Kidney Function Flashcards
Pair of bean-shaped organs located retroperitoneally on either side of the spinal column
Kidneys
T/F: Each kidney contains 1-1.5 million nephrons with a total of 2-3 million nephrons
T
Outer layer
Renal Cortex
Inner layer
Renal Medulla
The functional unit of each kidney
Nephrons
What is the main function of nephrons
Filter blood to produce urine
Enumerate the 5 basic parts of the kidney
Glomerulus
Proximal Convoluted Tubule
Loop of henle
Distal Convoluted Tubule
Collecting duct
Glomerulus aka
Bowman’s capsule/Catch basin
Facilitates non-selective filtration
Glomerulus
Glomerulus
Plasma are filtered:
○ <70,000 daltons: filtered
○ >70,000 daltons: not filtered
Tubular reabsorption (those filtered will be absorbed again)
Proximal Convoluted Tubule
Enumerate what the proximal convoluted tubule reabsorbs
water, sodium, chloride, bicarbonate, glucose, amino acids, proteins, urea and uric acid
How many percent are water, sodium and chloride are filtered and reabsorbed?
70%
How many percent are water, sodium and chloride are excreted?
30%
___% of glucose (renal threshold:
_________ mg/dL)
100%
160-180 mg/dL
98% - 100% of ________ will be reabsorbed
uric acid
_____ urea such as amino acids, vitamins and proteins (almost all are reabsorbed as they are essential)
40%
Maintains the hyperosmolality of the renal medulla
Loop of henle
Final site for urine concentration or dilution
Collecting duct
Enumerate the functions of Kidneys
I. Main function is urine formation
II. Maintenance of blood volume and electrolyte imbalance
III. Maintenance of acid-base balance
IV. Endocrine function
which functions of kidney is to release waste products
I. Main function is urine formation
Which function of the kidneys is for the osmolality (amount of solute dissolved in the blood)
II. Maintenance of blood volume and electrolyte imbalance
II. Maintenance of blood volume and electrolyte imbalance
90% of it is ____ (major)
Sodium
T/F: ↑ Sodium = hyperosmolality = release of ADH / Vasopressin = reserves H2O or initiate thirst
T
T/F: ↓ Sodium = hypoosmolality = prevent production of ADH = promotes urination and release of aldosterone(as sodium reabsorption and potassium secretion)
T
Which kidney function is responsible for maintaining blood pH
III. Maintenance of acid-base balance
Which kidney function promotes reabsorption and excretion of Bicarbonate
III. Maintenance of acid-base balance
○ ________: alkaline
○ ________: acidity
Excretion
Secretion
Plasma contains 20-35 mg/dL of NPN compounds
NON-PROTEIN NITROGENOUS COMPOUNDS (NPN)
Enumerate the NPN compounds
○ Urea (45%)
○ Amino acid (20%)
○ Uric acid (20%)
○ Creatinine (5%)
○ Creatine (1-2%)
○ Ammonia (0.2%)
Ammonia percent
0.2%
Produced by the catabolism of amino acids and by bacterial metabolism in the intestine
Ammonia
Neurotoxin
Ammonia
T/F: Amino acids → Ammonia (can produce glutamate and cause coma) → Urea (Krebs Henseleit Cycle)
T
AMMONIA
Most exist as _________ normal blood pH
ammonium ion (NH4+)
AMMONIA
Used for diagnosis
hepatic failure
Inherited deficiencies of urea cycle enzymes
Reye’s syndrome
In hepatic failure, liver is the site of _______
urea cycle
acute metabolic disorder in the liver that is most common in children and associated with viral infection and aspirin medications
Reye’s syndrome
AMMONIA
Reference value
19-60 ug/dL (11-35 mmol/L)
How many percent UREA NITROGEN (BLOOD) – BUN
45%
most abundant NPN (freely filtered by the kidneys)
Urea
Major end product of protein and amino acid catabolism
UREA NITROGEN (BLOOD) – BUN
Approximately 80% of the nitrogen excreted
UREA NITROGEN (BLOOD) – BUN
First metabolite to increase in kidney disease
UREA NITROGEN (BLOOD) – BUN
UREA NITROGEN (BLOOD) – BUN
○ _______ excreted through Kidney/urine
○ _______ excreted through GIT/skin
> 90%
<10%
UREA NITROGEN (BLOOD) – BUN
Reference value
8-23 mg/dL
Normal Bun:Creatinine Ratio:
10-20:1 mg/dL
Assays for urea were based on measurement of nitrogen content
UREA NITROGEN (BLOOD) – BUN
T/F: Urea: freely filtered but 60%% are reabsorbed by the PCT
F; 40%
Enmurate when UREA NITROGEN (BLOOD) – BUN is decreased
Low protein dietary intake, liver disease, severe vomiting or diarrhea, increase protein synthesis
UREA NITROGEN (BLOOD) – BUN
Concentration is determined by:
○ Renal function - freely filtered
○ Dietary intake
○ Protein catabolism rate = ↑ urea
T/F: Urea = complete structure
True
Urea nitrogen = how many nitrogen of the urea?
2
Also known as blood urea nitrogen, serum urea nitrogen or urine urea nitrogen
Urea nitrogen
T/F: Blood urea nitrogen is the correct term to use
F; Urea nitrogen
T/F UREA NITROGEN (BLOOD) – BUN is easily removed by dialysis
T
Enumerate the Clinical Application of UREA NITROGEN (BLOOD) – BUN
● Evaluate renal function
● To assess hydration status
● To determine nitrogen balance
● To aid in diagnosis of renal disease
● To verify adequacy of dialysis
Enumerate the Clinical Application of UREA NITROGEN (BLOOD) – BUN
● Evaluate renal function
● To assess hydration status
● To determine nitrogen balance
● To aid in diagnosis of renal disease
● To verify adequacy of dialysis
Almost all are excreted in the urine (always present in urine)
Creatinine
CREATININE
Synthesized primarily by the liver from ______, _______ and _________
arginine, glycine and methionine
Creatinine is synthesized In the tissues / liver and converted to ________
creatine-phosphate
Creatine to creatinine by ___________ (dehydration)
dephosphorylation
Partially secreted by the proximal tubules via the organic cation transport pathway
Creatinine
Measure the completeness of 24 hour urine collection (urine creatinine)
Creatinine
CREATININE
○ COMPLETE: _______
○ INC: _______
> 0.8 g/day
<0.8 g/day
Creatinine
Always filtered by _______
Glomerulus
T/F: Creatinine is released into circulation at stable rate proportional to muscle mass
T
Creatinine
Plasma creatinine concentration is a function of:
○ relative muscle mass,
○ rate of creatine turnover
○ and renal function
Index of overall renal function
Creatinine
Creatinine
Reference value for male
0.9 - 1.3 mg/dL
Creatinine
Reference value for female
0.6-1.1 mg/dL
Creatinine
Reference value for Child
0.3-0.7 mg/dL
Elevated Creatinine is found is abnormal _________
renal function
Enumerate
Measurement of creatinine concentration is used to determine:
○ sufficiency of kidney function
○ severity of kidney damage
○ monitor the progression of kidney disease
functional or structural abnormalities or markers of kidney damage (seen in blood, urine, tissue test, imaging studies) present for less than three months
Acute Kidney Injury (AKI)
Acute Kidney Injury (AKI)
Kidney markers:
NPN and other metabolic wastes
Retention of the metabolic wastes
Acute Kidney Injury (AKI)
CREATINE
Elevated in plasma and urine in:
Muscular dystrophy, hyperthyroidism, trauma
T/F: Elevation of creatine in plasma and urine is common because it is freely excreted
F; rare
From the muscle
Creatine
Immediate precursor of creatinine
Creatine
Plasma creatine levels usually normal, but urinary is elevated
Creatine
Elevated concentration of NPN in the blood
Azotemia
What are the NPNs elevated in the blood during azotemia?
Urea and Creatinine
Syndrome associated with high urea in plasma with renal failure
Uremia / Uremic Syndrome
AZOTEMIA
Causes of urea plasma elevations are:
○ Prerenal
○ Renal
○ Postrenal
Pre-Renal Azotemia
Causes: Anything that produces a decrease in functional blood volume, include:
○ Congestive heart failure
○ Shock
○ Hemorrhage
○ Dehydration
High protein diet or increased catabolism: _________________________
(Fever, major illness, stress)
State the process involving Prerenal Azotemia
Reduced Renal Blood Flow (most common)
↓
Less blood delivered to the kidney
↓
Less urea is filtered
“True Renal Disease”
Renal Azotemia
Renal azotemia
Causes:
○ Acute/chronic renal disease
○ Glomerulonephritis
○ Tubular necrosis
Renal azotemia
Enumerate the lab results considered
BUN
Creatinine
BUA
Anemia
Electrolyte imbalance
Renal azotemia lab results
BUN = ___ (_________)
↑
abrupt increase
Renal azotemia lab results
Creatinine – ___ (________;_______)
↑
slow increase: 20 mg/dL
Renal azotemia lab results
BUA - ___ (by: ________)
↑
12 mg/dL
Renal azotemia lab results
Anemia = _________
low RBC production
Renal azotemia
Complications
○ Coma
○ Neuropsychiatric changes
State the process involving Renal Azotemia
Damaged Kidneys
↓
Poor Excretion
↓
Increased Urea
Usually the result of urinary Tract Obstruction (In the ureter, urinary bladder, etc.)
Post-Renal Azotemia
Post-Renal Azotemia
Urea level is higher than creatinine due to _________ of ____ into the circulation
back diffusion
urea
Post-Renal Azotemia
Causes:
nephrolithiasis, renal calculi, cancer/tumors of genitourinary tract, severe infection
Chemical name of Uric Acid
2,6,8-trihydroxypurine (aka BUA)
It is the major product of purine (adenine and guanine in DNA) catabolism
Uric Acid
It is the final breakdown of nucleic acids catabolism in humans
Uric Acid
Uric Acid is formed from_______ by the action of ________ in the __________
xanthine
xanthine oxidase
liver and intestine
Uric acid is transported to kidney and filtered (___)
70%
Uric Acid
Remaining 30% by _____ (degraded by bacterial enzymes)
GIT
Source of nucleic acids (Ingestion and endogenous dead cells)
Uric Acid
Uric acid is measured to:
Asses ______ of purine metabolism
Inherited disorders
Uric acid is measured to:
Confirm diagnosis and monitor treatment of _____
gout
Uric acid is measured to:
To assist in the diagnosis of ________
renal calculi
Uric acid is measured to:
To prevent __________________ during chemotherapeutic treatment
Uric acid nephropathy
Uric acid is measured to:
To detect _______________
Kindey dysfunction
Uric Acid
Present in plasma as __________ (95%)
monosodium urate
Uric acid
● At plasma pH → relatively soluble/insoluble
insoluble
Uric acid
If prolonged = uric acid crystals will deposit in the joints causing ______
gout
Uric Acid
If pH of nephrons: _____ (acidic) = uric acid precipitates making crystals causing __________/_______________
<5.7
renal calculi / kidney stones
Uric Acid
Reference value male:
3.5-7.2 mg/dL
Uric Acid
Reference value female:
2.6-6.0 mg/dL
Uric Acid
Reference value child
2.0-5.5 mg/dL
Condition called when there is ↑ uric acid
Hyperuricemia
Most common hyperuricemia
Gout
Gout
● Crystals are differentiated by the________
birefringent
○ GOUT (+) = with ___________
○ PSEUDOGOUT (-) = _____ (_____________________________)
monosodium urate
CPPD (Calcium pyrophosphate dihydrate crystal deposition)
Primarily in men and first diagnosed between 3rd and 5th decade of life
Gout
Pain & inflammation of joints by precipitation of sodium urates in tissues
Gout
Gout
Uric acid is greater than _______
6.0 mg/dL
Increased risk of renal calculi/nephrolithiasis
Gout
hyperuricemia due to overproduction of uric acid (25- 30%)
Gout
INCREASED NUCLEAR METABOLISM - _________
Chemotheraphy
● causes elevated levels of uric acid because filtration and secretion are hindered
CHRONIC RENAL DISEASE
CHRONIC RENAL DISEASE
BUA: ______
> 10 mg/dL
● Inborn error of purine metabolism
LESCH NYHAN SYNDROME
It is deficiency of hypoxanthine-guanine phosphoribosyltransferase (involved in the uric cycle)
LESCH NYHAN SYNDROME
Other causes of hyperuricemia
- Secondary to glycogen storage disease
- Toxemia of pregnancy and lactic acidosis
- Increased dietary intake
- Ethanol consumption
Enumerate the causes of Hypouricemia
● Fanconi’s syndrome
● Wilson’s disease
● Hodgkin’s disease
● Overtreatment with allopurinol
● Chemotherapy (6-mercaptopurine, azathioprine)
● Alzheimer’s disease
● Parkinson’s disease
○ Filtered by the kidneys but not reabsorbed by the PCT
● Fanconi’s syndrome
Fanconi’s syndrome
○ Resulting to low uric acid as _________ are not reabsorbed
98%-100%
uric acid not reabsorbed, excreted in urine
Fanconi’s syndrome
○ Xanthine oxidase (gout)
Wilson’s disease
○ Enzyme for uric acid synthesis
Wilson’s disease
○ Low uric acid
● Overtreatment with allopurinol
○ Inhibited by the uric acid synthesis
● Overtreatment with allopurinol
________ - xanthine oxidase is inhibited
Allopurinol
● Best overall indicator of the level of kidney function
Glomerular Filtration Rate (GFR)
● Clearance of substances that are not bound to protein
Glomerular Filtration Rate (GFR)
Glomerular Filtration Rate (GFR)
○ High MW = ________
not filtered
Glomerular Filtration Rate (GFR)
● _______ of glomerular filtrate is produced daily
150 liters
Glomerular Filtration Rate (GFR)
● _______ of glomerular filtrate is produced daily
150 liters
Glomerular Filtration Rate (GFR)
GFR decreased by ____________ after age 20- 30
1.0 mL/minute/year
● Removal of the substance from plasma into urine over a fixed time.
Clearance
● It represents the volume of plasma that would contribute all the solute excreted.
Clearance
Clearance
● Plasma concentration is (directly/inversely) proportional to clearance
inversely
Specimen in clearance
○ 24 hour urine
○ Serum
Formula in clearance
(di ko malagay bahala k n)
Formula of clearance:
o U – conc. of analyte (______)
o P – conc. of analyte (______)
▪ What is measured
o Volume – Urine volume in mL (___ hours)
o Minutes – time required to collect urine (_____ minutes)
o _____ – ave. body surface of adult individual (0.717 for pediatric)
o A – _____ of patient
(nomogram: height and weight are taken)
urine
Plasma
24
1440
1.73
body surface
Enumerate the different methods in clearance
a. INULIN CLEARANCE TEST
b. CREATININE CLEARANCE
c. UREA CLEARANCE
● Reference method in clearance
a. INULIN CLEARANCE TEST
● Exogenous substance administered to the patient
a. INULIN CLEARANCE TEST
INULIN CLEARANCE TEST
Priming dose:
2.5 mL of 10%
INULIN CLEARANCE TEST
Continuous dose:
500mL of 1.5% inulin
● Not routinely done due to the necessity for continuous
a. INULIN CLEARANCE TEST
Alternatives to insulin:
○ Radioactive marker: 125I-iothalamate & 99mTc-DTPA
○ Iohexol and Chromium 51-labelled EDTA
○ Nonradiolabeled iothalamate
INULIN CLEARANCE TEST
Reference value male
127 mL/min
INULIN CLEARANCE TEST
Reference value female
118 mL/min
● Best alternative method to Inulin
b. CREATININE CLEARANCE
● Endogenous and all are still excreted
b. CREATININE CLEARANCE
T/F: Creatinine clearance is not affected by diet
T
CREATININE CLEARANCE
o approx. _________ is excreted
1.2-1.5g/ day`
● Excellent measure of renal function
CREATININE CLEARANCE
● Measure of completeness of 24 hour urine
(SERUM: collect within 24 hours)
CREATININE CLEARANCE
CREATININE CLEARANCE
Major limitation:
accurate urine collection
CREATININE CLEARANCE
Reference value for male:
85 - 125 mL/min
CREATININE CLEARANCE
Reference value for female:
75 - 112 mL/min
Creatinine clearance formula:
(di ko malagay bhl k n)
Traditional formula
CREATININE CLEARANCE FORMULA:
CREATININE CLEARANCE FORMULA
T/F: Affected by body surface area and correction for body mass should be included in the formula
T
● Commonly used in laboratory
COCKCROOFT-GAULT FORMULA
● Results are not corrected for body surface area
COCKCROOFT-GAULT FORMULA
Assumes that women will have a 15% lower creatinine clearance than men at the same level of serum creatinine
COCKCROOFT-GAULT FORMULA
● Accurate: does not involved body weight
MODIFICATION OF DIET IN RENAL DISEASE FORMULA (MDRD)
MODIFICATION OF DIET IN RENAL DISEASE FORMULA (MDRD)
● Multiply result by _______ if black
1.212
MODIFICATION OF DIET IN RENAL DISEASE FORMULA (MDRD)
● Multiply result by _____ if female
0.742
MODIFICATION OF DIET IN RENAL DISEASE FORMULA (MDRD)
Variables: _________________
Age, serum, race, gender
● One of the first clearance tests
c. UREA CLEARANCE
UREA CLEARANCE
● It is not reliable as some variables are still reabsorbed (_____)
40%
● Demonstrate progression of renal disease or response to therapy
c. UREA CLEARANCE
● Low molecular weight protease inhibitor and produced at a constant rate by all nucleated cells.
CYSTATIN C
● Presence will give problem to the reabsorption
CYSTATIN C
Why cystatin c’s presence will give problem to the reabsorption?
○ As it should be 100% reabsorbed and sent back to the circulation
● THE ONLY KIDNEY FUNCTION TEST that is never measured in the urine
Cystatin C
● Indirect estimate of GFR
Cystatin C
Not affected by muscle mass, age, diet and gender
Cystatin C
_______ is freely filtered by the glomerulus but completely reabsorbed by the tubules
Cystatin C
Cystatin C
Specimen:
Serum or Plasma
Cystatin C
Increased (↓ GFR):
acute and chronic renal failure, diabetic nephropathy
Cystatin C
Reference value of adults
0.5-1.0 mg/L
Cystatin C
Reference value of >65 years old
0.9-3.4 mg/L
Cystatin C
GFR is computed using ___________
Modified Cystatin C Equation:
● A low molecular weight glycoprotein
Beta Trace Protein
● Freely filtered by glomerulus and completely reabsorbed and catabolized by the PCT
Beta Trace Protein
● Belongs to the lipocalin protein family and functions as prostaglandin D synthase
Beta Trace Protein
● Isolated primarily from CSF
Beta Trace Protein
Beta Trace Protein
Increased: ________
Renal disease
GFR FORMULA USING B TRACE PROTEIN
White formula
Page formula
All should be in adequate amount
TEST FOR RENAL BLOOD FLOW
UREA NITROGEN METHODOLOGIES
Sample:
Serum, plasma, urine
o PLASMA: should never be in _________
fluoride or citrate
Fluoride and Citrate: inhibits ______
urease
T/F: Refrigerate sample if delay in testing is expected
T
T/F: If sample is not refrigerated. ○ bacteria that are urease positive will be inhibited (PMCKEYS (genus)))
T
Assays for urea were based on measurement of ________, hence the name blood urea nitrogen.
nitrogen
Atomic mass of Nitrogen
14 g/mol
Molecular mass of urea
60 g/mol
Urea = ___ nitrogen atoms
2
2 nitrogen atoms (______ of the total weight of urea)
46.6%
Formula of Urea to BUN
Urea = BUN x 2.14
3 methods of Urea nitrogen methodologies
- Chemical Method Diacetyl Monoxime (DAM) Method
- Enzymatic Method
- Isotope Dilution Mass Spectrometry (Reference Method)
Indicator dye and not specific
- Chemical Method Diacetyl Monoxime (DAM) Method
Enumerate the types of enzymatic method in urea nitrogen methodologies
UREASE BERTHELOT METHOD
UREASE GLUTAMATE DEHYDROGENASE METHOD (GLD)
Urea is from
Jack beans
In Urease Berthelot Method, ______ and ____ can be measured by different method to calculate the concentration of urea in the sample
Ammonia
CO2
UREASE GLUTAMATE DEHYDROGENASE METHOD (GLD)
● Uses:
○ Coupled Enzymatic Method
○ UV Enzymatic Method
Reference method for Urea Nitrogen Methodologies
Isotope Dilution Mass Spectrometry
Creatinine methodologies
Sample:
Serum, plasma, urine
CREATININE METHODOLOGIES
Interferences
Hemolysis, Ictericia, Lipemia
4 methods for Creatinine Methodologies
- Direct Jaffe Method (Chemical Method)
- Kinetic Jaffe Method
- Enzymatic Method
- Isotope Dilution Mass Spectrometry
- Direct Jaffe Method (Chemical Method)
● Principle: ________________
Folin Wu Method
- Direct Jaffe Method (Chemical Method)
End-product:
red-orange tautomer
Jaffe Reagent components
o Saturated picric acid
o 10% NaOH
When jaffe reagent is mixed, it produces:
▪ Picramic acid
▪ Methyl guanidine
● Uses spectrophotometry
- Direct Jaffe Method (Chemical Method)
- Direct Jaffe Method (Chemical Method)
Interferences: False Increase
▪ Creatinine-Like analytes: Uric acid, ascorbic acid, glucose, a-keto acids
▪ Medications: Cephalosporins, dopamine, Lidocaine
- Direct Jaffe Method (Chemical Method)
Interferences: False Decrease
Bilirubin, Hemoglobin
Types of Direct Jaffe Method
Folin Wu Method
Lloyd or Fuller’s earth method
