NU608 Module 6 Renal Disorders PDF

1 The kidneys are remarkable organs. The primary function of the kidney is to maintain a stable internal environment for optimal cell and tissue metabolism. Function of Kidney Non-excretory functions Produces renin  to help regulate BP Produces erythropoietin  stimulating RBC pro...

1 The kidneys are remarkable organs. The primary function of the kidney is to maintain a stable internal environment for optimal cell and tissue metabolism. Function of Kidney Non-excretory functions Produces renin  to help regulate BP Produces erythropoietin  stimulating RBC production Metabolizes Vit D  to its most active form…calciferol which is needed to help absorb calcium Degrades insulin 20% of insulin produced by pancreas is degraded in kidneys Produces prostaglandins (renal medulla produces PGA2 & PGE2  which are potent vasodilators) 2 We’re probably more familiar with the excretory functions of the kidneys: Maintains plasma osmolarity Maintains electrolyte balance Maintains water balance Excretes nitrogenous end products 3 Use your textbook or any A&P book to review the gross anatomy of the kidney 4 We are going to concentrate on the nephron as the nephron is the functional unit of the kidney. There are three major functions that the nephrons’ perform: 1. Filtration Which is the movement of plasma across a filtration membrane (Bowman’s capsule) due to a pressure gradient. 2. Reabsorption Movement of substances from the filtrate (urine) back into the blood This is the way the body recovers the salt, water, and other nutrients it needs 3. Secretion - active transport of substances into the nephrons for excretion. This helps refine the ion concentrations in the body to maintain blood homeostasis 5 As we said the nephron is the functional unit of the kidney. Each kidney contains about one million nephrons. They can be grouped into two categories A. Cortical nephrons  which make up 85% of the nephrons. They have short, thick loops of Henle B.The nephrons near the medulla are called juxtamedullary nephrons and they make up about 15% of all the nephrons and have longer loops of Henle’s than the others. (Approximately 1/3 of the million nephrons in each kidney must be functional to ensure survival). 6 Now, the nephron is comprised of 2 major parts: the renal corpuscle & the tubules. The renal corpuscle is just a tuft of capillaries (glomerulus) surrounded by a capsule (Bowman’s) through which fluid is filtered out of the blood and into the nephron. Blood enters by way of the afferent arteriole and leaves by way of the efferent arteriole (blue arrows above) Approximately 20% of the cardiac output is filtered through the Bowman’s capsule…this fluid becomes known as the filtrate  ~ 125 ml of filtrate is formed each minute The rate at which fluid filters from the blood into the Bowman’s capsule is known as the glomerular filtration rate (GFR)…hint! hint! important concept to remember because anything that affects cardiac output can affect GFR Approximately 99% of what is initially filtered is then reabsorbed throughout the remainder of the nephron tubules with < 1% of the original filtrate becoming urine Under normal conditions, ~ 1 ml of each of the 125ml that is formed is excreted as urine The other 124ml is reabsorbed in the tubules …so… the average output of urine is 60ml/hr 7 When looking at the function of filtration that the kidneys perform…we see that plasma passes through a filtration membrane…and it’s the Bowman’s capsule that serves as that filtration membrane). The filtration barrier consists of three distinct layers 1. Glomerular capillary endothelium (pores through which plasma must pass)  endothelial cells line the glomerulus and is in constant contact with blood flowing through capillary lumen 2. Basement membrane 3. Visceral epithelium (podocyte & feet) of the Bowman’s capsule  acts like a sieve. Podocyte cells prevent molecules >7 nm to pass through. Plasma proteins are slightly larger and are retained within the capillaries…so, protein should not be seen in urine. If protein is seen in the urine (the urinanalysis would show it) that is an indication that there may be damage to the glomerulus…since normally it should not be present. The barrier prevents entry of blood cells & protein into the nephron but allows other blood components to enter … H2O, urea, glucose, and ions. The glomerular capillary purpose is basically to produce a urine filtrate that is free of red blood cells and plasma protein. 8 This is a basic review of the filtrates passage through the nephron. The filtered blood follows a path from the glomerulus... 1. Blood enters the glomerulus (through the afferent arteriole…remember that the rate at which fluild filters from the blood into the Bowman’s capsule is known as GFR) 2. Filtrate is formed and passes into the Bowman’s capsule 3. It then flows into the proximal tubule... which lie in the cortex THE PROXIMAL TUBULE IS THE MAJOR SITE OF REABSORPTION Na+ is mainly reabsorbed here …60 to 70% of Na+ that’s initially filtered is reabsorbed (and where Na+ goes so does water) 4. The filtrate then flows through the descending and ascending loops of Henle... Descending loop  more reabsorption of H2O Ascending loop  more reabsorption of Na+ into the interstitium/ and Cl-, (also have reabsorption of KCL, HCO3, Ca) but the ascending loop is impermeable to water 5. There’s continuous recycling of Na between filtrate in the loop and the medullary interstitium This creates an osmotic gradient in the interstitium that helps in the final concentration of urine 6. Filtrate then goes to the distal tubule.... there’s more reabsorption of Na Here in the distal tubule the hormone aldosterone acts on DT to further increase reabsorption of Na Remember that aldosterone is known as a “salt-retaining” hormone but it also promotes the secretion of K+ into the tubules And filtrate gains K+, H+, ammonium ions (by tubular secretion) 7. Filtrate then enters the collecting tubules  there are 250 large collecting tubules each transmitting urine from ~ 4000 nephrons. Here in the collecting tubules another hormone (ADH-also known as vasopressin exerts its action) With sufficient ADH present...filtrate in the CT loses H2O into interstitium (the kidney will reabsorb more water… with the resulting fluid (urine) being highly concentrated 9 Hormonal Influences help the kidney with maintaining water and sodium Homeostasis: Renin-Angiotensin-Aldosterone System (RAAS) regulates the ECF volume by regulating sodium content. Stimulation of this system leads to: 1. Systemic vasoconstriction 2. Sodium retention in kidneys (along with Na+ goes H2O) 3. Expansion of ECF volume It does this through the stimulation of renin Renin is an enzyme produced by the juxtaglomerular cells of the nephrons. Which are cells are located in the walls of the afferent arteriole. They act as baroreceptors (responding to renal blood flow) 10 There are two ways renin is stimulated: 1. The primary stimulus for secretion is renal hypoperfusion… when renal perfusion is decreased  renin release is stimulated. So, anytime renal blood flow is decreased renin will be released. The second way... There are specialized cells in the distal tubule (macula densa) These cells sense the amount of Na+ and Cl- arriving at the site When the concentration of Cl- at macula densa falls renin is released 2. Renin then enters the general circulation acting on angiotensinogen (which is a protein produced in the liver) to convert it to Angiotensin I. 3. Angiotensin I passes through the lung and is converted (by ACE…angiotensin converting enzyme) to Angiotensin II. 4. Angiotensin II is physiologically active and is a potent vasoconstrictor.... Increasing PVR (peripheral vascular resistance) leading to increased BP 5. Angiotensin II also stimulates the adrenal cortex to release aldosterone (a salt- retaining hormone) Aldosterone acts mainly on distal tubule…in the presence of aldosterone Na (and H2O) is reabsorbed and K is secreted 11 Another hormone acting on the kidney is the Antidiuretic Hormone (ADH) -- is also known as arginine vasopressin. 1. It’s synthesized in the hypothalamus 2. Then, migrates to the posterior pituitary gland for storage. 3a & 3b. Present in the body are cells sensitive to changes in osmolality of the interstitial fluid and decreases in blood pressure. Secretion of ADH is stimulated by.... Increased plasma osmolality Decrease in effective BP (circulating blood volume) ADH has two effects... 4. It has an effect on blood vessels causing vasoconstriction  increasing BP 5. It has an effect on the kidney by increasing the permeability of the distal tubule and collecting duct membrane to water, so.... It increases reabsorption of water  increasing blood volume Because of increased water reabsorption from the filtrate the urine becomes more concentrated And there’s a decrease in the amount of urine produced 12 So, the actions of ADH have two important clinical correlates: In Diabetes Insipidus the individual has insufficient ADH being produced so: The CT is impermeable to water So, there is minimal to no reabsorption of water occurring in the collecting tubule UOP increases (as water is not being reabsorbed) And, the result is a dilute urine (decreased sp. Gravity…can be down to 1.0001) Clinically the patients are dehydrated (due to the increased UOP) infants, children, elderly, immobilized at riskothers with DI can increase their intake because they’re thirsty Increased serum Na Increased weight loss Can occur in patients with CNS disease Now , the opposite is Syndrome of Inappropriate ADH (Increased ADH release…to much is being produced) Increased reabsorption of water in the CT Decreased water in the filtrate UOP decrease (as the kidney is reabsorbing more water) Concentrated urine (increased sp gravity…can be over 1.020) Patients appear edematous Decreased serum sodium Increased weight gain Can be seen in patients with CNS disease, also there is increased ADH release when patients are in pain, have surgery, asphyxia, pneumothorax 13 Remember…I can’t stress it enough the GFR is the rate at which fluid filters from the blood into the Bowman’s capsule. GFR is dependent on renal blood flow (RBF). If you have good RBF then GFR will be good. And, since RBF is dependent on cardiac output anything that causes a decrease in cardiac output will ultimately decrease RBF and thereby decrease GFR important patho concept! 14 The major determinant of glomerular filtration is the Blood Pressure within the glomerular capillary network. This pressure is regulated by RBF which responds to changes in the smooth muscle of the arteries. Blood flows into the glomerulus via the afferent arteriole so if there’s vasoconstriction of the afferent arteriole occurring there will be decreased GFR. Blood leaves the glomerulus via the efferent arterioles so if there’s vasoconstriction of efferent arteriole this will increase GFR (less blood allowed out, it leaves more slowly, increasing time for filtration). This ability of the arterioles to dilate and constrict in order to maintain a constant GFR within the nephron is known as autoregulation. For GFR to occur RBF must remain both rapid and constant…Autoregulation of the renal blood flow allows the kidney to maintain relatively constant glomerular perfusion despite changes in Mean Arteriole Pressure (MAP). Studies have shown that in adults if the MAP falls 2.5 (reflects intrinsic) 3->5 RBC that’s hematuria (and remember if glomerulus is intact we should not see RBC’s) If 0-3 (hemoglobinuria or myoglobinuria) Hemoglobinuria seen during states of hemolysis blood transfusions, incompatibilities, elevated hgb Myoglobinuria seen with ischemia, crush injury  protein that makes up muscle…urine will look tea color, brownish, can precipitate in tubules breakdown products are toxic Glucose: normally present only in trace amounts Glucose (like Na+) is both filtered and reabsorped Glucose secondary to defect in tubular reabsorption Pyuria: presence of WBC doesn’t always mean a UTI WBC can also be seen in stress, asphyxia, fever, emboli to renal artery, hypercalcuria If see nitrates (with WBC)  indicates end-product of bacteria (esterases) In the microscopic exam, the urine sediment can be broken down into cellular elements: Epithelial cells: seen with tubular/interstitial injury  occasionally seen since the tubule is a living membrane and is always replacing itself Now, casts show evidence of damage as cast formation only takes place within the lumen of the nephrons (represents parts of decomposed cells). Hyaline casts: formed when protein within the tubules gel - Indicates possible damage of the glomerular capillary membrane Permitting leakage of protein through the filtration membrane (Seen in dehydration & when there’s massive amounts of protein in urine) RBC casts: glomerular injury WBC casts: infection, interstitial injury, tubular damage, renal inflammation Granular casts: represent partially decomposed cellular casts Broad casts: develop in atrophied and dilated nephrons  indication of nephron death 30 Chronic Renal Failure  represents a progressive and irreversible destruction of the kidney structures. Most common etiologies include: Diabetes Hypertension Glomerulonephritis Polycystic kidney disease 31  Different Stages of progress: Stage one to two is that of diminished renal reserve  GFR drops to ~60% of normal BUN, CR still normal, no symptoms May have only one kidney or be functioning on one kidney Stage three to four is that of renal insufficiency  GFR is 50 to 20% normal Azotemia Anemia Hypertension begins to appear (usually late 2 or 3) Stage (late) four to five is renal failure  GRF 20 to 5% normal Kidneys can’t regulate volume and solute composition Electrolytes abnormal Edema develops Topic Slide 32  Metabolic acidosis ESRD  GFR is less than 5% Dialysis or transplantation is necessary for survival Reduction in renal capillaries Scarring in glomeruli Atrophy & fibrosis in tubules REVIEW THE CRITICAL THINKING ACTIVITIES TO REVIEW THE MECHANISMS BEHIND THE CLINICAL MANIFESTATIONS OF CRF 32 Many causes of renal failure (both acute and chronic) can be related to glomerular disease in which the glomerulus of the nephron is injured: The patient may exhibit hypertension, edema, hematuria and azotemia. The abnormal laboratories seen are d/t decreased GFR. 33 The edema these patients develop is due to the person losing a lot of protein in their urine due to the damage in the glomerulus. The glomerulus which can no longer function allows protein to be in the filtrate. Because they lose a lot of protein in the urine, the protein (albumin) levels in the patient’s bloodstream is low. The low proteins in the bloodstream decreases capillary oncotic pressure (proteins help keep water in the vascular bed) so fluid leaves the vascular bed and goes into the interstitium causing edema in the person 34 Inflammation of the glomerulus is the leading cause of chronic renal failure in the U.S and accounts for ½ of the people who have end-stage renal disease. 35 PSGN is the most commonly recognized form of glomerulonephritis. It typically follows infection occurring about 7-12 days after the infection. Why do you think that is? Remember, it takes the body about 5-10 days to develop antibodies against an infection and PSGN is due to an antigen-antibody complex formation. It’s this complex that forms and for reasons we’re not quite sure they deposit on the glomerulus causing inflammation and injury to the nephron. If PSGN develops in children there is a generally favorable prognosis in that 95% will recover without any further renal damage. However in adults only 60% recover favorable. The remainder go on to develop permanent kidney damage. 36 And finally, I want to mention nephrotic syndrome…it’s not a specific glomerular disease but a constellation of clinical findings that a patient exhibits that are due to massive protein loss in the urine (no matter what caused the kidney damage). Patients with nephrotic syndrome loss over 3.5 g or more of protein in their urine per day. So they exhibit low serum protein leading to edema …but…we also see increased levels of lipids in the blood and d/t this elevated lipids in the blood they will also have increased lipids in the urine. Why does this happen? What do you think? Well…the body will attempt to replace the protein that is being lost in the urine by producing more protein. The liver is the organ that produces protein and when it “upregulates” to produce proteins it produces lipoproteins…so we see not only proteins but the increase in lipids. 37 Flow map of the clinical manifestations of Nephrotic syndrome. 38 Everyone needs a “smile” after this module…and I thought this picture would do it  39