The Amazing Nephron workshop PDF

The Amazing Nephron **[Learning Objectives ]** - Describe the structure of the nephron and the function of its different parts  - Describe the relation of nephrons to the renal cortex, medulla and pelvis  - Broadly explain how urine is formed and the contents of the glomerular...

The Amazing Nephron **[Learning Objectives ]** - Describe the structure of the nephron and the function of its different parts  - Describe the relation of nephrons to the renal cortex, medulla and pelvis  - Broadly explain how urine is formed and the contents of the glomerular ultrafiltrate in terms of electrolytes, glucose and plasma proteins   **[Session aim: ]** - Overview of the functional anatomy of each area of the nephron. - Basic overview of how anatomy relates to function and what each area does. **[Resources]** This topic is quite complex and it can be a challenge to understand it just by reading the overview below. Even though they are made about human kidneys, the videos below are a good way to help you to understand or consolidate the information at the end of the SDL. I would especially recommend watching the nephron anatomy one. - Renal Anatomy - Nephron Anatomy: - Nephron function: **[Additional (optional) reading/videos:]** **Text:** - The Renal System at a glance, 4^th^ Ed. Chris O'Callaghan (file attached to this SDL) 0 **Video:** This guy is much less boring to listen to\... but slightly more of a challenge to follow in terms of speed! - Crash Course-- Urinary System Part 1 - Crash Course -- Urinary System Part 2 **[Instructions:]** 1. Read the notes below which are a summary of the structure and function of the nephron. The nephron is what much of the urinary module will be based around and so your understanding of it as a functional unit is very important. Having a really good grasp of this material will help you to understand different disease processes and also where drugs might have their effects later in the module and course. 2. Watch some of the videos above\... choose to concentrate and make notes on the ones that you like! 3. Use the information that you have learned from the text and video to complete the tasks at the end. The worksheets will give you a really useful resource to look back at through the module and also to revise from. **[The Nephron ]** The functional unit of the kidney is the [nephron]. In basic terms, it is very similar in all mammalian species but there are some differences that we will come back to later in the module e.g. during the exotics teaching. There are about 400,000- 600,000 in each canine kidney and 200,000 in each feline kidney. Each one functions to filter plasma and produce urine. The body cannot regenerate nephrons and there are several causes of reduced numbers: - Normal ageing losses - Renal injury - Renal disease **[Nephron Anatomy and function]** [Renal Cortex and Medulla] The medulla is composed entirely of straight tubules and so appears striated in transverse section. In comparison, the cortex is made up of the glomeruli as well as straight [and] convoluted tubule segments. Nephrons can be classified by the location of their glomeruli in the cortex as **superficial** (near the caspule), **cortical**, or **juxtamedullary** (near the medulla). The juxtamedullary nephrons are long and due to this are adapted to resorb a lot of water back into the blood. This is really useful in animals that need to minimise the amount of water that they lose in urine, eg desert animals. Importantly, the ability to produce very concentrated urine is associated with a greater percentage of juxtamedullary nephrons. Diagram Description automatically generated Each nephron is specialised to filter blood components and make urine. A filtrate is formed when blood passes through the **glomerulus** which acts like a sieve. After this, the tubular components of the nephron (the **proximal convoluted tubule (PCT); Loop of Henle; distal convoluted tubule (DCT)** and **Collecting Duct**) adjust the make-up of the urine by moving things in or out. Water and electrolyte concentrations are adjusted from the original filtered fluid by many complex processes that result in variable resorption and secretion. Overall, the aim is fluid homeostasis: keeping body water, extracellular fluid concentrations and acid-base status stable in the body. We will look at each area of the nephron in detail, starting at the Glomerulus and moving towards the collecting duct.  The **renal corpuscle** is made up of a ball of capillaries (**the glomerulus**) where blood flows in and is filtered towards a double-walled capsule (**Bowman's capsule**). The glomerulus is formed by an afferent arteriole that divides into looping capillaries in a ball, which then join back up on the opposite side to make the efferent arteriole carrying the blood away. Intraglomerular mesangial cells and matrix occupy the spaces between capillary loops within the glomerulus. The arterioles (afferent and efferent) enter and exit at one end of the ball of the glomerulus (the "vascular pole") and the ultrafiltrate is created and enters the Bowman's capsule at the other end (the 'urinary pole"). Diagram Description automatically generated Blood entering via the afferent arteriole is pushed through the walls of the glomerular capillaries with a filtration effect towards the Bowman's capsule. The capsule is cup-shaped, with inner and outer layers separated by a cavity: the urinary space. This is where the filtrate is collected. The inner layer of the cup is called the visceral layer and is made up if specialised cells called podocytes that play an important role in filtration. Podocytes have foot-like processes that interdigitate with other podocytes. The processes make a layer that spreads out to cover glomerular endothelial cells and intraglomerular mesangial cells with a glomerular basement membrane in between. Mesangial cells are present to keep the glomerular basement membrane "clean" for blood filtration. They do this by having cytoplasmic projections that extend between the endothelial cells and GBM for phagocytosis of debris. **[The Renal "filter"]** Blood passes into the glomerular capillary and is filtered through 3 layers, with the filtered product (known as the "ultrafiltrate") collecting within the urinary space of the renal corpuscle.  The renal "filter" is made up of: 1. **[Endothelial cells of the glomerulus]** Endothelial cells have large fenestrations (pores) which allow many products to pass through. However, a lot of the material that makes up the pores is negatively charged and so there is a charge-barrier as well as a physical space restriction when passing through. Blood cells and most proteins are too large to pass through this layer. 2. **[Glomerular Basement Membrane (GBM)]** This is the main filtration barrier to cells and large molecules. It is also negatively charged. 3. **[Podocytes of the visceral layer of Bowman's capsule]** The podocyte projections don't completely cover the GBM as there are some gaps. They therefore make a discontinuous layer on the urinary space side of the GBM. The spaces between the foot projections are called filtration slits. Filtration of smaller molecules is blocked by the presence of a thin negatively charged membrane within the filtration slits. Overall, passage through the renal filter is dependent upon molecular size and charge. Blood cells and most proteins are stopped at the endothelial fenestrations and negatively charged macromolecules are repelled by the negatively charged components of all layers of the filter. The glomerular capillaries join up to form the afferent arteriole which takes blood away from the nephron. The afferent arteriole is usually wider than the efferent arteriole but both are regulated to maintain consistent **glomerular filtration rate (GFR)** over varying arterial pressures. A picture containing map Description automatically generated **[Juxtaglomerular apparatus (JGA)]** This is a region at the vascular pole of the glomerulus. It is made up of 3 types of cells: - Juxtaglomerular cells - Macula densa cells - Extraglomerular mesangial cells Juxtaglomerular cells are modified smooth muscle cells in the wall of afferent (and more rarely, efferent) arterioles. The cells contain **renin (see ENI module)** granules and may be called "granular cells". The macula densa are specialised epithelial cells in the wall of the TAL of the Loop of Henle and/or distal tubule. This area sits close to the afferent and efferent arterioles of the glomerulus. Macula densa cells detect changes in luminal sodium chloride (NaCl) concentration. The macula densa can signal changes in arteriolar resistance and so affect the blood flow to the glomerulus. The MD also signals the release of renin, causing a cascade of physiological reactions that result in increased systemic blood pressure. Increasing systemic BP also increases glomerular perfusion. The extraglomerular mesangial cells bridge the afferent and efferent arterioles and the MD cells and help coordinate the messages and effects of the JGA.  Diagram Description automatically generated Once the urinary filtrate is in the urinary space of the Bowman's capsule, it begins to flow towards the tubule. The volume and contents of the urinary filtrate will be adjusted by reabsorption and secretion as it passes through the different areas of the tubule. The different areas of the tubule are highly adapted to do specific jobs in the production of urine. The diagram above is important for you to familiarise yourself with as we will now be talking about the route through the tubule **[Proximal Convoluted Tubule (PCT)]** (also known as just the Proximal Tubule) This area of the nephron is very coiled and these segments makes up much of the renal cortex. This is one of the most active areas of the nephron and is where most solute reabsorption occurs. Cells here have a number of features that are suited to these roles: - Cuboidal epithelial cells - Apical intercellular tight junctions (try to stop "leakage" of molecules between cells but allow easy movement of water and some small ions) - Intercellular gap junctions (evidence of intercellular communication). - A layer of microvilli (brush border) -- a modification to increase surface area for absorption and intracellular transport of luminal material. - Basolateral intercellular interdigitations: increase the surface area between cells to maximise transcellular transport of materials. - Lots of mitochondria, especially close to all of the transport pumps on cell membranes **[Loop of Henle]** This part of the tubule descends into the medulla and then ascends back into the cortex. It has several parts: - **[The thick descending Limb]** Often described with the PCT as it is active in reabsorption. Simple cuboidal cells with less extensive cellular modifications than the PCT. - **[The thin descending and thin ascending limbs]** - Changes abruptly to flatter cells: simple squamous epithelium. - No brush border or lateral interdigitations (or very underdeveloped) - Few organelles - **[The thick ascending limb]** - Thicker again: simple cuboidal epithelium - Rises up towards the cortex and ends up next to the glomerulus and macula densa. **[Blood vessels associated with the LoH]** The efferent arterioles in cortical nephrons go on to form a second capillary bed -- **the peritubular capillaries** -- which surround the rest of the tubular system. The efferent arterioles from juxtamedullary nephrons are a bit different. They first form vascular bundles which give rise to both peritubular capillaries and straight vessels that form the **vasa recta**. The *descending vasa recta* follow the LoH down into the inner medulla and once down there divide to make a capillary bed before joining up and rising as the *ascending vasa recta*. The vasa recta are the sole blood supply to the medulla and are very important in creating a concentration gradient. We will discuss this further in the lecture on renal blood flow. **[The Distal Convoluted Tubule]** (or distal tubule) This part of the nephron is after the macula densa. It is shorter in length and has less developed microvilli than the PCT. However, it has lots of basolateral interdigitations and **even more mitochondria** than the PCT. **[Collecting Duct]** This has 3 sections according to their depth in the kidney: - Cortical collecting duct - Outer medullary collecting duct - Inner medullary collecting duct Several nephrons join the same collecting duct and several collecting ducts join to form a papillary duct.  **[Worksheets and Activities ]** **[Task 1]** Use the information in the session to annotate diagrams of renal and nephron anatomy A picture containing diagram Description automatically generated  **[Task 2]** Use the information gathered in this session to create a summary diagram of what each area of the nephron is specialised to do. You may want to come back and add to this diagram at different points in the module.