I recently have joined a Bartter and Gitelman group on Facebook. It is a collection of people from all over the English speaking world, each with a long standing chronic disease and all of them are on an diagnostic island where they have never met another person with the disease and are generally seeing docs who are just as unfamiliar with the disease as they are. A lot of them have questions on how the kidney works so this primer is for them
The functional unit of the kidney is the nephron. A functional unit is not a common term so let’s spend a sentence or two talking about what that means. a functional unit is the smallest fraction of a system that still accomplishes all the tasks of the entire system. For example, the functional unit of a muscle is a single muscle cell, a myocyte. A muscle’s, sole function is to receive a signal and respond by shrinking. They remain shrunk until the signal ends. A single myocyte can do that. Though a muscle contains thousands of myocytes one can think of it as one giant myocyte without losing much.
On the other end of the spectrum is the heart, the functional unit of a heart is the entire organ, it makes no sense to think about a heart without all four chambers and all the heart valves.
The kidney lies in-between these two extremes, the functional unit of the kidney is the nephron, a complex collection of blood vessels, tubes, nanopumps and filters. Each kidney is composed of a million nephrons but you can understand every function of the kidney and understand just about any type of kidney disease by understanding it’s affect on a single nephron. You can think of the kidney as being a single giant nephron and not lose much.
The primary role of the kidney is to keep the extracellular fluid (all the water that lies outside of the cells) in an ideal and balanced state. They manufacture the cellular atmosphere in which our cells live. To do this they:
- replace chemicals which are consumed
- excrete the variety of foreign substances absorbed by our indiscriminate gastrointestinal tracts
- excrete the byproducts of our metabolism (the ashes of our body fires)
The basic procedure that is used is can be thought of like cleaning out a closet, take everything out, then put back what is valuable and throw away the rest.
Here are the parts of the nephron that accomplish this:
The glomerulus is a colander that filters the blood. The blood cells and proteins of the body play the role of the pasta while the water, salts, and small molecules play the role of the water and flow through the colander into the tubules of the nephron. The primary difference between a colander and the nephron is that the water that passes through the colander is discarded as waste. In the body if you were to waste everything that was filtered you would quickly perish.
Following the glomerulus, the filtered water, salts and small molecules enter through the tubules. The primary role of the tubules is to reclaim all that is valuable and secrete additional waste that wasn’t filtered by the glomerulus. The end of the tubules is the renal pelvis which acts as the grand central station where the millions of tubules, one for every nephron, coalesce.
The tubules are further divided into functional regions. Here are the basic regions:
The proximal tubule does big, dumb, bulk reabsorption. Way too much fluid is filtered by the glomerulus.
over 3 ozs (100 ml) per minute, this means that in 30 minutes all of the water in the blood stream would be filtered and in 7 hours all the water in the body would be gone. Clearly this does not happen and the reason it doesn’t happen is that 99% of the filtered water is reabsorbed. This is the focus of the early nephron. Actually a way to look at the nephron is that as you move down the tubule from the glomerulus to the bladder less fluid is recovered and more fine tuning occurs.
The proximal tubule, reabsorbs two-thirds of the date, sodium, potassium and many other substances that are filtered. It recovers all of the amino acids, glucose and other carbohydrates needed for energy and building the body. There is some subtle forms of regulation that occurs in the proximal tubule but most control and fine tuning occurs downstream in other segments of the nephron. Many drugs are secreted in the tubule so it is a key site for cleaning the blood of substances that are found at lower concentrations or escape being filtered by the glomerulus for one reason or another.
Loop of Henle
After the proximal tubule, the nephron takes a strange shape. It stretches down deep into the center of the kidney, like a Texas wildcatter digging a deep well. The loop of Henle is the engine which powers both the dilution of urine and the concentration of urine. The control of what type of urine is made is executed at the last minute but the work that makes that happen occurs in the loop. Concentrating or diluting the urine is how the body conserves or wastes water. When you think of what type evolutionary changes were required for animals to leave the ocean, the ability to conserve water by making concentrated urine must have been one of the critical breakthroughs, concentrated urine can only occur if the loop of Henle is working properly.
A lot of sodium, and magnesium reabsorption occurs here. The common water pill furosemide (Lasix) acts on the loop of Henle. The defects in Bartter syndrome are here and act by limiting the reabsorption of sodium, chloride and potassium.
The other important aspect of the loop of Henle is that at the very tip of the loop, the deepest part of the well, the tissue fundamentally changes so that water can not flow through the cells. From this point to the toilet the tissues lining the tubules are impermeable to water, a characteristic found no where else in the body. The collecting tubules can allow water pass through its walls but only under strict control with the use of specific water channels.
Distal convoluted tubule
There is not much to understand about the distal convoluted tubule. It is the site where thiazide diuretics act and is where the mutations that cause Gitelman syndrome is expressed.
The last segment of the tubules is called the collecting duct and it has three primary roles:
- excrete excess acid
- excrete dietary potassium
- regulate the excretion of water
The big finish
After the collecting tubule there is the renal pelvis where all of the collecting tubules empty into a common chamber and then flows into the ureters, the long tubes that drain the kidney into the bladder where it is stored until voiding. After urine leaves the tubules it does not undergo any further chemical changes.
The perfect organ
The last bit that is important is the concept of balance. One of the perfect things about the kidney is that it keeps the body in balance. In patients that are not growing, all of the sodium that is consumed is excreted by the kidney. When I want to investigate whether a patient’s blood pressure might be due to excessive salt in the diet, I do not try to get the patients to remember and report what they eat, I simply have them collect all of their urine for 24-hours and measure the amount of sodium in the urine. If they have 3 grams of sodium in the urine, then they are eating 3 grams of sodium. This can be done with any substance that is ingested and then excreted unchanged by the body. Examples of intake that can be assessed with a 24-hour urine collection include:
– Posted using BlogPress from my iPad
– hat tip to Steve Rankin for fact checking