If you are attending the lectures, you may find it useful to bring along a printout of the gapped notes
for kidney part 1 and kidney part 2.
The areas covered in this lecture are
This document covers the outline of the lecture in brief. Much more detail on the different parts of the nephon are available from the following documents
.....if you haven't previously studied biology or your maths is a bit dodgy, you may find the following useful
This document covers the same ground as the lecture but in less detail, the other support documents cover additional ground in lots more detail. There are two reasons why I have so much material about the kidney. First, it is a pretty important organ. Second, I used to give a 10 lecture series on renal physiology and I wrote the first version of these notes to support the lectures. I'm told that they are useful so I have kept on updating them. How much do you need to know?
Why do we need Kidneys?
The short answer is so that we don't die of dehydration. That is the renal function that we would miss most quickly (paradoxically, dehydration is rarely a consequence of acute renal failure but rather may be a cause of it). The control of salt and water balance is what the kidney is most famous for and were you to ask the average medic-in-the-street, why do we need kidneys, that is almost certainly the answer you would receive.
I'd like to approach the kidney from a slightly different angle and pose a slightly different question, namely, What did the kidney evolve to do? It is possible to argue that the kidney has evolved to cope with fluid and electrolyte balance (most people do); but I would disagree. I think that the primary function, the raison d'etre of the kidney is not fluid and electrolyte balance but rather excretion. The kidney is the number one, the most important, excretory organ in the body. You may think that, qualitatively at least, this title belongs to another organ, but much of what emerges from the digestive tract, undigested food and bacteria for example, has never been inside the body proper at all. What counts, so far as excretion from the body is concerned, is removal of substances from the bloodstream and the kidney is a superb blood-scrubber. One happy consequence, a by-product if you like, of the mechanisms employed by the kidney to keep the blood free of waste products is a capacity to regulate salt and water balance.
To be a perfect blood scrubber, the kidney must be able to excrete anything, absolutely anything (including water) from the blood into the urine. We have looked at the mechanisms that cells use for transporting substances previously; diffusion between cells, diffusion through ion channels and active transport (primary and secondary). One possible approach to removing substances from the blood is to employ active transport mechanisms and pump waste products into the urine. In fact the kidney does do this. BUT, what about novel waste products or brand new toxins or substances so inert that there isn't a transport system for them. if the kidney can't excrete something because there is no active transport mechanism to carry it into the urine then this substance suddenly becomes massively toxic. Think about it. The body is so determined to preserve osmolarity that it will sacrifice fluid volume to compensate for an imbalance of salt. An un-excretable substance in the bloodstream will increase the osmolarity of the blood, the kidney will compensate by increasing fluid volume, but there can be no correction because there is no way of getting rid of the substance causing the osmotic inbalance.
There is only one way to guarantee removal of any substance from the blood plasma.
It is very simple.
Excrete all the plasma.
If everything is excreted then you can be certain that you aren't missing a single thing no matter how unusual or how inert it is.
This is what the kidney does.
You might regard this as overkill. Furthermore, you might argue (correctly) that this "solution" to the problem simply creates a whole new set of problems. It is not possible to simply excrete all the blood plasma and survive, clearly the kidney has got to recover salt and water and glucose and bicarbonate and so on..... BUT the recovery process is a problem which is solvable using active transport processes. The body "knows" what it needs to reclaim and so can install the necessary transport processes in the kidney.
In effect, the kidney has traded an otherwise insoluble problem; (being certain of excreting anything) for one that it can solve (recovering what the body needs).
If you can remember that this is what the kidney is doing and why it has to do it this way then the physiology of the nephron will make so much more sense.
As the kidney is excreting and reabsorbing massive quantities of salt and water as a necessary part of its job as an excretory organ, regulation of salt and water balance becomes a simple matter of adjusting the balance between excretion and reabsorption. If the body has, for example has taken on board too much water, it is a simple task for the kidney not to reabsorb the excess. Likewise salt. If the body is short of salt and or water then both can be conserved until the shortfall is made up.
Excretion of nitrogenous waste
The excretory function for which the kidney is probably best known is probably that of getting rid of nitrogenous waste. Nitrogenous waste, usually in the form of ammonia (NH3) is produced by the metabolism of protein and nucleic acids. NH3 is toxic and must be got rid of pretty sharpish. The liver converts NH3 into urea (see the ornithine cycle) and the urea is excreted by the kidney. Now you know why urine is called urine. Incidentally it isn't urea that makes urine yellow
Gross Anatomy and Bloody supply
|The kidney is, well a kidney-shaped organ. You have two, in the small of the back, either side of the spine. Each kidney is surrounded by a tough capsule. The outer part is called the cortex (a word that means "outer part") and the inner part is called the medulla (guess what medulla means). In cross-section, the kidney has "stripes" running through the medulla, these are the medullary rays which are in fact the loops of Henle and the Vasa Recta. The ureter, which carries the urine to the bladder emerges from a slit in the capsule called the hilus.|
Renal nerves travel along with the blood vessels into the kidney. Most of the renal innervation is via sympathetic efferent nerves. These nerves release noradrenaline in response to a drop in systemic blood pressure and cause renal vasoconstricion and also stimulate renin release. It seems unlikely that the renal nerves make any vital or irreplaceable contribution to the control of renal function because when they are absent, e.g. immedediately following kidney transplant, renal functions carry on as normal.
Renal blood suppy
In order to be an efficient blood scrubber, the kidney has got to come into contact with a lot of blood. It does. The kidney receives 25% of cardiac output, which is about 1200 ml/min or over 1700 l/day. Every day the kidney filters 180 l of plasma into the urine and, on an average day, reabsorbs 99.4% of it, leaving a daily urine production of about 1.5l
Blood is supplied to the kidney via the renal artery which enters the medulla of the kidney at the hilus (where the ureter leaves). The renal artery splits into several interlobar arteries which in turn split into arcuate arteries. These pass from the medulla into the cortex. Once in the cortex, branches come off the arcuate arteries at right angles, these are the interlobular arteries. The afferent arterioles branch off these. The venous drainage picks up after the peritubular capillaries and vasa recta etc., is more or less the reverse of the arterial supply and culminates in the renal vein which exits the kidney at the hilus.
The functions of the nephron, segment by segment.
There are many aspects of renal physiology that are hard to understand. However, the one redeeming feature of the kidney is that it is composed of a single repeating unit, the nephron. Each human kidney is composed of 1-1.5 million nephrons. By and large all these nephrons do the same job, so if you understand how one nephron works then you know how the whole kidney works.
Each nephron has Five distinct components
Bowman's capsule. This is where filtration occurs. The kidney is excreting plasma, not whole blood so the filter must be able to keep the blood cells back. Furthermore, the blood also contains plasma proteins that the body 'knows' it wants to hang on to. These are too big to be in solution, rather they are suspended in the blood and so the filter can keep these back too.
The proximal tubule is responsible for most of the reabsorption. Glucose, amino acids, and about 70% of the salt and water are all reabsorbed here by active transport mechanisms. Other substances that the body is certain it wants to excrete are actively secreted into the urine by the proximal tubule. There are two bits to the proximal tubule. The first bit is wobbly and therefore called the proximal
wobbly convoluted tubule or pars convoluta (the latin name could be useful should you happen to be talking to a dead roman or perhaps an elderly clinician). The next bit is straight and called the proximal straight tubule or pars recta. The convoluted tubule is the most important part so far as most of the absorptive and secretory functions are concerned, with the exception of organic anion secretion (see below) which occurs in the straight proximal tubule
The loop of Henle together with the collecting duct (N.B. one collecting duct receives the output from many nephrons) are responsible for reabsorbing most of the remaining 30% of the filtered salt and water that the proximal tubule can't manage. All of the other parts of the nephron are sited in the outer, cortical, part of the kidney the loop can extend deep into the central, medullary regions. Not all nephrons have a long loop of Henle. This is the only significant difference between nephrons. About 15% of human nephrons are juxtamedullary, the remainder are cortical (with short loops).
The distal tubule has a special responsibility in regulating sodium reabsorption.
The blood supply within the kidney has a unique configuration that mirrors the shape of the nephron. The glomerular capillaries are contained within Bowman's capsule, plasma is filtered here. The capillary bed then reforms, not into a vein but into an arteriole again. Glomerular capillaries therefore do not have arterial and venous ends, they have afferent arteriolar and efferent arteriolar ends. Glomerular capillaries are able to autoregulate blood flow so that there is constant flow over a wide (normal) range of blood pressure. The efferent arterioles split into a second peritubular capillary bed that surrounds the proximal tubule and also the distal tubule. There are specialised loops capillaries that descend into the medulla in parallel with the loop of Henle, these are called the Vasa Recta. Blood flow in the cortex (4-5 ml/min/g) is much greater than that in the outer medulla (0.2 ml/min/g) and massively greater than that in the inner medulla (0.03 ml/min/g). Mind you, blood flow to the cortex (per g of tissue) is greater than blood flow anywhere else in the body (e.g. brain = 0.5 ml/min/g, resting muscle = 0.05 ml/min/g)
The net result: reabsorption and secretion
Overall, the kidney is fantastically good at both filtration and reabsorption
|Total solute (mOsm)||54,000||100||700||53,400||87|
Each day the kidney filters and reabsorbs and incredible 1.5 Kg of salt dissolved in 180 litres of water.
Acid base balance
The pH of the body is determined by a bicarbonate based buffer system. To cut a long story short, pH depends on the concentration of bicarbonate and the partial pressure of CO2 (PCO2) in the blood and interstitial fluid (about 40mm Hg). The partial pressure of CO2 is regulated by the lungs (obviously) and the bicarbonate concentration is regulated by the kidney. Together the lungs and the kidney set and maintain pH. pH is one of those things really important for the wellbeing of the body and both the kidney and the lungs are capable of altering bicarbonate concentration or PCO2 respectively to compensate for an imbalance in PCO2 or bicarbonate concentration respectively so that pH is maintained for as long as it takes to correct the problem.
Renal Endocrine Functions
The kidney is the target of several hormones, most notably ADH and aldosterone, but also Atrial Natriuretic Peptide (ANP). ANP is released by cardiac atrial cells in response to atrial stretch, which is one of the results of increased circulating blood volume. In effect, ANP opposes the actions of aldosterone (just as diuresis means water-loss-through-the-kidney, natriuresis means sodium-loss-through-the-kidney) so ANP really stands for atrial sodium loss peptide. The actions of ANP include inhibition of sodium channels and the sodium pump in inner medullary collecting duct cells, inhibition of aldosterone release by the adrenal cortex, inhibition of renin release (which will ultimately reduce aldosterone release) and an increase in GFR. All of these actions will contribute to an increased loss of sodium in the urine.
As well as being the target of hormones, the kidney also produces a few of its own. Renin is the first one that springs to mind. This is a nice example of a feedback process because the ultimate target organ of the cycle initiated by renin release is the kidney itself.
All the rest of my super simple nephron diagrams are wrong in one important anatomical respect. After the proximal tubule and the loop of Henle, the nephron doubles back and, just as it becomes the distal tubule, makes contact with Bowman's capsule. (In fact this is used as an anatomical marker for where the loop of Henle ends and the distal tubule begins) The wall of the distal tubule at this point is called the macula densa and it contains specialised cells that respond to the composition of the fluid within the distal tubule. These cells come into close contact with both the afferent and the efferent arterioles as they enter and leave Bowman's capsule respectively. The cells in the wall or the afferent arteriole are also specialised, these cells are called juxtaglomerular or granular cells and they contain renin. The space between the arterioles and the macula densa contains extraglomerlar mesangial cells that rejoice in the name of Goormaghtigh cells. The whole lot is collectively known as the juxtaglomerular apparatus.
The cells of the macula densa respond to a decrease in sodium chloride levels in the distal tubule by releasing prostaglandins (mainly PGI2). The granular cells respond to the prostaglandins by releasing renin. The rest (angiotensin, aldosterone, increased sodium reabsorption, increased sodium chloride at the macula densa) you know already. Other things that lead to renin release are increased sympathetic activity, triggered by a reduction in extracellular fluid volume, sensed by baroreceptors in the carotid arteries and decreased renal perfusion pressure, sensed as reduced tension in the walls of the afferent arterioles.
Both glomerular mesangial cells and renal tubular cells are thought to produce erythropoietin in response to hypoxia. Erythropoietin is a glycoprotein hormone that targets the stem cells in the bone marrow that give rise ultimately to erythrocytes. Therefore, if your kidneys pack in, you are going to be anaemic as well.
The kidney is also responsible for activating vitamin D3.
Vitamin D (cholecalciferol) can either be ingested with food or made from 7-dehdrocholesterol by the action of ultraviolet light (sit out in the sun and make vitamin D). The liver converts cholecalciferol into 25-hydroxycholecalciferol and the proximal tubule cells of the kidney use the enzyme 25-hydroxyvitamin D-1?-hydrooxylase to convert 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. This is the active form of vitamin D3. Vitamin D is very important to dentists because (along with parathyroid hormone, PTH and calcitonin) it controls many aspects of calcium metabolism in the whole body. Vitamin D is involved in stimulating the absorption of calcium from the diet, in laying down of calcium into the bone and, most importantly (at least from the point of view of a dentist) in the mineralisation processes involved in dentinogenesis and amelogenesis. If you don't have enough vitamin D as a child you get rickets (bendy bones) and bad teeth. The traditional illustration of this is in Victorian child mineworkers who rarely saw the sun (and probably had a poor diet as well).
Until a few years ago, any introduction to vitamin D3 would have stopped here (it certainly did on this page). Nowadays, vitamin D has a whole new exciting second career as a regulator of the immune response. Vitamin D3 can tweak the innate immune response, quiet antigen presenting dendritic cells, alter T cell phenotypes and mess with B cells. Busy, busy busy.