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Dr Yolandie Hayden
Chemical Pathologist
Department Chemical Pathology, UFS
Aug2014
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2016-11-03
Structurally
Glomerulus
Tubuli
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Glomerulus
Glomerulus
Glomerular filtrate (GF) is an ultra filtrate of
plasma; that is, it has a similar composition to
plasma except it is almost free of proteins.
Proteins with mol mass <65 kDa (smaller than
albumin) will be filtered, except if strongly
negatively charged.
The normal glomerular filtration rate (GFR) is
approximately 120 mL/min, equivalent to a
volume of about 170 L/24 h.
However urine production is only 1 2 L/24 h,
depending on fluid intake.
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Tubuli
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Tubuli
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Loop of Henle
Descending limb passive reabsorption of
water.
Ascending limb chloride ions accompanied
by sodium, are pumped out of the loop of
Henle into surrounding interstitial fluid
The ascending limb is impermeable to water.
Thus the tubular fluid becomes increasingly
dilute as it passes up the loop of Henle.
Tubuli
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Tubuli
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Renin
Erythropoietin
Vit D (1,25 dihydroxycholecalciferol)
Secretion of these may be altered in renal
disease.
Secretion and inactivation of other hormones
may also be affected in renal disease.
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Urea
Dietary and Endogenous amino acids are important sources of energy via
the gluconeogenic pathway
This is detoxified in the liver via the Urea Cycle with the production of
Urea
Urea is a small molecule which freely diffuses through most body tissues
The kidney excretes 90% of the urea produced whilst the remainder is lost
through the skin and GIT
Urea is freely filtered by the glomerulus and passively moves out of the
nephron in response to the concentration gradients produced by water
reabsorption
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Decreased Precursors:
Decreased Protein Intake dietary, vomiting, IV feeding
Increased Protein Synthesis Infancy, Pregnancy
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Creatinine
Cyclic Anhydride of Creatine, that is produced as the final product of
decomposition of Phosphocreatine
Phosphocreatine is dependant on the mass of working muscle
The amount of Creatinine produced each day is fairly constant for a given
individual
Small amounts of Creatine are present in the diet mostly originating from
meat (High Temperature cooking of meat can increase the creatinine
content)
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It also follows that these subjects can have a fairly severe degree of renal
insufficiency but still have a plasma creatinine value within the normal
range
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A number of methods are used to measure the GFR Most involve the
kidneys ability to clear an exogenous or endogenous marker
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Creatinine Clearance
= UCreat X urine Vol (ml)
PCreat [60 X 24 ]time (min)
1. Serum sample
2. Timed/24h urine sample
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Cockcroft Gault
If Pt is Female X 0.85
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Renal Failure
Renal Failure is said to occur when the kidneys are unable to maintain a
normal internal environment
Laboratory Investigation
In most cases the cause of high plasma levels of creatinine and urea is
obvious from the clinical picture
In cases where the cause is obscure, evaluation of these may be helpful
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Potassium
There are several points worth bearing in mind when evaluating the plasma K
levels in pts with abnormal urea and creatinine
Bicarbonate
In Chronic Renal Failure, Metabolic Acidosis usually does not occur unless
the disease is advanced
It is usually a High Anion Gap Metabolic Acidosis
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Urea
Serum urea levels vary widely with the diet, protein metabolism, liver
function and the GFR
Mildly raised levels upto 10mmol/l can occur in the absence of intrinsic
renal disease
The serum Urea usually does not rise until the GFR falls to < 50%
The rate of renal urea excretion varies with the urine flow rate, whereas
the rate of Creatinine excretion is only a function of the GFR
The plasma urea represents a balance between production and excretion
Creatinine
It is generally accepted that the serum creatinine is a better indicator of
the GFR than Urea because the latter is affected by the protein intake
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In Pre-renal Uraemia (low GFR but normal renal function) the ratio
increases because the tubular absorption of urea increases with low rates
of urine flow more than that of Creatinine
In Intrinsic Renal Disease the excretion of both analytes decreases
proportionally and the ratio will remain normal
Therefore, the ratio can be used to distinguish pre-renal from Renal
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Cystatin C
Cystatin C is a Low Molecular Weight protein synthesized by all nucleated
cells
Its physiological role is a cysteine protease inhibitor
The promoter region has been identified as of the housekeeping type with
no known regulatory elements
The production rate of Cystatin C is considered to be constant
Plasma concentrations appear to be unaffected by muscle mass, diet or
gender
There are no known extrarenal routes of elimination
There are a number of reports documenting the correlation between
Cystatin C and Creatinine and GFR
Correlation of Cystatin C is consistently superior to that with creatinine
Polyuria
Urinary Volume > 3L/day
The causes can be divided, for diagnostic purposes, into:
1. Water Diuresis
2. Solute Diuresis
Water Diuresis
Decreased ADH Secretion
Physiological: Compulsive H2O secretion
Pathological: Neurogenic Diabetes Insipidus
Defective ADH Action on the Kidney
Congenital Nephrogenic Diabetes Insipidus
Acquired Nephrogenic Diabetes Insipidus
1. Renal Disease eg) Pyelonephritis, Analgesic Nephropathy
2. Hypokalaemia, Hypercalcaemia
3. Drugs eg) Lithium
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Solute Diuresis
Sodium Increased intake, diuretic therapy, renal salt losing disorders
Urea Hypercatabolic states, CRF, Postobstructive Nephropathy, Post ATN
Glucose Diabetes Mellitus
Laboratory Investigations
Urine Osmolality: Pts with a water diuresis will have a urine osmolality
<200 mmol/kg, whereas in solute diuresis, the urine osmolality will be
similar to the plasma osmolality
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Causes:
Primary
Secondary
a) Autoimune Dx
b) Nephrocalcinosis
c) Drugs (Amphotericin B, Analgesics, Toluene)
d) Renal Transplant
e) Pyelonephritis
f) Obstructive Uropathy
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Causes:
Primary
Secondary
a) Drugs eg)acetazolamide
b) Multiple Myeloma, Sjogrens Syndrome, Amyloidosis, Heavy Metal Poisoning
c) Renal Transplant Rejection
d) Inborn errors of metabolism eg)cystinosis, Wilsons Dx, Lowes Syndrome
Type 4
Due to aldosterone deficiency or an inability of the distal nephron to
respond to aldosterone
Failure of distal Hydrogen and Potassium ion secretion
Characteristics:
Hyperchloraemic Metabolic Acidosis
Hyperkalaemia
Ability to lower the urinary pH to below 5.5
Causes:
Mineralocorticoid Deficiency Syndromes
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Laboratory Investigation
The minimal laboratory investigations required for the investigation of
suspected RTA are:
1. Plasma Electrolytes and Creatinine
2. Blood Gases
3. Urinary pH during Systemic Acidosis
Proteinuria
Higher Molecular Weight proteins are retained within the circulation by
the Glomerular Filter.
Lower Molecular weight proteins are freely filtered and reabsorbed and
catabolized within the Tubular Cells.
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Nephrotic Syndrome
Gross changes in glomerular permeability characterize the nephrotic
syndrome
Nephrolithiasis
Renal Calculi occur in 2-3% of the population
The majority of the stones contain Calcium
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Laboratory Investigations
Depends to a certain extent on the composition of the stone
Other Information
Plasma: Electrolytes, Calcium, Urate
Urine: pH, Calcium, Phosphate, Urate, Oxalate, Cystine, Xanthine
Laboratory Evaluation should be delayed for 4-6 wks after the passage of
stones as this process may induce renal tubular abnormalities which may
be misinterpreted
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Case 1
A 46 yr old man (70kg) with Septicaemia, Dehydration and Oliguria
Plasma
Na 138 mmol/l 135-148
K 3.7 mmol/l 3.5-5.0
Cl 104 mmol/l 98-108
T-CO2 21 mmol/l 22-28
Urea 26 mmol/l 3.0-6.8
Creat 210mmol/l 60-120
Osmol 305 mosm/kg 285-300
Urine
Na 9 mmol/l
Creatinine 7.7 mmol/l
Vol/24hrs 630 ml
Osmolality 529 mosm/kg
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Case 2
The ffg pt had dehydration and a low urine output due to vomitting and diarrhea
Plasma
Na 1 37 mmol/l 135-148
K 4.1 mmol/l 3.5-5.0
Cl 98 mmol/l 98-108
t-CO2 23 mmol/l 22-28
Urea 16 mmol/l 3.0-6.8
Creat 215 umol/l 60-120
Osmol 297 mosm/kg 285 300
Urine
Na 51 mmol/l
Creat 10.7 mmol/l
Vol/24hr 790 ml
Osmolality 560 mosm/kg
FeNa 0.72%
U/P Creat 51
In this case the Urine [Na] suggests ATN but the other parameters indicate
PRU
The high Urine[Na] is a reflection of the concentrating ability of the kidney
and not Tubular Dysfunction
Thus the FeNa is a better indicator of tubular function than the
Urinary[Na]
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Case 3
A pt with severe crush injuries and oliguria
Plasma
Na 136 mmol/l 135-148
K 6.5 mmol/l 3.5-5.0
Cl 96 mmol/l 98-108
t-CO2 15 mmol/l 22-28
Urea 35 mmol/l 3.0-6.8
Creat 710 umol/l 60-120
Osmol 335 mosm/kg 285-300
Urine
Na 55 mmol/l
Creat 5.3 mmol/l
Osmol 360 mosm/kg
FeNa 6%
U/P Osmol 1.07
U/P Creat 6.7
Acute Renal Failure usually occurs over a short period (hrs/days) and is
usually, but not always associated with oliguria (Urine Output < 400 ml/d)
The 2 main features of ATN are Decreased GFR and Tubular Dysfunction
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Case 4
45 yr old Women with a hx of Analgesic Abuse
Plasma
Na 133 mmol/l 135-148
K 5.4 mmol/l 3.5-5.0
Cl 101 mmol/l 98-108
t-CO2 16 mmol/l22-28
Urea 34.5 mmol/l 3.0-6.8
Creat 988 umol/l 60-120
Osmol 315 mosm/kg 385-300
CorrCa 1.69 mmol/l 2.15-2.55
PO4 2.81 mmol/l 0.60-1.25
Urine
Na 26 mmol/l
Creat 5.8 mmol/l
Vol/24hr 1450 ml
Osmol 467 mosm/kg
Sodium
K
Bicarb
Urea and Creat
Ca and PO4
Osmo
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