Electrolyte and Renal Function Test Flashcards

(51 cards)

1
Q

➢ The volume of plasma that would theoretically have to be “cleared” of the substance to account for the amount of the substance excreted in the urine during a given period.

➢ Relates the rate of urinary excretion of material to the plasma concentration of that material

A

RENAL CLEARANCE

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2
Q

➢ That amount of substances that is concentrated in the urine

➢ The plasma concentration of the substance to determine the volume of plasma needed to account for the material excreted

A

Cx=(UxV) / Px mL/minute

Note: Cx – clearance of a substance x

Ux – concentration of the substance in urine

Px – concentration of the substance in plasma

V – volume of urine per unit time

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3
Q

Clearance in mL/24 hours can be converted to clearance in mL/minute

➢ Dividing the value by

A

1440 (because 24 hours equals 1440 minutes)

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4
Q

Best overall indicator of the level of kidney function

Declines with age

➢ After age 20 to 30 years

➢ Decrease by ~1.0mL/min/1.73 m2 per year

A

GLOMERULAR FILTRATION RATE

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5
Q

Important! Molecular marker to determine GFR must be _____________________________ and __________________

A

minimally reabsorbed and minimally secreted by the renal tubules

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6
Q

MEASUREMENT OF GFR WITH EXOGENOUS SUBSTANCES

A

Inulin clearance

Alternative measures

➢ Urinary clearance of exogenous radioactive markers

➢ Plasma disappearance of exogenous substances

Nonradiolabeledbiothalamate in blood and urine

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7
Q

MEASUREMENT OF GFR WITH ENDOGENOUS SUBSTANCES

A

➢ Urea

➢ Creatinine

➢ Cystatin C

➢ B trace protein [BTP]

➢ B-2 microglobulin

➢ Tryptophan glycoconjugate

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8
Q

MEASUREMENT OF GFR WITH ENDOGENOUS SUBSTANCES that is most widely used*

A

*urea & creatinine – widely used; readily available

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9
Q

➢ Endogenous substance

➢ MW: 113 Da

Sources: ➢ Produced by the muscle from creatine and creatine phosphate through a nonenzymatic dehydration process

Rate of production of is proportionate to the creatine - creatine phosphate pool, which, in turn, is proportionate to the muscle mass

➢ Ingested meat or dietary supplements

A

CREATININE AS MEASURE OF RENAL FUNCTION

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10
Q

What are the sources of creatinine?

A

Sources:

➢ Produced by the muscle from creatine and creatine phosphate through a nonenzymatic dehydration process

Rate of production of creatinine is proportionate to the creatine - creatine phosphate pool, which, in turn, is proportionate to the muscle mass

➢ Ingested meat or dietary supplements

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11
Q

o The rate of in vitro conversion of creatine to creatinine in meat is dependent on ________ and _______.

A

temperature and acidity

NOTE :o High temperature and low pH increase conversion

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12
Q

Why is Creatinine widely used as a marker of GFR?

A

➢ It is an endogenous substance with a fairly constant rate of production

➢ It is not bound to plasma protein; therefore it is filtered freely by the glomerulus

➢ It is not reabsorbed by the renal tubules, and only a small amount is secreted by the tubules

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13
Q

Creatinine as a Measure of Renal Function Drawbacks:

A

➢ Although the rate of production is fairly constant, it has substantial individual variation, depending mainly on the muscle mass

o Presence of severe muscle wasting, production of creatinine could be reduced to less than 25% to the amount predicted from the body weight

Quantity of meat ingestion can substantially influence total daily production

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14
Q

➢ A number of chromogens, both endogenous and exogenous, interfere with its measurement by this technique

➢ Most widely used method of creatinine measurement

A

Alkaline picrate method

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15
Q

➢ reaction of creatinine with trinitrophenol, an explosive, a compound also known as picric acid, enhanced by alkaline condition

A

Jaffe reaction

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16
Q

alkaline picrate method falsely high result in the presence of:

A

 high levels of glucosediabetic ketoacidosis

 hyperglycemic coma

 dialysate fluid used in peritoneal dialysis

 cephalosporin antibiotics

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17
Q

➢ alkaline picrate method

  • falsely low result in the presence of:
A

 bilirubin  haemoglobin

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18
Q

➢ creatinine is partially secreted by the ______________________

A

proximal tubules via the organic cation transport pathway

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19
Q

➢ tubular secretion is blocked by various drugs

A

cimetidine, trimethoprim, pyrimethamine, and salicylate

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20
Q

➢ presence of renal dysfunction

o tubular secretion could involve as much as___________ of the excreted in the urine

A

50%

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21
Q

Creatinine Measurement

A

➢ Alkaline picrate method

➢ Enzymatic measurement with the use of creatinine amidohydrolase or creatinine iminohydrolase

➢ Converting creatinine to creatineaminohydrolase

➢ Isotope dilution – mass spectrometry (IDMS)

22
Q

FORMULAS TO ESTIMATE CREATININE CLEARANCE OF AN ESTIMATE OF GFR

Cockroft-Gault formula (mL/minute) (cockroft, 1976):

A

([140-age]•[IBW])/(72xSCr); multiply by 0.85 if female

NOTE :Where IBW is ideal body weight and SCris serum creatinine concentration

IBW is calculated by the following formula:

Males: IBW = 50kg + 2.3kg for each inch over 5 feet

Females: IBW = 45.5kg + 2.3kg for each inch over 5 feet

23
Q

Schwartz Formula:

A

GFR = 0.55 x height (cm)/serum creatinine (mg/dL)

GFR = 48 x height (cm)/serum creatinine (umol/L)

24
Q

Modified Schwartz Formula:

A

GFR = (mL/min/1.73 m2 ) = 39.1[height (m)/Cr (mg/dL)]0.516 x [1.8/cystatin C (mg/L)]0.294 [30/BUN (mg/dL)]0.169 [1.099]0.210 [height (m)/1.4]

25
➢ main waste product of **nitrogen-containing chemicals** in the body ➢ molecular weight – 60 Da ➢ expressed only by the nitrogen content of urea ➢ use “serum or urine urea nitrogen”
Urea
26
➢ widely used as a measure of renal dysfunction ➢ NOT used as a measure of GFR
Serum Urea
27
Why is urea not used as GFR?
➢ Urea concentration in the serum **depends not only on renal function but also on the rate of urea production,** which **depends largely on protein intake** ➢ **Rate of protein intake varies widely from individual to individual**
28
MEASUREMENT OF UREA
Isotope dilution mass spectrometry Measurement of urea by colorimetric method Measurement of urea by enzymatic method
29
➢ Gold standard for UREA ➢ used only as a reference method ➢ high cost
Isotope dilution mass spectrometry
30
➢ Based on a reaction of urea with **diacetyl monomer**
Measurement of urea by colorimetric method
31
➢ Hydrolysis of urea by urease -\> ammonia
Measurement of urea by enzymatic method
32
OTHER MEASURES OF GFR
Cystatin C Serum concentration of cystatin C β-2-Microglobulin β Trace Protein (BTP) Plasma BTP Tryptophan Glycoconjugate Serum level of MPT
33
➢ Inhibitor of cysteine proteinase ➢ **Produced by all nucleated cells** ➢ Production rate is **relatively constant from age 4 months to 70 years** ➢ Rate of production is **not affected by muscle mass, sex, or race** ➢ Freely filtered at the glomerulus at the same concentration as in the plasma o Filtered peptide is completely reabsorbed by the proximal tubule o BUT it is then destroyed rather than reentering the circulation
Cystatin C
34
➢ used as indirect estimates of GFR
Serum concentration of cystatin C
35
➢ Component of the major histocompatibility complex class I molecule ➢ Present in all nucleated cells ➢ Needed for production of CD8 cells ➢ Freely filtered at the glomerulus, and then is reabsorbed and metabolized completely by the proximal tubule ➢ Acute kidney injury o Plasma level increases o Appears in the urine o Reabsorption is completely because of proximal tubular damage ➢ Common cause of dialysis-associated amyloidosis o Tendency to fold into a β-sheet configuration
β-2-Microglobulin
36
➢ Functions as **prostaglandin D synthase** (major prostaglandin in the brain) ➢ Isolated primarily from **cerebrospinal fluid**
β Trace Protein (BTP)
37
➢ Originates from the brain and is freely filtered at the glomerulus, then is absorbed completely by the proximal tubule and is catabolized there ➢ Increased in patients with renal disease o In the presence of constant production, filtation is reduced
Plasma BTP
38
➢ Glycoconjugate of tryptophan produces Mannopyranosyl-l-tryptophan (MPT ) ➢ It is filtered at the glomerulus freely and is not reabsorbed ➢ Measured only by the high-perfprmance liquid chromatography (HPLC) method o Time consuming and experience
Tryptophan Glycoconjugate
39
➢ Increases progressively with declining renal function ➢ Not affected by muscle mass
Serum level of MPT
40
- actual injury occurs to the kidney **either biochemically or histologically** - “Functional or structural abnormalities or markers of kidney damage including abnormalities in blood, urine, or tissue tests or imaging studies present for less than three months.” –AKI Network
Acute Kidney Injury (AKI)
41
-all causes of renal failure from prerenal azotemia to obstructive uropathy
Acute renal failure (ARF)
42
Why use urine biomarkers?
➢ May be **produced by the kidney** as the result of kidney injury or **may be filtered by the glomerulu**s but not well reabsorbed by the tubules because of injury to the tubules ➢ The levels **often increase long before any changes in serum creatinine or urea nitrogen** or urine output occur ➢ Help to: o Reveal **primary location of injury** - proximal tubule, distal tubule, interstitium, or vasculature o Distinguish **among different subtypes** of AKI - prerenal, intrinsic renal, postrenal o **Delineate causes of AKI** - ischemia, toxins, sepsis, or a combination ➢ Serum samples are **ready available** ➢ Serum biomarkers are **more stable**
43
Why not use serum biomarkers?
➢ Serum biomarkers may reflect the systemic response to a
44
➢ Type I cell membrane glycoprotein contains: * immunoglobulin-like domain * mucin domain (extracellular region) – shed into the urine after proximal tubular injury ➢ levels increase after kidney injury ➢ serves as an **earlier diagnostic indicator of kidney injury** ➢ expression is **limited to the kidney**, and **no systemic source**
KIDNEY INJURY MOLECULE-1 (KIM-1)
45
➢ a.k.a “**lipocalin 2**” and **“human neutrophil lipocalin”** ➢ source: • synthesized during a **narrow window of granulocyte maturation in the bone marrow** • induced in epithelial cells in the setting of inflammation or malignancy ➢ **early marker of AKI** • increased concentrations within **2-6h of the result** —preceding changes in serum creatinine by 1-3 days ➢ **contrast-induced nephropathy** ➢ however.. elevated in inflammatory and infective conditions
NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL)
46
➢ significantly upregulated in the proximal tubule following ischemia-reperfusion injury, inflammatory/autoimmune nephritis, and cisplatin-induced nephrotoxicity Urinary IL-18 levels ➢ elevated in patients with AKI and delayed graft function compared with normal subjects and patients with prerenal azotemia, UTI, chronic renal insufficiency, and nephritic syndrome ➢ early marker of AKI—preceding changes in serum creatinine by 1-2 days
INTERLEUKIN-18 (IL-18) Renal IL-18 mRNA levels
47
➢ Urinary L-FABP • Chronic kidney disease * Diabetic nephropathy * Immunoglobulin A nephropathy • Contrast nephropathy
FATTY ACID-BINDING PROTEINS (FABPs)
48
Urinary L-FABP levels significantly increased before the increase in serum creatinine
AKI post contrast dye
49
** Direct correlation** was found between urinary L-FABP level and both **peritubular capillary blood flow** and ischemic time of the transplanted kidney
Kidney transplant patients
50
Increases in serum creatinine occurred 2-3days post surgery, whereas **urine L-FABP levels increased at 4h after surgery**
AKI following cardiac surgery
51