2.

MYOCARDIAL RHYTHM AND CONTRACTILITY (K+ , MG2+,

OSMOLALITY AND ELECTROLYTES 2. ARGININE VASOPRESSIN HORMONE (AVP) CA2+)
WATER • ANTIDIURETIC HORMONE (ADH) 3. NEUROMUSCULAR EXCITABILITY (K+ , MG2+, CA2+)
A. INTRODUCTION • ↑ REABSORPTION OF WATER IN KIDNEYS 4. COFACTORS IN ENZYME ACTIVATION (MG2+, CA2+, ZN2+)
• 40-75% OF BODY WEIGHT ▪ SUPPRESSED IN EXCESS H2O LOAD 5. REGULATION OF ATPASE ION PUMPS (MG2+)
• 30L fluid: passes from blood > tissue spaces ▪ ACTIVATED IN H2O DEFICIT 6. ACID-BASE BALANCE (HCO3-, K+, CL-)
• FUNCTION: 7. PRODUCTION & USE OF ATP FROM GLUCOSE (MG2+, PO4-)
a. TRANSPORT NUTRIENTS TO THE CELLS
b. REMOVES WASTE PRODUCTS SODIUM (Na)
• LOCATION: Aka: Natrium
a. ICF: 2/3 (24 Liters) RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)  major extracellular cation
b. ECF: 1/3 (16 Liters)  principal osmotic particle outside the cell
salt content: main determinant of ECF volume  major contributor of osmolarity: together with Cl and
Sweat: 50 mmol/L sodium + 5 mmol/L potassium HCO3
↓ vasopressin: 10-20 L fluid excretion daily  concentration depends on intake and water excretion
Edema: 3 L fluid retention  (+) serum abnormalities = urine Na & osmolarity
Plasma: 12% ↑ fluid content than whole blood  every 100 mg/dL ↑ in glucose = ↓ 1.6 mmol/L Na
• INTRAVASCULAR (25%) AND INTERSTITIAL FLUID (75%)  Reference value: 135-145 mmol/L (serum)
136-150 mmol/L (CSF)
 Critical value: 160 mmol/L (hypernatremia)
120 mmol/L (hyponatremia)
HORMONES
1. Aldosterone
4. ANP: ↑ NA+ & H2O EXCRETION IN THE KIDNEY
- Na (sodium) retention and K (potassium) excretion
5. GFR: ↑ W/ VOL. EXPANSION & ↓ W/ VOL.
2. Atrial Natriuretic Factor (ANF)
DEPLETION
- Antihypertensive agent
6. VOLUME RECEPTORS
B. OSMOLALITY - Tissue source: Cardiac atria
• CONCENTRATION OF IONS IS MAINTAINED BY: SOLUTE/KG - Block aldosterone and renin secretion
iii. DETERMINATION
SOLVENT - Inhibits action of Angiotensin II and Vasopressin
• OSMOLALITY (SERUM OR URINE)
1. PASSIVE TRANSPORT - Promotes natriuresis.
• ANY SUBSTANCE DISSOLVE IN A SOLVENT WILL:
• PASSIVE MOVEMENT OF 1. ↓FREEZING POINT BY 1.858°C
IONS ACROSS A MEMBRANE METHOD OF ANALYSIS
2. ↑BOILING POINT BY 0.52°C
2. ACTIVE TRANSPORT 1. Emission Flame Photometry
3. ↓ VAPOR PRESSURE (DEW POINT) BY 0.3 MMHG
• REQUIRES ENERGY TO MOVE 2. Ion selective electrode
4. ↑ OSMOTIC PRESSURE BY 17,000 MMHG
IONS ACROSS A MEMBRANE - Glass aluminum silicate: most commonly used.
• MAIN CONTRIBUTORS ARE NA+, CL-, UREA & GLUCOSE
• ATPASE-DEPENDENT ION PUMPS 3. Atomic absorption spectrophotometry
OSMOL GAP - NORMALLY: 290 MMOL/KG
4. Colorimetry
OSMOLALITY AND BLOOD VOLUME - Na precipitated as Zn uranyl acetate
ELECTROLYTES
End color: YELLOW
i. DEFINITION  Ions are capable of carrying an electric charge.
> CONC. OF SOLUTES PER KG OF SOLVENT (MILLIMOLES/KG) o Cations - CARRY (+) CHARGE AND MOVE
HYPERNATREMIA
> REGULATOR TOWARD THE CATHODE - ↑ Na conc.
• E.G. NA+, K+, MG2+, CA2+ - >145 mmol/L
ii. REGULATION: o Anions - CARRY (-) CHARGE AND MOVE - 150-160 mmol/L: moderate water deficit
TOWARD THE ANODE - >165 mmol/L severe water deficit
1. THIRST SENSATION
• E.G. CL-, HCO3-, PO4 Causes: Loss of water, gain of Na or both
• RESPONSE TO CONSUME MORE FLUIDS
 Electroneutrality: equal number of cations & anions 1-2% water deficit = severe thirst
• PREVENTS WATER DEFICIT
Perspiration & breathing: 1 L/day water loss.
FUNCTIONS OF ELECTROLYTES Chronic hypernatremia: Indicative of Hypothalamic disease
1. VOLUME AND OSMOTIC REGULATION (NA+, CL-, K+)
 EXCESS Diabetes ↑ INTAKE Hyperaldosteronism POTASSIUM (K)  renal failure: most common, ↓ GFR & tubular
WATER insipidus, Renal OR (Conn’s disease),
LOSS tubular disorder, RETENTION Sodium bicarbonate  aka: kalium secretion
Prolonged infusion, ↑ oral or  major intracellular cation
diarrhea, IV intake of NaCl,
 reduced distal delivery of sodium.
Profuse Ingestion of  total plasma body potassium = 2%
↓ renal excretion Acute/ chronic renal Extracellular Acidosis,
sweating, seawater  K in RBC: 105 mmol/L
Severe burns, ↓ WATER INTAKE failure, Severe shift Muscle/ cellular
Vomiting,  filtered in glomeruli, reabsorbed by proximal tubule
dehydration, injury,
Hyperventilation  ascending loop pf Henle: K, Na, Cl
Addison’s disease Chemotherapy,
 single most important analyte
HYPONATREMIA ↑ intake Oral or IV infusion Vigorous
- ↓ Na conc.  function: heart contraction, neuromuscular
Use of Tacrolimus and exercise,
- >135 mmol/L excitability, ICF volume and hydrogen ion regulation
- 125-130 mmol/L - + symptoms immunosuppressive Cyclosporine Digitalis
- 130 mmol/L – clinical concern  Reference value: 3.5-5.2 mmol/L
drugs intoxication
- <125 mmol/L – severe neuropsychiatric symptoms  Critical values: 6.5 mmol/L: hyperkalemia
PSEUDOHYPERKALEMIA
- + glucose or mannitol, glycine & ketones (seen in 2.5 mmol/L: hypokalemia
Diabetes Mellitus) - ↑ plasma K levels w/ normal ECG
- SIADH: ↓ aldosterone, ↑ water retention Causes: Hemolysis, Thrombocytosis, Prolonged tourniquet
↑ sodium Diuretic use, ↑ water SIADH, Hepatic METHODS OF ANALYSIS
loss saline infusion retention cirrhosis, Primary application, Fist clenching, High blast counts (leukemia),
↑ water Renal failure, polydipsia, CNS  Hemolysis of 0.5% RBC = ↑ 0.5 mmol/L
Recentrifugation of SST, Blood stored on ice, IV fluid
retention Nephrotic abnormalities,  platelet release: plasma levels are ↓ 0.1-0.7 mmol/L
syndrome, Myxedema,
Aldosterone Barter’s compared to serum
HYPOKALEMIA
def., Cancer Syndrome  muscular activity:
- plasma K levels: 3.0-3.4 mmol/L (mild)
NOTE: K & Na have inversely relationship in kidney ↑ 0.3-1.2 mmol/L: mild-moderate exercise
- ↓ Mg = ↓ K
reabsorption ↑ 2-3 mmol/L: vigorous exercise, fist clenching
- ↓ plasma K (retained) to balance secrete another
 prolonged contact of serum to RBC
HYPONATREMIA with NRF cation (NH4 ion)
Cause Serum Urine 24hr Urine Serum  prolonged tourniquet application
Impaired renal function/ Renal loss – ↑ aldosterone
NA Na urine osmolarit K
 preferred sample: heparinized plasma
Na y Extra renal loss – Diarrhea
Overhydration ↓ ↓ ↓ ↓ N-↓ METHODS OF ANALYSIS Gastrointestinal Gastric suction & Renal Diuretics,
Diuretics ↓ ↓ ↑ ↓ ↓ loss laxative abuse, loss Hyperaldosteronism,
1. Emission Flame Photometry Intestinal tumor & Cushing’s syndrome,
SIADH ↓ ↑ ↑ ↑ N-↓
malabsorption, Cancer Leukemia, Barter’s
Adrenal failure Mild ↑ N ↑ ↑ 2. lon selective electrode valinomycin gel
& radiotherapy syndrome, Gitelman’s
Barter’s ↓ ↓ ↑ ↓ ↓
3. Atomic absorption spectrophotometry Intracellular shift Alkalosis, Insulin syndrome, Malignant
syndrome overdose hypertension
Diabetic ↓ N N N ↑ 4. Colorimetry Lockhead and Purcell Na cobaltinitrite
hyperosmolarity PSEUDOHYPOKALEMIA
End color: BLUE VIOLET
- Leukocytosis: ↓ K levels if left at room temperature
PSEUDOHYPONATREMIA
- Systematic error in measurement HYPERKALEMIA EFFECTS TO CARDIAC MUSCLE
- Artifactual hyponatremia: hyperlipidemia & HYPERKALEMIA HYPOKALEMIA
- ↑ K concentration.
hyperproteinemia ↓ resting membrane potential (RMP) ↑ resting membrane potential (RMP)
↓ Na ↑ Lipids - 3 major mechanisms of ↑ K: ↑ cell excitability ↓ cell excitability
↑ Proteins Plasma levels: Arrhythmia and paralysis
↑ Hemoglobin
 reduced aldosterone: hyporeninemic 6-7 mmol/L alter ECG
8 mmol/L lack of muscle excitability
↑K hypoaldosteronism.
10 mmol/L fatal cardiac arrest
CESSATION OF CONTRACTION
pH imbalance, drugs, hormones  slightly lower values: post prandial specimen 2. Parathyroid hormone (PTH)
Hyperkalemia Hypokalemia
Acidosis - ↑ 0.2-1.7 mmol/L Alkalosis - ↓ 0.4 mmol/L  Cl = ↑ HCO3 interference: bromide, cyanide, cysteine • ↑ kidney reabsorption, mobilization from bones,
↓ insulin ↑ aldosterone 1. Mercuric titration (Schales and Schales) activates bone resorption
Therapeutic K Insulin and catecholamines indicator: diphenylcarbazone • ↓ urinary Ca loss
Hyperkalemic drugs
end product: HgCl2 end color: blue violet • stimulates Vit D Vit D3 (kidneys)
2. Spectrophotometric 3. Calcitonin
A. Mercuric Thiocyanate (Whitehorn titration method): reddish • thyroid hormone
complex • secreted by parafollicular C cells
B. Ferric perchlorate: colored complex • inhibits: PTH, Vitamin D3, bone resorption
3. Coulometric Amperometric titration • ↑ urinary Ca loss THYROID
a. Cotlove Chloridometer
4. Ion Selective Electrode - ion exchange membrane most METHODS OF ANALYSIS
commonly used - specimen of choice: serum
- pH of reagent: + liberation of Ca from albumin
CALCIUM (Ca) 1. Precipitation and redox titration
 99% is the bone; 1% in blood and ECF  Clark Collip precipitation
 maximally absorbed in the duodenum end product: Oxalic acid
 absorption is best at acidic pH end color: purple
 urinary excretion: major net loss b. Ferro Ham Chloranilic Acid precipitation
 function blood coagulation, neural transmission, end product: Chloranilic acid
enzyme activity, the excitability of skeletal and end color: purple
cardiac muscle 2. Ortho-Cresolpthalein Complexone dyes (colorimetric)
 Reference value: dye: arzeno III
Total calcium: 8.6 to 10 mg/dl (adult) Mg inhibitor: 8-hydroxyquinolone (chelator)
8.8 to 10.8 (child) 3. EDTA titration (Bachra, Dowel and Sobel)
Ionized calcium:4.6 to 5.3 mg/dl (adult) 4. lon selective electrode: liquid membrane
4.8 to 5.5 mg/dl (child) 5. Atomic Absorption Spectrophotometry: reference method
IONIZED CALCIUM 50% 6. Emission Flame Photometry orange-red
CHLORINE (Cl) PROTEIN BOUND CALCIUM 40%
 major extracellular anion DIAGNOSTIC SIGNIFICANCE
COMPLEXED W/ ANIONS 10%
 chief counter ton of sodium
 functions: water balance, osmotic pressure (Na & Cl), IONIZED CALCIUM: sensitive & specific for calcium disorders + SYMPTOMS: Total calcium levels <7.5 mg/dL (1.8 mmol/L)
blood volume, electroneutrality ↓ 1g/dL serum albumin= ↓0.8 mg/dL total Ca+2 ↓ Ca ↑ Ca
 enzyme activator: AMS
Prolonged contact to pRBC, Recumbent Venous occlusion, Acidosis,
 excreted via: urine and sweat FACTORS AFFECTING CALCIUM LEVELS
 Reference value: 98-107 mmol/L posture, Alkalosis, Tetany, Parathyroid Dehydration, Hemoconcentration,
1. 1,25-dihydroxycholecalciferol (Activated Vitamin D3)
disease (primary hypocalcemia), Renal Parathyroid hormone-related protein
METHODS OF ANALYSIS • ↑ intestinal absorption, kidney reabsorption,
failure, Estrogen (PTHRP), Secondary
 marked hemolysis: Cl levels (dilution) mobilization from bones
hyperparathyroidism (ionized Acium)
PHOSPHORUS (P) end color: blue METHODS OF ANALYSIS
 counter ion of K wavelength: 340 nm at alkaline pH 1. Colorimetric method
 omnipresent: 85% in bones, 15% in the ECF a. Calmagite method: reddish-violet complex
 inverse relationship with calcium DIAGNOSTIC SIGNIFICANCE b. Formazen dye method: colored complex
 maximally absorbed in jejunum HYPERPHOSPHATEMIA HYPOPHOSPHATEMIA c. Magnesium thymol blue method: colored complex
 function: phosphorylation of glucose, co-entry of K Hypoparathyroidism, Renal Alcohol Abuse, Primary 2. Atomic absorption spectrophotometry: reference method
 inorganic phosphate: most predominant in serum failure, Lymphoblastic leukemia, hyperthyroidism, 3. Dye-Lake method
 Reference values: 2.7-4.5 mg/dl (adult) Hypervitaminosis D, Renal Avitaminosis D, a. Titan yellow dye
4.5-5.5 mg/dl (child) tubular defects (↑ phosphate, Myxedema, Transcellular • Clayton yellow
<1.0 g/dL or 0.3 mmol/L (severe) calcium, ↑ BUN and Creatinine) shift (major) • Thiazole yellow
INORGANIC PHOSPHORUS
1. Organic phosphate: principal anion within the cells MAGNESIUM (Mg) DIAGNOSTIC SIGNIFICANCE
2. Inorganic phosphate: part of the blood buffer  2nd major intracellular cation HYPERMAGNESEMIA HYPOMAGNESEMIA
FORMS OF PHOSPHORUS  4th most abundant cation in body Diabetic coma, Addison's Acute renal failure,
1. Free or Unbound form: 55%  enzyme activator: CK and ALP disease, Chronic renal failure, Malnutrition, Malabsorption
2. Complexed with lons: 35% 3. Protein bound: 10%  stored in: 53% bones, 46% muscles and soft tissues, ↑ intake of antacids, syndrome, Chronic
HORMONES AFFECTING PHOSPHATE LEVEL 1% serum and RBC enemas, and cathartics alcoholism, Severe diarrhea
1. Parathyroid hormone - ↓ phosphate by renal excretion  ↓ Mg= ↓ K
2. Calcitonin - inhibits bone resorption  reference values: 1.2-2.1 mEq/L BICARBONATE
3. Growth hormone - ↑ renal phosphate reabsorption 5 mmol/L (life threatening)  2nd most abundant anion in the ECF
 function: vasodilator, uterine hyperactivity in  HCO3 = undissociated NaHCO3, carbonate,
METHODS OF ANALYSIS eclampsia; ↑ uterine blood flow; maintaining carbamate
- fasting is required: ↑carbohydrate diet = ↓ structures od DNA, RNA, ribosomes; synthesis of  accounts 90% of total CO2
phosphorus CHO, CHON, lipids; neuromuscular transmission;  ↑ bicarbonate: renal failure
- pH dependent cofactor, regulate movement of K in the myocardium  function: major component of the blood buffer
- separate pRBC and serum immediately system
- PO4: form measure in the laboratory FORMS OF MAGNESIUM  specimen: blood anaerobically collected
- mEq/L: unit of measurement 1. Free/lonized form: 55% (serum/heparinized)
- circadian rhythm: ↑ in late morning, evening 2. Protein bound: 30%  specimen left uncapped: + 6 mmol/L
1. Fiske Subbarow method (Ammonium molybdate method) - 3. Complexed with ions: 15%
most commonly used METHOD OF ANALYSIS
reducing agents: HORMONES AFFECTING MAGNESIUM LEVELS 1. lon selective electrode
a. Pictol (Amino naphthol sulfonic acid) 1. Parathyroid hormone  pCO2 electrode
b. Elon (Methyl amino phenol)  + renal reabsorption of magnesium 2. Enzymatic
c. Ascorbic acid  ↑ intestinal absorption of magnesium  phosphoenolpyruvate carboxylase
d. Senidine (N-phenyl-p-phenylene diamine hydrochloride) 2. Aldosterone and Thyroxine  phosphoenolpyruvate dehydrogenase
end product: ammonium molybdate complex  ↑ renal excretion of magnesium