The Final Exam: Tuesday, May 8th 8:00 – 11:00 AM Livingston Recreation Center on LIV Lecture 9 – Renal Morphology 1. Depolarization rate refers to the rate of change of membrane potential during a particular phase of an action potential. So in the SA node (phases 4, 0, 1, 2, 3), let’s focus on phase 0. The rate of depolarization is quantified as change in membrane voltage over change in time. Conduction velocity is the rate at which an action potential moves from one location to another. This is expressed in centimeters per second, etc. a. Are the two related in any way? Yes. Conduction velocity in any place in the system is dependent on several things, one of which is depolarization rate. If the slope of the depolarization rate is stepper, conduction velocity is faster. This change is a change in membrane excitability. The more excitable a cell is, the faster they depolarize and the faster they conduct velocity. Kidney Structure (Slide 1) 1. An understanding of the physiology of the organ is the only way to understand its function. 2. Kidneys are bilaterally arranged organs that sit on either side of the vertebral column, with the top at about the level of the 11th or 12th vertebrae. Each kidney in a small woman weighs about 100g. In a large man, it could way 175g – 200g. They are located in the retroperitoneal position, meaning behind the innermost epithelial lining of the abdominal cavity. They are not technically abdominal organs because they are outside the cavity. The adrenal gland sits on top of the kidneys. There is a ureter from each kidney that leads to a common urethra that drains from the body. 3. A transverse, or saggital, section shows us a bean-shaped kidney. The outer curvature is convex. The inner is concave. From the outside, the kidney has a tough, nondistensible renal capsule that encases the structure. Just beneath it, there is a region called the renal cortex. Inside the cortex, you have the renal medulla. This is a pyramid-shaped structure. The cortex contains the nephrons, the functional unit of the kidneys. The kidney sinus, or medullary sinus, is created by the major calix. 6. The renal hilus contains regions where all tubes entering the kidney are located (renal artery, renal vein). A single renal artery branches as soon as it enters the hilus. Many move toward the top pole of the kidney. Not as many go to the inferior or south pole. Most go to the inferior wall instead of the anterior. 7. Each kidney has 10-15 medullar pyramids, which help define the path of the vasculature. Interlobular arteries pass between the pyramids. If you look down into the lumen of a pyramid, you can see openings in the tip (20-30), called the Ducts of Bellini. These ducts are the convergence of a bunch of collecting ducts. These ducts are also the final tubular component of each individual nephron. Kidney Nephron, The Functional Unit (Slide 2) 1. Each kidney has a million nephrons per kidney, more for large men and fewer for small women. 2. Renal capsule ( cortex ( outer medulla ( inner medulla. The inner medulla has an orifice at the bottom that is the Duct of Bellini. 3. Following the Duct of Bellini backwards, we get to the outer medullar collecting duct. That is the region of the duct that is located in the outer medulla and has no branches. This is the last true segment of the collecting duct from the nephron. 4. Upstream to the outer medullary collecting duct is the cortical collecting duct. That cortical collecting duct joins to the initial collecting tubule. There is a large connecting tubule next. Upstream from the connecting tubule is the distal convoluted tubule. 5. Further upstream is the thick ascending limb (TAL) that is part of the structure called the loop of Henle. The TAL leads to the thin ascending limb. Going around the hairpin loop, you get to the thin descending limb. Next is the proximal straight tubule (PST). Next comes the proximal convoluted tubule (PCT). 6. Finally, we come to a structure called Bowman’s capsule. Inside the capsule are glomerular capillaries. 7. Within the kidney, there are superificial or cortical nephrons (80-58%) as well as juxtamedullary nephrons. They serve similar functions but behave physiologically different. a. Cortical ones are at the surface of the kidney while the loop of Henle of juxtamedullary nephrons dips deep into the renal medulla. b. Functionally, the only difference is that juxtamedullary nephrons also function in maintaining an osmotic gradient in the renal medulla that is crucial to the kidney’s ability to produce highly concentrated urine, thus conserving water under certain conditions. Glomerular Details (Slide 3) 1. This is the glomerulus. It is surrounded by Bowman’s capsule, and the two structures put together are called a renal corpuscle. It also contains Bowman’s space, along with glomerular capillaries. 2. There is a distal tubule that is very close to arterioles coming from the glomerular capillaries. This is called the juxtaglomerular apparatus (JGA). 3. The yellow region in Bowman’s space are cells called podocytes. They attach to glomerular capillaries and surround them over their entire length. Each podocyte has a nucleus, and it also has filopodia. 4. These filopodia surround all capillaries in the glomerulus except at the very center. That area is called the mesangium. The podocyte in the mesangium does not have filopodia. Mesangium is a regulatory tissue in kidneys where extracellular matrix is formed. It is a protein depot for creating other structures of the glomerulus and is also a regulatory center. Summary (Slide 4) 1. Macroscopic structure of the kidneys 2. Renal circulatory system 3. Tubular system of the nephron Glomerular Filtration Barrier (Slide 5) 1. Purpose 2. Structural components 3. Alterations 4. This a landmark property of the kidneys: filtration. They are designed to filter plasma. 5. This filtration barrier, or glomerular membrane, is made up of the capillary endothelial cell, a basement membrane and epithelial cells in Bowman’s space (lumen of Bowman’s capsule). SEM Of Glomerular Capillaries (Slide 6) 1. The round structures are capillaries, while all the other foot-like extensions are podocytes. These extensions come off the basement membrane and into Bowman’s space. They run perpendicular and parallel to the capillaries, forming a meshwork. 2. There are also smaller extensions running on the capillary side of the filtration barrier. These podocytes are smaller than those on the side of Bowman’s space. SEM Of Lumen Of Glomerular Fenestrated Capillary (Slide 7) 1. The most remarkable feature is that renal capillaries are fenestrated. These pores are very small, about 700 nanometers (0.7 µm) and are located all along the filtration barrier. 2. They are so small that no cells can penetrate through them, but proteins and macromolecules may. Ultrafiltration Barrier Of The Glomerulus (Slide 8) 1. We see at least 3 layers of tissue that separate the lumen of the capillaries from Bowman’s space. Again, the three layers are the capillary endothelial cells, basement membrane and Bowman’s capillary endothelial cells. These three layers make up the filtration barrier. Anything that makes it across becomes known as ultrafiltrate; it is not urine. It is a reflection of plasma. 2. As it passes into the tubular system, it has the potential to be modified (reabsorbed, secretion into it or nothing may happen). The end product after the collecting duct becomes urine. 3. The layer on the left shows individual fenestrations of the endothelium in the glomerulus. Their main function is to prevent cellular elements inside the capillaries from getting into Bowman’s space. This includes larger proteins and molecules. Under normal conditions, there are no proteins below Bowman’s space in the ducts. So, ultrafiltrate is not technically a reflection of plasma in that aspect. 4. The basement membrane after the fenestri has either three layers or just one. On the other side are filopodia, and spaces between are called filtration slits. There is a slit diaphragm, tissue that connects two adjacent filopodia, which is porous. They are 4-14 nanometers in diameter, smaller than fenestri. Most likely, this will trap all proteins and not let them pass. 5. Many proteins cover the layers within Bowman’s space. They carry a net negative charge, so that if a protein does escape, the negative charge will repel it back. It is unlikely that any proteins, under normal physiological conditions, will ever appear in the ultrafiltrate. Selective Permeability Of Glomerular Filtration Barrier (Slide 9) Substance Mol wt Mol rad Rel concen (UFx/Px) Na+ 23 0.1 1.0 Glucose 180 0.33 1.0 Inulin 5200 1.48 .98 Myoglobin 16900 1.88 0.75 Plasma albumin 69000 3.55 <0.01 1. The larger the protein, the less likely they are to appear in the ultrafiltrate. This is due to pore size. Filterability Of A Solute (Slide 10) 1. We are looking at how filterability is dependent on charge and size. 2. First, we see that anything with a molecular radius less than 2 nm is almost always freely filterable. As radius increases to about 4 nm, it becomes nonfilterable. 3. Secondly, the three curves represent a neutral molecule in the middle, a cation up top and an anion on the bottom. If you compare the cationic curve to the anionic curve, the anionic polymer shifts the curve to the left, meaning its filtration is going to be less for any size molecule. Cationic polymers shift the curve to the right, meaning its filtration is going to be greater for any size molecule. This is due to the negatively charged proteins that line Bowman’s space. 4. Heavy exercise impairs the filtration barrier. It has some effect on the negative charge that covers the barrier, allowing protein to get across into your ultrafiltrate. So if you have been exercising strenuously and take urine test, you will have proteinuria, meaning there will be some protein in the urine. Summary (Slide 11) 1. Microscopic structure of the kidneys 2. Filtration barrier and ultrafiltrate 3. Solute size and charge General Function of Nephrons (Slide 12) 1. Filtration, reabsorption, secretion, excretion 2. Specialized cellular makeup and function 3. Experimental techniques 4. Micturition reflex Urinary Excretion Of A Solute (Slide 13) 1. You have two arterioles and two capillary beds. The afferent arteriole runs into the glomerulus while the efferent arteriole runes out of the glomerulus. The first capillary bed is the glomerular one while the second is the peritubular carpillary. This figure illustrates the basic physiological processes that occur in the nephron. 2. The important processes that occur are: filtration, reabsorption into peritubular capillaries, secretion from the peritubular capillaries back into the tubes and finally, excretion. All these processes are physiologically regulated. 3. If the excrete is greater than the filtrate, then secretion has occurred. If the excrete is less than the filtrate, then reabsorption has occurred. 4. Amount filtered – amount reabsorbed + amount secreted = excretion. Specialized Cellular Structure (Slide 14) 1. There are differences in cell types up and down the nephron. The type of cell that characterizes a specific section of the tubule determines what occurs in that section. 2. The proximal convoluted and straight tubules – under physiological conditions, the vast amount of the ultrafiltrate that will be reabsorbed is taken in through those two regions. There are fingerlike projections that increases surface area for reabsorption. They are also densely packed with mitochondria to generate much energy. 3. The cells in the loop of Henle are very permeable to water. 4. The collecting duct: the epithelial cells are designed to handle water. This is where most of the water regulation occurs. ADH prominently affects the collecting duct in these kidneys. It increases the synthesis and insertion of protein water channels and inserting them into water ducts. Experimental Methods (Slide 15, not on exam) Bladder Filling And The Micturition Reflex (Slide 16) 1. The bladder wall is made up of smooth muscle. There are two sphincters at the urethra, an internal and an external one. The internal is controlled by autonomic nervous system, the external by the somatic nervous system. 2. As volume in the bladder increases, the visceral smooth muscle gets stimulated. This sends signals up to the CNS and initiates a reflex. Three components are: parasympathetic nerves, and ACH causes the muscle to contract. The sympathetic nerves that innervate the internal sphincter are also excited. 3. Only the strain on the external sphincter and your decision can control urination.