Renal Function

Dr Manal AbdAlla Associate Professor Clinical Pathology

Renal Function
Renal Anatomy Kidneys Bilateral ureters Nephrons 1. Glomerulus 2. Proximal convuluting tubules 3. Loop of Henle 4. Ascending Loop of Henle 5. Distal convuluting tubules 6. Collecting ducts

Functions of the kidney

regulation e.g. homeostasis, water, acid/base and electrolytes excretion e.g. urea, creatinine and uric acid endocrine e.g. renin, Erythropoietin and prostaglandin 1,25 dihydroxycholecalciferolconversion only in kidney!

The major NPN eliminated by the renal system 1. Urea 2. Creatinine 3. Uric acid 4. ammonia

Indication of Renal function tests

Assessment of renal diseases Detection of water balance disorder Evaluation of acid base state disorder

Renal function

Glomural function : Filtration of plasma Tubular function: Reabsorbtion Secretion Synthsis

Filtrate isToxic waste products and Substance valuable to body The kidney return the valuable substance and excrete the toxic wast products

Kidney Function
A

plumbers view

Input Arterial

Filter

Processor

Output Venous

Output Urine

How do you know its broken?

Input Arterial

Decreased urine production Clinical symptoms Tests

Filter

Processor

Output Venous Output Urine

Where can it break?

Input Arterial

Pre-renal

Filter

Renal

(intrarenal)
Processor

Post-renal
Output Venous Output Urine

(obstruction)

Causes of kidney functional disorders

Pre-renal e.g. decreased intravascular volum Renal e.g. acute tubular necrosis Postrenal e.g. ureteral obstruction

Renal function tests

Renal

function tests include : Blood urea and blood urea nitrogen Serum creatinine Creatinine clearence Serum uric acid Urine analysis

Nonprotein Nitrogen (NPN)

Monitored through renal (kidney) functions by measuring excretion or absorption of by products. Consist of 15 compounds that can be analyzed to monitor renal functions

Nonprotein Nitrogen (NPN)

Monitored through renal (kidney) functions by measuring excretion or absorption of by products. Consist of 15 compounds that can be analyzed to monitor renal functions

Urea: Blood Urea Nitrogen or BUN : Constitutes of the NPN substances in circulating blood. Synthesized in the liver from CO2 and NH4 arising from deamination of A.A. by the Kreb cycle. Transported by plasma to kidneys and filtered by the glomerulus. Most urea is excreted in urine 40% is reabsorbed by renal tubules. This is good indicator of renal function.

Plasma urea (BUN)

=

BUN (blood urea nitrogen) Urea: product of protein catabolism Synthesized by liver, majority excreted by kidney, partially reabsorbed in tubuli Plasma concentration increases with decreased GFR

Blood Urea Nitrogen (BUN)

Urea is the major end product of protein and amino acid catabolism and it is generated in the liver through the urea cycle. Most of the urea is ultimately excreted by the kidneys. Urea is freely filtered by the glomeruli. depending on the state of hydration and therefore the rate of urine flow, 40% to 80% of the filtered urea is passively reabsorbed with water, mostly in the

Plasma Urea
Reference range 15- 40 mg / dl Causes of increased plasma urea : Pre-renal: High protein diet Dehydration CHF Catabolic state (fever-trauma-burn ) GIT haemorrhage These conditions are accompanied by normal serum creatinine level

Plasma Urea
Renal causes: decreased excretion Loss of functioning nephrons e.g. acute or chronic glomuerulonephritis, and acute chronic renal failure Both urea and creatinine are increased proportionally Postrenal causes : Obstruction of the urinary tract by :stones, enlarged prostate Both urea and creatinine are increased but the increased urea is more than creatinine

Prerenal: related to the renal circulation. The flow of blood to the kidneys. Ex: Urea goes through the kidneys for excretion and reabsorption. If there is a prerenal problem, the urea doesnt make it to the kidneys to be filtered, so there is an increase or build-up of urea in the blood. Diseases: Congested Heart Failure, Shock, Hemorrhage, dehydration Azotemia: Increased in urea in the blood .

Renal: involves the kidney there is a lack of ability to function correctlydecrease ability to excrete. Decrease renal function see an increase in blood urea levels. Diseases: acute/chronic renal failure, glomerulonephritis, tubular necrosis, chronic nephritis, polycystic kidney.

Renal: involves the kidney there is a lack of ability to function correctlydecrease ability to excrete. Decrease renal function see an increase in blood urea levels. Diseases: acute/chronic renal failure, glomerulonephritis, tubular necrosis, chronic nephritis, polycystic kidney.

Post renal: obstruction of the flow of the urine from the kidneys. Kidney function impaired- unable to excrete normally. Diseases: Kidney stone, tumor, UTI or other sever infection

Enzymatic conductivity rate method for measuring urea

Urea + H2O urease

2NH4 +Co2 NH4+salicylate+NaCIO by action of nitroprusside results in

Urease solution

Decreased Plasma urea

causas of decreasa urea: Severe prolonged starvation Malabsorbtion (low amino acid ) Severe chronic liver diseases Decreased urea find in overdilution in cases of increased secretion of ADH Excessive plasma dilution in I.V

Urea in patients with kidney diseases

Useful test but must be interpreted with great care, urea plasma level is more than creatinine dependent on protein intake Most useful when considered along with creatinine High in high protein intake, low in severe liver dysfunction Urea level normaly 2.5 -6.6 mmol/L

Urea cycle
CO2 NH3 Urea Cycle 3 ATP aspartate

Urea

Urea
Blood urea nitrogen (BUN) = blood urea / 2.14 Normal blood urea nitrogen =7 18 mg/dl (2.5 6.5 mmol / l )

Normal blood urea = 20 40 mg/dl Mgm /dl x o.36 = mmol/l

creatinine
Creatine:

synthesized in the liver from arginine, glycine and methionine. Transported to muscles to be converted to phosphocreatine- energy.

creatinine
Muscles

creatine phosphate is reservoir of phosphoryl group needed for formation of ATP as catalyzed by creatine kinase enzyme(CK)

Plasma creatinine and renal functions

Creatine phosphate +ADP+H produce

ATP + Creatine H2O

Creatinine (Waste product)

Creatinine: anhydride of creatine!

creatinine

In most circumstances the measurement of plasma creatinine can provide a

specific test of glomerular function. Serum creatinine concentration is often interpreted as a measure of glomeurlar filtration rate and is used as an index of renal function in clinical practice.
.

creatinine

The reference range is wide. . Its level is function of muscle mass affected greatly by changes in muscle mass. Plasma creatinine should not be measured until 8 hours after a meal as there is some evidence that the concentration increases after meat ingestion. Insensitive monitor- see after >50% of damage has occurred.

creatinine
Everyday

up to 20 % of muscle creatine and its phosphate dehydrates and cycles to form creatinine ( waste products )

Creatinine
Creatin

is waste product of muscle metabolism Urea is waste product of protein metabolism

Creatinine
Creatinine

molecular weight is 113 it is ready filtered by the glomurli and unlike urea not reabsorbed by renal tubules .However small amounts secreted by the renal tubules at high serum concentration

creatinine
Normal
Or

level = 55 120 micromole / liter

0.7 1.4 mgm /dl

Cr

A better index would related creatinine to muscle mass or lean body weight

Cr
By virtue of its relative independence from such factors as diet (protein intake), degree of hydration, and protein metabolism, the plasma creatinine is a significantly more reliable screening test or index of renal function than is the BUN. The plasma creatinine tends to increase somewhat more slowly than the BUN in renal disease but also decreases more slowly with hemodialysis.

Evaluate with BUN as a ratio to help differentiate between renal and prerenal disease of azotemia. Increase ratio: prerenal (shock, CHF, dehydration) Decrease ratio: renal

Analytical methods: 1. Jaffe: Colormetric method: looks for a red to orange color change. Utilizes picric acid Disadvantage: nonspecific and subject to interference from pyruvate glucose, ascorbate and acetone.

2.

Fuller method: More accurate Uses fullers earth or Lloyd reagent Use a protein free filter for the sample- less interference.

3.

Kinetic Jaffe: Various enzymatic methods Utilizes reagent picirate- measures rate of color change in absorbance @ 520nm @ 20 seconds and 80 seconds. Disadvantage: substance interference Advantage: inexpensive, rapid and easy.

 Specimen:

Serum, plasma

or urine Avoid hemolysis, lipemic, and icteric Urine needs to refrigerated.

Jaffe reaction for measuring creatinine, simple, but better is enzymatic method
Creatinine + alkaline picrate solution Bright orange/red colored complex absorbs light at 485nm

(many interfering substances in blood Can be minimized using rate method)

Decreased plasma Creatinine

In sever muscle wasting diseases In cases of starvation In vegetarian person Treatment with corticosteroid( protein catabolic effect ) Pregnancy due to dilution

Plasma Creatinine
Causes of increased serum creatinine :
Pre-renal : e.g., impaired renal blood flow as in decreased blood bressure , fluid depletion and renal artery stenosis Renal causes : Loss of the functioning nephrons as in acute or chronic glom. Nephritits and acute or chronic renal failure Post renal causes : Obstruction

Plasma creatinine
Other causas of increase creatinine Large muscle mass High meat intake in diet Vigrous muscle exercise Analytical errors as in case of medication such as acetoacetate ,cephalosporin,salsylate and cemitidine

Plasma creatinine vs. GFR not linear, hyperbolic correlation!

[pCreat] Change within an individual patient is usually more important than the absolute value

0 mL/min (0%)

GFR

140 mL/min (100%)

Creatinine Clearance

It is the amount of plasma which is completely cleared from creatinine per unite time Normal level 70 110 ml/min

Clearance of a substance is the volume of plasma from which the substance is cleared in the urine in a unit time Many substance can be used for clearance as urea , creatinine and inuline

Creatinine Clearance
Creatinine is the best used substance because : It is endogenous substance synthesized at a constant rate It is filtered by the glom. And not reabsorbed and is only slightly secreted by PCT It is analysed inexpensively

Glomerular filtration rate

Glomerular filtration= major physiologic responsibility of kidney, GFR used as index of overall excretory function Methods: clearence of creatinine

GFR= Ux x V (V=volum of urine/ 1 minute or 1 second) P x x= clearence of substance used

Glomerular filtration rate

GFR

in children, value always adapted to the BSA!! Ideal BSA in adults is 1.73m2

Ratio
Blood

urea nitrogen /creatinine ratio = 20 : 1 High ratio means increased urea this occures in pre-renal causes Increased urea but normal creatinine

Ratio

Normal ratio with marked increas in urea and creatinine is seen in renal and postrenal causes

Uric Acid
Uric acid is the end product of the metabolism of purines Uric acid is filtered at the glomeruli, reabsorbed in the proximal convoluted tubule, followed by secretion in the lower portion of the proximal tubule, and further reabsorption in the distal tubule