Laboratory Diagnosis
EXIMIUS
RENAL FUNCTION 2021
Dr. Cauan December 2018
EVALUATION OF RENAL FUNCTION, ELECTROLYTES AND • Urea is the main waste product of nitrogen-containing
ACID BASE BALANCE chemicals in the body 1
• β-2-microglobulin, a polypeptide with molecular weight of
11.6 kDa and length of 99 amino acids, is a component of
the major histocompatibility complex class I molecule.
BODY FLUID
Extracellular fluid
• Serve as a conduit among cells and organs
• Regulation of intracellular volume and its ionic strength
• Any alteration in extracellular osmolality is followed by an
identical change in intracellular osmolality, which is
accompanied by a reciprocal change in cell volume.
• Low volume – impaired organ perfusion
• Excess volume – vascular congestion and edema
Body Fluid Volume
Total body water is 54% of body weight
Total body water (L) = body weight (lb)/4
Intracellular volume: 24 L (60%)
Extracellular volume: 16 L (40%)
Interstitial volume: 11.2 L (28%)
Plasma volume: 3.2 L (8%)
Transcellular volume: 1.6 L (4%)
* Normal man weighing 73kg (160lb) is used as a model.
Composition of the Body Fluid
Extracellular
• Sodium, Chloride and Bicarbonate are the main solutes
• Concentration of electrolytes in plasma is increased by about
7% when expressed in plasma water
• Differences in electrolyte concentrations beween plasma and
interstitial fluid can be predicted by the Donnan equilibrium
Intracellular
• Potassium, magnesium, phosphate and proteins are the main
solutes
• Electrolyte composition is not identical throughout the tissues
E.g. Chloride: 3 mmol/L (muscle); 75 mmol/L (RBCs)
OSMOLALITY
RENAL FUNCTION TEST
• Clearance of inulin, a complex polysaccharide produced by
Number of moles of solute in a kg of water
certain plants,has been widely regarded as the gold standard
for measuring GFR.
EXOGENOUS
Creatinine is an endogenous substance with a molecular weight of 113
Reference range: 275-295 mOsm/kg
Da. It is produced by the muscle from creatine and creatine phosphate
Effective osmols: glucose, mannitol, sodium
through a nonenzymatic dehydration process.
Ineffective osmols: Urea, alcohol
ENDOGENOUS
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When osmolal concentration of the ECF increases by accumulation of Serum/Plasma: 136-142 mmol/L
solutes that are restricted to the ECF (effective osmols) Urine (24 h): 75-200 mmol/d, varies with diet
Osmotic equilibrium is reestablished as water shifts from the cell to the CSF: 136-150 mmol/L
ECF, increasing the intracellular osmolality to the same level as the
extracellular
Effect of Hyperglycemia on serum sodium
• Glucose is osmotically active and induces diffusion of
water from the cells to the ECF thus diluting its
electrolytes
• When the extracellular osmolality increases by the
accumulation of solutes that can enter the cell freely
(ineffective osmosis)
• Osmotic equilibrium is achieved by entry of those solutes
into the cell
ELECTROLYTES
Ions capable of carrying an electric charge
Classified into anions and cations
Functions:
Volume and osmotic regulation
Myocardial rhythm and contractility
Cofactors in enzyme regulation
Regulation of ATPase ion pumps
Acid-base balance
Blood coagulation
Neuromuscular excitability
Production and use of ATP from glucose
Potassium
Major intracellular cation
Functions include regulation of neuromuscular excitability,
contraction of the heart, ICF volume and H+ concentration
Reference ranges:
Serum: 3.8-5 mmol/L
Urine (24h): 40-80 mmol/d
Sodium
Most abundant cation in the ECF (90%)
Largely determines the osmolality of of the plasma
Reference ranges:
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Hypochloremia
EXCESSIVE LOSS
Prolonged vomiting
Diabetic ketoacidosis
Aldosterone deficiency
Salt-losing renal diseases
Bicarbonate
Second most abundant anion in the ECF
Accounts for 90% of total CO2 at physiologic pH
Major component of the buffering system in the blood
Reference ranges: 21-28 mmol/L
Decreased:metabolic acidosis
Increased: metabolic alkalosis
Magnesium
} Second most abundant intracellular, ion
} 50% in bone, 46% in muscle and other soft tissue, less than 1%
I serum and RBCs
} Functions: essential cofactor for enzymes
◦ Glycolysis
◦ Transcellular ion transport
◦ Neuromuscular transmission
◦ Synthesis of carbohydrates, proteins, lipids and
nucleic acids
◦ Release of and response to certain hormones
} Reference range: 0.63-1.0 mmol/L
Causes of Hypermagnesemia: Rare and usually iatrogenic
Chloride
Major extracellular anion
Involved in maintaining osmolality, blood volume and electric
neutrality
Shifts secondarily to a movement of sodium and bicarbonate
Reference ranges:
Plasma/ serum: 95-103 mmol/L
Urine (24h): 140-250 mmol/d, varies with diet
Hyperchloremia
Excess loss of HCO3- as a result of GI losses, RTA or metabolic
acidosis
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Phosphate
80-85% is present in the skeleton (hydroxyapatite and calcium
phosphate)
15% in ECF (inorganic phosphate) and intracellular (organic
phosphate)
Inorganic phosphate exists as both divalent (H2PO42-) and
monovalent (H2PO4-) which represent important buffers
Important constituent of nucleic acids
Contained in phospholipids and phosphoproteins
Essential for normal muscle contractility, neurologic function,
electrolyte transport and oxygen-carrying by hemoglobin (2,3-
diphosphoglycerate
Reference interval:
Adult: 2.3 to 4.7 mg/dL (0.74-1.52 mmol/L)
Children: 4.0 to 7.0 mg/dL (1.29-2.26 mmol/L)
Calcium
Best measured in fasting morning specimen due to diurnal
Essential for myocardial contraction
variation
Decreased ionized calcium impairs myocardial function
Reference ranges:
} Total Calcium: 2.30-2.74 mmol/L
} Ionized/free: 1.0-1.2 mmol/L
} Total Calcium-Urine: 2.5-6 mmol/d, varies with diet
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ACID BASE DISORDERS Causes of L-Lactic Acidosis
Type A Lactic Acidosis Due to Tissue Hypoxia
Bicarbonate and Carbon Dioxide Buffer System Circulatory shock
All body buffers are in equilibrium with protons (H+)and Severe hypoxemia
therefore with pH Heart failure
pH = pK + log A-/HA Severe anemia
Henderson-Hasselbalch equation: Grand mal seizure
Type B Lactic Acidosis (No Tissue Hypoxia)
pH = 6.1 + log HCO3-/pCO2 x 0.03 Acute alcoholism
Drugs and toxins
pH increases when the ratio increases (alkalosis) Diabetes mellitus
pH decreases when the ratio decreases (acidosis) Leukemia
Deficiency of thiamine or riboflavin
ACID – substance that donates a proton in a reaction Idiopathic
BASE – substance that accepts a proton in a reaction
D-Lactic acidosis
Characterized by severe acidosis accompanied by neurologic
manifestations (mental confusion and staggering gait), mimicking
ethanol intoxication
Ketoacidosis
• Keto acids, acetoacetic acid and B-hydroxybutyric are produced in
the liver from free fatty acids and are metabolized by extrahepatic
tissues
• Insulin deficiency – increased mobilization of FFA from the adipose
tissue
• Glucagon excess and insulin deficiency stimulate conversion of FFA
to keto acids in the liver
METABOLIC ACIDOSIS
Results from reduction in the bicarbonate content of the body SERUM ANION GAP
2 minor exceptions: AG = Na+ - (Cl- + HCO3-)
Dilution of body fluid by administration of large AG = UA - UC
amount of saline solution that does not contain alkali
(dilution acidosis)
Shift of H+ from the cell
Extrarenal acidosis – due to primary increase in in acid
production
Renal acidosis – primary reduction in net acid excretion
Causes of Metabolic Acidosis According to Net Acid Excretion
RENAL ACIDOSIS:
Uremic acidosis
Renal tubular acidosis
Distal renal tubular acidosis (type I)
Proximal renal tubular acidosis (type II)
Aldosterone deficiency or unresponsiveness (type
IV)
EXTRARENAL ACIDOSIS:
Gastrointestinal loss of bicarbonate
Ingestion of acids or acid precursors: Ammonium chloride, Decreased AG – reduction in serum albumin
sulfur Increased AG – accumulation of anions of acids such as sulfate,
Acid precursors of toxins: Salicylate, ethylene glycol, lactate and ketone anions
methanol, toluene, acetaminophen, paraldehyde
Organic acidosis • Normochloremic acidosis with increased AG
L-Lactic acidosis o Bicarbonate is replaced by another anion
D-Lactic acidosis o Cl-concentration remain unchanged
Ketoacidosis • Hyperchloremic acidosis with normal AG
o Bicarbonate concentration decreases without another
anion replacing it.
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o Electrical neutrality is maintained by a higher Cl-
concentration
Compensation of Respiratory Acidosis
• Increase HCO3- concentration in an attempt to minimize
reduction in pH
• Tissue Buffering
o CO2 + H2O H2CO3
o H2CO3 + KBuff Hbuff +KHCO3
o Increased concentration of cellular HCO3- causes an
extracellular shift of HCO3- in exchange for Cl-
o Occurs within a second
Renal Compensation
Compensation of Metabolic Acidosis } Increase net acid excretion in the form of NH4+
Hyperventilation results in decreased pCO2 } Increase excretion of NH4+ is accompanied Cl-
Maximal compensation is completed within 12 – 24 hours } As new HCO3- is retained, Cl- is lost
Maximal compensation requires 5 days
METABOLIC ALKALOSIS
Requires two conditions: RESPIRATORY ALKALOSIS
• Mechanism to increase plasma bicarbonate • Decrease in pCO2
• Mechanism to maintain an increased condition • Two most common causes:
o Advance renal failure o Hypoxic stimulation of the peripheral respiratory
o Renal threshold for bicarbonate is increased center
o Stimulation through pulmonary receptors caused by
various disorders of the lung
Compensation of Metabolic Alkalosis
• Hypoventilation that results in increased pCO2 Compensation of Respiratory Alkalosis
• Compensation is least effective • Lower plasma HCO3- and minimize the increase in blood pH
• Maximal compensation is completed within 12-24 hours • Tissue buffering
o Hbuff + HCO3- H2CO3- + Buff
RESPIRATORY ACIDOSIS o H2CO3 CO2 + H2O
Increase in pCO2 o As cellular HCO3- is consumed in the buffer reaction
extracellular HCO3- enters the cell in exchange for
cellular Cl- that enters the ECF
• Renal Compensation
o Reduction in net acid excretion
o Increased excretion of HCO3- and later reduced
excretion of NH4+ and titrable acid
o Compensation is most effective
o Process is completed within 2-3 day
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MIXED ACID-BASE
• Clinical condition in which two or more primary acid-base disorders
coexist
• One obvious disturbance with an inappropriate compensation
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