Biochemistry of the kidney Flashcards
What is the purpose of the glomerulus?
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
What are the two aspects of glomerular function?
- How well the filtration works -> Glomerular filtration rate
- Proteinuria - if there is too much protein in the urine, the filtration isnt working properly
How is the glomerular function assessed?
GFR
What is the ideal marker of GFR?
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
What is inulin?
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
What are the features of urea wrt ideal marker for GFR?
the end product of protein metabolism Very easy to measure Endogenous Freely filtered at the glomerulus Not secreted into the renal tubule
Why is urea not suitable to be an ideal marker for GFR ?
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
What is the importance of creatinine?
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
What is a normal GFR?
GFR > 120 ml/min
What happens to the creatinine when the GFR goes down?
Only a small change despite steep fall in GFR
But If GFR<15 the creatinine shoots up, by them biochemical kidney disease obvious
What could the creatinine be for people before dialysis?
Predialysis creatine - 600-700 (micromol/L)
What happens if the GFR 120 falling down to 60 (if the GFR falls down)?
not much change in the creatinine though about 50% of the kidney function lost
What are the confounders of serum creatinine?
Muscle mass Diet Age Sex Ethnicity
How do we get around the confounders of creatinine?
use proxies
Younger and male -> more creatinine than in older, females
What is the eGFR?
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)
What is the porblem in the sensitivity of creatinine to GFR?
Creatinine isn’t sensitive to the changes in the GFR until GFR is quite low
What would the creatinine levels look like even if the GFR is 60?
it could be normal as creatinine isn’t really sensitive
What is the solution to solving the problem of creatinine sensitivity?
Urinary creatinine clearance
What is urinary creatinine clearance?
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
urine creatine clearance for the huge guy vs the lady
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
How can CKD be classified wrt eGFR rate?
CKD 1 - >90 CKD 2 - 60-90 CKD 3 -30-60 CKD 4 -16-29 CKD 5 - <15
How is eGFR better?
eGFR better than serum creatinine alone
even that is not accurate
What is the use of protein?
Estimate of filtrate
24 hr urine collection
How is the protein level assessed?
24 hr urine collection/
if >150 ml protein per day -> glomeruli not working properly
is there a dipstick reading seen in microalbumnaria?
Dipstick reading for protein in a patient with diabetes -> doesn;t show wiht microalbuminaria
Multiple myeloma
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
Nephrotic syndrome
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
What is the term for extreme oedema resulting from nephrotic syndrome?
anacarca - seen in pitting oedema in feet and ankles
What is microalbuminuria?
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
What is the tubular function?
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
How are the pathologies in the kidney classified?
Pre-renal
post-renal
renal
Tubular function
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
What is the commonest proteinuria?
glomerular proetinuria
How do we assess glomerular function?
GFR
Proetinuria
How do we assess tubular function?
Via urine and serum osmolality comparison
the more similar the values of urine and serum osmolality, the worse the function of the kidney
