PDF: The Urinary System Transcribed - Anatomy & Physiology

The Urinary System Transcribed Part 1 Welcome to the session on the urinary system. This part focuses on the overview of the whole- body system which as a whole creates urine in order to lose waste from the body. Beginning with the structures involved, the urinary system consists overall of 2 kidn...

The Urinary System Transcribed Part 1 Welcome to the session on the urinary system. This part focuses on the overview of the whole- body system which as a whole creates urine in order to lose waste from the body. Beginning with the structures involved, the urinary system consists overall of 2 kidneys, 2 ureters, 1 bladder and 1 urethra. The two kidneys are joined by the two ureters to the one bladder before one vessel, the urethra, carries urine out the body. The two kidneys are the site of urine formation, specifically this occurs in the nephrons within the kidneys, so the rest of the system is simply carrying urine. So, the ureters are just tubes to move the urine from the kidneys to the bladder, the bladder is then a storage vessel, and the urethra is the exit route. So, it’s a really quite simple anatomical system, although the kidneys are pretty complicated organs in themselves, but we’ll get back to that later. Like all other body systems, the urinary body system’s overall function is fundamentally all about homeostasis, and this is in relation to balancing the levels of solutes and water in the body, so the body is functioning correctly. The urinary system has several roles working together to help achieve this balancing act overall. So, if there were just 4 key words to remember about how the urinary system does all of this, then it would be filtration, absorption, secretion and excretion as these words do outline the most important roles that the urinary system actually does. Going on from there if you were to list the urinary systems roles that are achieved by these 4 key words being carried out then there are 8 primary roles to consider. So the main roles of the urinary system is regulating the blood in terms of the ions, the pH, the volume, the pressure and the osmolarity. Plus there’s hormone secretion, helping in glucose regulation and there’s a role in excretion, which includes excreting drugs after metabolism in the body. I’m going to look at these more in the next part. If you have any confusion on what osmolarity means, please go back to the basic physiology e-learning session now, or double check online as this plus osmosis and hydrostatic pressure will keep cropping up in this package and it’s going to be really difficult to follow without understanding the basic concepts first. So for now, before getting into more detail, I’m going to briefly summarise the whole thing and how the urinary system works as a whole. So firstly, the kidneys filter the blood plasma, key word there is filter. Then most, not all, of this filtered water and solids are then re-absorbed and returned into the bloodstream, note the key word of absorption. But some water and some solutes remain in the urinary system to become urine, and these are joined by other waste solutes which are secreted into the urinary system, note the word secretion. Before the fluid leaves the kidneys, travels along the ureters and is stored in the bladder. Finally, the urine is excreted through the urethra through a process called urination or micturition or voiding or uresis. Part 2 The urinary system has 8 main roles, many of which relate to regulating the balance of certain substances within the blood. We start with ions in the blood. The urinary system regulates the levels of blood ions and really importantly, this includes the regulation of sodium (Na+), chloride (Cl-), potassium (K+), calcium (Ca2+) and phosphate (HPO42-) ions. From the knowledge you have start considering the widespread effects an electrolyte balance will have. Phosphate and calcium ions are needed in the body for bone and teeth growth and repair, but also think about action potentials in the heart and the nervous system and which electrolytes are needed for them to work effectively and just keep going on from there in terms of signs and symptoms. Chloride ions are the main negative ions found inside cells, along with potassium and sodium, have a role in maintaining the negative charge of the resting membrane potential, so they have a role of maintaining that -70mV inside the neuron in the nervous system for instance. So, with too much or too little of one of these ions around, then what might happen to maintain that membrane potential successfully? Again, think about action potentials, especially cardiac ones and how severe cardiac arrhythmias or cardiac arrest could well follow if you have a severe enough electrolyte imbalance, and it does depend on the ion type of course. Paramedics very often check for hyperkalaemia, too high of a potassium levels on an ECG recording, which initially shows up as widespread high peaked T waves before the p waves start to get flatter and smaller. But hyperkalaemia is usually only seen if there are kidney problems. If severe enough, hyperkalaemia can lead to cardiac arrest, but with normal functioning kidneys, hyperkalaemia should not occur, even if you eat a very potassium rich diet such as a diet full of bananas, potatoes, tomatoes. So, if your kidneys are working normally, then they will regulate the potassium levels adequately. ** So have a think about signs and symptoms, look up the effects of hyperkalaemia, hypokalaemia, hypernatremia, hyponatremia, hyperchloremia, hypochloraemia to get some background.** You’ll see that each type of ion imbalance has different effects due to a larger or lesser extent. Overall, it does show why someone with acute or chronic kidney failure will suddenly become broadly unwell. The urinary system also importantly regulates blood pH, and it does this by excreting acidic hydrogen ions and conserving bicarbonate ions so they can be used for buffering. The overall aim is to keep the blood between 7.35 and 7.45 pH, this is a really tiny pH variation to maintain. Should the blood become acidotic, then the kidneys have a role in rebalancing that pH, which is known as metabolic compensation. An acidotic patient will also breathe more rapidly to lose acidic carbon dioxide from the blood, this is called respiratory compensation. So, if the acidity is severe enough, both the metabolic and the respiratory route will be used to try and achieve blood pH homeostasis. The urinary system also regulates blood volume by excreting or conserving water through urine concentration. Blood pressure regulation is intertwined with blood volume, clearly an increased volume will increase the blood pressure. But blood pressure regulation also relies on the secretion of renin which is used in the renin-angiotensin-aldosterone pathway which I’m going to talk about more in a later part. Blood osmolarity, or blood osmolality as it’s now usually referred to as, is a measurement of the solutes dissolved into a liquid, the concentration effectively. So, you’re looking at a proportion of the number of particles per litre of solution and in this context it’s a measurement of the concentration of all dissolved particles found in the fluid part of the blood. So, osmolality is also regulated in the urinary system with an increased osmolality leading to an increase in antidiuretic hormone (ADH) secretion, which then retains fluid. So, to give you an example, if your dehydrated, then your osmolality increases since the fluid in your body has become more concentrated. This osmolality increase is detected, an anti-diuretic hormone (ADH) is then secreted from the posterior pituitary gland after it’s produced. So, this will then have the effect of reducing how much you urinate, retaining more fluid in the body, and your blood osmolality will then decrease. Aside from this, alcohol decreases ADH secretion, which is why you tend to urinate more when you drink it, and of course this will dehydrate you as your osmolality control is temporarily impaired. Then there’s hormone production in the kidneys to assist in calcium homeostasis and to stimulate red blood cell synthesis. These two hormones (calcitriol and erythropoietin) have already been discussed in the endocrine and blood sessions in other recorded elearning sessions, so I won’t discuss them any further in the session for now. If you want to review them, please go back and do so. Gluconeogenesis occurs in the livers and in the kidneys too and this is the production of glucose molecules from a non-carbohydrate source. For example, from amino acids and this of course helps with blood glucoses regulation by creating glucose from another source. Then finally there’s the excretion of unwanted waste such as urea, ammonia, bilirubin, creatinine, uric acid and excess ions. Plus, there’s drugs after metabolism and environmental toxins and of course the excretion of these products will be within the urine itself. Urea and ammonia are created from the deamination of amino acids in the liver, so this is when a structural chemical group called the amino group (NH2) is removed from one end of the amino acid as a part of a metabolic process, if there’s an excess protein around. Bilirubin is one of the byproducts of haem breakdown in the liver, so it’s from haemoglobin. Whilst Creatinine is from the breakdown of creatinine phosphate in the muscle fibres. Do look back on the musculoskeletal session if you need a reminder of what this is. But a high level of Creatinine in the urine could mean abnormality in the muscles or the kidneys. Uric acid is created when purines are broken down, remember that purines are found in nucleic acid such as DNA and RNA, so when cells are broken down as part of cell turn over, uric acid will be created. But a diet high in purines, for example if you drink lots of beer, it will lead to more uric acid creation and a combination of a dietary intact high in purines, decreased uric acid excretion and high cell turn over can lead to gout. Gout is caused by an accumulation of sodium uric crystals in the joints and these crystals form when the amount of uric acid in the body reaches a high level. Finally, there’s the pharmacology angle. So, after absorption, distribution, metabolism, drugs can then be excreted through the urinary system. Some drugs are designed to alter during their metabolism so they can be excreted more easily through the water in the urinary system. So as a clinician you should be aware that renal or kidney function reduces as you age and that renal function is also different for paediatrics, especially those under the age of 2 years. You should bare this in mind with patients. Part 3 By now you should have done a bit of reading on the overall structure of the kidneys. You should be able to identify their location in the body, particularly to be able to find them on palpation clinically. In particular you should understand that its 10-12cm long where the renal hilum, renal pelvis, renal capsule, the cortex, medulla and renal pyramid are and what the 3 layers around the kidney should consist of (Renal capsule, Adipose tissue and Renal Fascia). As an extra bit of information to add to this overall, you should also be aware that the right kidney is slightly lower than the left due to the liver taking up space in the upper abdomen. If you’ve looked at how the kidneys are held in position, then be aware that you can get a problem with something called a floating kidney called Nephroptosis. It can happen in very thin people if the adipose tissue or the renal fascia becomes insufficient, leaving the kidney with the capacity to move slightly when a person stands up. So, if a kidney can move, then the ureter might kink, which is very dangerous as the backing up of urine back into the kidney causes damage to the kidney and pain and it is more common in females. The blood supply to and from the kidney branches directly off of the main descending aorta and vena cava respectively, creating the left and right renal arteries and renal veins. It will become apparent to you why the blood supply to the kidneys has to be excellent after you learn more about how they work. In all the kidneys receive 20-25% of the resting cardiac output from the right and the left renal arteries, so it has a massive blood flow through. It’s about 1,200ml per minute in both kidneys inside an adult. Inside each kidney is around 1 million nephrons and these are the massive processing factories, the functioning units of the kidneys which undertake the filtration, absorption, and secretion that I mentioned earlier. From the nephron collecting duct, the urine has a pathway. It flows through the papillary duct in the renal pyramid, from the collecting ducts of the nephrons (minor calyx and major calyx), and eventually joins the renal pelvis before leaving the kidney to join the ureter and then the bladder. The bladder which stores urine has stretch receptors which signals to the brain that you need to urinate, and this involves the parasympathetic nervous system for control. As a storage vessel, when the volume of urine exceeds more than 200-400mls then the urge to urinate is there, although the bladders capacity is generally 700 – 800mls. It is smaller in females due to the uterus sitting on top of the bladder. In order to actually urinate there needs to be a relaxation of the internal and external urethral sphincter muscles, plus a contraction of the bladder wall. We’re going to look at nephrons in the next part but carry out the prereading first to help you make sense of this. Part 4 Nephrology is the study of the kidneys in terms of its function and the problems that can occur from diseases or conditions. Having now looked at the nephrons now a bit more closely, I hope that you are appreciating that nephrons are the functional unit of the kidney. So, I can now start to give you a little bit of an overview of how they carry out filtration, absorption and secretion to make the urine ready for excretion. So, keep a diagram of the Nephron handy as we go through this so you can refer to it. So a nephrons basic three functions as a functioning unit are through glomerular filtration, tubular re-absorption and tubular secretion. There’s a glomerulus, glomerular capsule (or bowman’s capsule) and there’s a renal tubule. These are the main structures to be aware of. There’s an afferent and efferent arteriole by the peritubular capillaries in and out of the glomerulus, so it’s not an arteriole in and a vein out, it’s an arteriole in and out, which is very different. The glomerulus is basically a long capillary network of glomerulus capillaries, creating a massive surface area. So the afferent arteriole just becomes lots of capillary vessels with oxygenated blood flowing through before they rejoin back together to make an efferent arteriole. The glomerular capsule, or the bowman’s capsule, is the first section of the nephron and the huge surface area of glomerular capillaries is needed for glomerular filtration. So, a very large quantity of blood plasma filters from the glomerulus due both to its relatively large pores and the hydrostatic pressure of the blood itself. The glomerulus is positioned next to the glomerular capsule, or the bowman’s capsule, and these two structures have a gap in between them. So what happens is that the blood flow enters the glomerulus from the afferent arteriole, and as the blood flows through the capillary network of the glomerulus, fluids and solutes are non-selectively filtered from the plasma in the glomerulus into the capsular space of the glomerular capsule. This space is the gap between the glomerulus and the glomerular capsule so this gap there gets filled with filtrate and this then continues on into the renal tubule. So, this is the filtration part I kept talking about, glomerulus and the glomerular capsule work together to move the filtered fluids and solutes from the blood stream and into the renal tubule. Once in the renal tubule, then 99% of all of that fluids and solutes that were filtered into the tubule are then reabsorbed back into the blood stream. Specifically, they are reabsorbed into the peritubular capillaries, but 1% is left behind to continue on along the tubule. Tubular secretion then follows on, so waste substances like excess ions and metabolised drugs move from the blood stream into the tubules adding to the fluids and solutes in there and creating a urine ready for excretion. It might help to think of all of this through the analogy of a recycling centre. So, the rubbish trucks dump a huge load of items at the site, and it all goes into a hopper, then the items go onto a conveyer belt where the workers can remove useful bits for reuse, leaving the rest of the bits unwanted on the conveyer belt. After this, any further unwanted rubbish that cannot be recycled or reused can be added onto that conveyer belt too, before this final load goes to landfill or disposed. So, what exactly is filtered from the bloodstream at the glomerulus, reabsorbed back into the bloodstream at the renal tubules, or secreted from the bloodstream further down the renal tubule? Well, you’ll see that it’s really massive. Water, small proteins, peptides, ions (sodium, chloride, bicarbonate, potassium), glucose, urea, uric acid, creatinine metabolised drugs are filtered substances. Water (99% of it), small proteins, peptides, ions (sodium, chloride, bicarbonate, potassium), glucose (99.9% of it), urea , uric acid and creatinine are re-absorbed into the bloodstream. Water, ammonium ions, trace proteins, drug metabolites, and variable amounts of everything that was re-absorbed earlier, and trace amounts of glucose are excreted in urine. Glucose is important in terms of reabsorption. Virtually all of the glucose is reabsorbed and if it isn’t, it indicates a blood glycaemic issue. The glucose is reabsorbed by active transport, by symporters to be accurate, but if there’s a very large amount of glucose in the filtrate that needs reabsorption, then the glucose transporters become saturated. By this I mean they’re doing their job fully to 100% level, so they’re saturated and they cant do anymore. But despite this glucose is still remaining in the filtrate to become urine as the transporters have reached their transport maximum. Try thinking of this like branches moving downstream of flowing water, with some branches being lifted and hooked out, once the hooks full, it’s full, and all the other branches will have to continue along downstream until the hook returns to take another load. In the same way the glucose symporters are full, leaving some glucose to be lost in urine, this can be an indicator of diabetes militias. So if glucose is found in a routine urine sample dip test, further tests such as a blood glucose and a glucose tolerance test may well follow on from that later. Finally in this part I want to illustrate the network of blood vessels around the nephrons before we go back and discuss filtration even further. Remember there’s an afferent arteriole going into the glomerulus and an efferent arteriole leaving it. Well, the efferent arterioles divide into the peritubular capillaries after the glomerulus. These capillaries are found all the way around the tubule where reabsorption and secretion occur between the bloodstream and the renal filtrate in the nephron. There needs to be a huge blood vessel network as there’s so much reabsorption and secretion altogether and so the blood can be regulated effectively overall. After the peritubular capillaries have played their role, they eventually become venules before they join into veins, and finally into the renal vein for the blood flow to exit the kidney and join the vena cava. In the next couple of parts I will look at filtration, absorption and secretion in more depths as this part was kind of an overview, as I need to describe why this filtration, and absorption occurs and exactly what is secreted from the renal tubule. Part 5 This part is about glomerular filtration and this and this is the process of filtration of the glomerulus by using pressure to move water and solutes out through the filtration membrane and into the renal tubule. The filtration membrane is essentially the walls of the blood capillaries of the glomerulus itself so movement through the membrane is a passive process as the membrane is adapted with fenestrations (or pores) big enough to allow blood plasma components through but small enough to retain blood cells. Podocytes have footlike projections which creates slits for filtration of small substances. Overall, during glomerular filtration large plasma proteins remain in the bloodstream to maintain colloid osmotic pressure, along with blood cells and platelets, whilst small molecules move through. You can also probably appreciate that a large thin surface area is going to be needed to enable this large quantity of filtration, moving fluids and solids non-selectively out of the bloodstream. You do need to be clear that glomerulus blood pressure has a role to play on this too. A patient glomerular blood pressure should be higher than the BP you record on the patient’s brachial artery, and that this higher glomerular blood pressure is needed to help supply hydrostatic pressure and enable glomerular filtration. So if you’ve got a patient who’s haemorrhaging badly and their BP falls, then their kidneys will be effected as hypovolaemic shock develops. So the kidneys role in regulating the blood for example will fall, causing systemic problems. The pressure part of filtration is where it starts to get more complicated to get your head around as there’s three pressures that come to play here to achieve a net filtration pressure. This is the net amount of filtrate pressure available in order to push out the water and solutes so their filtered from the blood stream into the renal tubule. The net filtration pressure should be about 10mmHg and the glomerular net filtration rate will be about 125ml/m, although this is dependent on a couple of things and it requires regulation, I’m going to come back to this point in a minute. For now, the three pressures to know and understand are the glomerular blood hydrostatic pressure (55mmHg), which will apply pressure to encourage filtration, the bloods colloid osmotic pressure (30mmHg), which opposes filtration, alongside capsular hydrostatic pressure (15mmHg) which also opposes filtration. So you have one force pushing filtration, and two repelling it. So to break them down a little, The GBHP is pretty much what it says on the tin. It’s the hydrostatic pressure created by the fluid of the blood and the pressure is around 55mmHg. But opposing this pressure is the BCOP and due to things like albumin and globulins in the blood it creates a pressure of around 30mmHg in order to hang on to the fluids and solutes and it slows down the filtration rate. Joining in is the CHP at around 15mmHg which is created by the filtrate already in the capsular space of the glomerular capsule, and again this pressure opposes glomerular filtration. Despite this, we still have a net filtration rate of 10mmHg. This is because we have a total filtration which promotes pressure at 55mmHg against a pressure total of 44mmHg, creating a 10mmHg net filtration pressure. Some kidney disease can affect the glomerular capillaries and damage them, so that the large proteins of the blood move into the filtrate, which lowers the BCOP colloid osmatic pressure inside the filtrate instead. This is going to affect the overall net filtration rate and pressure, and it also leads to more fluid being lost in urine along with large proteins in the urine too. Since these bloodstreams are now lacking these large proteins, it affects the balance between the interstitial fluid and the vascular system in general in the body. So, more fluid sits in the interstitial spaces causing oedema. This means that losing plasma proteins in urine due to some kidney disease will lead to oedema. The glomerular filtration rate, or GFR, is the amount of filtrate formed by the kidneys per minute, it’s about 125ml/min. You need to filter so much as it makes for a really efficient excretion system, where the body can get rid of wastes rapidly and monitor the situation constantly. It also creates flexibility as the body can then regulate stuff such as pH or blood osmolality very tightly. So in normal circumstances GFR is usually regulated by the flow of blood through the glomerulus and by the glomerulus surface area. So you can see that a reduced amount of blood flowing through the glomerulus will mean that less plasma and less solutes are going to be filtered out of it. So all of the GFR has to be regulated, and it’s under the control of 3 things using negative feedback mechanisms. Both the blood flow and the surface area can be altered to alter the amount of filtrate formed. Keep it in your head that the GFR is going to change based on the net filtration pressure, so if the net filtration pressure gets too low, then GFR will have to fall too. If blood flow through the glomerulus falls due to a drop in systolic BP, then GFR will fall too. If your patients systolic BP is below 50mmHg, filtration will actually have to stop. So, a patient with a very low blood pressure for a very long period will be progressively worsening in terms of their blood ions, pH and the waste build up in their bloodstream. If the systolic BP eventually improves, the kidneys are going to have a backlog to deal with and the patient will be really unwell just from the lack of kidney function. So, returning to how the glomerulus surface area and the blood flow through the glomerulus can be altered, there are 3 mechanisms involved in regulation. Firstly, there’s renal autoregulation, which lowers blood flow and decreases GFR. This is either by the myogenic route, where the muscle fibres contract, which narrows the lumens of the afferent arterioles. Or by the tubuloglomerular route, where the quantity of localised nitric oxide release is reduced, restricting afferent arterioles. Then secondly there’s neural regulation, where the sympathetic nervous are stimulated into releasing norepinephrine and constricting afferent arterioles. This is going to lower blood flow and decrease GFR. Finally there is hormone regulation involving angiotensin II which will constrict both the afferent and the efferent arterioles. Conversely there is ANP which is secreted by atrial stretching of the heart and causes the cells in the glomerulus to relax and increase their surface area for more filtration to occur. Part 6 Reabsorption of the filtrate is next, so this reabsorption of the solutes and water, the filtrate, from the renal tubule back into the bloodstream. First I want to trace the overall route of the filtrate through the renal tubule before what is left exits as urine. The renal tubule is subdivided into segments such as the proximal convoluted tubule and the descending and ascending loop of henle, before it becomes the distal convoluted tubule. Each area has a slightly different role in that the electrochemical gradient of the filtrate changes as it travels through the tubule, so the composition of the filtrate changes. This is going to alter the gradient of what is inside the renal tubule and what is outside. This then affects osmotic and hydrostatic pressure too, so all of this will in turn affect things such as diffusion, active transport and osmosis, so this will affect what substance moves where. The loops of Henle can extend to the medulla, and they have areas of thicker and thinner walls, which has a bearing on absorption itself, especially as much of the water absorbed occurs in the descending loop. At the end of the nephron, the distal convoluted tubules of several nephrons empty their urine into one collecting duct before they move into the papillary duct. This is an orchestrated system where a large number of all doing the same thing to achieve the overall roles I discussed in part 2, such as regulating the blood and losing waste from the body. So how does this filtrate reabsorb? It’s a combination of diffusion, active transport and osmosis along with changing pressures electrochemical gradient changes too. Thinking first at the peritubular capillaries that network around that renal tubule, they have a declining hydrostatic pressure and an increasing colloid osmotic pressure which will encourage osmosis and 99% of the water in the filtrate will be reabsorbed overall. At the very beginning of the tubule, the tubular fluid is hypotonic to the blood. So it has a reduced osmotic pressure in relation to the bloodstream and so the water is drawn out into the bloodstream by osmosis. Lets look at each section in turn, because of all the electrochemical gradient changes, they all occur at different stages of the tubule. Right at the beginning of the tubule is the proximal convoluted tubule. A convoluted area like this is coiled so it’s got a larger surface area and osmosis is occurring here moving water from the tubule into the bloodstream and is made up of epithelial cells with microvilli and large mitochondria. About 80% of the filtrate is absorbed here in the proximal tubule because added to the water absorption that’s going on, there’s also passive absorption due to diffusion of some ions and urea. Plus, there’s active transport for glucose and ions including sodium (bicarbonate specifically). Finally, there’s also secretion of some ions, creatinine and urea. Urea is a waste nitrogen-based substance, and it’s filtered, reabsorbed and secreted which allows a fine tune of its balance. Since this urea movement affects the osmolality of the filtrate then this in turn affects water reabsorption. Most of the secretion for the renal tubule happens in the proximal convoluted tubule area, from tubule and duct cells that line walls of the renal tubule. Overall secretion is very useful for helping control things like blood pH through hydrogen ion loss in pH case. It’s also a route to lose unwanted substances from the body such as creatinine and drug metabolites. The filtrate that enters the loop of Henle is already of a different composition than it was in the proximal convoluted area (composed of simple squamous epithelial cells). Absorption and secretion have began to change the filtrates composition, which in turn means that gradients of substances in and outside of the tubule is changing. In the loop of henle, which is a large U shape, you have the descending and ascending sides. The descending side is the major site of water reabsorption, whilst some ions continue to diffuse out into the bloodstream, plus the active transport of sodium, chloride and potassium ions continues too. Secretion from the bloodstream into the tubule is mainly urea, so it can be pretty confusing keeping up with what is absorbed and whats secreted at different points in the tubule. The fluid in the descending loop gets more and more concentrated as the loop descends, due to the water absorption across the thin, permeable walls. The reason the water absorption can occur is due to the increased osmotic pressure in the capillaries which can draw the water in, leaving much of the solutes still in the tubule. Then when the loop ascends, the tubule walls get thicker, decreasing permeability, so there’s now a reversal. There’s now a high volume of solutes inside that tubule, so these solutes can move down its concentration gradient and leave the tubule, leaving the tubular fluid to get increasingly watery. This is why the ascending loop is called the diluting segment of the tubule as the fluid gets more and more dilute as the solutes exit the tubule. This system maximises both water and useful solutes for reabsorption simply by altering how concentrated the tubular fluid is at different points in the tubule. This then alters the chemical gradients of the contents of the tubule and outside the tubule. The distal convoluted tubule is the next point the filtrate reaches and its another area of increased surface area as it’s coiled and it joins into the collecting duct with some ionic reabsorption occurring and some secretion of potassium and hydrogen ions too. Water reabsorption is now under ADH control, so the amount of water reabsorbed now depends on the level of ADH secreted. This leads into the last place which ultimately sorts out the final concentration of urine, this is at the collecting duct, under ADH control, with some last tweaks to reabsorption too. What leaves the collecting duct to go into the adrenal medulla is now classed as urine. **Summary of changes in tubular fluid:** Proximal convoluted tubules: Largest point of solute and water (aprox 80%) re-absorption, secrete urea, creatinine, hydrogen and ammonium ions Loop of Henle: Reabsorbs water om descending loop only, plus more ions Distal convoluted tubule: reabsorbs water and ions Collecting duct: by now 90-95% of filtered solutes and water returned to bloodstream; fine- tuning of potassium and hydrogen ion loss through secretion Part 7 The renin-angiotensin-aldosterone system is the pathway in the renal system that regulates blood volume and so it also controls blood pressure. As clearly the volume of blood in the CVS will also affect the blood pressure too. This pathway is designed to raise BP and blood volume, so inhibiting this pathway is a route used by anti-hypertensive drugs called ACE inhibitors, or angiotensin enzyme inhibitors. For instance, ramipril or lisinopril. The RAAS has a role in controlling the re-absorption and secretion of electrolytes. In doing so, it can then affect the re- absorption of fluids, leading to blood volume changes. Funnily enough, the pathway involved uses three key substances: renin, angiotensin, and aldosterone. The whole pathway is triggered by a fall in blood volume and blood pressure. In order to appreciate how they work, we should start by looking at the basic negative feedback pathway involved. So, the fall in blood pressure and blood volume is detected by stretch receptors in the walls of the afferent arterioles, but it can also be triggered by detection of low sodium ions in the bloodstream or by a sympathetic nervous response. So, whatever the stimulus, it leads to renin release, an enzyme, which is secreted from the kidneys, especially the juxtaglomerular apparatus. This is a structure found between the afferent arteriole and the ascending loop of Henle just at the junction of the distal convoluted tubules. The renin, once released, cleaves off a peptide for a protein called angiotensinogen to create the active angiotensin I. From there angiotensin I becomes angiotensin II due to the involvement of an enzyme called angiotensin converting enzyme or ACE. So linking back to what I said earlier, you can see that an ACE inhibitor medication simply stops the pathway at this point. But assuming an ACE inhibitor isn’t involved, then you have angiotensin II formed and angiotensin II has 4 main effects which raises blood volume and BP. Firstly, it causes the vasoconstriction of blood vessels to increase BP, but it also vasoconstricts the afferent and efferent arterioles at the glomerulus. Remember the glomerulus in the nephron? The site of filtration? Well vasoconstriction of the afferent and efferent arteriole will ensure blood flow through the glomerulus is maintained at normal, even if BP has fallen slightly. The glomerulus filtration rate is not affected despite the systemic BP fall. Secondly, angiotensin II promotes the absorption of more sodium and chloride ions from the renal tubule. So, if more solutes are moving into the bloodstream, then it affects the osmolality of the bloodstream by causing it to increase. With increased osmolality in the bloodstream, then the water is drawn in too. So together this leads to increased water absorption, so blood volume will increase and so will blood pressure. Thirdly, the angiotensin II stimulates aldosterone release from the cortex of the adrenal glands. Aldosterone is a hormone and as such is part of the endocrine system. It promotes even more reabsorption of sodium and chloride ions, and it encourages potassium secretion too. Again, this is going to increase the osmolality of the bloodstream, leading to the movement of the water from the collecting ducts into the bloodstream, so yet again its about promoting water uptake from the tubular fluid, then using ionic water concentration to assist with this. Finally, angiotensin II promotes the secretion of ADH, or anti-diuretic hormone, which also works with its own negative feedback loop to promote water reabsorption too. So, if the plasma and interstitial fluid is detected as being increased in osmolality by osmoreceptors, so if its too concentrated, then ADH is secreted from the posterior pituitary gland, leading to increased water reabsorption in the nephrons and osmolality returns to normal. So, all of this is going to raise blood volume and therefore blood pressure. Once sodium and chloride levels and BP is corrected, and the body becomes rehydrated, the levels of renin int eh bloodstream can fall and therefore the amount of aldosterone in the blood also falls, meaning more water is excreted in the urine again. The negative feedback system is working by resetting with the stimulus or lack of stimulus This negative feedback works unless an ACE inhibitor medication is involved to breakup the cycle and stop angiotensin I in becoming angiotensin II. If you consider loop diuretics such as furosemide, they can also affect blood pressure, they inhibit some of the transport of sodium ions so the sodium remains in the tubule ready for excretion. Since the sodium has not been reabsorbed into the bloodstream, less water will be reabsorbed into the bloodstream also as there’s less osmotic pressure in the bloodstream. The unfortunate side effect is the loss of too much potassium ions as well, and if you think about potassium and its use around the body, for instance in terms of action potentials, then you can see why this might lead to issues long term if you’re using furosemide for too long. Spironolactone is an alternative diuretic used and its classed as potassium sparing as it acts on inhibiting aldosterone as part of its action. The renin angiotensin aldosterone system is one you should really understand as a paramedic, since not only can you administer furosemide, but understanding blood pressure regulation is so important within blood pressure control overall. So please spend some time on this to really ensure you understand it. Part 8 Changing age through life affects how the kidneys will work. So, for example at birth, the glomerular filtration rate of a baby is just 20% of an adult and so children’s kidneys need time to develop and work at the same capacity as adults. This makes paediatrics prone to dehydration, its one of the reasons that baby food has little to no salt, as babies and young children are at risk if they consume too much salt, leading to hypernatremia, high sodium levels, kidney damage and very sadly death if too much is consumed. During pregnancy, cardiac output increases, which increases the volume and flow of blood in the kidneys. As we age, the kidney function declines from the age of 40 onwards. By the age of 80, about 50% of the glomeruli are no longer functioning well, so this has a large effect on dehydration in elderly patients. Many elderly people also have a reduced thirst sensation, so there’s less triggers for them to drink fluids, plus there maybe a reduced hormone production such as a production in ADH, adding to the dehydration risk as well. Unfortunately, blood pressure also rises as we age, its risk factor to developing hypertension just ageing. But if its undiagnosed this can further lead to kidney damage. The decline in kidney function also affects medication use as renal excretion is ultimately responsible for elimination of most drugs after they’ve been metabolised. Remember the key pharmacokinetics – absorption, distribution, metabolism and excretion, well metabolism can often make the drug less lipid soluble so its easier to excrete in the watery urine than be reabsorbed. Don’t forget the metabolism usually takes place in the liver. We’re going to talk about renal damage and pathophysiology’s in the taught session, but in the meantime, you should be aware that renal damage can be acute or chronic. The old term to describe kidney damage has altered from acute renal failure (ARF) to acute kidney injury (AKI), with an acute episode leading to the sudden reduction or loss of urine production. So, this is one of the reasons those with kidney issues and catheterisation have their urine output measured in hospital, to look out for chronic or acute injury. An acute injury could be due to a blockage like a kidney stone or multi-organ failure, or low blood volume or low cardiac output. I mentioned in an earlier part that a very low systolic BP will affect glomerular filtration rate and so the kidneys will no longer be working as normal in a situation where low cardiac output continues. If the kidneys are not working its going to lead eventually to signs and symptoms, some relating to the ionic imbalances that are steadily worsening such as cardiac arrhythmias, nerve transmission problems, headache, irritability, seizures, vomiting, weakness, or dehydration with hypotension. Conversely, there’s also the potential for fluid overload, causing shortness of breath due to pulmonary oedema, increased JV pressure, hypertension and peripheral oedema. You might well have noted that these symptoms are very similar to heart failure, which in a prehospital environment is going to make it difficult to distinguish between the two. Although if you find an acutely swollen bladder and you know there’s little to no urine output, it might show that the kidneys are primarily involved. Of course, as the body systems work together, if there’s AKI it’s going to affect the cardiovascular injury, so you can’t consider the two systems in isolation anyway. But do keep the kidneys in mind when you consider your patient and specifically, don’t forget the range of vital roles they carry out. Chronic kidney disease (CKD) is classified into 5 stages as the glomerular filtration rate declines. Stage I is normal function, and unfortunately as the kidneys are so good at compensating for any damage, a patient in stage I or stage II CKD renal failure will probably have no symptoms. This issue may only be picked up during a routine blood test for urea and electrolytes which will highlight any electrolyte changes. As a paramedic, you will have a role in promoting overall health, you should always consider the risk of undiagnosed hypertension, not just in cardiac and stroke terms, but in relation to kidney damage. You need to refer a patient with high BP to their GP surgery, if you’re not already transporting them to hospital, as this may help limit kidney damage long term if the hypertension is brought back under control. Going back to CKD though, next is stage III, moderate impairment, where the wastes are beginning to build up in the blood. Stage IV the function is severely impaired. Finally, stage V is classed as established renal failure, or ERF. The glomerular filtration rate will be very low and the patient will be very unwell and the patient will need dialysis in replacement of their failing kidneys.