L80 - Biochemical Investigation of Urogenital Diseases I Flashcards

(102 cards)

1
Q

Give examples of reabsorption in kidney?

A

Glucose, amino acids, electrolytes, proteins

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2
Q

What are the 2 metabolic functions of the kidney?

A

Synthetic: glutathione, glyconeogenesis, ammonia

Catabolic: hormones, cytokines

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3
Q

Sequence of intermediates in Vitamin D production? Start from Previtamin D3 in skin.

A

Previtamin D3 [skin] > Vitamin D3

+ Vitamin D2 and D3 from diet

> > 25-hydroxyvitamin D [liver]

> > 1,25- hydroxyvitamin D [Kidney] (active form)

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4
Q

What are some endocrine functions of kidney?

A

Erythropoietin synthesis, activation of vitamin D,

renin release

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5
Q

What is the urine formation rate?

A

~ 1.5 L/day

1 mL/min

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6
Q

What is the normal GFR?

A

100-125mL/min/1.73m^2

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7
Q

Equation for filtration fraction?

A

filtration fraction is the ratio of the glomerular filtration rate (GFR) to the renal plasma flow (RPF)

FF = RPF/ GFR

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8
Q

What is the normal Hematocrit (Hct) level?

A

Ratio of the volume of red cells to the volume of whole blood

45% to 52% for men and 37% to 48% for women.

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9
Q

What is the normal Renal blood flow rate?

A

1200 mL/min

~ 20% Cardiac Output

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10
Q

How much H2O in glomerular ultrafiltrate is reabsorbed by the kidney??

A

99%

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11
Q

How is Minimal Volume of Urine Water calculated?

A

= Waste product of metabolism (mOsm/day) / Maximal urinary concentration attainable

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12
Q

What is the minimal vloume of urine water excreted per day?

A

about 400 mL/day

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13
Q

Lower than ~ 400 mL/day/ minimal volume of urine water excreted leads to what?

A

Azotaemia is inevitable with daily Urinary Output < 400 mL

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14
Q

Purpose of assessing GFR?

A

assess the severity and course of renal disease

adjust the dosage of drugs primarily excreted by kidney (or highly nephrotoxic)

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15
Q

Describe GFR?

A

Volume of volume of glomerular filtrate produced by BOTH kidneys per unit time

  • glomerular filtrate = Volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule*
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16
Q

Define renal clearance?

A

Clearance of a substance:

The volume of plasma
from which that substance is completely cleared by the kidneys per unit time

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17
Q

What are the ideal parameters of a substance used to measure GFR?

A
  • Freely filtered at the glomerulus
  • Not reabsorbed by the renal tubules
  • Not secreted by the renal tubules or other
    organs of the body
  • Not synthesized or metabolized by the renal
    tubules
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18
Q

What is the formula for GFR?

A

M = substance filtered freely

GFR = ( UM x V ) / PM

UM = conc of M in Urine 
PM = conc. of M in Plasma

V = volume of Urine per unit time

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19
Q

If a substance is ideal for GFR, what is the rate of excretion and filtration of that substance?

A

Mass excreted / Time = Mass filtered / Time

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20
Q

What is the formula betwen mass, volume and concentration?

A

Mass = volume x concentration

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21
Q

If a substance is freely filtered, what is the concentration of it in the filtrate vs in plasma?

A

conc in filtrate identical to the conc in plasma

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22
Q

What does the Maintenance of a normal GFR depend on?

A

adequate number of nephrons

Intact glomerular function

normal renal perfusion

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23
Q

Fall in GFR is associated with raised plasma levels of what?

A

retention of metabolic wastes

> > raised Creatinine and Urea levels in plasma

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24
Q

A decreasing GFR precedes __?

A

Renal failure in all forms of progressive renal disease

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25
Level of GFR is a strong predictor of __?
the time to onset of renal failure
26
Name 3 substances used for GFR measurement?
Inulin Urea Creatinine
27
Urine collected over 10 hours = 1 Liter Urine INULIN concentration = 300 mg/L Concentration of INULIN in Plasma = 4 mg/L Calculate GFR?
UV/P = GFR Volume per hour = 1/10 = 0.1 U = 300mg/L P = 4mg/L 300 x 0.1 / 4 = 7.5L/ hour = 125 mL/min
28
If inulin was secreted in body, what would the GFR be?
Higher than true GFR
29
Why is inulin not used clinically?
requires infusion of the polysaccharide at a continuous and constant rate for several hours >> inconvenient and costly
30
Why is Creatinine used over inulin? Limitation?
released into the blood at a relatively constant rate >> endogenous, no need for intravenous infusion
31
Limitation of using creatinine for GFR?
Creatinine Clearance only gives an approximation of the true GFR ** small amount of Creatinine is secreted by the renal tubules ** overestimate the true GFR
32
Why is very accurate GFR not required clinically?
requires blood sampling and timed urine collections >> error-prone due to inaccurate timing of urine collection
33
2 ways to measure GFR?
Creatinine in blood (plasma / serum) or measurement of Creatinine Clearance (CrCl)
34
How does creatinine flow to kidneys?
not protein bound, non-polar, small size (113 D) freely filtered and carried in blood, filtrate
35
Relationship between Plasma creatinine and GFR?
Plasma CREATININE is inversely related to GFR
36
Show how Plasma CREATININE is inversely related to GFR?
Creatinine Excretion = Creatinine Filtered (GFR x Plasma Creatinine Conc) GFR x Plasma Creatinine = Constant so GFR = Constant / Plasma Creatinine
37
Why creatinine not perfect for detecting changes in GFR?
Inability to detect mild to moderate reduction in GFR GFR has to drop by 40-50% before plasma creatinine levels raise
38
What influences creatinine production?
muscle mass Difference in Age, gender and ethnic
39
Rise in GFR by how much warrants an investigation
rise in blood Creatinine of ≥ 20% from previous levels ***even if the Creatinine level still remains within the reference interval***
40
What is Flag L and Flag H?
H = abnormally high creatinine L = abnormally low ''
41
Why is GFR using creatinine not great for giving signs of acute kidney function deterioration?
Early acute kidney injury >> GFR reduced but not enough time for creatinine to accumulate >> cannot reflect severity of kidney disease
42
Blood level rise causes what to rise?
Renal tubular and gastrointestinal mucosal secretion
43
trimethoprim (UTI drug), H2-blocker cimetidine can influence GFR, how?
increase the level of the | serum creatinine by decreasing creatinine secretion
44
What other biomarkers can interfere with creatinine levels?
very high level of bilirubin and acetoacetate lead to spuriously low and high creatinine results
45
Describe the relationship between GFR and serum creatinine in acute kidney disease?
GFR may fall considerably before serum creatinine is significantly increased
46
What changes in muscle mass and kidney status leads to increased plasma creatinine?
Normal muscle mass + diseased kidneys Increased muscle mass + normal kidneys Reduced muscle mass + diseased kidneys
47
What change in muscle mass and kidney status can mask kidney disease and poor function?
Reduced muscle mass + Diseased kidney The serum creatinine level is low due to low muscle mass, but diseased kidney removes less creatinine >> mask disease
48
Compare a skinny vs muscular person, at the same rate of decline in GFR, the skinny person's serum creatinine level increases at higher or lower GFR than muscular?
Lower
49
Change in creatinine due to: aging?
Decrease
50
Change in creatinine due to: Female Sex
Decrease
51
Change in creatinine due to: Muscular body
Increase
52
Change in creatinine due to: Amputation
Decrease
53
Change in creatinine due to: Obesity
No change
54
Change in creatinine due to: Malnutrition, inflammation, deconditioning
Decrease
55
Change in creatinine due to: Neuromuscular diseases
Decrease
56
Change in creatinine due to: Vegetarian diet
Decrease
57
Change in creatinine due to: Ingestion of cooked meat
Increase
58
What is urea made from?
waste product of amino acid metabolism, | synthesized by the liver from ammonia and CO2
59
Urea clearance depends on what?
Urine Flow Rate
60
Movement of urea in kidneys?
Filtered freely by the glomeruli readily diffuses back into the circulation through renal tubular membrane
61
Plasma urea Excretory load is dependent on?
protein intake net body protein metabolism
62
Name 2 conditions that raises plasma urea levels?
Cushing syndrome, severe burn raised urea levels due to accelerated protein breakdown
63
How does kidney disease impact plasma urea level?
Kidney disease > decrease Renal perfusion or nephron no. > More urea diffuse back to plasma > raise plasma urea level
64
Why is urea not good as a GFR indicator?
1. Decrease production or low protein intake >> lower plasma urea level to falsely indicate renal insufficiency 2. GFR has to drop 40% before plasma urea rises 3. Increase production or high protein intake rises plasma GFR > mask renal impairment
65
List factors that raises plasma urea levels?
* High Protein Diet * Tissue Trauma * Glucocorticoids * Tetracycline * Gastrointestinal Bleeding
66
List factors that lowers plasma urea levels?
* Liver Disease | * Malnutrition
67
What does Renal function test profile?
measurement of Creatinine and Urea conc in serum/plasma | also Na+, K+, Cl-, HCO3-
68
Why is RFT convenient but rather insensitive?
significant reduction of GFR but levels still within reference Subject to various factors independent of renal function
69
Unit of Creatinine clearance?
mL/min
70
Name 1 pro and 2 cons of creatinine clearance as estimation of GFR?
Pro: - More reliable than formula-predicted GFR Cons: - 24-hour urine collection is inconvenient and error-prone - Measurement Uncertainty may be up to 30%
71
What is Cockroft and Gault formula based on?
plasma / serum Creatinine, Age, Body Weight, Gender (diff. equations for adults and children)
72
What is good about the MDRD equations for eGFR?
more sensitive than plasma / serum Creatinine especially in detecting mildly impaired GFR
73
GFR estimated by Cockroft and Gault formula tend to ____ GFR in advanced renal failure?
overestimate GFR in advanced renal failure
74
Cockrodt and Gault formula correlates better with measure GFR provided__?
Renal impairment is not severe and relatively stable No inhibition of tubular secretion of creatinine by medications Plasma [creatinine] is not within normal range
75
Difference in what Cockroft and Gault meansures vs MDRD?
``` MDRD = eGFR Cockroft = creatinine clearance ```
76
Name 4 pros of the MDRD eGFR formula?
- No need for timed urine collection - No need for body weight - Adjusted for body size (to 1.73m^2 standard) - Evaluated in subjects with varyinging renal insufficiency
77
Name 1 con of the MDRD eGFR formula?
Not validated in subjects <18 and >70 yrs, pregnant women
78
What is needed to be applied to the MDRD eGFR formula for Asians?
Asian ethnic co-efficient
79
What is the advantage of CKD-EPI over MDRD?
much less bias at | eGFR greater than 60ml/min/1.73m2
80
Name 2 benefits of CKD-EPI?
Minimising the over-diagnosis of CKD with the MDRD equation Lower prevalence of CKD and better risk prediction
81
Out of all the formulas, which one is now used for eGFR?
CKD-EPI equation
82
Name of formula for eGFR in children?
Schwartz formula for estimation of GFR in Children
83
What does the Schwartz formula include as metrics?
serum Creatinine (mg/dL), child’s height (cm) and a Constant (k) k is a constant that depends on muscle mass
84
Define CKD?
abnormalities of kidney structure or function, present for >3 months, with implications for health.
85
How much Albuminuria in CKD?
Albuminuria >30 mg/day
86
Why is Plasma Creatinine & Formula-predicted GFR not good for acute renal failure?
very rapid deterioration in renal function may be underestimated by the eGFR
87
What is Goulash effect?
80% rise in creatinine after 300g of cooked beef
88
How to limit Goulash effect?
Less variability in early morning creatinine
89
How much does Strenuous exercise increase creatinine?
14%
90
Which patients are harder to measure muscle mass?
``` oedematous patients Late pregnancy severe muscle wasting amputee extreme body habitus ```
91
What diseases can highly affect plasma creatinine?
liver disease profound hyperbilirubinaemia
92
What drugs can affect creatinine ?
Drugs inhibiting tubular creatinine secretion | e.g., trimethoprim, cimetidine, probenecid, amiloride
93
Factors affecting tubular secretion of creatinine?
Only one: Drugs that induce inhibition of secretion e.g. fenofibrate
94
Factors affecting extra-renal elimination of creatinine?
Dialysis Drugs inhibit gut creatinase in bacteria Increase by large volume losses of extracellular fluid
95
Main use for Cockroft & Gault formula?
Widely accepted for drug-dosing | decisions
96
Main use for Creatinine Clearance by timed urine collection?
For extremes of body composition
97
Gold standard for GFR measurement?
GFR measured by | infusion studies
98
Cystatin C is made where? Affected (or not) by what?
Cysteine protease inhibitor Synthesized by all nucleated cells and produced at a constant rate Not affected by muscle mass, gender and diet
99
What increases Cystatin C by a small amount?
modest increase in production is seen in obesity, | hyperthyroidism, and inflammation
100
Renal circulation of Cystatrin C?
Freely filtered at glomerulus Reabsorbed and metabolized by proximal tubules only a minute amount present in urine
101
What does Cystatin C measure/ mark for?
Increases in urinary excretion= marker for PCT injury or dysfunction
102
Con of Cystatin C?
relatively high assay cost Assay not widely available.