Kursk State Medical UniversityNormal Physiology Department Regulation Of Kidney ∙Methods and Determination of Kidney Function Hess Amanda B. Repalova Natalya V. Kursk 2012 Group 20
Plan• Autoregulation of the kidneys o (Tubuloglomerular feedback, glomerulotubular balance, pressure diuresis)• Role of kidneys in regulation of osmolarity and volume• Renal sodium regulation• Renal potassium regulation• Renal calcium regulation• Methods for studying renal function o (Tubular fluid-to-plasma concentration, determination of the renal blood volume, dilution test, micro-puncture, microperfusion, patch-clamp method, determination of clearance, insulin clearance, creatinin clearance, Zimnitsky’s test, concentration test)
Autoregulation Of The Kidneys• Includes 3 components: 1) Tubuloglomerular Feedback 2) Glomerulotubular Balance 3) Pressure Diuresis
1) Tubuloglomerular Feedback• Has 3 components: afferent arteriole, efferent arteriole and macula densa.• The macula densa cells sense the changes in the volume of delivery to the distal tubule. Decrease in NaCl concetration initiates a signal from the macula densa cell what has two effects: 1- it increases renin release from the juxtaglomerular cells of afferent and efferent arterioles. 2- it decreases resistance of the afferent arterioles (dilation).
• Renin: enzyme, which catalyses the destruction of angiotensin (plasma protein produced in the liver) into angiotensin I (catalysed by converting enzyme to form (glomerular filtration rate) angiotensin II).• Effects of Angiotensin II: o Stimulates aldosterone secretion o Constrict the arterioles and ↑ arterial pressure o Stimulates Na+ reabsorption, mainly in the proximal tubulles o Constrict efferent arterioles o Facilitates release of ADH o ↑ thirst o Facilitates release of prostaglandins
2) Glomerulotubular Balance• Is the intrisic ability of the tubules to increase their reabsorption rate in response to increased tubular inflow.• (The balance between reabsorption of solutes in the proximal renal tubules and glomerular filtration, which must be as constant as possible. If the glomerular filtration rate rises or falls, the rate of tubular reabsorption must rise or fall proportionally. Balance is maintained by neural, hormonal, and other mechanisms).
3) Pressure Diuresis• Is a phenomena which shows that even a small increase in arterial pressure often causes marked increase in urinary excretion of Na+ and water.• (increased urinary excretion of water when arterial pressure increases, a compensatory mechanism to maintain blood pressure within the normal range).
Role of the Kidneys in Regulation of Osmolarity and Volume• Kidney excretes excess water in hyperhydrationin the form of dilute urine or save water in dehydration by excreting concentrated urine.• Central osmoreceptors (hypothalamus) and peripheral osmoreceptors (kidneys, liver, spleen and blood vessels) sense changes in blood osmolarity and send information to the hypothalamus, which regulates the concentration of ADH in the blood.
• Also volume receptors in blood vessels and the left atrium baroreceptors send impulses to the CNS to regulate the volume of blood.• ADH increases the water permability of the distal tubules, collecting tubules and collecting ducts. More water is retained in the body to help stabilize the extracellular volume.
Renal Sodium Regulation• Na+ excreted= Na+filtered – Na+ reabsorbed• The low total body Na+: causes low cardiovascular pressure, which from venous, atrial, arterial baroreceptors, initiates reflexes that: o 1) restore the cardiovascular pressure (from direct action on the cardiovascular system – SNS) o 2) lower GFR (glomerular filtrate rate) and increase Na+ • Stimulates Na+/K+ active reabsorption (aldosterone). transport in the basement membrane• Aldosterone: stimulates the • Stimulates Na+ reabsorption (and production of proteins that secretion of K+) in the function as Na+ channels in the intestine, sweat glands, salivary luminal membrane. glands.
Methods Studying Renal Function• Tubular Fluid-to-Plasma concentration (TF/P) o TFosm/Posm=1 (tubular fluid is isosmotic with respect to plasma) o TFosm/Posm<1 (tubular fluid is hyposmotic with respect to plasma) o TFosm/Posm>1 (tubular fluid is hyperosmotic with respect to plasma)• (collect fluid inside and outside of nephron with micropipete and compare).
Determination of the Renal Blood Volume• Indirect method for • 1)insert PAH in the blood measuring the secreting capacity of the renal • 2)check the tubular cells (renal plasma [PAH], collected from flow). blood• PAH (para aminohippuric acid) is secreted by cells of renal tubules, if PAH is • 3)after pass through present in arterial blood in kidney, collect the blood low , blood is completely again and check the free from PAH after passes [PAH]. through kidney. • If blood has a low [PAH], means that kidney has a good flow and function.
Dilution Test• This method is used to • Test is hold for 12 hours. examination of dilution and excretion abilities of the kidneys. • The patients drinks 1,5L• Normal kidney function: of water. great part of the drunk fluid will be excreted during first 4 hours • During next 4 hours, (density of urea: 1,002 – volume and density of 1,001). urea are determined• During next 8 hours, portions of urea each 30 minutes, and decrease gradually in during next 8 hours, volume and becomes each 2 hours. normal by the end of the test.
Concentration Test• This method is used to examination of concentration and excretion abilities of the • The patient is not kidney. allowed to take fluid during 12 hours and• Normal kidney every 2 hours the concentration: volume volume and density of of urea will be greatly urea is determined. decreased (up to 100ml and less) and density will be increased (up to 1,030)
Micro-Puncture Test• Microfusion of separate renal tubules plays an important role in studying the formation of urine.• Main idea: fluid was derived from glomerular capsule with a micropipete by Richard in 1st time.• How changes the concentration of urine in each part of neprhon. (Not destroys the nephron)
Microperfusion • 1st: insert concrate(A) (A’) substance (A) • 2nd: collection of fluid before the 2nd block/vent (A’) • [A]→[A’] - How change the concentration? - -Present or not reabsorption?
Patch-Clamp Method• Used to study the role of each nephron part in urine production and the mechanism of transport of substance in tubular cell membrane. - (How much iondiffusion per unit of time?)
Determination of CFR (glomerular filtration rate - clearance)• Clearance: measure of • Glomerular filtration rate the volume of plasma (GFR) is the volume of completely free of a fluid filtered from the given substance per renal (kidney) glomerular unit. capillaries into the Bowman’s capsule per• Renal Clearance of a unit time. Central to the given substance is a physiologic maintenance ratio of the renal of GFR is the differential excretion of the basal tone of the afferent substance to its and efferent arterioles. concentration in the blood plasma. (unit: ml/min)
Insulin Clearance• Fructo-polysacharide is used for determining renal filtration.• Insulin: only filtered, not • Cx/Cins=1 (only filtered) absorbed or secreted (does not combine with plasma protein). • Cx/Cins<1 (filtrated and• Since insulin is neither reabsorpted) reabsorbed nor secreted by the kidney after • Cx/Cins>1 (filtrated and glomerular filtration, its rate of excretion is secreted) directly proportional to the rate of filtration of water and solutes across the glomerular filter.
Creatinin Clearance• One method of • Normal range: 80- determining GFR 110mL/min (plasma) (glomerula filtration per 1,73m of body rate) from creatinine is surface area. to collect urine (usually • Plasma (creatinin) for 24 hours) to remains constant through life (0,8- determine the amount 1mg/dL) of creatinine that was • Creatinin is produced removed from the by muscle blood over a given metabolism, and time interval. decrease with age (muscle ↓ action = nephrons ↓ activity)
Zimnitsky’s Test (clinical test for kidneys)• At 6 am the patient • Zimnitskys test based empties his bladder, on a study of the untill 6 am of the next relative density of day, he collects urea in individual urine emitted 8 pots. (limit 1,5L/day) during random• Normal result: urination during the common amount of day in a certain urea daily is 1-2L. rhythm. The study was o Density of urea: 0,010 – 1,025 conducted in the (such changes during the day are normal feeding regime normal – reaction of the kidneys on changing water/food regimen without loss of fluid. along all day)
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