Download The kidneys - Philadelphia University Jordan

The kidneys
Presented by
Dr. Abeer shnoudeh
Dr. Mohammad Saadeh
The requirements for the Clinical Chemistry
Philadelphia University
Faculty of pharmacy
Renal functions
 Excretion of metabolic waste products of
urine:
The end products of proteins & nucleic acid
metabolism are eliminated from the body.
(urea, creatine, creatinine, uric acid, sulfate &
phosphate).
 Maintenance of Homeostatic:
Regulation of Water–electrolyte balance &
Acid - base Balance in the body.
Renal functions
 Endocrine function: Producing a number of hormones such as:
1. Arginine vasopressin (AVP) OR antidiuretic hormone (ADH) :
Acts to influence water balance. (retain water in the body and to constrict blood vessels)
2. Erythropoietin:
stimulates hemoglobin synthesis and formation of erythrocytes.
3. Parathyroid hormone (PTH):
promotes synthesis of 1,25-Dihydroxycholecalciferol (calcitriol):
• Activation of vitamin D (increasing intestinal absorption of Calcium)
• Promoting absorption of calcium from the gut and increasing renal
tubular reabsorption of calcium.
4. Renin: leads to aldosterone production which is involved in regulation
of electrolyte balance. (tubular Na,Cl reabsorption, K excretion and H2O retention).
ACE
AngiotensinogenRenin angiotensin I
angiotensin II
aldosterone
Renal functions

Endocrine function:
(Calcitriol)
Renal anatomy and physiology
• Nephron is the functional unit of kidney.
• 106 nephrons/kidney.
• Nephron, consist of a
Bowman's capsule (with
blood capillaries),
proximal convoluted
tubule (PCT), loop of
Henle, distal convoluted
tubule (DCT) &
collecting tubule.
 Nephron performed three
functions:
 Glomerular functions:
1.Glomerular filtration.
 Tubular functions:
2.Tubular secretion.
&Tubular reabsorption.
 Water conservation
3. Remove water from
the urine and returns it
to blood, concentrates
wastes
What gets filtered in the glomerulus?
•









Freely filtered
H2O
Na+, K+, ClHCO3, Ca +2
Mg+2, PO4-2
etc…….
Glucose
Urea
Creatinine
Insulin
•




None filtered
Proteins > 68 kDa
Immunoglobulins
Ferritin
Blood cells
Biochemical tests of renal function
Disease affecting kidney can be selectively damage glomerular
or tubular function.
Biochemical tests of renal function
 Test of glomerular function
Measurement of GFR
Clearance tests (creatinine, urea)
Serum creatinine
Blood urea
Proteinuria (the presence of excess proteins in the urine)
 Tubular function tests
Glycosuria (The excretion of glucose into the urine).
 Urinalysis
 Routine examination of urine-volume, pH, specific
gravity, osmolality & presence of certain abnormal
constituents (proteins, blood, ketone bodies, glucose etc).
Measurable of Glomerular Filtration Rate
(GFR)
Reflects no of functional nephrons
Measurable of Glomerular Filtration Rate
(GFR)
describes the flow rate of filtered fluid through the kidney.
 Measurement is based on concept of clearance:
“measuring urinary excretion a substance (X) that is
completely filtered from the blood by glomeruli"
Measurable of Glomerular Filtration Rate
(GFR)
 If clearance=GFR; then substance X properties:
Freely filtered by glomeruli
Not secreted or reabsorbed or metabolized by tubular cells.
Non-toxic and easily measurable
Example creatinine
Determination of creatinine clearance
The clearance is a measurement of the volume of plasma from which a
substance is completely removed per unit time.
 GFR or Clearance(ml/min) = (U x Vml/min) / P
Where
U: urinary concentration of substance X=creatinine (mg/ml).
V urine flow in (ml/min).
P: serum or plasma concentration of substance X=creatinine
(mg/ml).
If the urine volume collected in 24 hours so divided by 24x60
to give the volume produced per minute, the way GFR is
usually expressed.
Creatine & phosphocreatine converted to a waste product, creatinine
Creatine is a nitrogen containing compound formed from glycine, arginine,
methionine in the liver.
Liver
Muscles
Muscles
Amino Acids
Creatine
Phosphocreatine
Creatine
Phosphocreatine
Creatinine
Creatinine
Estimation of GFR:
 The amount of creatininr produced each day is related to the muscle mass,
age, sex, diet or exercise.
Estimation clearance= [(140-age )x wt(kg) / serum creatinine(umol/L)X.81X0.85
 For women, multiply the result by 0.85.
Estimation Creatinine clearance = 110 ml/min
 Creatinine dose not greatly vary from day to day because creatinine is
endogenously produced and releases in to body fluid at constant rate and it is
plasma levels are maintained within narrow range.
 Creatinine can be measured as an indicator of glomular filtration rate (GFR).
Therefore; Plasma creatinine is a function of glomerular filtration
Unaffected by other factors
It’s a very good test to evaluate renal function
Plasma Creatinine
60-120 umole/l
• Physiological
• Physiological
ELEVATED
 High meat intake
 Vigorous exercise
DECREASED
 Children
 pregnancy
Plasma Creatinine
• Pathological
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
ELEVATED
Acute or chronic glomerulonephritis
(fail in GFR)
High pressure at nephrons Urinary
obstruction
Diabetes mellitus
Hypothyroidism
Salicylate toxicity
• Pathological




DECREASED
Starvation
Treated with corticosteroids
Gentamicin or tetracycline
Wasting disease (Transmissible
spongiform encephalopathies (TSEs),
also known as prion diseases)
Plasma Creatinine
Plasma creatinine concentration inversely related to GFR
 GFR can
decrease by 50%
before plasma
creatinine rise
beyond normal
range
or GFR
Cystatin-C
not included
 Protease inhibitor enzyme
 Cystatin C is freely filtered at the glomerulus
 less dependent on age, sex, race and muscle mass compared to
creatinine
Therefore, Cystatin-C are a more precise test of kidney function
than creatinine
 predict the risk of developing chronic kidney disease
 Plasma Cystatin-C concentration rise reflect GFR (fail in GFR)
Urea in serum
 Urea is nitrogen containing compound formed in the liver
as the end product of protein metabolism and digestion.
 More than 90% of urea is excreted through the kidneys in
urines.
 Urea is regarded as a test of renal function.
 Less function than creatinine because 50% of filtered urea
is reabsorbed by tubules.
Urea in serum
• Pathological
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
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
ELEVATED
Impaired renal function
High protein intake
Hypovoluemia, burns
Myocardial infarction
Dehydration
• Pathological
DECREASED
 Starvation
 Low protein diet
 Sever liver disease (impaired
synthesis)
 Gastrointestinal (GI) bleeding will cause serum urea to be elevated,
and this does not indicate that glomerular is compromised
When upper GI bleeding occurs, the blood is digested to protein. This
protein is transported to the liver via the portal vein, and metabolized to
BUN in the urea cycle.
Not included
Other test for assessing kidney function
β2-microglobulin (BMG) Small protein (MWt.=11.8kDa)
 Not affected by muscle mass or diet
 BMG is filtered in glomerulus but is reabsorbed in renal tubules
Urinary BMG levels are increase in renal tubular disorder
Heavy metal poisoning
AIDS
Renal allograft rejection
Proteinuria
• Glomerular basement membrane does not allow passage of
albumin and large proteins.
• Microalbuminuria between normality 30 to 300 mg/day in urine
• Significant damage to the glomerular when increase a albumin in
urine more than 250 mg/day
The classification of proteinuria
1. increased quantity
of proteins in serum
No disease in
glomerular and tubular
2. Glomerular
disease
3.Tubular
disease
4. THP excretion
in urine may
provide defense
against urinary
tract infections
Tubular function tests
.
 Glycosuria is The presence of glucose in the urine
 Urine don't contains glucose because the kidneys are able
to reabsorb all of the filtered glucose from the tubular fluid back in to
the blood stream.
 Urinary glucose levels are increase in renal tubular disorder,
Diabetes mellitus, pregnancy.
Urinalysis
general urine examination
It is general test for evaluation of renal function
1. Physical (color & turbidity),
2. Biochemical (protein, glucose, ketone bodies, bilirubin, blood,
leukocyte esterase & nitrites) and
3. Microscopic examination includes (sediments, RBCs, WBC &
crystal)
Urinalysis
Physical examination includes
Appearance - clear
Turbidity: (infection, nephritic syndrome, proteinuria)
Colour: amber light
Coloured-haemoglobin, myoglobin, jaundice, drugs, beet.
Urine pH
Normally acidic
Normal
4.5-8
Acidic
4.5-5.5
Alkaline
6.5-8
Urine osmolality
Normal average : 400-900 mOsm/kg H2O, Max 1200
mOsm/kg
Purpose = assess the ability of kidneys to dilute or concentrate
urine-tubular function
Urinalysis
Physical examination includes
Urine osmolality
• Increase values
 Dehydration
 Diabetes mellitus
 Hyperglycemia (high blood sugar)
 Hypernatremia
• Decreased values
 Overhydration
 Hyponatremia
 Diabetes insipidus
Hypernatremia: rise in serum sodium concentration to a value exceeding 145 mmol/L.
hyponatraemia, is a low sodium level in the serum (low than 135 mmol/L).
Specific Gravity 1.005-1.030
A measure of the DENSITY of urine compared with the density of water.
High specific gravity = more concentrated the urine
• Increase values
Diabetes mellitus (excess glucose)
Nephritis ( inflammation of the kidneys)
• Decreased values
Diabetes insipidus (excessive thirst and excretion of large amounts of severely dilute urine due
to deficiency in Arginine vasopressin (retain water in the body and to constrict blood vessels).
Urinalysis
Biochemical examination includes
Proteinuria
increase in significant damage to the glomerular.
Glycosuria
 Urinary glucose levels are increase in renal tubular disorder,
Diabetes mellitus, pregnancy.
Ketones
 Small amount are normally present in urine
 Products of fatty acid break down
 Diabetic ketoacidosis
 Alcoholism
Bilirubin
Bilirubin is not normally present in urine
A positive urine dipstick signifies presence of conjugated
hyperbilirubinemia.
Urinalysis
Biochemical examination includes
urobilinogen
Elevated
 Hemolytic jaundice
 Hemolytic or pernicious anemia
(pernicious anemia: Vitamin B12 deficiency anemia)
 Hepatitis
 Cirrhosis
Decreased
 Hyperbilirubinemia syndrome
 Use drugs that acidify urine
(ascorbic acid)
Blood
Blood in urine consideration of hematuria, hemoglobinuria, or
myoglobinuria or Malignancies.
Nitrite
Positive test of nitrite suggests the presence of bacteria in the urine that
convert nitrates to nitrites.
Leucocytes (WBCs)
Leucocytes in urine suggest acute inflammation or urinary tract infection.
Urinalysis
Biochemical examination includes
Renal calculi
Hyperuricamia
Hypercalciuria & hyperparathyroidism
infection
Inherited metabolic disorder (cystinurea)
Renal Disorders
Failure of renal function may occurs rapidly or over a period of
time.
 Acute renal failure (ARF)
 Chronic renal failure (CRF)
Classification of acute renal failure (ARF)
 Pre-renal: the kidney fails to receive a proper blood supply.
 Post-renal: the urinary drainage of the kidneys is impaired
because of an obstruction.
 Renal: intrinsic damage to the kidney tissue. This may be due to
a variety of diseases, or the renal damage may be a consequence
of prolonged pre-renal or post-renal problems.
High plasma urea (Uremia or Azotemia)
Azotemia = elevated urea
Acute renal failure can be subdivided to:
1. Prerenal: (blood loss and hypovolaemia)
Occurs when a sudden reduction in blood flow to the kidney
Ure/cre > 20; Urine osmolality >500 mOsm/kg
Urine Na concentration <20 mmole/L
2. Renal (internsic kidney, tissue damage)
Intrinsic renal disease
Ure/cre between 10-20; Urine osmolality <350 mOsm/kg
Urine Na concentration >40 mmole/L
3. Postrenal (ureteric/urethral obstruction)
Obstruction to urine outflow
Ure/cre >15; Urine osmolality <350 mOsm/kg
Urine Na concentration >80mmole/L
High plasma urea (Uremia or Azotemia)
Azotemia = elevated urea
Biochemical
feature
Urine sodium
Pre-renal
failure
<20 mmole/L
Intrinsic renal
damage
Post-renal
>40 mmole/L
>80mmole/L
Urine osmolality >500 mOsm/kg
<350 mOsm/kg
<350 mOsm/kg
Ure (mg/dl)/cre > 20
(mg/dl) in serum
10-20
>15
Urine urea
/serum urea
<3:1
> 10:1
Urine osmolality > 1.5:1
/plasma
osmolality
<1.1:1
Renal Disorders
Acute renal failure (ARF)
Consequences of ARF
Increased serum urea/ creatinine
Hyponatremia (decreased serum Na+), increased Na+ in urine.
Hyperkalaemia (increased serum K+)
Metabolic acidosis (increase serum H+) and reduce bicarbonate
Hypocalcaemia and hyperphosphatase
Note: diabetes cause decrease in GFR
Renal Disorders
Chronic renal failure (CRF)
 Chronic kidney disease includes irreversible damage to the kidneys
and decrease their ability to keep the healthy by doing the jobs listed.
 CRF patient may be without symptoms until GFR falls to very low
values <15 ml/min.
 Chronic kidney disease may be caused by diabetes, high blood
pressure and other disorders.
Consequences of CRF
Increased serum urea/ creatinine
Hyperkalaemia (increased serum K+)
Metabolic acidosis
Hypocalcaemia, hyperphosphatase and hyperoarathyroidism
Osteodystrophy (ALP raised, 2 or 3 hyper Parathyroid hormone (PTH).
Normochromic normocytic anemia
Hypocalcaemia and hyperphosphatase
hypernatraemia, is a high sodium level in the blood. normal serum
sodium levels are 135 - 145 mmol/L (135 - 145 mEq/L). Hypernatremia is
generally defined as a serum sodium level of more than 145 mmol/L.
hypernatraemia cause Osmotic pressure and Cellular dehydration due to
excessive losses of water from the urinary tract, which may be caused
by glycosuria.
Hyponatraemia, is a low sodium level in the blood. Symptoms can vary
from none to severe. Mild symptoms include a decreased ability to
think, headaches, nausea, and poor balance.