BMED 603 Lecture 13 - Urinary System (part 1) PDF

https://xkcd.com/749/  Learning objectives Today our goals are to: Know the components of the urinary system, including each section of the nephron’s tubule Describe the histological structure of the urinary system’s various components, including each section of the nephron...

https://xkcd.com/749/  Learning objectives Today our goals are to: Know the components of the urinary system, including each section of the nephron’s tubule Describe the histological structure of the urinary system’s various components, including each section of the nephron’s tubule Explain how the structure of the urinary system’s various components supports their function Components of the urinary system  Functions of the urinary system Fluid balance – water intake (from the digestive system) must equal water loss The urinary system is the primary source for water removal Osmoregulation & Electrolyte balance – the osmolarity of bodily fluids must be tightly controlled so that intracellular & extracellular fluid fractions are maintained The urinary system is the primary osmoregulator, recovering solutes from the filtrate and returning them to circulation The urinary system is selective about what solutes are recovered in order to maintain proper concentrations of salts in the body Waste excretion – waste solutes are not recovered and are excreted with H2O The urinary system is the primary route for removing nitrogenous waste, some hormones, and some toxins The urinary system actively reabsorbs nutrients to preserve them  Gross anatomy of the kidney All vessels (blood & lymphatic, plus nerves & the ureter) enter/exit at the renal hilum. Just inside the fibrous capsule of the organ is the renal cortex. The middle layer of the kidney is the medulla, which contains many renal pyramids, separated The apex byofthe each pyramid terminates on a minor calyx – these renal collect columns. urine made by the kidney’s filtration units (nephrons). Minor calyces converge to form major calyces, which converge to form the  Kidney histology Identify the cortex, medulla, renal pyramids, renal columns, calyces, and arteries.  Blood supply of the kidney The kidneys are highly vascularized – ~20% of your blood flows through per minute. Extensive capillary beds in the renal cortex provide the fluid supply for the kidney’s filtration units, which are called nephrons.  Microscopic anatomy of the kidney Each nephron is a composed of a convoluted tube surrounded by capillaries. The nephron is the functional unit of the kidney (there are ~1.3 million per kidney). Types of nephron Cortical & juxtamedullary nephrons function similarly overall, but there are a couple of key differences. Cortical nephrons are 85% of all nephrons and are responsible for most of the kidney’s filtration. Their loops do not descend very far into the medulla. Juxtamedullary nephrons are the remaining 15%. Their loops of Henle on are much longer and dive deep into the medulla. This allows for more water reabsorption and thus  Components of the nephron Nephrons start at a renal corpuscle, which is made of the glomerulus (a capillary network) surrounded by Bowman’s capsule. The function of the corpuscle is ultrafiltration – removal of fluid and small solutes from the blood. Filtrate flows into the proximal convoluted tubule (PCT), down through the loop of Henle (nephron loop), up into the distal convoluted tubule (DCT), and out into a collecting duct. The function of these tubule  Function of nephrons (ultra)Filtration – filtrate fluid (primarily water, ions, and small molecules; excludes most macromolecules in the blood and all cells) is extracted from blood at the glomerulus-capsule interface (the entry point into the nephron) Reabsorption – components of the filtrate that we want to keep (e.g. ions, sugars and other small molecules) are reabsorbed by the cells lining the nephron (the collecting system) and transported back into the bloodstream Tubular Secretion – cells lining the nephron can also adjust the composition of the filtrate by secreting unwanted molecules into the collecting system (this is coordinated by hormonal signals received by the cells lining the tubules/ducts). Cells of the nephron Production of filtrate The afferent arteriole supplying blood to the glomerulus is larger diameter than the efferent arteriole that exits it. This raises blood pressure in the glomerulus, forcing fluid out through fenestrations in the endothelial cells (osmotic and hydrostatic pressure in the capsule space are overwhelmed by capillary fluid pressure).  Renal corpuscle histology The large spaces filled with purplish circles of cells are the corpuscles. The purplish clusters are the glomeruli, and the white crescents around them are the lumens of the capsules, where the filtrate produced is funneled into the nephron tubules. The small SEM of cortical blood vessels A general caveat about 2D sections of 3D tissue  Renal corpuscle histology At higher zoom, the dense capillary network of the glomerulus is visible. Note the cells between the capillary endothelial cells, the simple squamous layer that forms Bowman’s capsule, and the afferent arteriole. Near the afferent arteriole is the  Production of filtrate Podocyte Fluid forced through the fenestrations (which block cells, but not proteins) must still pass through the lamina densa (basement membrane) that fills filtration slits formed by specialized podocyte cells. The filtration slits are less than 10 nm wide, which Production of filtrate We make about 125 mL of filtrate per minute (on average) – this is the glomerular filtration rate (the GFR). We reabsorb 99% of the filtrate through the action of our nephrons. GFR is a major clinical measure of kidney function. Glomerular filtration is a passive process, but the rate can be modulated by vasoconstriction or vasodilation to control the diameter of the efferent arteriole. The GFR can be modulated  Renal corpuscle histology Note the dark, solid staining of the cytoplasm of podocytes (arrows), which wrap around the capillary endothelial cells. Between the capillaries there are mesangial cells, contractile cells that hold the capillaries together and phagocytose any macromolecules that  Renal corpuscle TEM histology Note the capillary lumens (with solid RBC cross-section), the lamina densa, and the podocytes surrounding it. Find the mesangial cells, the lumen of Bowman’s capsule, the simple squamous capsule cells, and their lamina propria.  Renal corpuscle TEM histology Note the capillary lumens (with solid RBC cross-section), and the single podocyte. Find the fenestrations in the endothelial cell membrane, the lamina densa, and the pedicels (feet) of the podocyte with filtration slits in between them. SEM of podocyte filtration slits Overview of filtrate processing (reabsorption) PCT reabsorption: Na+ (65%) DCT Nutrients reabsorption: (~100%) Na+ (5%) Water (67%) Water (varies, up to 8%) cortex medulla (salty  hyperosmotic) Collecting duct Loop reabsorption: reabsorption: Na+ (varies)* Water (15%) Water (varies)* Na+ (25%) Filtrate processing in the PCT The PCT is the primary site for resorption of: nutrients (e.g. glucose) buffers (e.g. bicarbonate) There is also significant reabsorption of: water ions There is also secretion of: protons (hydrogen ions) Filtrate processing in the PCT Essentially 100% of important organic molecules (like glucose) are reabsorbed in the PCT via facilitated diffusion and/or cotransport. Ions like sodium are actively transported out of the PCT and into the peritubular capillaries. Reabsorption lowers the osmolarity of filtrate; therefore, water follows the ions into the cells via osmosis. Maintenance of the sodium gradient allows Na+-H+ antiporters to secrete protons into the PCT. Acidification drives  Proximal convoluted tubule histology The PCT is immediately recognized by the brush border of microvilli and the ‘bubbly’ appearance of the cytoplasm in their cuboidal epithelium (an artifact of fixation). Some of these tubules appear collapsed in the section, but they are filled with precipitate from the Proximal convoluted tubule TEM histology The microvilli of the PCT are more clearly resolvable with EM. Proximal convoluted tubule SEM histology The microvilli (Mb) of the PCT are more clearly resolvable with EM.  Renal thresholds While the kidneys are excellent at reabsorption, there is a limit on their capacity to remove desirable molecules from the filtrate – these limits are renal thresholds. For amino acids, this limit is 65 mg of AA solute per dL (100 mL) of filtrate The presence of amino acids in the urine is called aminoaciduria This could occur normally after something as simple as a protein-rich meal How can we test for abnormal AA reabsorption? Fasting – removing variables like recent meals is one reason why clinicians often want to measure metabolites while we are fasting AA in the urine while fasting might be indicative of amino acid processing disorders such as phenylketonuria or liver failure  Diabetic nephropathy Uncontrolled diabetes mellitus is the leading cause of chronic kidney disease. A constellation of factors lead to progressive loss of function.  Dialysis Dialysis is extracorporeal filtration of the blood, used to mitigate the loss of kidney function in patients with kidney disease (usually while waiting for a transplant).