Nephrology and toxicology Notes for Internal State Exam
1. Functional investigations of the urinary system
Assessment of renal function:
GFR – product of average filtration rate of each nephron, multiplied by the number of
nephrons in the kidney.
o Normal GFR – 130ml/min for men
o 120/ml/min for women
o GFR cannot be measured directly it is measured as urinary clearance
Urinary clearance – amount of substance x excreted in the urine can be calculated as product
of urinary flow rate (V) and urinary concetration (ux): Cx = (Ux x V)Px
Plasma clearance
Exogenous filtration markers – inulin, iothalamate, 99mTc-DTPA bolus, 51Cr-EDTA, Iohexal
Endogenous filtration markers – creatinine, cystatin C
Markers of tubular damage – cystatin C, B2M, interleukin-18, retinol binding protein, a1-
macroglobulin
Urinalysis – colour – medications that change colour of urine include:
o Rifampicin yellow-orange red
o Phenytoin red
o Chloroquinine and nitrofurantoin brown
o Triamterene, propofol green
Urianlysis – turbidity – high turbidity due to excess particles – cells, casts, crytstals, bacteria.
Odor – due to ammnonia, usually due to UTI, sweet odor, ketones
Specific gravity – low – urinary dilation, DI, water intoxication.
pH – low – metabolic acidosis, high, renal tubular acidosis
protein – physiologic proteinuria does not exceed 150mg/24hr
o 24 hour protein excretion, 24hr urinary collection for protein measurement is the
gold standard test for proteinuria.
Protein-creatinine ratio, microalbuminuria, tubular proteins
Urine microscopy – RBC, WBC, casts, crystals, tubular cells, epithelial cells
o Hyaline casts, normal
o Hyaline granular casts – renal disease + GN
o Granular casts – acute tubular necrosis
o Waxy casts – renal impairment
o Fatty casts – glomerular disease
o RBC casts – bleeding or interstitial nephritis
o Leukocyte casts – pylenephritis, nephritis
Crystals – uric acid, calcium oxalate, calcium phosphate, cholesterol, struvite (triple
phosphate)
Imaging methods
Intravenous urography (not so often used)
o Retrograde pyelography
o Anterograde pyelography – via percutaneous renal puncture
o Cystography
Ultrasound + doppler , CT, MRI, nuclear medicine scanning most often used
Angiography – gold standard for diagnosis of renal artery stenosis and fibromuscular dysplasia
Nuclear medicine scans – renal scintigraphy, with MAG3 99mTcDTPA, renogram
Voiding cystography (for VUR), renal biopsy
, 2. Hematuria. Proteinuria
Hematuria = presence of red blood cells in the urine. Healthy individuals may have
occasional red blood cells in the urine, up to 12,500 cells per ml. the presence of visible
(macroscopic) hematuria or non-visible (microscopic) hematuria warrants further
investigation as it indicates significant bleeding from somewhere in the urinary tract.
Microhematuria – changes only seen on microscopy or urine dipstick
Macrohematuria (gross hematuria) – visible discolouration due to frank blood in the
urine
Glomerular hematuria – damage to the glomeruli
Non-glomerular hematuria – damage to the kidneys or upper or lower urinary tract
Other causes of red urine not due to hematuria are drug induced (rifampicin, phenytoin) or
discolouration due to myoglobinuria, porphyria or beetroot consumption.
Types of hematuria
Initial hematuria – occurs at the beginning of weeing, disappears by end
o Due to urethral injury
Terminal hematuria – passage of blood or clots only during the last part of voiding
o Damage to the bladder neck, prostate or trigone e.g. prostatitis, BPH
Total hematuria – passage of blood or clots through entire micturition
o Due to damage to bladder, ureter, kidney – UTI, urolithiasis, Polycystic
disease
Painless Hematuria – without any symptoms
o Suggests malignancy – transitional cell cancer, renal cell carcinoma, prostate
cancer
According to origin
Glomerular hematuria
o Nephritic syndrome
characteristic of glomerulonephritis
Hematuria + proteinuria is considered GN until proven otherwise
o Isolated hematuria
Due to strenuous exercise infection
If persistent – IgA nephropathy, Alport syndrome, thin basement
membrane disease
Non glomerular hematuria
o Urolithiasis
o Infection – cystitis, urethritis, prostatitis
o Malignancy – urothelial cancer, renal cell Ca, prostate Ca, wilms tumor
o Coagulation disorders
o Urinary tract obstruction
o Polycystic kidney disease
o Renal papillary necrosis – due to sickle cell disease, pyelonephritis, DM,
analgesics
o Drug induced – cyclophosphamide, sulfonamides, warfarin, heparin
,Ask about additional symptoms, family history, travel history
Urine dipstick – shows heme in urine
Urine sediment – to confirm hematuria via microscopy, if there >3RBC/HPF (high power
field)
, Proteinuria
Proteinuria = urinary protein excretion of >150mg/day
Causes – fever, exercise, dehydration, GN, multiple myeloma
There are 3 different pathophysiological mechanisms that may lead to proteinuria
o Glomerular
o Tubular
o Overflow (overproduction of low molecular weight proteins)
1. Functional investigations of the urinary system
Assessment of renal function:
GFR – product of average filtration rate of each nephron, multiplied by the number of
nephrons in the kidney.
o Normal GFR – 130ml/min for men
o 120/ml/min for women
o GFR cannot be measured directly it is measured as urinary clearance
Urinary clearance – amount of substance x excreted in the urine can be calculated as product
of urinary flow rate (V) and urinary concetration (ux): Cx = (Ux x V)Px
Plasma clearance
Exogenous filtration markers – inulin, iothalamate, 99mTc-DTPA bolus, 51Cr-EDTA, Iohexal
Endogenous filtration markers – creatinine, cystatin C
Markers of tubular damage – cystatin C, B2M, interleukin-18, retinol binding protein, a1-
macroglobulin
Urinalysis – colour – medications that change colour of urine include:
o Rifampicin yellow-orange red
o Phenytoin red
o Chloroquinine and nitrofurantoin brown
o Triamterene, propofol green
Urianlysis – turbidity – high turbidity due to excess particles – cells, casts, crytstals, bacteria.
Odor – due to ammnonia, usually due to UTI, sweet odor, ketones
Specific gravity – low – urinary dilation, DI, water intoxication.
pH – low – metabolic acidosis, high, renal tubular acidosis
protein – physiologic proteinuria does not exceed 150mg/24hr
o 24 hour protein excretion, 24hr urinary collection for protein measurement is the
gold standard test for proteinuria.
Protein-creatinine ratio, microalbuminuria, tubular proteins
Urine microscopy – RBC, WBC, casts, crystals, tubular cells, epithelial cells
o Hyaline casts, normal
o Hyaline granular casts – renal disease + GN
o Granular casts – acute tubular necrosis
o Waxy casts – renal impairment
o Fatty casts – glomerular disease
o RBC casts – bleeding or interstitial nephritis
o Leukocyte casts – pylenephritis, nephritis
Crystals – uric acid, calcium oxalate, calcium phosphate, cholesterol, struvite (triple
phosphate)
Imaging methods
Intravenous urography (not so often used)
o Retrograde pyelography
o Anterograde pyelography – via percutaneous renal puncture
o Cystography
Ultrasound + doppler , CT, MRI, nuclear medicine scanning most often used
Angiography – gold standard for diagnosis of renal artery stenosis and fibromuscular dysplasia
Nuclear medicine scans – renal scintigraphy, with MAG3 99mTcDTPA, renogram
Voiding cystography (for VUR), renal biopsy
, 2. Hematuria. Proteinuria
Hematuria = presence of red blood cells in the urine. Healthy individuals may have
occasional red blood cells in the urine, up to 12,500 cells per ml. the presence of visible
(macroscopic) hematuria or non-visible (microscopic) hematuria warrants further
investigation as it indicates significant bleeding from somewhere in the urinary tract.
Microhematuria – changes only seen on microscopy or urine dipstick
Macrohematuria (gross hematuria) – visible discolouration due to frank blood in the
urine
Glomerular hematuria – damage to the glomeruli
Non-glomerular hematuria – damage to the kidneys or upper or lower urinary tract
Other causes of red urine not due to hematuria are drug induced (rifampicin, phenytoin) or
discolouration due to myoglobinuria, porphyria or beetroot consumption.
Types of hematuria
Initial hematuria – occurs at the beginning of weeing, disappears by end
o Due to urethral injury
Terminal hematuria – passage of blood or clots only during the last part of voiding
o Damage to the bladder neck, prostate or trigone e.g. prostatitis, BPH
Total hematuria – passage of blood or clots through entire micturition
o Due to damage to bladder, ureter, kidney – UTI, urolithiasis, Polycystic
disease
Painless Hematuria – without any symptoms
o Suggests malignancy – transitional cell cancer, renal cell carcinoma, prostate
cancer
According to origin
Glomerular hematuria
o Nephritic syndrome
characteristic of glomerulonephritis
Hematuria + proteinuria is considered GN until proven otherwise
o Isolated hematuria
Due to strenuous exercise infection
If persistent – IgA nephropathy, Alport syndrome, thin basement
membrane disease
Non glomerular hematuria
o Urolithiasis
o Infection – cystitis, urethritis, prostatitis
o Malignancy – urothelial cancer, renal cell Ca, prostate Ca, wilms tumor
o Coagulation disorders
o Urinary tract obstruction
o Polycystic kidney disease
o Renal papillary necrosis – due to sickle cell disease, pyelonephritis, DM,
analgesics
o Drug induced – cyclophosphamide, sulfonamides, warfarin, heparin
,Ask about additional symptoms, family history, travel history
Urine dipstick – shows heme in urine
Urine sediment – to confirm hematuria via microscopy, if there >3RBC/HPF (high power
field)
, Proteinuria
Proteinuria = urinary protein excretion of >150mg/day
Causes – fever, exercise, dehydration, GN, multiple myeloma
There are 3 different pathophysiological mechanisms that may lead to proteinuria
o Glomerular
o Tubular
o Overflow (overproduction of low molecular weight proteins)
