Biochemistry of the kidney

Question 1

What is the purpose of the glomerulus?

Answer 1

It is a filter

most of the filtrate is reabsorbed in the proximal collecting tubule and then it is fine tunes in the distal collecting tubule

Question 2

What are the two aspects of glomerular function?

Answer 2

1. How well the filtration works -> Glomerular filtration rate
2. Proteinuria - if there is too much protein in the urine, the filtration isnt working properly

Question 3

How is the glomerular function assessed?

Answer 3

GFR

Question 4

What is the ideal marker of GFR?

Answer 4

Appears at a constant rate
Be freely filtered at the glomerulus (if it isnt filtered then we cant identify it)
Not to be reabsorbed from the renal tubule (false low)
Now to be secreted by the renal tubule(false hgih)
Not undergo extra-renal elimination

Question 5

What is inulin?

Answer 5

Plant carbohydrate -> checks all the points of ideal marker for GFR

has to check inulin clearance - but has to be checked very frequently, not easy to measure, it is not endogenous (has to be injected to check for clearance)

Impractical for daily use

Question 6

What are the features of urea wrt ideal marker for GFR?

Answer 6

the end product of protein metabolism 
Very easy to measure
Endogenous
Freely filtered at the glomerulus
Not secreted into the renal tubule

Question 7

Why is urea not suitable to be an ideal marker for GFR ?

Answer 7

Doesn’t appear at a constant rate (dependent on the diet - if you eat meat it goes up)

Significantly absorbed from the renal tubule (especially from the area that isn’t working properly)

Undergoes significant extra-renal elimination - goes back to the gut

Question 8

What is the importance of creatinine?

Answer 8

Produced by the muscles. Increased muscle mass -> increased creatinine

Endogenous
Easy to measure
appears at a constant rate
freely filtered
not reabsorbed from the renal tubule
doesn't undergo extra-renal elimination

though -> secreted into the renal tubule

Question 9

What is a normal GFR?

Answer 9

GFR > 120 ml/min

Question 10

What happens to the creatinine when the GFR goes down?

Answer 10

Only a small change despite steep fall in GFR

But If GFR<15 the creatinine shoots up, by them biochemical kidney disease obvious

Question 11

What could the creatinine be for people before dialysis?

Answer 11

Predialysis creatine - 600-700 (micromol/L)

Question 12

What happens if the GFR 120 falling down to 60 (if the GFR falls down)?

Answer 12

not much change in the creatinine though about 50% of the kidney function lost

Question 13

What are the confounders of serum creatinine?

Answer 13

Muscle mass
Diet
Age
Sex
Ethnicity

Question 14

How do we get around the confounders of creatinine?

Answer 14

use proxies

Younger and male -> more creatinine than in older, females

Question 15

What is the eGFR?

Answer 15

dependent on the creatinine levels and the four variables (age, sex, diet, ethnicity)

even if creatinine normal, eGFR can change according to the MDRD (cant give a number if the creatinine >60 ml/L)

Question 16

What is the porblem in the sensitivity of creatinine to GFR?

Answer 16

Creatinine isn’t sensitive to the changes in the GFR until GFR is quite low

Question 17

What would the creatinine levels look like even if the GFR is 60?

Answer 17

it could be normal as creatinine isn’t really sensitive

Question 18

What is the solution to solving the problem of creatinine sensitivity?

Answer 18

Urinary creatinine clearance

Question 19

What is urinary creatinine clearance?

Answer 19

doesn’t have to be from the urine -> can be from anywhere (blood or faeces)

you can then workout what the urinary clearance is from that

Question 20

urine creatine clearance for the huge guy vs the lady

Answer 20

guy:
(6800micromol x 2500ml)/ 100 micromol(serum creatinine level) x 1440 min(no. of minutes in a day)) -> greather than the concentration in the blood) = 118 ml/ min

though he has filtered a lot of creatinine gfr is okay

Lady:

(4200 micromol (production of creatinine by muscle) x 2000 ml - urine volume for the day)/ 100 micromol (serum creatinine) x 1440 min) = 58 ml/ min

normal gfr regardless of higher creatinine levels

Question 21

How can CKD be classified wrt eGFR rate?

Answer 21

CKD 1 - >90
CKD 2 - 60-90
CKD 3 -30-60
CKD 4 -16-29
CKD 5 - <15

Question 22

How is eGFR better?

Answer 22

eGFR better than serum creatinine alone

even that is not accurate

Question 23

What is the use of protein?

Answer 23

Estimate of filtrate

24 hr urine collection

Question 24

How is the protein level assessed?

Answer 24

24 hr urine collection/

if >150 ml protein per day -> glomeruli not working properly

Question 25

is there a dipstick reading seen in microalbumnaria?

Answer 25

Dipstick reading for protein in a patient with diabetes -> doesn;t show wiht microalbuminaria

Question 26

Multiple myeloma

Answer 26

Malignancy in the plasma cells - pattern V, big protein band- immunoglobulin produced in gross excess, skeleton produces lesions in the bone (holes in the skeleton)

The overprdtn of immunoglobulin is so high that the glomeruli can’t seive it and thus there is a proteinuria

normally how to recognise plasma cells - eccentric nuclei (not in the middle of the cell, at one side of the cell)

Multiple types of white cells -> b lymphocytes -> plasma cells -> immunoglobulins

Question 27

Nephrotic syndrome

Answer 27

overflow proteinuria, proteins appearing in the filtrate in large quantities

the oncotic pressure of the blood side ofthe capillary membrane is lost and the fluid lost from the capillary to the interstitial fluid. lost lots of protein =s in the urine, hence blood less protein hence fluid flows from the blood to the interstitial fluid

Question 28

What is the term for extreme oedema resulting from nephrotic syndrome?

Answer 28

anacarca - seen in pitting oedema in feet and ankles

Question 29

What is microalbuminuria?

Answer 29

Abnormally high production but less than what is detected in a dipstick test

earliest expression of diabetic nephropathy

if you prescribe ACEi to patients with diabetes -> to slow down the progression of diabetic nephropathy to the fullest form

Question 30

What is the tubular function?

Answer 30

loss of blood - pre-renal problems -> loss of renal function (tubules not working as not enough blood)
post-renal - can develop intrinsic renal problems as well

Question 31

How are the pathologies in the kidney classified?

Answer 31

Pre-renal
post-renal
renal

Question 32

Tubular function

Answer 32

Urine osmolality -> patient was reabsorbing water from the filtrate making the filtrate more concentrated

comparing the serum and urine

the most similar they are -> the worse it is, but tif they are different -> the better the renal function is

Question 33

What is the commonest proteinuria?

Answer 33

glomerular proetinuria

Question 34

How do we assess glomerular function?

Answer 34

GFR

Proetinuria

Question 35

How do we assess tubular function?

Answer 35

Via urine and serum osmolality comparison

the more similar the values of urine and serum osmolality, the worse the function of the kidney