Renal Physiology.docx

Body water About 60% of total body weight is made up if water. 20% of the water is made up of ECF (extracellular fluid), which includes plasma, interstitial fluid, and transcellular water. 40% of the water is made up of ICF (intracellular fluid). ECF Transcellular water makes up 1% of ECF. It is loc...

Body water About 60% of total body weight is made up if water. 20% of the water is made up of ECF (extracellular fluid), which includes plasma, interstitial fluid, and transcellular water. 40% of the water is made up of ICF (intracellular fluid). ECF Transcellular water makes up 1% of ECF. It is located in: Lymph within lymph nodes Synovial fluid within joints Cerebral spinal fluid (CSF) in the brain Aqueous humor and vitreous body of the eyes Endolymph and perilymph within the ears Pleural, peritoneal, and pericardial fluid between serous membranes Glomerular filtrate in the kidneys For cells to survive, the fluid in the ECF must stay within their specific location limits. This is why injecting fluids within a patient in one of these locations won’t impact the fluid levels in one of the other locations listed above. Water Balance Water is brought into the body by: Drinking liquids Eating food Metabolic water (water oxidation) Water is lost from the body by: Urine Sweat from the skin Lungs exhaling water vapor Fecal mater from the GI tract Kidneys The kidneys are the main organ regulating and stabilizing the volume and ion concentration within the ECF. Therefore, the kidneys are the main thing that allow for mammal survival when in conditions with variable water and salt access. The kidney’s functions include: Urinary excretion Blood filtration Waste and xenobiotic excretion Retrieve necessary metabolic substances such as water, electrolytes, glucose, and low MW proteins Respond to water, electrolytes, and acid-base disturbances to keep water content and plasma tonicity (extracellular osmolality) maintained. A major issue with terrestrial animals is avoiding dehydration. This is relevant to the kidneys because water reabsorption happens here. By absorbing water in the renal tubules, urine can be concentrated. Concentrated urine allows animals to not have to drink so much water to stay hydrated. Gluconeogenesis Hormone production associated with systematic blood pressure, RBC (red blood cell) production, and calcium metabolism The kidneys are made of a cortex and a medulla. The kidneys are located adjacent to the upper abdominal wall. Endocrine functions of the kidneys include producing the hormones: Calcitriol which is stimulated by PTH in response to hypocalcemia. Renin which is apart of RAAS (renin angiotensin aldosterone system), activates hormones, and regulates renal blood pressure. Erythropoietin which is a hormone (growth factor, glycoprotein) essential for erythropoiesis (the maturation of RBC). Some athletes will partake in “blood doping” with is injecting themselves with erythropoietin (EPO), to increase their number of RBC, allowing their muscles to work harder and longer without cramping. Urinary Tract System The urinary system consists of the urinary bladder, ureters, urethra, and kidneys RAAS (Renin angiotensin aldosterone system): Pathway Step 1: The kidneys sense low blood pressure, and respond by releasing renin from the juxtaglomerular apparatus (JGA) Step 2: Renin converts angiotensinogen into angiotensin 1. Step 3: ACE converts angiotensin 1 into angiotensin 2. ACE inhibitors, within medications will inhibit this process. Step 4: Angiotensin 2 will cause vasoconstriction, increasing blood pressure. Angiotensin 2 will also stimulate the adrenal glands to secrete aldosterone. Step 5: In the kidneys, aldosterone promotes the reabsorption of sodium and water. Step 6: This results in the circulating blood volume to increase, which will then increase the blood pressure. To memorize think: Kidneys=Renal=Renin. The kidney (Renal system) sense low blood pressure, causing the Release of Renin. Pathway is called RAAS, so “A” is next. Renin converts Angiotensinogen to Angiotensin 1. After 1 is 2. The next letter in RAAS is “A”. So, ACE will convert Angiotensin 1 into Angiotensin 2. The major issue was that blood pressure was too low, so what will Angiotensin 2 do? Cause vasoconstriction and INCREASE blood pressure. Angiotensin 2 will also stimulate the Adrenal gland to secrete Aldosterone. What is a reason for low blood pressure? Low sodium. So, Aldosterone will increase reabsorption of sodium, and water (which has an osmotic relationship with sodium), thus also increasing blood volume and blood pressure. Calcitriol Synthesis: Pathway Step 1: Low calcium levels will trigger the release of PTH. Step 2: PTH will stimulate the kidney enzyme 1-alpa hydroxylate to convert calcidiol into calcitriol. Step 3: Calcitriol will increase intestinal calcium reabsorption, this increases blood calcium levels. Some species have precursors to make calcitriol just from sunlight absorption, but not many can do this. Nephrons of the Kidneys The nephrons are the functional unit of the kidneys. Humans have about 1 million nephrons per 1 kidney. Cows have 4 million. Dogs have 400,000. Cats have 190,000. Nephrons can only partially regenerate and can NOT be replaced. The kidneys contain 2 types of nephrons and each have their own set of capillaries. The 2 types include: Cortical nephron The medulla is located far from the medulla/cortex junction. Uses peritubular capillaries for it’s blood supply Short Loop of Henle Juxtamedullary nephron Glomerulus is located near the medulla/cortex junction Extremely long Loops of Henle, which is very important for urine concentration. Efferent arterials give rise to long straight capillaries (vasa recta) that descend into he renal medulla. Nephron structure includes: Renal corpuscle (AKA: Malpighian body) It is located in the renal cortex. It consists of the glomerulus (capillaries) and Bowmans capsules (double walled capsule). Bowman’s space refers to the capsular space between Bowman’s capsule and the glomerulus. Proximal tubule It is the longest part of the nephron. It consists of the proximal convoluted tubule (PCT) and a straight part (PST). The proximal tubules (PT) reabsorbs water through aquaporins (AQP) and solute reabsorption. sodium reabsorption favors water absorption in cells and interstitium. Loop of Henle It consists of: Thick descending limb (extends into renal medulla) Thin descending limb The thin descending limb reabsorbs water via osmosis. Thin ascending limb (only in nephrons with long loops) Thick ascending limb (AKA: TAL or macula densa) Distal tubule This includes a convoluted part (DCT), and a straight part (DST) Collecting ducts (CD) This extends through the renal cortex and medulla. The renal papilla CD opens in the renal pelvis, travels to the ureter, then to the urinary balder, then to the urethra, and then exits the body. The collecting ducts are last to reabsorb water. Water reabsorption is adjustable by ADH-sensitive AQP. The CD is water permeable and determines the osmolality of urine excreted. ADH absence cause the CD to become relatively impermeable to water, resulting in diluted urine. Glomerular Filtration: General Info In urine formation, the first step is the filtration of large amounts of fluid through the glomerular capillaries within the Bowmans capsule. The glomerulus filters blood, forming the primary urine. Majority of water and solute absorption takes place in the proximal tubules. The thin limbs of Henle’s Loop reabsorbed water, sodium, and chloride. The glomerulus is a compact network of vesicles that retain cellular components and proteins (that are of medium to high molecular weight). The glomerulus has a semi-permeable membrane. Most (99%) of what is filtered through the glomerulus is reabsorbed, leaving less than a liter (highly variable) to be excreted from the body. Filterability of substances is based on molecular weight. Water, sodium, and glucose are small substances and are filtered. Myoglobin, hemoglobin, and albumin are large substances and stay within the blood, rather than being filtered. Electrolytes (like sodium) and small organic compounds (like glucose) are filtered as freely as water. Glomerular Selective Filtration Filtration in the glomerulus can be impacted by: Electrical charge The glomerular basement membrane has a negative charge, causing cationic (positive charge) substances to be more easily filtered than anionic (negative charge) substances. Plasma protein binding Plasma protein binding impacting glomerular filtration is a protective mechanism for some solutes like calcium. Some drugs are retained in circulation for a set period of time before they are filtered. Things bound to transport proteins wont go through the kidneys for filtration because they are too big. Primary Urine Primary urine is the filtrate that accumulates in Bowman’s Space. It contains the same concentration of salt and glucose as plasma. Tubular Fluid Tubular filtrate the filtrate inside of the tubular system. While passing through the nephron’s tubular system, the tubular fluid is being constantly modified by tubular reabsorption and becomes “final urine”. Tubular reabsorption recovers most filtered substances. Osmolality vs Osmolarity Osmolality is the number of osmoles of solute per kilogram of solvent. Osmolality is also NOT dependent on temperature, making it more suitable for living organisms. Osmotic/Oncotic pressure will pull water towards the higher concentration of solutes. Osmolarity is temperature dependent. Osmolarity and hydrostatic pressure impact fluid movement Glomerular Capillary Hydrostatic Pressure Filtration of fluid from glomerular capillaries into bowman’s space, follows the same principles as filtration out into other capillaries. The main driving force for filtration is the glomerular capillary hydrostatic pressure. The forces opposing filtration are the hydrostatic pressure of bowman’s space and oncotic pressure of blood plasma. Oncotic pressure of the filtrate is essentially non-existent. Medullary Segment and Urine Concentration Increased osmolality of plasma will trigger ADH (anti-diuretic hormone) release. ADH release will cause more concentrated urine. A diuretic will Decrease water reabsorption in the kidneys. An anti-diuretic would increase water reabsorption in the kidneys. If there is a deficiency of ADH, there would be less water reabsorbed in the kidneys, causing a buildup of water in the urine, allowing it to be very dilute. Osmoreceptor-ADH feedback Water deficiency will increase the extracellular osmolarity. This increase in osmolarity will stimulate the osmoreceptors of the hypothalamus, resulting in ADH release by the posterior pituitary gland. Increase ADH concentration will allow for more water permeability in the CD.