2018 .02.13 CLS 304 Notes Lec 03 Renal Function PDF

Preview

Summary

Payman Nasr...

Description

2018.02.13 CLS 304 Urinalysis and Bodily Fluids Spring 2018, Payman Nasr

 

Renal Function   

Urine Composition  Normal ranges are wide as urine volume and solute composition can vary greatly depending on: o Diet o Physical activity o Health  Kidneys are principal organ for regulating body fluid composition  Renal excretion is primary elimination route of soluble metabolic wastes  Wastes exclusively excreted by kidneys can be used to assess kidney function (creatinine, urea)  Glomerular Filtration Rate (GFR): measures how well blood is filtered thru nephrons o Afferent arterioles bring the blood in  capillary blood  efferent arteriole  peritubular capillaries  vasa recta o If there is fat obstruction in afferent arteriole, GFR would be low o Waste products like creatinine (creatine phosphate in your muscles) and urea (from metabolism of nucleic acids, amino acids, etc.)

 



Creatine phosphate is source of energy that you can store Everywhere else in body, you can’t store ATP But in muscle, you can store energy in creatine phosphate Break creatinine phosphate to release creatinine Creatinine good molecule used to determine GFR  Produce creatinine at same, constant rate  Heavy exercise increases creatinine production  On average, we all produce creatinine at specific rate, certain rate, per volume  Intrinsic molecule that is produced by the body Urea is absorbed into the blood or into the filtrate in interstitial space Used to use inulin, a sugar that your body cannot use  Gets 100% filtered in kidneys at nephrons and none will be deserved back  This test is not on spot urine  Must collect 24 hour urine, then measure creatinine  Must have IV for 24 hours to measure how much inulin is injected and how much is cleared thru urine Creatinine is not a perfect measure of kidney function  7-10% Creatinine is secreted by the tubules: not



filtered thru the glomerulus of the nephron o Secreted primarily of PCT  Efferent arteriole  peritubular capillaries  vasa recta  Will secrete 20% of creatinine at level of PCT Kidney function doesn’t usually go down immediately: progressive, chronic, slow disease  Look at creatinine level  can det. Approx. GFR

Measures of Concentration of solutes in urine  Osmolality o Osmoles per kilogram (osmo/kg) (milliosmoles used for convenience; m osmo/kg to avoid decimals) o Affected by solute number, not size or weight o Final osmolality determined in distal and collecting tubules when antidiuretic hormone (ADH) is present o Normally urine osmolality is 1 to 3 times that of plasma  275/275 = 1  1000/275 = 3.xxx o Concentration of solutes in serum: 275-300 mosm/kg o Concentration of solutes in urine: 275 – 1400 (dehydrated) o Osmolality is much more accurate det of concentration of solutes: Only depends on number of solute particles  Specific gravity: Good way to screen patients o Comparison of density of urine to that of water o Normally ranges from 1.002 to 1.035 o Depends on number of particles and mass (how big is it?) (size or weight). This

o

means a glucose molecule with C6H12O6 influences the specific gravity when compared with sodium ion (Na+). Method #1: Refractometer  Look at movement of light thru distilled water (calibrated to be 1.000)  Look at movement of light thru urine, which has solutes  Depending on concentration of solutes, 1.000 can increase  Bigger the number, the more concentrated the urine  If someone’s sp gravity is always at 1.000 even when they are exercising, something is wrong (can’t concentrate urine)

Fixation of Solute Concentration  Example: NaCl o If you put in water, NaCl will ionize into Na+ + Cl Example: CH4No2 (urea) common in urine, but does not ionize  NaCl has more effect than CH4NO2  No effect on osmolality, but does have an effect on specific gravity  In some chronic renal diseases, concentrating ability slowly diminishes until specific gravity or osmolality are unchanging  Urine concentration same as ultrafiltrate  Specific gravity of 1.010 or mOsm of ~300 mOs/kg  Causes polyuria Urine Volume  Polyuria – greater than 3 L/day o Conditions with water diuresis (osmolality 750 mOsm/kg: Can concentrate urine

Children: Takes 1-2 years for nerves to grow and innervate skeletal muscle  So will wet bed Anuria – no urine; less than 50 mL urine/day o Progressive renal disease or renal failure o Solution: Kidney transplantation and dialysis o



Testing Renal Concentrating Ability  Osmolality preferred o More accurate reflection of kidney’s concentrating ability, since only solute number affects it (not affected by size of solute)  Three most prevalent solutes: o 2% Urea o Chloride o Sodium o 94-96% water



300 mOsm/kg Water deprivation test: Tell patient not to consume any liquid for 12 hours. Come in the morning. Patient comes. Draw serum osmolality and collect urine. Expect for urine to be concentrated.  But it’s not concentrated! Tells you there’s a problem with ADH.  Treatment: DDAVP = Synthetic ADH administered via injection  After injection of DDAVP, you expect concentration of urine to be higher in case of neurogenic case. In case of nephrogenic case, osmolality will still be low. Psychogenic polydipsia:  Example: schizophrenia (mental disease is as much of a disease as physical disease of body)  Psychiatric drugs can dry their mouth to the point where they hella drink water 

o o

o

Fluid Deprivation Tests  Used to differentiate causes of polyuria o “Neurogenic” diabetes insipidus  Antidiuretic hormone (ADH) decreased o “Nephrogenic” diabetes insipidus

    

Lack of renal response to ADH Water consumption restricted Urine specimen checked about 12 hours later If concentrated, test is ended. If not, test continues. Can compare with plasma concentration or administer ADH to see if that helps

ADH Regulation ↑Body Hydration = ↓ADH = ↑Urine Volume ↓Body Hydration = ↑ADH = ↓Urine Volume Renal Clearance Tests to Assess Glomerular Filtration Rate (GFR)  Golden molecule is neither absorbed or concentrated at tubules o GFR is reported in mL/min o Can use: Creatinine, inulin, or urea o We don’t have a perfect molecule, but none are perfect  Creatinine secreted by tubules into filtrate and not by glomerulus  Volume of plasma in milliliters that is completely cleared of a substance per unit of time  Volume of plasma filtered directly affects volume and composition of urine excreted  Calculate renal clearance (C) using plasma concentration of substance (P), urine concentration (U), and volume of urine (V)

Creatinine Clearance 

 

Tests for glomerular filtration rate (GFR) use substances removed solely by glomerular filtration (inulin)Problems! Creatinine is a waste product in muscles, produced at a relatively constant rate Requires a timed specimen (usually 24-hour urine) creatinine (U) and serum creatinine (P) drawn sometime during urine collection period, urine

 

volume (V), and an estimate of body surface area (from height and weight) Plasma and urine creatinine tests easily performed Small amount of creatinine secreted by tubules (7% to 15%), resulting in an increased urine concentration of creatinine

Creatinine Clearance Formula

Urine volume: must use mL (1 L = 1000 mL)  1440 min (= 24 hours); you have to collect 24 hours of urine to perform this test  If you have a patient where it’s impossible to collect urine in 24 hrs, you have to adjust in the minutes  BSA = Body Surface Area; size of person’s body o Creatinine production depends on muscle o More muscle? Higher body surface area  1.73 is average body surface are of average adult Reference Range (mL/min) adult male 74-129 

adult female   

65-123

Values are lower in older people Normal reference range of plasma creatinine is 0.5 to 1.5 mg/dL Nomograms are available to adjust for body surface area (BSA) usually about 1.73 for an average sized adult

Nomogram

   

1st column: height of individual 3rd column: weight of individual The number which the line connecting those dots are on passes thru is BSA Freezing point analysis: Primary way to measure osmolality o dI water freezes at 0 C o Urine will have solutes in it: presence of solutes will change freezing pt of specimen

o o

More specimen, lower T Thru concentration curve, you can det concentration of solutes in water

Beta2-Microglobulin:  Used to determine that problem is level of tubules  A low-molecular-weight protein found on surface of nucleated cells and shed into plasma o Even RBC’s in bone marrow have it o But RBC’s in circulation don’t have it o Routinely shed at a constant rate o Blood brings it to kidney  Readily passes through glomeruli and is 99.9% (100%) reabsorbed by proximal tubules  If you find Beta2-Microglobulin in urine, then you know it’s a problem with absorption function of proximal tubules  Marker of reduced tubular function when it increases in urine  Used clinically to: o Identify early kidney transplant rejection o Differentiate tubular and glomerular diseases  Other molecules: o P-aminohippurate: measures secretion in tubules Screening for Albuminuria : First signal of renal dysfunction  Albuminuria appears early in diabetic nephropathy  Presence of albumin is caused by increased glomerular permeability  Early detection of low levels of albumin in urine (microalbuminuria) signals need for intervention o Has to be done separately o Looks at much lower concentration of urine o Suspect that patient has renal failure o Lower the threshold of detection  Renal disease is slow and progressive o Can be reversible if you catch it in time



Single most important change associated with glomerular proteinuria is hyperglycemia o 50% of people who have diabetes will lose their renal function if they live long enough o If other things don’t kill them, their kidneys will shut down o Hyperglycemia will affect things: Thickening of tissue, things cannot pass through, etc.  Cataracts  Hypertension  Renal failure

Most Commonly Used Tests for Evaluating Renal Function  Creatinine clearance for assessment of glomerular filtration rate (GFR)  Urine osmolality for tubular concentrating ability  Urine protein electrophoresis to evaluate glomerular permeability to plasma proteins o There are certain proteins found in urine o Develop an agar or acrylamide gel o Get urine protein and put it in well o Put it in solution o Allow electrical charge by connecting to electricity o Proteins with negative charge will move towards positive end of gel o Based on size and charge, they will travel at different rates o Gamma proteins  Plasma creatinine o Plasma creatinine is first step in determining kidney function  Blood Urea Nitrogen (BUN) o Urea and creatinine increase in plasma suggest renal problems  Calculated vs. measured osmolality o Subtract; should be less than 10...