kidney function.ppt

Kidney Function

Kidney

The kidney is primarily concerned in the elimination of nitrogenous waste products that one might think of it purely as an excretory organ. The kidney should not be viewed only as an organ which removes end products of metabolism and other waste products of foreign substance dissolved in the plasma but, also make continuous adjustments in the concentration of normal constituents in the plasma regulatory.

THE GENERAL FUNCTIONS OF THE KIDNEYS:

ELIMINATION OF METABOLIC WASTE PRODUCTS THROUGH THE FORMATION OF URINE

REGULATION OF THE PLASMA AND WATER VOLUME.

REGULATION OF IONIC EQUILIBRIUM MAINTENANCE OF ACID BASE BALANCE ENDOCRINE FUNCTION

THREE MAJOR GROUPS OF KIDNEY FUNCTION TESTS:

TEST MEASURING GLOMERULAR FILTRATION RATE (GFR)

TEST MEASURING RENAL BLOOD FLOW TEST MEASURING TUBULAR FUNCTION

TEST MEASURING GLOMERULAR FILTRATION RATE

Tests which measure the rate of glomerular filtration- are generally called CLEARANCES

TYPES OF CLEARANCE

CREATININE CLEARANCE TEST– Creatinine occurring through metabolic production

is eliminated from the plasma by glomerular filtration and therefore a measurement of its rate of clearance affords a measure of the process.

– Normal Values: 107-139 ml/min

TYPES OF CLEARANCE

INULIN CLEARANCE TESTS – Inulin freely passes the glomeruli but is neither

secreted nor reabsorbed by the nephric tubules. – Considered to be the most accurate measure of

GFR.– Normal value: 250 ml/min. - men (due to

larger renal mass) ; 110 mi/min - women

TYPES OF CLEARANCE

UREA CLEARANCE TEST – Urea is freely filtered by the glomeruli but variably

reasbsorbed in the tubules depending upon the transit time (rate of urine flow along the course of nephric tubules) of urea filtrate

TOTAL NON-PROTEIN NITROGEN PROCESS

DIGESTION PROCEDURE:– KJELDAHL DIGESTION PROCESS

The nitrogen ion in the PFF of the specimen in converted to ammonia using hot concentrated sulfuric acid in the presence of a catalyst (copper sulfate, selenium oxide or mercuric- sulfate)

MEASUREMENT OF AMMONIA:

NESSLERIZATION – The ammonia formed when it reacts with the

Nessler's reagent (double iodide of potassium and mercury, K2Hg2I2) in the presence of a colloidal stabilizer (gum ghatti) forms a colloidal suspension of dimercuric ammonium iodide (NH2Hg2l2), which is said to be yellow in color, if nitrogen is present in low to moderate concentration, and orange brown, if nitrogen is present in high concentration

MEASUREMENT OF AMMONIA:

BERTHELOT'S REACTION – The ammonia formed reacts with phenol and

alkaline hypochlorite using sodium nitroprusside as catalyst to form indophenoi blue.

BLOOD UREA NITROGEN (BUN)

Urea is the principal waste of protein catabolism.

In severe liver damage, levels of urea decreases. It is also the first metabolite to increase in kidney disease,

It is used as a screening test for kidney disease.

Urea is readily removed by dialysis.

BLOOD UREA NITROGEN DETERMINATION:

ENZYMATIC AND NESSLERIZATION– Urea in the PFF is made to react with urease

glycerol extract in the presence of buffer and heat-forming ammonium carbonate which is then reacted with Nessler's reagent to form a yellow dimercuric ammonium iodide.


Urea is hydrolyzed to ammonium carbonate by urease and ammonia reacts with phenol and sodium hypochlorite in an alkaline medium forming a blue indophenol.


ENZYMATIC AND ACID TITRATION– Urea is hydrolyzed by urease forming ammonia

which is then titrated with a weak acid.

a. Van Slyke Cullen

b. Urograph


DIRECT MEASUREMENT OF UREA– DiacetyI Monoxime Method (DAM)

Urea is made to react with diacetyl monoxime to produce a yellow diaxine derivative (Fearon's reaction).

Arsenic thiosemicarbazide is added to enhance color formation and to exclude protein interference.

CONSIDERATION IN BUN DETERMINATION

The determination is affected by high protein diet, hydration and other physiologic functions.

Whole blood should be deproteinized to eliminate interferences of hemoglobin.

Ammonium-containing anticoagulants are contraindicated in enzymatic methods.

Sodium fluoride inhibits the action of urease. Upon prolonged standing, ammonia concentration

in the sample rises 2-3 times the original value due to enzymatic deamination of labile amide like glutamine.

CONSIDERATION IN BUN DETERMINATION

NORMAL VALUE: 7-18 mg/dL (2.5 - 6.4 mmol/L)

CONVERSION FACTOR: 0.357

CLINICAL SIGNIFICANCE:

Pre-renal causes - conditions in which circulation through the kidneys is less efficient than usual.

– Hemorrhage (blood loss) – Cardiac decompression – Increased protein catabolism– Heatstroke (Dehydration)– Burns (Fluid loss)


Renal causes - characterized by the presence of lesions on the parenchyma itself (tubular injury).

– Chronic nephritis – Acute glomerulonephritis (AGN) – Polycystic kidney – Nephroschlerosis – Tubular necrosis


Post-renal causes - due to the obstruction in the-urinary-tract due to:

– Stones – Prostatic enlargement – Tumors


AZOTEMIA - ("azo”) - nitrogen containing a- biochemical abnormality that refers to an increase in BUN and creatinine levels which is largely related to decrease glomerular filtration.


UREMIA - defined as the increased in urea and creatinine (azotemia) with accompanying clinical signs and symptoms of renal failure like:– Metabolic acidosis due to failure of the kidneys to

eliminate acidic products of metabolism– Hyperkalemia due to failure of potassium

excretion– Generalized edema due to water retention

CREATININE

Creatinine is the principal waste product of muscular metabolism derived mainly from creatine (alpha-methyl guanidoacetic acid).

It is synthesized form three amino acids (methionine, arginine and lysine)

CREATININE DETERMINATION:

Creatinase Method– Available on Ektachem analyzer wherein

creatinine is hydrolyzed to N-methyldantolin and ammonia by creatinase. The ammonia is then made to react with alpha-ketoglutarate and NADH in the presence of glutamate dehydrogenase forming glutamate and NAD. The decrease in NADH is followed fluorometrically.

CREATININE DETERMINATION:

Creatinine Aminohydrolase Method– Creatinine is hydrolyzed'to creatine

by,creatinine aminohydrolase followed by a series of coupled enzyme reactions in which creatine reacts with creatinine kinase, pyruvate kinase, and !actate dehydrogebase, culminating in the oxidation of the NADH.

DIRECT JAFFE REACTION METHODS

It is the formation of red tautomer of creatinine picrate when creatinine in serum is made to react with a freshly prepared alkaline sodium picrate solution (alkaline picrate - Jaffe reagent).

Creatinine Determination

NORMAL VALUE: 0.6 - 1.2 mg/dL (53-106 umol/L)

CONVERSION FACTOR: 88.4


Aside from renal diseases, it is also elevated in myopathies like: – Muscular dystrophies – Familial periodic paralysis – Myasthenia gravis – Dermatomyositis

BLOOD URIC ACID (BUA)

Uric acid is the major end product of purine metabolism formed in the liver and intestinal mucosa from xanthine by the action of xanthine oxidase.

BLOOD URIC ACID (BUA)

Normally, 89% of the filtered UA is reabsorbed.

It is relatively insoluble When it accumulates, it may be deposited in

the joints (tophi) or in the genitourinary tracts as uric acid stones.

BLOOD URIC ACID (BUA) DETERMINATION

DIRECT REDOX METHODS– Uric acid is oxidized to allantoin and C02 by

phosphotungstic acid reagent (protein precipitant and color reagent in alkaline solution. In the process of phosphotungstic acid is reduced to tungsten blue


ENZYMATIC METHOD (BLAUNCH and KOCK or URICASE METHOD)

– Differential or Absorption Spectrophotometry – Uric acid is destroyed by the action of uricase to

form carbon dioxide and allantoin. Since uric acid has a maximum.absorption peak at 290-293 nm, white allantoin has no absorption at this point, the decrease in the absorbance is positively related to the uric acid present in the sample

CONSIDERATION IN BUA DETERMINATION:

Uric acid is stable for several days at room 'temperature and longer if refrigerated

Addition of thymol increases its stability to bacterial destruction.

Any of the common anticoagulants, can be used except for potassium oxalate which forms potassium phosphotungstate promoting turbidity.

Purine like foods like legumes, visceral organs and others may affect uric acid assay


NORMAL VALUES:

4.0 - 8.5 mg/dL(0.25 - 0.50 mmol/L) – men

2.7 - 7.3 mg/dl (0.16 - 0.43 mmol/L) - women

CLINICAL SIGINIFCANCE:

Gout - a defect in uric acid metabolism which causes an excess of the acid and salts to accumulate in the bloodstream and joints.


Chronic alcoholism increases uric acid in the bloodstream because alcohol inhibits its excretion.


Leukemia and other malignant conditions due to increased turnover of nucleoproteins


Uric acid levels are elevated in decreased renal functions either due to over production of uric acid or decreased rate.of excretion.


Fatal poisoning with chloroform and methanol, excessive exposure to X-rays and radioactive radiators, due to excessive cell breakdown and nucleic acid catabolism


Genetic disease such as: Lesch-Nyhan syndrome and Von Gierke's disease

AMMONIA

Ammonia determinations contribute very little or none at all in renal impairment.

It has its significance in impending hepatic coma and terminal stages of hepatic cirrhosis.

AMINO ACIDS

Quantitative amino acid determinations are important in congenital renal disorder wherein aminoaciduria resuIts.

CREATINE

Synthesized from amino acid arginine, methionine, and glycine. It is increased in muscular dystrophies.

TESTS MEASURING TUBULAR FUNCTIONS

EXCRETORY TEST:– Para-amino Hippurate Test (PAH) or Diodrast

Test– Phenolsufophthalein (PSP) Dye Excretion Test

TESTS MEASURING TUBULAR FUNCTIONS

CONCENTRATION TEST – Specific gravity– Osmolality– Fishberg Concentration Test

kidney function.ppt

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