Week 7 Renal I PDF

Renal I October 30, 2023 8:23 AM - Great deal of homeostasis is required to fulfill these functions - Ex. With a very salty diet, eyes get puffy and increased body swelling the next day, and there is less urination, so the body has to internally regulate the ions - Kidneys are the only place where...

Renal I October 30, 2023 8:23 AM - Great deal of homeostasis is required to fulfill these functions - Ex. With a very salty diet, eyes get puffy and increased body swelling the next day, and there is less urination, so the body has to internally regulate the ions - Kidneys are the only place where can we excrete H+ ions - They also play a big role in making bicarb Week 7 Page 1 - Regulates blood volume: ○ Ex. If drinking lots of water, you will pee lots of fluid ○ in stressful situations, the body will conserve water to ensure good cardiac output - BP regulation - Blood osmolarity/osmolarity ○ This is the concentration of particles in water ○ We need the solute-to-water ratio to be good - Kidneys produce hormones: ○ erythropoietin can stimulate maturation of rbcs ○ the main location for this is in the kidneys ○ The kidneys can also make renin to help regulate BP ○ calcitrol is released by kidneys to convert vit D into an active form to help with bone formation - Regulate blood glucose level (not a key role, but in extreme situations it can) - Excrete wastes and foreign products Poor kidney fxn: - If ppl don't have good functioning kidneys, body will have trouble with K+ regulation. - We excrete a lot of K+, and if can't excrete it, this will lead to cardiac and other problems. - Kidneys also excrete phosphate - Can lead to HTN - Causes fluid retention - Ppl with dialysis, don't make enough rbcs b/c they can't make erythropoietin, so give them EPO to manufacture rbcs - With profound renal failure, kidneys have problems with bones, b/c no calcitriol is produced, and can't activate vit D, and can't absorb the calcium they need - Ppl who smoke have higher bladder ca risk; carcinogens from smoking sit in bladder until urinate, thus higher risk of bladder cancer - With medications - check kidney functions to make sure pt can excrete them well. - Will focus on kidney functions Week 7 Page 2 - Kidneys in retroperitoneal area R lower than L b/c the liver is in the way Can palpate the R kidney But can't palpate the L b/c too high up CVA tenderness - want to bump the back here to check for CVA tenderness ○ Pt with pyelonephritis will experience severe pain in this area Kidneys are the size of a bar of soap Colour of kidneys are red, b/c takes 10-20% of cardiac output but takes only 8-10% of O2 a lot of the functions are passive, so red/brown colour is b/c of deoxygenated blood Won't have kidney s/s unless kidneys have lost 75% function ○ In an acute situation, can repair this quickly ○ But huge problem for chronic functional decline, and have no way to measure this until lose 75% of function, and hard to recover the effects of that and save the kidneys after this point Week 7 Page 3 - 3 main parts: ○ Outer cortex (surrounded by fibrous capsule)  Mose prominent ○ Inner component: medulla, renal pyramids, renal columns in between pyramids  8-18 renal pyramids ○ Renal sinus Urine formation: - Nephrons --> colleting duct-->papillary duct-->minor and major callices-->renal pelvis--> ureter-->bladder - Ureter has SM - Ex. Kidney stone - sharp peristaltic waves of pain R and L renal artery, directly off aorta (high rich O2 blood)--> segmental arteries -->interlobar (in renal columns)-->arcuate artery (between renal cortex and medulla)-->cortical radiate (supply cortex)--> afferent (supply into nephron)-->glomerulus-->efferent-->peritubular - There is no segmental veins, only segmental arteries - Urine collection in the renal pelvis - Ex. ppl with kidney stones tend to get the stones on the same side --> b/c most ppl sleep prefer one side than the other, so urine collection occurs in pelvis in one side over the other Week 7 Page 4 - - The most functional part of kidney Highly specialized tubes and structures Afferent tubule in, and efferent out Blood supply around kidneys Renal Corpuscle: ○ Capillaries ○ Bowman's capsule PCT (distortions and goes all over the place) LOH ex. Loop diuretics work on here DCT CD Tuft of capillaries Afferent is wider than efferent Week 7 Page 5 - 85% of nephrons are in cortex - Juxtamedullary nephrons - 15-20% --> LOH nephron goes deep into the medullary area - Peritubular vessels stay in cortex - Vasa recta, goes deep into medulla, --> these vessels allow us to concentrate our urine Week 7 Page 6 - Bowman's Afferent coming in Efferent out Outermost layer of bowman's - parietal layer? Visceral layer = podocytes, which sit on top of capillaries, that have foot processes On top of podocytes have mesangial cells__________contract??? Afferent arteriole is wider than efferent (slightly more dilated) - Macula densa - associated with DCT - Top of LOH or first part of DCT are essentially the same thing - For every nephron, feedback to the LOH will come back from the macula densa cells, between the afferent and efferent arteriole  inside the cells of afferent and efferent arterioles have macula densa with chemoreceptors that sense chemicals  It gives direct info about Na, Cl and water that is flowing past it  If too much water is coming off, it will give feedback to the LOH and slow filtration  If not enough water and solutes, it will give feedback to the LOH to dilate and increase filtration - JG cells  Associated with the afferent arteriole, with some efferent response  Located in walls of artery with mechanoreceptors, detecting pressure  If pressure or stretch on walls goes down, and JG cells recognizes these, associated with low BP, and will release renin and inc BP  If stretch is high (high BP), lots of hydrostatic pressure on afferent/efferent arterioles, so will act to lower BP Week 7 Page 7 - - Plasma made up of primarily water - only 20% of ECF - Intracellular fluid - largest component of water - F vs M - Females tend to have a bit less fluid, have a bit more of a solid base - Genetically, males have more muscle, females have more adipose tissue, which is hydrophobic - 2/3 of water is intracellular - 1/3 is extracellular --of this, 20% is blood Week 7 Page 8 - Intake water Cross GI system Cross CVS membrane to get to interstitial fluid membrane All membranes selectively permeable, to allow water to move Output: need to get water to areas where we can get rid of if Need homeostasis - Get fluid from fluid intake, food intake - Lose fluids: Lose more fluids than gain through breathing, sweating, GI system(diarrhea), urination, menstruation Week 7 Page 9 - If look at intake and output, should be equal - If worried about pt with mismatch, will add 50-75ml/hr to compensate for the losses **Fyi only** Week 7 Page 10 1. Temperature regulation - water regulates temperature, push fluid to the superficial capillaries of skin and allow fluid to go off. If temp inc, water helps to dissipate heat 2. Cushioning - there are places where we need water to help cushion - CSF (gives brain buoyancy), and amniotic fluid (fluid surrounds fetus in utero) 3. Lubrication - synovial fluid in joints, serous fluid between parietal and visceral layers of heart and lungs 4. Reactant - hydrolyze, to break water to a small bond to be used 5. Solvent - can dissolve ex. Eaten cracker can dissolve 6. Transport - plasma needs water medium to circulate blood 7. Cell shape - gives cell shape - Plasma contains electrolytes that have positive and negative ions Week 7 Page 11 - Plasma contains electrolytes that have positive and negative ions Proteins have slight negative charge Non-electrolytes RBCs are not dissolved in plasma What's in plasma and intracellular space is very diff - the semi permeable membrane is what makes it different - Whole blood - Plasma sample: - Centrifuge to get diff components - Clear, straw component - Clotting factors, proteins - Serum: - Sst yellow tube - Has clotting factors, - Getting rid of cells, rbcs, platelets, no proteins, and clotting factors - Gives you just electrolytes - Fyi only** Week 7 Page 12 - Cofactors for enzymes - ex. CO2 and water makes carbonic acid via use of enzyme carbonic anhydrase. - This catalytic enzyme needs a small amount of zinc, thus microminerals/electrolytes that need to be used for reactions - Nerve and muscle function - Neurotransmitters: moving of ions across membranes to potentiate the AP - Muscle contraction - Acid/base balance - bicarb, H+ ions - Secondary active transport uses electrolytes to move ions across - Osmosis Week 7 Page 13 - Blood plasma and interstitial fluid is similar - Interstitial fluid has very little protein - **intracellular fluid has significant difference, very little Na, lots of K-->d/t very selective permeable membrane - Positive ions = cations ex. Na, K, Ca, Mg - Anions = bicarb, cl, phosphate sulfate, protein anions - In ECF, most prominent cation (Na) & anion (Cl) Week 7 Page 14 - Look at concept, don't memorize - Compare plasma and intracellular space for cations and anions - When add up plasma, cations and anions, they are equal - Looking at the electrochemical gradient - there is balanced neutrality between cations and anions in plasma - But there is a difference in cations/anions between plasma and intracellular space-- there is a gradient between them - The electrical energy matches within the cell too, and this neutrality is maintained using the selective permeable membrane and electrochemical gradient - Low serum osmolality - dec number of particles and high amount of water - Inc osmolality - inc number of particles, and proportionately less water--> body will try and Week 7 Page 15 - Inc osmolality - inc number of particles, and proportionately less water--> body will try and conserve fluid - Top left - normal osmotic equilibrium - osmolality in ICF and ECF are equal - Top middle: If add solute (hyperosmotic condition) to the ECF, the osmolality will increase - body wants to keep ICF and ECF osmolarity the same, so water moves outside cell to ECF to equalize it. - Now the compartment number has increased to 18L - Ex. HTN pt with high solute diet, these pts will have to pull water from somewhere (cells), and lead to further inc in HTN - Bottom left --> adding free water, so osmolality will go down, and water will move from ECF to ICF, and leads to cerebral edema (lethal) Week 7 Page 16 - Isotonic - NS, D5W--> no change to RBC - Hypertonic solution given --> water moves outside of RBC and it shrinks - ex. 3% and 5% NS, given to ppl with cerebral edema, don't give boluses or continuous administration for days (water moves out of intracellular space and into plasma) - Hypotonic solutions--> ex. 1/2 NS, 1% NS, given for dehydration Week 7 Page 17 - Going for run - With dehydration, lose water and cells can shrink, osmotic proteins are more concentrated, and facilitates water moving outside the cells - Ex. Ketodiet - high in protein, low in carbs, protein going into plasma that circulates, and proteins will pull water towards it and pee a lot - Hypotonic hydration: only drinking water, no electrolytes, leading to cerebral edema - Pediatric population - advise fluids, putting kids at risk if only giving water, need to give electrolytes, given chicken soup Week 7 Page 18 - Hypertonic saline - popcorn - increase in osmolarity/osmolality - Isotonic saline - popcorn + drink = no change in osmolarity/osmolality - Hemorrhage - leaking plasma and solute, so osmolality won't change, but volume will dec Week 7 Page 19 - Stimulate hypothalamic thirst center if high ECF osmolality or lose plasma volume (5-10%) - People who have post-op bleeds, internal hemorrhage, with small group of ppl complain that they're very thirsty Week 7 Page 20 ADH aka vasopressin: - Released from posterior pituitary (in addition to oxytocin) - Ex. When there is an Inc in osmolality (inc Na conc), ADH is released, which acts on kidney CD, and causes aquaporins to be seen in CD = water reabsorption - Ex. With a loss of plasma volume, baroreceptors will give feedback to posterior pituitary to release ADH - Ex. Alcohol inhibits ADH release, thus will inc urination Week 7 Page 21 Week 7 Page 22 - Amount of fluid into nephrons starts as filtrate before becoming urine - 180 L of urine made into filtrate - A lot of it starts as filtrate - over 99% gets reabsorbed and put back into plasma - only 1% manipulated to get excess - It's a nonspecific and passive process - Filtration membrane, made of glomerular endothelial cells, which has a BM or basal lamina, and podocyte epithelium - Integrity of filtration membrane should be working to get things across, if have big holes and blood gets across, tells us something wrong (ex. Hematuria or proteinuria) - Fenestrated capillaries, should be small enough holes to prevent RBC crossing - BM or basal lamina have slight negative charge, which helps keep protein in blood and not getting across - Albumin - creatinine ratio: looking at amounts of protein getting across glomerulus - Slit membrane Week 7 Page 23 - Plasma - Filtration slit - Podocytes Week 7 Page 24 - Passive, doesn't consume energy Nonselective Huge SA - with ball of capillaries in bowman's capsule Mesangial cells - associated with endothelial cells and foot processes Thin and porous BP - hydrostatic pressure kept high to promote filtration Oncotic pressures - proteins will pull filtrate back into circulation - Don't need to compare arterial and venous pressures in glomerulus, b/c there are no veins…only has afferent and efferent ARTERIOLES - HPg - pressure put on the walls of artery, b/c have larger afferent arteriole - HPc - this process is always happening, always fluid in bowman's capsule and little fluid will create back pressure - OPbld - oncotic pressure of albumin and plasma pressure Week 7 Page 25 - OPbld - oncotic pressure of albumin and plasma pressure - OPc - theoretical, there shouldn't be proteins in filtrate, and if some escape, there may be a pressure = (55-30) - (15-0) = 25-15 = 10 (55-15) - (30-0) = 40-30 = 10 (55-30) - (15-0) = 25-15 = 10 = promote filtration - prevent filtration = (55+0) - (15+30) = 55-45 = 10 Week 7 Page 26 GFR - amount of fluid filtered every minute eGFR - estimate Amounts are FYI Implications: - if body doesn't control GFR and GFR is too high, there will be too many substances that will get lost. - If GFR is low, we will reabsorb everything and don't excrete things that we want to get rid of - Mechanisms to control - Week 7 Page 27 - Mechanisms to control - Renal: controls GFR, fine tuning to release urine and keep what we need - Neural - Hormonal GFR depends on net filtration pressure and filtration coefficient - Smaller SA, smaller GFR; higher SA = inc GFR - Inc permeability = inc GFR GFR = NFP x Filtration coefficient Week 7 Page 28 d) If vasoconstrict the afferent arteriole --> less blood comes into nephron, GFR will dec, and overall dec in hydrostatic pressure in bowman's capsule e) If inc resistance in efferent arteriole-->less blood flow coming into nephron, b/c gets dammed up ad backup in glomerulus, and inc pressure in glomerulus, and inc in GFR - If dec resistance in afferent arteriole, inc blood flow due to hydrostatic pressure, inc GFR, inc renal blood flow Week 7 Page 29 - Autoregulation - ability of individual nephrons to change afferent and efferent arterioles, allowing GFR to stabilize - Between a MAP of 80-180 - With BP higher, afferents will constrict - With low BP, afferents will dilate 1) Myogenic response - stretch receptors in afferent arterioles a. If too much distention, it will start to constrict b. If not enough stretch, it will relax to bring back more blood flow Myogenic Response - When high BP, high GFR: ○ Stretch receptors activated in afferent arterioles ○ causes arteriolar vasoconstriction-->dec flow = low GFR - When low BP, low GFR: ○ Less stretch in afferent arterioles ○ Causes arteriolar vasodilation --> inc blood flow = inc GFR Week 7 Page 30 - If inc GFR: macula densa cells will tell the nephron that GFR is too high, and will give feedback to JG cells, to decrease release of NO, which constricts afferent arteriole and dec GFR - If GFR low, macular densa cells will tell JG cells to stop the release of vasoactive chemicals ○ Afferent arterioles will dilate and inc GFR Tubuloglomerular feedback mechanism: - High BP, inc GFR: ○ Inc Na filtered into kidney tubules ○ In DCT - Macula densa cells senses high NaCl sensors and releases adenosine  Adenosine Acts on afferent arteriole and causes vasoconstriction = low GFR, thus low Na filtered and excreted  Adenosine acts on JG cells, inhibits release of renin from granule cells, thus no inc in BP - Low BP, low GFR ○ Low Na filtered into kidney tubules ○ Macula densa cells sense low NaCl and release PG and NO  Act on SM of afferent arteriole and causes vasodilation-->inc GFR-->Inc Nacl filtration and excretion  Act on JG cells, releasing renin-->inc BP-->inc GFR Week 7 Page 31 - Neural control: ○ Low BP sensed by dec baroreceptor activation systemic circulation  SNS causes: □ Vasoconstriction of systemic peripheral arteries via alpha1-SM receptors □ Stimulation of granular cells of JGA to release renin via beta1-R - Other mediators (PG and NO - vasodilators) - adenosine & endothelin (vasoconstrictors) Extrinsic mechanisms to regulate BP: 1) SNS: - Low BP, low GFR, low urine output ○ Baroreceptors in carotid sinus, stimulates medulla, releasing NE/E  Acts on B1 receptors on heart-->inc HR, inc SV-->Inc CO-->Inc BP  Acts on alpha1 receptors on afferent arteriole -->vasoconstriction-->dec GFR  Acts on alpha1 on systemic peripheral arteries --> vasoconstriction-->inc systemic vascular resistance --> Inc BP  Acts on B1 on JG cells of afferent arteriole-->release renin-->activates ANGII--> release aldosterone-->Inc Na reabsorption-->Inc BP - High BP-->opposite from above 2) RAAS: - Low BP, low GFR: ○ JG cells sense low BP-->release renin ○ Liver releases angiotensinogen  Renin converts it to ANG ○ ANGI converted to ANGII by ACE(lungs)  ANG II stimulates post pituitary to release ADH-->acts on CD to inc water reabsorption via aquaporins = inc blood volume = inc BP  ANG II acts on adrenal cortex to released aldosterone-->acts on DCT and makes permeable to Na and water= inc Na and water reabsorption = inc blood volume = inc BP  ANG II acts on kidneys □ Causes vasoconstriction of efferent arteriole = inc GFR □ Acts on PCT-->inc reabsorption of Na and water= inc blood volume = inc BP Week 7 Page 32 BP  ANG II causes systemic peripheral artery vasoconstriction = inc systemic vascular resistance = inc BP - High BP, high GFR: ○ Heart releases ANP-->blocks ANG II  No ADH release  No aldosterone release  No vasoconstriction of efferent arterioles  No Na & water reabsorption in PCT  Causes vasodilation of afferent arteriole = **inc GFR-->**inhibits renin release-->low BP Low BP, dec serum Na , PG release causes = Renin release from kidneys Angiotensinogen, released from liver, allows renin to convert to ANG I ANG I converted to ANG II by ACE ANG II binds to receptor, causes aldosterone release, which causes Na reabsorption and promotes systemic peripheral artery vasoconstriction - Inc in BP - Ex. ACE-Inhibitot, will prevent ACE from making ANG II, thus no vasoconstriction, thus keeps BP low - ANG I-R blockers ('-sartans'), allows ANG I to convert to ANG II, but no effect of ANG II for vasoconstriction (no aldosterone release) - ACE activates bradykinin, which builds up in lungs is an irritant, which causes dry, chronic cough for pts who use ACE-inhibitors. Can cause cough after first dose, or also after months of being on med Week 7 Page 33 ANP - released from myocardial cells, stimulated with inc of BP -->thus helps to lower BP, b/c inc NaCl and water excretion Week 7 Page 34 Week 7 Page 35 - 20% of plasma is pulled off, over 19% gets reabsorbed back into plasma into systemic circulation - Less than 1% goes as urine Week 7 Page 36 - Week 7 Page 37 - Give Inulin - Use Creatinine - byproduct of muscle breakdown, freely filters across - Glucose, will all be reabsorbed and none should be filtered in urine (none filtered, all Week 7 Page 38 - Glucose, will all be reabsorbed and none should be filtered in urine (none filtered, all reabsorbed) - Urea (nitrogen byproduct), filtered and some is reabsorbed (filtration, reabsorption = net reabsorption) - Penicillin - freely filtered, but some receptors can push more penicillin into the urine. Some pts can give a med to prevent penicillin from being fully filtered and allowing more in circulation. (filtration, reabsorption, secretion = net secretion) Week 7 Page 39