the absence of ADH.
To Make Another Waterfall = collecting duct, downward (fall) structure that reabsorbs water
Collecting Duct: All of the distal tubules converge onto the collecting duct system where urine is ultimately excreted out of the kidneys. Water reabsorption occurs, mediated by antidiuretic hormone.
To Make Another Waterfall = collecting duct, downward (fall) structure that reabsorbs water
“Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”
Every = proximal tubule, nearly everything filtered can be reabsorbed
Waterfall = descending loop, water reabsorption as descending loop falls
Raises Sodium = ascending loop, sodium reabsorption as ascending loop rises
In Exchange for Potassium = distal tubule, potassium secretion - sodium reabsorption
To Make Another Waterfall = collecting duct, downward (fall) structure that reabsorbs water
Practical Applications
Understanding the structure and basic function of each component of the nephron becomes clinically relevant when discussing certain medications, disease states, and physiological responses in the body.
These will all be discussed further in separate posts. However, I briefly wanted to practically apply the material discussed above.
Medications
You can appreciate how certain medications function by acting on various components of the nephron.
For example, aldosterone antagonists will inhibit responses mediated by aldosterone including sodium reabsorption and potassium secretion in the distal tubule. This will produce a diuretic response from increased sodium and water levels in the renal tubules.
Decreasing sodium reabsorption can help treat hypertension, and augmenting diuresis can help treat symptoms of heart failure.
You can also appreciate that antagonizing aldosterone inhibits potassium secretion as well. This is why aldosterone antagonists are referred to as potassium-sparing diuretics. Consequently, a potential side effect to aldosterone antagonists is hyperkalemia.
Other diuretics such as loop diuretics and thiazide diuretics function to treat hypertension and heart failure through sodium reabsorption inhibition at the loop of Henle and distal convoluted tubule respectively.
Pathology
There are many disease states that can affect nephrons at both the renal corpuscle and renal tubule level.
For example, filtration at the renal corpuscle can be affected by glomerulonephritis and nephrotoxic medications. This could lead to decreased GFR levels and overall decreased renal function.
Furthermore, larger plasma content such as red blood cells and proteins may inappropriately pass through filtration leading to hematuria or proteinuria.
Renal tubular acidiosis and diabetes insipidus are conditions that affects the renal tubule secondary to failure to regulate blood/urine pH and failure to produce/respond to ADH respectively.
Physiological Responses
You can also appreciate how the kidneys play a role in certain physiological responses, especially to compensate for different types of shock.
For example, increased sympathetic activity, increased renin-angiotensin-aldosterone activation, hyponatremia, and hypotension will all trigger increased sodium and water reabsorption to improve blood pressure and/or fluid or electrolyte status.
Changes in acid-base status will trigger bicarbonate reabsorption/secretion and/or hydrogen ion reabsorption/secretion.
GFR
Lastly, you can appreciate why GFR is clinically important to assess overall renal function as this measures the glomerular filtration rate between the glomerulus and Bowman’s capsule within the renal corpuscle.
RTA = Renal Tubular Acidosis
Conclusion
I hope that helps to summarize the various components and functions of the nephron.
The nephron consists of 2 parts: the renal corpuscle and renal tubule.
The renal corpuscle, consists of the glomerulus and Bowman’s capsule, and is where plasma is filtered to initiate urine production.
The renal tubule continues to form urine through reabsorption and secretion of substances to ultimately be excreted.
There are 5 components to the renal tubule and the physiology of each can be remembered using “Every Waterfall Raises Sodium in Exchange for Potassium to Make Another Waterfall”.
Medications such as diuretics act on various components of the nephron. Lastly, there are conditions that can disrupt the normal physiology of nephrons.
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PTH = Parathyroid Hormone