A day in the life of the kidney
May 15, 2014
From the Desk of Dr. Voorheis
A quick apology for not having a blog for you all to read last week. It was another busy week and Dr. Voorheis was knee deep in critter care. And as we all know by now, the critters come first. However, I did allude to a kidney blog that I had in the works and as promised a couple of weeks ago, I have finally finished the piece on the kidney. I have wrestled with this topic for a couple of weeks now and finally decided to do what I should have done in the first place. The intent is to write a blog that is both interesting and informative but as I reviewed current veterinary literature and current available information for clients (handouts, Dr. Google etc.), most of what I found was lacking substance. Most literature is only vaguely informative of what a kidney does, why is it so vital, and why protecting it is so important. We could start answering that last question right away. Any organ that receives 20% of cardiac output directly has got to be pretty important, right? That also makes the kidney exquisitely sensitive to toxic insult. It seems that the only thing most people know about the kidney is that it acts as a filter. Well, it does that but it also does so much more. I’m going to try to tackle this topic in two parts. Part one being the healthy kidney and part two being the sick kidney. This week it’s important to start by laying some ground work and giving you all a good sense of what the kidney actually does for the body. We’ll talk about the sick kidney next week and I will divide that blog into two parts as well. Those parts being acute and chronic renal failure.
Most information regarding kidney function mentions excretion of metabolic waste products as the only function of the kidney, a.k.a “a filter“. What most literature available to the lay person fails to mention is that an equally important function is the regulation of the volume and composition of extracellular fluid, i.e. the body’s internal environment. You can think of it this way – the composition of bodily fluids is determined NOT by what the mouth takes in but what the kidneys retain. In addition, the kidneys have a critical role in red blood cell production and calcium/phosphorus balance (homeostasis).
In most mammals, the kidneys are paired, bean shaped organs located near the top of the back in the dorsal lumbar region. They are bean shaped in the dog and cat but interestingly heart shaped in a horse. They are separate from the rest of the abdomen because they are covered with peritoneum, the lining of the abdomen. That makes them referred to as “retroperitoneal”. Blood is carried to the kidneys by renal arteries which arise directly off the aorta. As stated above, 20% of cardiac output reaches the kidneys with each beat of the heart.
If I were to slice a kidney open along its long axis, it would be immediately apparent they are two distinct areas, the outer area called the cortex and the inner area called the medulla. The striations (lines) that are seen are formed by an arrangement of the nephron which is the functional unit of the kidney. The kidney’s currency if you will. I’ll explain later.
The concave portion of the kidney is where blood vessels enter and leave through the renal artery and renal vein. Also exiting from this area is the ureter which is the tube that collects urine and transports it to the bladder. Not shown in the diagram above are things like renal lymphatics and renal nerves.
Ok, now back to those nephrons I mentioned above. As I said, the functional unit of the kidney is the nephron. In dogs, each kidney has about 415,000 nephrons. In cats, each kidney has about 190,000 nephrons. Humans have about a million nephrons in each of our kidneys. Ok, I can‘t resist. Here comes the classic rocker in me. As I was typing this up, I thought about the Beatles song “A Day in the Life”. Maybe they got the same guy to count nephrons as counted holes in Blackburn, Lancashire. So here is some trivia for you – how many holes does it take to fill the Albert Hall? All I can say is that guy’s job was easy compared to the job of “counting nephrons”.
The functional unit of the kidney is pictured above. That’s our new friend the nephron. This guy makes all the magic happen. This guy is also responsible for weeding out more pre-veterinary and pre-medical students from those lucky ones who make it. I suppose renal physiology must take its place next to organic chemistry as a major challenge in undergraduate curriculum. The point being that this is complex stuff and I’m only going to skim the surface in this week‘s blog.
Here is where we dive deeper and get our hands dirty so to speak. Prepare for medical vocabulary. In actuality, there are two types of nephrons. They are named for their location in the kidney and for how “deep” their “Loops of Henle” penetrate into the medulla. The exception is the cat whose nephrons are always “juxtamedullary” with 100% long looped nephrons. The juxtamedullary nephrons are those nephrons that develop and maintain the osmotic gradient from low to high. Huh? The what? The concentration gradient. Ok, we are halfway home so stay with me. The glomerulus is the “tuft” of capillaries (tiny blood vessels) through which filtration takes place. Branches of arteries become important here because certain drugs act on them which can help treat some types of kidney disease. The “afferent arteriole” is a tiny branch of the kidney artery that feeds blood directly to the glomerulus and the “efferent arteriole” is a tiny branch of the kidney artery that takes blood away from the glomerulus. This blood leaving through the efferent arterioles goes into another bed of capillaries called peritubular capillaries which supply the nephron tubules. The vasa recta are capillary branches from the peritubular capillaries associated with the long looped nephrons. After perfusion of the kidneys, blood is returned to the caudal vena cava by the renal veins. Filtrate from glomerulus is collected by the Bowman’s capsule and is subsequently directed through the proximal tubule, loop of Henle, and distal tubule. The distal tubule then empties into a cortical collecting tubule. A cortical collecting tubule is not unique to a single nephron because it receives tubular fluid from the convoluted portion of several distal tubules. When the collecting tubule turns away from the cortex and passes down into the medulla, it is known as a collecting duct. The tubular fluid is subjected to reabsorption and secretion. Successive generations of collecting ducts unite to form progressively larger collecting ducts. The tubular fluid is finally discharged from the larger collecting ducts into the pelvis of the kidney and is conveyed from there by ureters to the urinary bladder for storage until discharge through the urethra.
We now enter the phase of renal physiology that causes pre-vets to drop out and decide to do something else. The statement highlighted in bold is the one that holds some very complex physiology (how things normally work) and even more complex pathophysiology (what happens when things go wrong).
I don’t intend for this blog to be too complex and teach renal physiology (I know, I know…too late!). So I’m going to try to summarize some important points in an effort to demonstrate that the kidney is more than a filter. Some of you have had a CBP (complete blood profile) done for your dog or cat and therefore some of you have heard me mention BUN and Creatinine. Have you ever wondered what those are? Well, here’s where you find out. There are some terms that will need explanation so I’ll start there. Renal blood flow (RBF) is the rate at which blood is delivered to the kidneys. Another term is renal plasma flow and this refers to the liquid part of the blood. As long as there is renal blood flow, (except in some disease circumstances) there will be a glomerular filtrate formed. Remember it’s at the glomerulus that the filtrate starts. All of these components are measured at milliliters per minute. So that allows us to compute a ratio, we can compute something called filtration fraction. The filtration fraction is that value that we get when we divide GFR by RPF. In reality, in clinical medicine we are most interested in GFR. So we measure two compounds that because of their usual even production and filtration, allow us an assessment of glomerular filtration rate. Those two compounds are blood urea nitrogen (BUN) and creatinine (Cr). Elevations in those two substances usually mean that there is a decrease in glomerular filtration rate. GFR can be decreased due to dehydration, renal disease or post renal obstruction. Probably a bit complicated but interesting none the less I think.
The kidney uses some complex mechanisms to try to keep GFR constant. It can sense decreases in volume of blood being provided to it and it will immediately begin to act. The afferent renal arteriole will open and the efferent renal arteriole will narrow and this acts to increase the flow rate at the glomerulus. In addition, in the glomerulus there are cells called the macula densa. If these cells sense a decreased volume of filtrate to distal tubules, they act to increase sodium and chloride ions in the ascending loop of Henle. They also increase the release of an enzyme called rennin. Rennin increases the formation of angiotensin which is converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II acts to constrict the efferent arteriole and thus increases GFR. Angiotensin II also stimulates the production of a hormone called aldosterone. Aldosterone causes reabsorption of sodium – all of which assist the kidneys to regulate volume. So you see, the kidney has a big job to do. Actually, many big jobs.
The amazing miracle of kidney function continues as we follow the filtrate into the proximal convoluted tubule, the descending loop of Henle and the ascending loop of Henle and on into the collecting ducts. There is a vast network of capillaries right next to these tiny tubules. Through a mechanism called “Countercurrent exchanger” and “Countercurrent multiplier”, essential substances that the body needs to conserve are conserved. Glucose and amino acids are absorbed along with sodium in a rather complex dance that allows for concentration of urine, the excretion of toxic nitrogenous wastes, secretion of potassium and hydrogen and conservation of water.
The two illustrations below show the glomerulus in a little more detail and also show a pretty good diagram the countercurrent exchange and multiplier system. Fascinating stuff!
What about hormones? Don’t they play a part in all this too?Yes they do! I briefly mentioned the hormone aldosterone above. Aldosterone is produced by the adrenal gland. Aldosterone increases sodium absorption in the tubule and is critical in regulation of potassium by promoting the secretion of potassium.
ADH and Osmoregulation
Anti-diuretic hormone (ADH) is a hormone secreted by the pituitary gland that acts on the collecting tubules and ducts to affect their permeability for water. The degree of hydration of extracellular fluid is detected by receptor cells in the hypothalamus. When the cells of the hypothalamus detect and increase in plasma osmolality (concentration), they stimulate the posterior pituitary to secrete more ADH. The secreted ADH is circulated by blood to the kidney tubules where the water permeability change takes place. The thirst center is also located in the hypothalamus and is stimulated by hyperosmolality. A water deficit requires water intake for correction and these guys will seek water.
Parathyroid Hormone (PTH)
PTH is secreted by the parathyroid glands and acts on the kidney tubules to increase reabsorption of calcium, while at the same time promoting the excretion of phosphorus. PTH hormone is secreted in response to low concentrations of calcium in the ECF. Another role of the kidney in response to decreasing calcium involves the formation of the active form of Vitamin D, also known as calcitriol. Active vitamin D promotes Ca absorption from the intestine. PTH controls the formation of active vitamin D by the kidney.
EPO is a hormone produced in response to the tissue need for oxygen and stimulates the production of new erythrocytes by its activity in the bone marrow. The kidney is the major site, and the only site in dogs, of EPO production in adult mammals. EPO is produced by peritubular interstitial cells located within the inner cortex and outer medulla of the kidney. Extrarenal EPO production in certain animals and humans helps to maintain erythropoiesis during anemia caused by severe kidney diseases. Anemia is a common side effect of chronic interstitial nephritis in dogs because of the lack of an extrarenal source of EPO.
For any given molecular size, positively charged molecules are more readily filtered than negatively charged ones. This happens because the glomerular membrane has a load of negatively charged proteins in it that attract positive charges and repel negative charges. Hang with me I’m trying to make a point. Plasma albumin is a relatively small protein as compared to globulins, and might be filtered through; however, they have a negative charge. So they generally escape being lost into the urine. In kidney disease, in which poor perfusion may become a factor, the electrostatic charge of the glomerular membrane can change and molecules previously restricted from filtration can be filtered and gain entrance to the capsular space. My point – in some kidney diseases proteins are lost in the urine.
Other kidney diseases affect other parts of the nephron. Some toxins attack and affect the proximal convoluted tubule or transport of critical ions due to membrane damage along the loop of Henle. We’ll talk more about that next week.
Well, that is the kidney in as small a nutshell as I could manage to put it in. Now, to give credit where credit is due. Much of the work of this week’s blog and my understanding of renal physiology must go to the classic textbook, Functional Anatomy and Physiology of Domestic Animals, by Dr. William O. Reece, D.V.M. Ph.D. Dr. Reece is a Professor of Biomedical Sciences at the College of Veterinary Medicine, Iowa State University of Science and Technology, Ames, Iowa. It is gratitude that I have for those teachers who make difficult subjects understandable. I have tried to that here for all of you.
So, now you’ve all got one week to absorb this day in the life of the kidney. Next week we will talk about what happens with a sick kidney when all the fascinating components aren’t playing nicely with each other. Team work is certainly required for the kidney to do all of its jobs properly and when the team work goes down the tubules (joke), it isn’t pretty.
Until next week,