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 Feedback2) Glomerulotubular Balance3) 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 angiotensin II).

• Effects of Angiotensin II:o Stimulates aldosterone

secretiono Constrict the arterioles and ↑

arterial pressureo Stimulates Na+ reabsorption,

mainly in the proximal tubulleso Constrict efferent arterioleso Facilitates release of ADHo ↑ thirsto Facilitates release of

prostaglandins

(glomerular filtration rate)

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

• Stimulates Na+/K+ active transport in the basement membrane

• Stimulates Na+ reabsorption (and secretion of K+) in the intestine, sweat glands, salivary glands.

• 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+ reabsorption (aldosterone).

• Aldosterone: stimulates the production of proteins that function as Na+ channels in the luminal membrane.

Renal Potassium Regulation

• K+ excreted= K+ filtered – K+ reabsorbed + K+ secreted

• Factors that stimulate K+ secretion by the principal cells: -↑extracellular fluid [K+]

- ↑ aldosterone - ↑ tubular flow rateShift K+ into cells(↓ extracellular [K+]): insulin, aldosterone, β-adrenergic stimulation, alkalosis.

Shift K+ out cells (↑ extracellular [K+]): insulin deficiency (diabetes mellitus), aldosterone deficiency (Addison’s disease), β-adrenergic blockade, acidosis, cell lysis, strenuous exercise, ↑ extracellular fluid osmolarity.

Renal Calcium Regulation

• ↓ Ca²+ excretion:-↑PTH (parathyroid hormone)-↑plasma phosphate-↓extracellular fluid volume-↓blood pressure-metabolic acidosis-vitamin D3

• ↑ Ca²+ excretion:-↓PTH-↓plasma phosphate-↑extracellular fluid volume-↑blood pressure-metabolic alkalosis

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

• 1)insert PAH in the blood

• 2)check the [PAH], collected from blood

• 3)after pass through kidney, collect the blood again and check the [PAH].

• If blood has a low [PAH], means that kidney has a good flow and function.

• Indirect method for measuring the secreting capacity of the renal tubular cells (renal plasma flow).

• PAH (para aminohippuric acid) is secreted by cells of renal tubules, if PAH is present in arterial blood in low [], blood is completely free from PAH after passes through kidney.

Dilution Test• Test is hold for 12

hours.

• The patients drinks 1,5L of water.

• During next 4 hours, volume and density of urea are determined each 30 minutes, and during next 8 hours, each 2 hours.

• This method is used to examination of dilution and excretion abilities of the kidneys.

• Normal kidney function: great part of the drunk fluid will be excreted during first 4 hours (density of urea: 1,002 – 1,001).

• During next 8 hours, portions of urea decrease gradually in volume and becomes normal by the end of the test.

Concentration Test

• The patient is not allowed to take fluid during 12 hours and every 2 hours the volume and density of urea is determined.

• This method is used to examination of concentration and excretion abilities of the kidney.

• Normal kidney concentration: volume of urea will be greatly decreased (up to 100ml and less) and density will be increased (up to 1,030)

Micro-Puncture Test

(Not destroys the nephron)

• 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.

Microperfusion

• 1st: insert concrate substance (A)

• 2nd: collection of fluid before the 2nd block/vent (A’)

• [A]→[A’]- How change the

concentration?- -Present or not reabsorption?

(A) (A’)

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 ion diffusion per unit of time?)

Determination of CFR (glomerular filtration rate -

clearance)• Glomerular filtration

rate (GFR) is the volume of fluid filtered from the renal (kidney) glomerular capillaries into the Bowman’s capsule per unit time. Central to the physiologic maintenance of GFR is the differential basal tone of the afferent and efferent arterioles.

• Clearance: measure of the volume of plasma completely free of a given substance per unit.

• Renal Clearance of a given substance is a ratio of the renal excretion of the substance to its concentration in the blood plasma.

(unit: ml/min)

Insulin Clearance

• Cx/Cins=1 (only filtered)

• Cx/Cins<1 (filtrated and reabsorpted)

• Cx/Cins>1 (filtrated and secreted)

• Fructo-polysacharide is used for determining renal filtration.

• Insulin: only filtered, not absorbed or secreted (does not combine with plasma protein).

• Since insulin is neither reabsorbed nor secreted by the kidney after glomerular filtration, its rate of excretion is directly proportional to the rate of filtration of water and solutes across the glomerular filter.

Creatinin Clearance• Normal range: 80-

110mL/min (plasma) per 1,73m of body surface area.

• Plasma (creatinin) remains constant through life (0,8-1mg/dL)

• Creatinin is produced by muscle metabolism, and decrease with age (muscle ↓ action = nephrons ↓ activity)

• One method of determining GFR (glomerula filtration rate) 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.

Zimnitsky’s Test (clinical test for

kidneys)• Zimnitsky's test based

on a study of the relative density of individual urine emitted during random urination during the day in a certain rhythm. The study was conducted in the normal feeding regime without loss of fluid.

• At 6 am the patient empties his bladder, untill 6 am of the next day, he collects urea in 8 pots. (limit 1,5L/day)

• Normal result: common amount of urea daily is 1-2L.o Density of urea: 0,010 –

1,025(such changes during the day are normal – reaction of the kidneys on changing water/food regimen along all day)

Thank You For Your Attention!!

THANK YOU FOR YOUR ATTENTION!!