What do the kidneys produce that regulate blood cell count?
What do the kidneys produce that affects Vit D synthesis?
1 alphahydroxylase (activates VitD)
How can kidney function be known?
How much fluid is being filtered? (GFR i.e how much fluid is it filtering per minute)
How leaky is the kidney?
How good is the kidney at clearing waste
How is GFR assessed?
What is the limitations of using creatinine clearance for understanding renal function?
It can not detect rapid, acute, injury to the kidney because creatinine levels take time to reflect changes in overall state of the kidneys.
Someone who has more muscle will produce more creatinine and elderly have higher creatinine clearance than younger people.
What are the 3 main functions of the kidney?
What is GFR?
Amount of blood cleared through kidney per minute and this cna only be done through the kidney.
Formula for renal clearance
C = UV/P
C = clearance U = Urine concentration (mmol/L) V = Urine volume flow rate (ml/min) P = Plasma concentration (mmol/L)
How can GFR be estimated?
What affects renal clearance of creatinine clearance? How can this knowledge be used?
(Muscle breakdown elevates creatinine levels)
Instead of looking at standard levels finding history of creatine level changes within a single individual is a good way of measuring its changes.
What is being done to measure changes in eGFR more accurately?
What are the limitation?
Being standardised for age, race, and sex.
Routinely reported with creatinine which is unreliable for short term changes.
Not reliable for extremes of body size/age or acute kidney to injury
Not validated in children or pregenancy
What is the Cockroft and Gault Creatinine Clearance?
A way to estimate GFR. 1.23(140-age) x Mass (kg) / pCreatining(umol/L)
In females x1.04
What is the Cockroft and Gault Creatine Clearance formula used for?
What is Cr Clearance formula?
Cr Cl (ml/min/1.73m2) = U Cr x u Vol x 1.73 /P Cr x T x BSA
Corrected for surface area (height and weight)
Reference intervals based on plasma and urine samples which makes it inaccurate due to inaccurate timing on samples.
What is the problem with using urea to estimate GFR?
Rate of production is not constant; 40 - 50% of urea is reabsorbed which makes it less useful as a measurement.
It is affected by Volume status/hydration protein intake tissue breakdown steroids GI haemorrhage Liver disease
How can tubular function be tested?
Plasma U + E’s
Urine pH, anion gap, Na, Cl, HCO3, aminoacids
How much protein gets into urine each day?
Normally only a small amount of protein gets into the urine (20 - 150mgs/day) This is predominantly albumin.
What are the mechanisms of proteinuria?
Overflow (lots in the blood emptying into urine)
What happens to urine when it is high in protein?
Becomes frothy and bubbly
What is the cause of glomerular proteinuria?
What happens during glomerular proteinuria?
Loss of large proteins of increasing molecular weight starting with albumin.
What is lost during tubular proteinuria?
Loss of increasing amounts of low MW proteins that don’t include albumin
What are conditions that cause tubular proteinuria?
Fanconi syndrome and lead toxicity
What is lost during overflow proteinuria?
Loss of low MW proteins with high plasma concentrations
Free haemoglobin, myoglobin, immunoglobulin light chains and amylase
What are the types of benign proteinuria?
Orthostatic proteinuria is proteinuria caused by change in position from supine to standing.
Other benign glomerular proteinurias such as fever or exercise induced proteinuria (<1g/day loss)
How much protein is typically lost by a young adult from benign orthostatic proteinuria?
The proteinuria can be up to 1g/day
How is protein checked for in urine?
ACR - albumin / creatinine ratio (on first morning spot urine sample recommended screening test
What are some other tests for detection of proteinuria?
Spot protein/Cr ratio
24 hour urine albumin/protein concentration which is an inaccurate collection
Dipstick test which is semi-quantitative protein non-specific or albumin specific
What is microalbuminuria associated with?
Associated with increased renal and CV risk
What kind of proteinuria does nephrotic syndrome cause?
What causes nephrotic syndrome?
Minimal change disease
Focal Segmental Glomerulosclerosis
How is nephrotic syndrome diagnosed?
Hypoalbuminuria and in turn peripheral oedema
Other features include hypercholesterolaemia, lipiduria, thrombosis, and infection
What is the difference between renal factors and rerenal factors for acute kidney disease?
Caused by problems with glomeruli and tubules
Prerenal is due to drop in blood pressure in the kidneys
What happens if the cause of acute kidney injury is pre-renal?
The kidney tries to reabsorb as much sodium and water as possible resulting in concentrated urine production and elevated BP
What is chronic kidney disease defined as?
GFR < 60 for more than 3 months
Or evidence of kidney damage with or without decreased GFR that is present for more than 3 months
What is used as evidence of chronic kidney disease?
Haematuria after exclusion of urological causes
What are the most common causes of End Stage KD in Australia?
Polycystic kidney disease
How is Chronic Kidney Disease staged?
Stage 1 (>90 GFR with evidence of kidney damage)
Stage 2 (60 - 89 with evidence of kidney damage)
Stage 3a (45 - 59)
Stage 3b (30 - 44)
Stage 4 (15- 29)
Stage 5 (ESKD <15)
*it starts to get severe from 3b onwards
What changes in the body during CKD?
In the blood we have more Urea, Creatinine, potassium, urate, and phosphate.
Water drinking must be monotiored more closely due to inability to regulate water levels.
Sodium reabsorption may decrease
increase in parathyroid horomone
Decrease in haemoglobin as a result of less EPO production
What are the most common causes of renal stones?
Calcium oxalate or phosphate stones
Struvite stones associated with infection (Proteus UTI)
Uric acid stones
What are the risk factors for renal stones?
Low urine flow
Increased urine calcium, oxalate, uric acid, cysteine
Decreased citrate, Mg, glycoproteins
Abnormal pH (alkaline risk increases Calcium oxalate and struvite stones, acidic risk increases uric acid and cystine stones)
Infection (such as proteus which produces urease)
Diet high in oxalate, animal protein and salt or low in calcium
How can renal stones be investigated?
Test for plasma Calcium phosphate, and uric acid.
24 hour urinary calcium and oxalate
Spot urine microscopy, culture, pH
How is acid removed from the body?
Breathing out CO2 (to remove volatile acids) this method eliminates 10000 mmol of H+ per day
Nonvolatile acids are eliminated by the kidneys such as sulphuric and phosphoric acid.
Organic acids are too negligable to affect pH of the blood much but they are often oxidised into CO2 and H2O
What are the 3 main methods for pH balance in the body?
Blood buffers which act within seconds such as HCO3, proteins, and HPO4
Lungs through CO2 excretion
Kidneys which take days to ramp up and allow absorption of bicarb and excretion of other stuff
What does analysis of pH tell us?
If it is high then it means high blood alkalosis
If it is low acidosis
What does analysis of PCO2 tell us?
High means respiratory acidosis
Low means respiratory alkalosis
What does analysis of bicarb tell us?
High means alkalosis
Low means acidosis
What does analysis of base excess tell us?
Negative means metabolic acidosis
Positive means metabolic alkalosis
How can you tell if alkalosis/acidosis metabolic or respiratory?
Bicarb means metabolic
CO2 means respiratory
Compensation is possible from one system or the other
What causes metabolic acidosis?
Increased production of acid through lactica acidosis, ketoacidosis, or toxins such as ethanol, methanol, salicylate, ethylene glycol
Decreased excretion of acid
Loss of bicarbonate
What are the causes of Metabolic Acidosis?
Increased anion gap metabolic acidosis
Methanol Uraemia Diabetic ketoacidosis Propylene glycol and other glycols Iron, isoniazid, inborn errors of metabolism Lactic acidosis Ethanol and other alcohols Salicylates
Normal anion gap metabolic acidosis
Diarrhoea RTA Addisons Acetazolamide Ammonium Cl
What causes metabolic alkalosis?
Loss of acid (GIT - vomiting, nasogastric suction, kidney - diuretic therapy, mineralocorticoid excess or high dose hydrocorticosterone)
Increased exogenous bicarbonate (Oral/IV bicarbonate, antacid therapy, organic acid salts)
What causes metabolic alkalosis? (Pneumonic
Upper GI loss
Endocrine (conns, cushings, CAH)
What causes respiratory alkalosis?
Pregnancy (Due to progesterone)
Acute pulmonary oedema