Lecture 4: Nephrology Flashcards
What are the physiologic functions of the kidney?
- Filtration of plasma
- Reabsorption of certain solutes
- Secretion of certain solutes
- Excretion of urine into CT and ureter
- Maintains acid-base status, electrolyte concentration and removal of toxins
- Activates Vit D and secretes erythropoietin
How is renal function regulated?
1.Renin and aldosterone
2. ADH
How does renin and aldosterone regulate renal function?
Renin is released by the juxtaglomerular apparatus when blood flow is decreased. It then catalyzes the conversion of angiotensin into angiotensin I. Angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II promotes release of aldosterone from adrenal gland. This results in an increase in renal perfusion and blood pressure.
How does ADH regulate renal function?
ADH binds to receptor in renal tubule which causes the movement of aquaporins to the cell membrane. This result in an increase of the reabsorption of water. Hence, an increase in ADH will result in more concentrated urine.
How can we quantify kidney function? What is the normal range for this characteristic?
Glomerular filtration rate
Normal = >90 mL/min/1.73m²
How do we measure glomerular filtration rate?
We cannot. Instead, we must estimate the glomerular filtration rate based on how well the kidney can clear a specific molecule.
eGFR = [molecule]ᵤᵣᵢₙₑ x volume/[molecule]ₛₑᵣᵤₘ
Urine used is collected over a 24 h period
What are the properties of an ideal molecule used for estimating GFR?
- Released at a regular rate
- Not metabolized or filtered through glomerulus completely
- Not reabsorbed or secreted through tubules
What is the molecule used for GFR? Is there a better molecule? If so, why don’t we use that molecule instead?
Creatinine
Yes, inulin is a better molecule. However, it is not used because it is complicated and time consuming. Hence, it is only used for research.
What are the different stages of CKD and what do they tell us about the kidney function and eGFR?
1:
Normal to high kidney function, eGFR > 90
2:
Mild decrease in kidney function, 60-89
3a:
Mild to moderate decrease in kidney function, 45-59
3b:
Moderate to severe decrease in kidney function, 30-44
4:
Severe kidney dysfunction, 15-29
5:
End-stage renal disease, <15
What is the definition of GFR?
The clearance of a molecule only excreted by glomerulus and not reabsorbed/secreted by tubules
Why is creatinine clearance (CrCl) only an estimate of eGFR?
Creatinine is secreted by the tubules which results in an overestimate of the GFR.
CrCl = [Cr]ᵤᵣᵢₙₑ x volume/[Cr]ₛₑᵣᵤₘ
What are pre-analytical factors in CrCl?
- Errors in urine collection
- Increased tubular secretion of creatinine which happens when glomerular function worsens in kidney disease
Why is creatinine used?
- Filtered via glomerulus
- Secreted by renal tubules but not reabsorbed
- Eliminated by GI tract
- Constant and proportional to muscle mass
- Inversely proportional to eGFR
What is the formula used to calculate eGFR? What are the conditions to use this formula?
175 x sCr¹.¹⁵⁴ x age⁻⁰.²⁰³ x 0.742 (Female)
175 x sCr¹.¹⁵⁴ x age⁻⁰.²⁰³ x 1.212 (African American)
- [Cr] and [cystatin C] must be stable
- Only ages >18
- Cannot confirm normal
What are the different methods used to measure creatinine?
- Jaffe method
- Enzymatic method
- Mass spectrometry based method
How does the Jaffe method work to measure creatinine?
The reaction between creatinine and alkaline picrate results in a red-orange product that can be measured at 490 nm - 500 nm
What are some problems with the Jaffe method?
- Picrate can react with a lot of different molecules
- The reaction between creatinine and alkaline picrate is temperature dependent
What can we do to alleviate some of the problems that come with using the Jaffe method to measure creatinine?
Use the kinetic approach, because different reactants react with picrate at different times (ex. one at 20s, one at 80s), we can measure the rate of reaction at both of those times.
How does the enzymatic method work in measuring creatinine?
Creatinine + water ➔ Creatine
Creatine + water ➔ Sarcosine + urea
Sarcosine + oxygen + water ➔ formaldehyde + glycine + Peroxide
Indicator + Peroxide ➔ Oxidized indicator + water
What are some problems that come with the enzymatic method?
Strong reducing agents can react with peroxide
What are some problems with measuring creatinine?
- Dependent on muscle mass
- Can increase after eating meat
- Only can estimate GFR when renal function is stable and not ideal in the case of acute kidney injury
- Creatinine excretion is higher in males than women
What other substances can we use aside from creatinine?
Urea
How do we measure urea?
Urea reacts with water to form ammonium and carbonate
The concentration of ammonium is quantified
What are some problems with measuring urea?
High or low protein diet
GI bleeding
Hypovolemia
Dehydration
Congestive heart failure
Catabolic state
Severe liver disease
What does a high urea to creatinine ratio indicate?
Dehydration
What is another molecule we can use to estimate GFR?
Cystatin C
What are the benefits of cystatin C over creatinine for the estimation of eGFR?
Not affected by muscle mass
Why is cystatin C not widely used?
Not available everywhere
Measured by immunoassay hence, expensive
When do we use cystatin C?
Recommended test for ruling out CKD when diagnosis is not certain
What are other lab tests we can use to measure kidney function?
Electrolytes
Acid-base
Phosphate
Calcium
Hb
Urine output
Imaging
Urinalysis
What are the clinical manifestations of acute kidney injury? List the subcategories of acute kidney injury.
Rise in Cr concentration
OR
Decrease in urine output that happens in a few hours to days
Pre-renal: decreased blood flow to kidney
Renal: intrinsic diseases of kidney
Post renal: obstruction
What is the clinical definition of chronic kidney disease (CKD)?
Reduced renal function for at least 3 months from any cause
GFR < 60 mL/min/1.73m2
What are the lab parameters indicating CKD?
Hyperphosphatemia
Hypocalcemia
Anemia
Edema
What are the different glomerular diseases?
- Nephrotic syndrome
- Glomerulonephritis
What is nephrotic syndrome and what are the signs?
3.5g protein/ 24 h urine collection
Signs:
Proteinuria
Hypoalbuminemia
Hyperlipidemia
Edema
What is glomerulonephritis and what are the signs?
Inflammatory conditions of glomerulus
Signs:
Proteinuria
Hematuria
Oliguria
RBC casts
Azotemia
Hypertension
What is tubular necrosis and what causes it?
Damage to tubules
1. Acute kidney injury
2. Drug/toxins
What are the different types of renal tubular acidosis and what causes it?
Type 1:
Distal tubule unable to secrete H
Type 2:
PT unable to reabsorb bicarbonate
Type 4:
Hyporeninemic
Hypoaldosteronism
What are the different concentrations of K in renal tubular acidosis?
Type 1:
Very low
Type 2:
Low
Type 4:
High
