Lecture on renal disease

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Department
Laboratory Medicine and Pathobiology
Course
LMP299Y1
Professor
Kenneth Yip
Semester
Winter

Description
Lecture 6: Renal disease Objectives: • give overview of renal function in waste removal • explain causes of acute renal failure • explain progression of chronic renal failure • discuss treatment in end-stage renal disease (ESRD): dialysis and transplantation Renal Failure • protein metabolites from catabolism or the diet will accumulate and cause toxic effects unless the kidney removes them • nitrogenous wastes and sources: o ammonia (from protein—amino acids) ammonia is toxic, buildup of it is dangerous and conversion to urea is much safer o urea (from ammonia—converted in liver) o uric acid (from nucleic acid) • creatinine is product of muscle metabolism that is removed at the kidney • plasma creatinine is dependent on muscle mass Renal function • nephron: is the functional unit of kidney o 2 major parts:  As blood from artery comes in, there is glomerulus and this is where blood is filtered and filtrate is formed, cells don’t pass thru but plasma and small molecules can go thru, but large proteins like albumin cant go thru  Filtrate then enters into tubule and water is resorbed and important nutrients as well they are not lost in urine  What is not resorbed goes down the urethra and into bladder and is then excreted  The amount of blood flowing thru kidney is very large o Measure of GFR: measures the amount of creatinine that passes thru kidney in 24hr clearance  Estimation of GFR is odne thru relation to plasma creatinine as if plasma creatinine doubles from 100 to 200 then that means GFR has dropped by half as GFR is inversely proportional to plasma creatinine o One method of determining GFR from creatinine is to collect urine (usually for 24 hours) to determine the amount of creatinine that was removed from the blood over a given time interval. If one removes, say, 1440 mg in 24 hours, this is equivalent to removing 1 mg/min. If the blood concentration is 0.01 mg/mL (1 mg/dL), then one can say that 100 mL/min of blood is being "cleared" of creatinine, since, to get 1 mg of creatinine, 100 mL of blood containing 0.01 mg/mL would need to have been cleared. o Creatinine clearance (C ) is calculated from the creatinine concentration in the collected Cr urine sample (U Cr urine flow rate (V), and the plasma concentrationCrP ). Since the product of urine concentration and urine flow rate yields creatinine excretion rate, which is the rate of removal from the blood, creatinine clearance is calculated as removal rate per min (UCrV) divided by the plasma creatinine concentration • Blood flow to kidney o ~1200mL/min of blood o ~120mL/min of filtrate produced=glomerular filtration rate (GFR) • GFR can be measured by estimating the creatinine clearance based on creatinine in plasma and a 24hr urine sample Acute renal failure • ARF has a rapid onset in the course of hours or days • Reversible if fluid balance is restored in time • Common in the severely ill • Early detection relies on sequential monitoring of renal functions tests (urea and creatinine) • Usually the urine output falls to less than 400mL/day, (oliguria). If there is no urine at all=anuric • If renal tubular dysfunction is the main problem in the illness than the urine flow may remain high  less filtrate means less output, but urine output alone does not tell you if you have renal failure, we need to use creatinine as the main marker • Pre-renal: extrinsic • Renal: intrinsic • Post-renal: extrinsic Pre-renal causes • Hypovolemia o Most common cause and is associated iwth hypotension o If significant blood losses or extracellular fluid losses (>5% of body weight) decrease in renal blood flow o E.g: hemorrhage, burns, crushing injuries, heart failure, diarrhea, vomiting, inadequate fluid intake, bacterial shock o Decrease in blood pressuredecrease intra-renal blood flow increase resorption of Na and water oliguria o Urine is small in volume and concentrated but low in Na • Insufficient amount of blood is getting to kidney so decreases renal blood flow so kidney will respond by holding onto water hence stimulating renin-aldosterone sys to resorb sodium and water and hence oligouria (low urine output), that urine will be very concentrated and due to aldosterone, sodium level will be low in it • Treatment by fluids and electrolytes and the condition is reversible if carried out soon enough • Sometimes function does not return sufficiently and an osmotic diuretic is given o It is an agent that is in blood and doesn’t do anything but hold onto water, as it passes thru the kidney it pulls water to it and helps restore function o Goal to get blood and filtrate flowing thru o If filtrate has nowhere to go, it can get backed up and builds up pressure andblood, and heart can’t pump against such high resistance o An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and Na. They are pharmacologically inert substances that are given intravenously. They increase theosmolarity of blood and renal filtrate o Osmotic diuretics works by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney. This washes out the cortical medullary gradient in the kidney. This stops the loop of Henle from concentrating urine, which usually uses the high osmotic and solute gradient to transport solutes and water. o Normally, water molecules follow Na out of the proximal tubule, resulting in Na and water reabsorption. When osmotic diuretics are introduced, they hold onto water molecules in the tubule. Since the luminal membrane is quite leaky to Na , this causes a + high back leak of Na into the tubule. o Na is normally followed by K and Cl out of the proximal tubule. When there is high back + leak of Na , these electrolytes stay in the tubule and are lost through urine. o Note: Glucose is completely reabsorbed by the kidneys but not Mannitol. • If this treatment can be fatal if the failure is intrinsic or post renal • The cause of death is congestive heart failure Renal causes • Acute tubular necrosis o Poisoning (toxic ATN) o Tubular cells that die from toxin or poisoning or they lose function • Protein deposition in the nephron o Myoglobin (muscle trauma), myeloma protein (cancer) o Myoglobin is an oxygen carrier in the muscle, recall some protein might get into urine o Myoglobin and myeloma are small, 30 000kDa and can get into tubules, but if there is lots of these 2 produced from the muscle cells or from cancer, they can get stucked to the nephron and deposit there • Glomerulonephritis o Inflammation—WBCs attacking the glomerulus • On the recovery, the urine contains brown granular casts (protein plugs from the shut down kidney), tubular epithelial cells and many other formed elements o Casts are flushed out, and they were formed on the inside of tubule, protein material Case • Creatinine level was really high, indicative of renal failure (recall it is a marker of renal function) • Urea was also really high, due to renal failure • Potassium is increased as from crush injury, muscles were damaged thus those muscle cells released their contents Post-renal causes • Obstruction urine can’t get out o Injury o Stones (renal calculi) can create blockage o Inflammationswelling causing obstruction o Tumor (prostate, cervix, bladder) growth of tumour mass starts to pinch against hence blocking urine flow • Case: o Prostate hypertrophy and chronic urinary retention o Overgrown prostate, urea and creatinine are both high so acute renal failure might have occurred Hypertension (high bp due to volume overload in body) • In normal kidneys a small rise in bp produces a large rise in salt excretion • However, ppl with advanced renal disease develop volume dependent hypertension o When you have kidney disease, you get a lot of water retention that occurs so thus volume dependent hypertension • Excess aldosterone, catecholamine, or renin-angiotensin activity may contribute but rarely • One or both renal arteries may be narrowed (stenosis), and prolonged hypertension causes degeneration of arterial walls= nephrosclerosis hypertension—lose nephrons hypertension gets worst and cycles • Glomeruli are destroyed and thus the renal functional capacity is decreased o Loss of nephron means lost of kidney function and inability to get rid of salt and water Chronic renal failure • The end result of progressive renal damage (chronic kidney disease CKD) is chronic renal failure (CRF) • The progression of chronic kidney disease may be slowed by o Decreasing protein intake which reduces GFR and (less load and burden on kidney) o Lowering bp with angiotensin converting enzyme inh
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