WATER COMPARTMENTS of the kidney.

Renin will convert

- 40-75% of total weight Angiotensinogen to Angiotensin I.
- Decline as we age and for obese Angiotensin I will be converted by
- Women has a lower water content Angiotensinogen converting enzyme (in the
than men which results in higher fat lungs) to Angiotensin II.
content Angiotensin II is vasoconstrictor it will
Function promote the blood pressure to increase.
- Solvent for all processes in the Angiotensin II will stimulate in the adrenal
human body gland particularly in Adrenal cortex to
- Transport nutrients to cell release ALDOSTERONE.
- Remove waste product through ALDOSTERONE is a hormone that promotes
urination the re-absorption of sodium and elimination
of potassium.
INTRACELLULAR FLUID Aldosterone stimulate the kidney to
- 2/3 (60%) of the total body of water reabsorb more sodium. Also elimination of
- Fluid inside cells like RBC and WBC potassium
Extracellular fluid
- 1/3 (15%) of the total body of water ELECTROLYTES
- All the body fluids found outside
cells of any multicellular organism SODIUM REGULATION
INTERSTITAL FLUID (3/4) - Natrium
- Found outside of the cells 1. Aldosterone
INTRAVASCULAR FLUID (1/4) - Absorb Na
- Plasma - Retention of Na and excretion of K
Proteins such as albumin regulates oncotic - 92% ECF in Na
pressure, and now regulate the movement 2. Atrial Natriuretic Factor (ANF)
of water from in and out of blood vessel. - Inhibits angiotensin II, blocks
aldosterone and renin reabsorption
Metabolic processes happen in ICF - Excretion of sodium is in the form of
Sample gets from ECF urine
- Causes natriuresis
ECF OSMOLALITY
- Increased ECF osmolality, lower HYPERNATREMIA
water concentration and vice versa - Normal reference value is 135-145
mmol/l
RAA SYSTEM- Renin-Angiotensin- - >145 mmol/L
Aldosterone System Major cause of hypernatremia
Hyponatremia- low sodium in the blood - Excess water loss, gain of sodium or
Hypotension- low blood pressure both
Hyperkalemia- Elevated potassium in the - Decreased water intake
blood - Increased intake of sodium
Excess water loss
These three will stimulate the release of - Prolonged diarrhea
protein (RENIN) in the juxta glomerular cells - Renal tubular disorder
 - Vomiting - Saline infusion
- Fever
- Hyperventilation Increased water retention
- Renal failure
Increased intake or retention - Aldosterone deficiency
- Hyperaldosteronism (conn’s disease) - Cancer (excessive of proliferation of
- Increased intake of sea water cell)
- Hepatic cirrhosis
HYPONATERMIA
- <135 mmol/L Pseudohyponatremia
- It more often happens than - Systematic error in measurement
hypernatremia and maybe med-tech
- Renal failure or kidney disease which - Upon distraction of RBC or In-vitro
you cannot reabsorb sodium hemolysis. Water from ICF will go
- Wherever sodium goes water follow, out of ECF which will dilute the
more solute than solvent. Thus sodium. Because there is greater
activation of thirst center to intake amount of solvent compared to
more water to lessen the sodium in solute cause pseudohyponatremia
the body and to lower osmolality - Potassium on the other hand will
increased if there is in-vitro
Glucose and mannitol hemolysis which potassium will go
- It induces diffusion water from ICF out of ICF to ECF
to ECF of plasma cell which will - Chloride, will decreased same with
cause to dilute electrolytes sodium
specifically the sodium causing SODIUM ASSAY
hyponatremia. - FEP
- ISE- glass membrane
Potassium deficiency - AAS
- Tubules will conserve more - Colorimetry (Albanese-Lein)
potassium, in exchange for that
more sodium will be eliminated
causing hyponatremia
- <125 mml/L in serum sodium level
will lead to severe neuropsychiatric
symptoms

Major causes of hyponatremia

- Increased sodium loss - The darker the color, the higher the
- Increased water retention analyte present in the solution and
- Water imbalance vice versa.

Disorders
Increased sodium loss
- Diuretic use
POTASSIUM - Diabetic individuals who are under insulin
- Kalium treatment are prone to develop
- Major ICF cation (inside the rbc) hypokalemia.
- Only 2% are in the circulation of - Insulin forces potassium to enter the cell.
plasma - If insulin elevates in the blood, it pushes
- 105 mmol/L potassium back to the
- It is filtered in the glomeruli and ICF, leading to decreased levels in the
reabsorbed in proximal convoluted blood.
tubule through active and passive
diffusion Therapeutic K administration
- Ascending limb of henle’s loop will - most common cause of hyperkalemia
reabsorbed potassium and sodium among hospitalized
as well as chloride individuals
- Most important analyte, and if its - potassium is usually given with the
above or lower than normal value is dextrose
fatal
- Reference value is 3.5-5.2 mmol/L Major Causes of Hyperkalemia
- Hyperkalemia (6.5 mmol/L) Decreased Renal Excretion
- Hypokalemia (2.5 mmol/L) - Sodium is reabsorbed by the kidneys. As a
- Conversion factor 1 response, there will be excretion of
potassium.
Hyperkalemia: Effects to cardiac Muscle - If there is decreased excretion, more will
- Decreases the resting membrane potential be reabsorbed, going back to the blood.
of the cells
- Severe hyperkalemia: can cause a lack of Extracellular shift
muscle excitability - From the ICF going to the ECF (i.e. through
- 6-7 mmol/L: may alter ECG lysis)
- involves movement and pumping of the
heart Increased intake
- 10 mmol/L: cardiac arrest - Administration of potassium through IV or
above or equal to 10 mmol/L: fatal which oral drugs
can result to cardiac arrest
Use of immunosuppressive drugs
Acidosis: Increased plasma potassium - Immunosuppressants will elevate the level
- When blood pH becomes acidic, there will of potassium because they suppress or
be increased levels of potassium in the reduce the excretion of potassium done by
blood. This is because the hydrogen ions the kidneys.
will enter the RBC, and in exchange, there
will be movement of potassium going to the Differential diagnosis of Hyperkalemia
ECF. 1. Rule out psuedohyperkalemia
- Low insulin levels: increased serum - If abnormal of ECG results, it is not
potassium psuedohyperkalemia
 - Higher serum potassium during - Gitelman’s syndrome is salt wasting
platelet clotting then eliminate that disorder, problem in reabsorption of
it is cause by pseudohyperkalemia potassium.
2. Differentiate among the 3 major - Bartter’s syndrome, problem of
causes of hyperkalemia reabsorption
- Increased intake of potassium
- Extracellular shift, shifting potassium Intracellular shift
from ICF to ECF - Greater movement from ECF to ICF
- Impaired renal excretion of renal will results low level in the blood in
potassium the intravascular fluid or plasma
3. 24 urine K+ distinguishes increased
intake Mild hypokalemia- 3.0-3.4 mmol/L
- If this is increase maybe because of Hypomagnesemia leads to hypokalemia
intake of potassium
- However if it normal or lower, it is Impaired renal function is the most
not cause by increased intake of common cause
potassium - Increased activity of aldosterone
Chronic hyperkalemia or renal cause which
measures the: plasma renin activity, plasma Extra renal loss
aldosterone, and urinary of sodium and - Diarrhea
potassium. - Vomiting
Effects to Cardiac Muscle
MAJOR CAUSE OF HYPOKALEMIA
Gastrointestinal loss - decrease cell excitability by increasing
- Problems of reabsorption in the resting membrane potential resulting in
small intestine of potassium arrhythmia and paralysis
- Laxative abuse
- Cancer Psuedohypokalemia
- Vomiting and diarrhea-
Renal loss - leukocytosis can falsely decrease
- Low reabsorption of potassium potassium levels if sample is left at
- Diuretics- greater loss of potassium RT
through urine or stool - false decreased,
- Hyperaldosteronism- elevated of - active leukemic cell is left in the RT
aldosterone which greater will now consume potassium in the
elimination of potassium ECF that’s why it can decreased
- Cushing syndrome (increased level potassium
of cortisol, it promotes reabsorption
of sodium. Sodium and potassium Potassium Assay: Specimen consideration
are inversely. If there is greater
reabsorption of sodium their will be 1. hemolysis
greater elimination of potassium 2. plasma levels are lower compared to
serum levels
3. muscular activity
 4. prolonged contact of serum and red - 1000x faster than sodium electrode
cell
5. prolonged tourniquet application CHLORIDE

Potassium Assay - Major anion of the ECF

- Excreted in the urine & sweat
- FEP- Flame emission photometry - Disorders of chloride are the same
- ISE- Valinomycin as sodium
- AAS- Reference value: 98-107 mmol/L
- Colorimetry (Lockhead and puricell)
Functions:
- Maintain plasma osmolality, blood
volume & electroneutrality

Specimen consideration

Marked hemolysis or in vitro hemolysis-

decreased
- It induces diffusion water from ICF
to ECF of plasma cell which will
cause to dilute electrolytes
Differential Diagnosis of Hypokalemia specifically the chloride
1st step: measurement of urinary excretion
of K+ Post-prandial specimen(sample are taken
after eating of patient) - slightly lower
Low urinary K+ excretion: - Chloride is used for digestion,
causing acidity in the stomach
- Low intake causing low level of chloride
- Extrarenal loss of K+ (be -
- Intracellular shift Conditions with high HCO3 levels- lower Cl-
Normal/increased urinary excretion: - Chloride shift- once there is
- Renal loss: movement from the ICF to the ECF;
Next step- measurement of plasma there will be movement of chloride
renin activity and plasma aldosterone from the ECF to the ICF to maintain
the electroneutrality
ISE (Ion selective Electrode): sodium and
Potassium Chloride: Assay
- Direct and Indirect method
Mercurimetric Titration (Schaled and
Sodium Electrode Schales)
- Glass membrane Indicator: Diphenycarbazone
End product: HgCl2
Potassium Electrode
- Valinomycin membrane Spectrophotometric method
 Mercuric Thiocyanate (Whitehorn - If the protein is increased in the CSF,
Titration Method) may be there is a problem in BBB
- Reddish complex (Blood brain barrier)

Ferric Perhlorate Reference value: 115-132 mmol/L

- Colored complex
Visible results is dependent on the - Low levels of bacterial meningitis
chromogen or the dye used - Increased of CSF protein and low CSF
chlorides it is an indication of
Coulometric Amperometric Titration bacterial meningitidis
Cotlove Chloridometer
- Direct concentration of chloride Urinary Chloride
present in the sample - Greatly varies with chloride intake
Reference value: 110-250 mmol/day
ISE (Ion Selective Electrode) used Low levels: patients on low-salt diets
membrane
- Silver sulfide and silver chloride Sweat Chloride
- ISE is the most common; it can give - Diagnostic cystic fibrosis
result in just 30 secs - Sweat chloride is elevated
- Chloride channel is defective; there
Hyperchloremia should reabsorb of sweat in sweat
- Renal tubular acidosis duct cells
- Diabetes insipidus - Less reabsorption of sweat chloride
- Salicylate intozication in sweat duct cell and more
- 1 hyperparathyroidism elimination of sweat chloride
- Metabolic acidosis
- Prolonged diarrhea CALCIUM
- Most abundant cation in the body
Hypochloremia - 99% found in the bone, 1% found in
- Prolonged vomiting the plasma
- Aldosterone deficiency - Absorption: duodenum
- Metabolic alkalosis- greater - Reference value:
increased of bicarbonate, there will Total calcium: 8.6-10 mg/dL (Adult)
be movement from ECF to the ICF, 8.8-10.8 mg/dL (Adult)
causing low level of chloride Ionized calcium:
- Salt-losing nephritis- greater 4.6-5.3mg/dL (Adult)
elimination of chloride 4.8-5.5mg/dL (Adult)

CSF chloride Functions:

- Higher than that of serum (because - Blood coagulation
of protein concentration is low CSF) - Enzyme activity
- Protein is large and cannot passed - Excitability of skeletal and cardiac
through CSF muscle
- Protein is also a negatively charge - Maintenance of blood pressure
 (It is necessary the dilate or constrict for the movement of calcium from
the blood vessel for the regulation the bone to the plasma cell)
of the blood pressure) - Suppresses urinary loss of Ca++
(Calcium rich diet will decreased - Stimulates the conversion of inactive
blood pressure) vitamin D to active vitamin D3

Regulation of calcium Calcitonin

- 1,25 Dihydroxycholecalciferol - IS THE ONLY HYPOCALCEMIC
- PTH HORMONE
- Calcitonin - Inhibits PTH and vitamin D3
- Inhibits bone resorption
Calcitriol - Promotes urinary excretion of ca++
- 1,25 Dihydroxycholecalciferol/
Vitamin D3 Forms of Calcium
- Vitamin D3 is active form of vitamin 1. Ionized (Active) calcium (Most
D abundant)
- Derived from successive - It is not bound to protein
hydroxylation in the liver and in the 2. Protein-bound calcium
kidney 3. Complexed with anions (Low level)
- Increased parathyroid hormone and
decreased phosphate will stimulate
the release of vitamin D3 Factors Affecting Ca++ Level
- The vitamin D3 is inhibit when
decreased of parathyroid and Decrease in plasma CHON-
increased of phosphate, this will concentration
block the release of calcitriol
- Calcium can be absorb with the help - decreased total calcium level
of vitamin D3 (Ionized calcium, protein-bound
It increases in: calcium, complexed with anions)
- Intestinal absorption of Ca++
- Reabsorption in the kidneys Prolonged contact of serum with the
- Mobilization of Ca++ from the bones clotted blood

Parathyroid Hormone (PTH) - decreased calcium level

- Conserves calcium
(There is no need PTH If there is Recumbent posture
hypercalcemic and increased level of - lying/resting position: decreased
calcitriol because it is not needed calcium
- Increases the Ca++ level)
- Activates the process of bone Venous occlusion
resorption - Example: traumatic venipuncture.
(If there is low calcium, There will be an occluded (naglubo ang
disintegration of osteoclast in bone ugat upon venipuncture)
 Vein, hematoma or a small clot. Calcium D; this will promotes greater
will increase because of the obstructed production of calcium
vein since it will not allow excretion of - Hyperthyroidism (promote bone
calcium into the urine. resorption)
- Milk-alkali syndrome
Acidification
- Decreased/Acidic pH or when the CHIMPS- Cancer, hyperthyroidism,
sample is exposed to acid: Iatrogenic causes, Multiple myeloma,
Hyperparathyroidism, sarcoidosis
Calcium bound to proteins will be
liberated, resulting to elevated calcium Hypocalcemia
in the blood
- Tetany (initiated by fall of calcium
Acid ph will promote dissociation or levels) (affected are ionized or active
separation of calcium to protein causing protein)
increased level of calcium - Alkalosis (inverse of acidosis)
vitamin D deficiency
Increased urinary excretion - 10 hypoparathyroidism
- Acute pancreatitis
- Increased excretion, decreased calcium - Hypomagnesemia
in the blood - Malabsorption Syndrome
- Renal Tubular Failure
Calcium Disorders
CHARD- Calcitonin, hypothyroidism,
Hypercalcemia Alkalosis, renal failure, vitamin D deficit

- 10 hyperparathyroidism Hypocalcemia
- Cancer (lung and breast Ca) (when
the calcium is advance or dugay na) 10 hypocalcemia: low PTH
(because of excessive secretion of
PTH) (Cancer will promote bone - Nothing will stimulate to produce calcium
resorption)
- Acidosis - Something is wrong with the parathyroid
- increased vitamin D, more to be gland. There is impaired secretion of PTH.
converted into active form
- MM (Multiple myeloma) (increased
20 hypocalcemia: high PTH
of bone resorption)
- Sarcoidosis Hyperthyroidism
- Nothing is wrong with the parathyroid
(unregulated level of calcium that’s
gland or PTH.
why it increased the calcium level)
(presence of inflammatory cells and
- Consequence of low magnesium or
they continue to grow; it will form a
phosphate levels. The body is trying to
lumps called granulomata or compensate the level of calcium.
granuloma and it activated vitamin
Severe hypocalcemia Along with the entry of phosphorus into the
cell, potassium will follow inside the cell,
- total calcium levels: <7.5 mg/dL particularly in the RBC.

Pseudohypercalcemia Reference value (blood/serum):

Dehydration or hemoconcentration 2.7-4.5 mg/dL (adults)

- One factor contributing to
hemoconcentration is the elevation of 4.5-5.5 mg/dL (Children)
albumin. Calcium can bind with albumin so
there will be false elevation of total calcium. Forms of Phosphates
Ionized calcium, however, is normal.
Free or unbound form (55%)
PHOSPHORUS - considered as active form

Exists as inorganic PO4 or as organic PO4 Complexed with ions (35%)

esters - Those that exist in the serum which are
most inorganic forms are those complexed
- organic PO4: principal ion within with ions.
anion(?)
Protein-bound (10%)
- Inorganic is part of blood, in the ECF.
PTH
- 85% of phosphorus in bone. 15% in ECF in
the form of inorganic PO4. - Decrease phosphate level by renal
excretion.

Omnipresent in its distribution - Promotes excretion of phosphorus

particularly phosphates through the urine
- Omnipresent: Anywhere with living cells,
phosphorus is present. Calcitonin

Inversely proportional to Ca++ - Inhibits bone resorption of phosphate and

so there will be decreased phosphate level
Absorbed in the jejunum in the blood.

- maximal absorption Growth Hormone

- Increase phosphate level by renal
reabsorption.
Essential for the insulin-mediated entry of
glucose into cells

- Particularly phosphate. Phosphate is

involved in the phosphorylation of glucose.
Practical considerations - Affected by diet.

Fasting is required - Patient should fast, and sample should be

- Protein-rich diet leads to decreased level collected early in the morning.
of phosphorus.
Fiske-Subarrow
Serum must be separated from the red cells
- If red top is used instead of SST, separate - Colorimetric method
immediately to avoid the results being
affected. Hyperphosphatemia

Phosphorus: Assay Renal failure

Phosphorus is measured in terms of PO4 - If there is impaired kidney or renal

- Among the three forms, only inorganic disease, the excretion of phosphate is
phosphate in the serum can be measured inhibited leading to high level in the blood.
in the laboratory.
- The tubules Proximal convoluted tubule
(PCT) are responsible for the reabsorption.
Laboratory results cannot be expressed in If the tubules are nonresponsive with
mEq/L Parathyroid hormone (PTH), the levels of
phosphate will be elevated.
- For electrolytes (Na, K, Cl), the
conventional unit is mEQ/L. - Once phosphate increases in the blood, it
can cause greater loss of calcium.
Blood collection is affected by circadian
rhythm - Hyperphosphatemia, hypocalcemia, and
elevation of BUN and creatinine are all
- Consider the time of day for collection of indicative of renal disease, specifically of
samples for inorganic phosphate tubular failure wherein reabsorption is
measurement. impaired.

- Late in the morning to near noon: levels Lymphoblastic leukemia

of phosphorus will be elevated.
Hypervitaminosis D
- Late in the evening, phosphorus will be
low. Hypophosphatemia

- Best time to take sample is in the Alcohol abuse

morning. - most common cause

Fasting serum PO4 is controlled by 1° hyperparathyroidism

parathyroid gland Avitaminosis D
Myxedema
Patients receiving carbohydrate Functions
hyperalimentation
- Maintains structures of DNA, RNA
Severe hypophosphatemia: and ribosome
- Synthesis of CHO, CHONs and Lipids
<1.0 g/dL or 0.3 mmol/L - Neuromuscular transmission
- Cofactor
Note: -Cellular shift: Phosphate will enter - Regulates movement of potassium
into the cell. across the myocardium

MAGNESIUM Note: -Potassium is important for

myocardial contractility. Along with
2nd abundant cation of ICF that, the function of magnesium is also
- Most abundant is potassium needed.

Forms of Magnesium
4th abundant cation in the body

Stored in the bones, muscles, and soft Free Mg++/ ionized (55%) (Active form, amo
tissues, serum and RBC ni ang maka-function
- Majority of magnesium is in the form of
- 53% bones ionized form or is unbound to protein

- 46% muscles and soft tissues Protein-bound Mg (30%) (para maka-

circulate in the blood)
- 1% in serum
Complexed with Ions (15%)
Decreases uterine hyperactivity and
increase uterine blood flow Regulation of Magnesium

- Vasodilator PTH
- For women during pregnancy (helps for - Produce by parathyroid gland and its
the prevention of pre-mature delivery) function is to elevate the level of
magnesium
Loss of magnesium leads to decreased - Ex, in the patient with
intracellular K+ shift (Low magnesium hypomagnesemia, thus we need
increased potassium in the ESF or in the PTH, this will absorption of
plasma magnesium by kidney and increased
absorption of magnesium in the
Reference Value: 1.2 -2.1 mEq/L intestines. Through this ways the
magnesium will be regulated
- Life-threatening levels: 5mmol/L - increased renal and intestinal
reabsorption
Aldosterone and Thyroxine Magnesium in Relation to pH Imbalance
- Increases the excretion of magnesium
- Mg++ diffuses out of the cell in
- Elimination of magnesium exchange for Cl- (Chloride Shift)
- Buffering system of the blood is
Hypermagnesemia maintained by a reversible exchange
process between bicarbonate and
Diabetic coma chloride
Addison’s disease Note: - Chloride shift: Chloride will
Chronic renal failure go into the cell, and bicarbonate will
Increased intake of antacids, enemas, and go out to maintain electroneutrality.
cathartic
BICARBONATE
Enema: a medical procedure wherein a
liquid is forced to pass through the anus to - 2nd most abundant anion in the ECF
the intestine so that feces will be normally - Most abundant is chloride
excreted by the body. Certain medications
are used which can elevate the magnesium Accounts for 90% of total CO2 at
level in the blood. physiologic pH

-Cathartic: laxative, a medication is used for Composition:

easy movement of bowel. The medications
affect the level of magnesium in the body. - Undissociated NaHCO3
- Carbonate
Hypomagnesemia - Carbamate

Acute Renal Failure Functions:

Malnutrition
Malabsorption Buffers excess hydrogen ions
Chronic Alcoholism
Severe Diarrhea - Acid-base balance
- Buffering capacity.
Magnesium: Assay - Major component of the buffering
system in the blood.
- Calmagite method- wide used
titration indication Maintenance of high plasma bicarbonate
- Formazan Dye Method concentration
- Magnesium Thymol Blue
- AAS (Atomic Absorption Bicarbonate Assay:
Spectrophotometry)- Reference
method ISE
- Dye-Lake Method - Uses pCO2 electrode

Note: - First three are colorimetric methods.

Enzymatic Method AG= (Na+ + K+) - (Cl- + HCO3-)
- Colored reaction involving two enzymes
(phosphoenolpyruvate carboxylase, Reference value: 10-20 mmol/L
phosphoenolpyruvate dehydrogenase)
Note: -For conditions with decreased
Bicarbonate in Relation to pH Imbalance albumin (hypoalbuminemia), it is expected
that there will be decreased unmeasured
- Diffuses out of the cell in exchange anions (chloride, bicarbonate).
for Cl- (Chloride shift) -For those with hypercalcemia, there will be
- Buffering system of the blood is elevated unmeasured cations.
maintained by a reversible exchange
process between bicarbonate and
chloride
WHAT’S COMMON WITH FEP AND AAS?
Anion Gap
Difference between unmeasured cations - They both uses flame
(Na and K) and unmeasured anions (Cl and
bicarbonate)

A QC for the analyzer

- To measure level of electrolyte

Monitoring of recovery from diabetic

ketoacidosis
- Healthy individuals without DKA but with
abnormal anion gap is indicative of machine
defect not the person being sick.

Anion Gap: Increased Level

Uremia/renal failure
- Greater retention of phosphate and
sulfates
Ketoacidosis
Poisoning of methanol, ethanol, glycol, or
salicylate
Lactic acidosis
Hypernatremia
Instrument Error

Anion Gap: Formula

AG= Na+ - (Cl- + HCO3-)

Reference Value: 8-16 mmol/L