Major Extra and Intracellular electrolytes - Pharmaceutical Inorganic Chemistry B. Pharma 1st Semester

Major Extra and Intracellular electrolytes

Contents

• Body fluid compartments

• Electrolytes

• Hormones which regulates the electrolyte

• Functions of electrolytes

• Physiological role of acid, bases, buffers, sodium ion, Chloride ion, bicarbonate ion, Phosphate ion, calcium ion, magnesium ion and potassium ion

• Buffer system present in human body

• Metabolic acidosis and metabolic alkalosis

• Monograph analysis of compounds used as electrolyte replenisher

Learning Objectives

At the end of this lecture, the student will be able to:

• Define electrolytes

• List, describe and compare the body fluid compartments

• Compare the compositions of intracellular and extracellular fluids

• Identify the hormones that play important roles in regulating fluid and electrolyte balance

• Describe the function of Electrolytes

• List the normal concentration of cations and anions present in the body fluid compartments

• Describe the physiological role of sodium ion and potassium ion

• Describe the physiological role of:

 Chloride ion

 Bicarbonate ion

 Phosphate ion

 Calcium ion

 Magnesium ion

• Calculate the amount of electrolyte in terms of milliequivalnet

• Discuss the physiological role of acid and bases and buffers

• Describe the different buffer system present in the body

• Define metabolic acidosis and metabolic alkalosis

• Explain the monograph analysis of:

 Sodium Chloride

 Potassium chloride

 Calcium Gluconate

 Oral dehydration salts

Introduction

Electrolytes: Substances whose molecules dissociate into ions when they are placed in water

Medically significant / routinely ordered electrolytes include:

CATIONS (+)

ANIONS (-)

Cation: Positively Charged particles

Sodium (Na+)

Potassium (K+)

Calcium (Ca++)

Magnesium (Mg++)

Anion: Negatively charged particles

Chloride (Cl-)

Bicarbonate (HCO3-)

Phosphate (HPO4-)

The Composition of the Human Body

Body Fluids: Introduction

• Total amount of fluid in the human body is approximately 70% of body weight

Body fluid has been divided into two compartments:–

Intracellular fluid (ICF)

• Inside the cells

• 55% of total body

Extracellular fluid

• Outside the cells

• 45% of total water body water

Extracellular fluid includes

Interstitial fluid

Present between the cells

Approximately 80% of ECF

Plasma

Present in blood

Approximately 20% of ECF

Also includes

Lymph

Synovial fluid

Aqueous humor

Cerebrospinal fluid

Compartment separation:

Barriers separate ICF, interstitial fluid and plasma:

Plasma membrane:

Separates ICF from surrounding interstitial fluid

Blood vessel wall:

Separate interstitial fluid from plasma

Body Fluid Compartments in human system

Composition of body fluids

Inorganic substances	Organic substances
• Sodium • Potassium • Calcium • Magnesium • Chloride • Phophate • Sulphate	• Glucose • Amino acids • Fatty acids • Hormones • Enzymes

Methods of fluid & electrolyte movement

• Diffusion

• Osmosis

• Active Transport

• Filtration

Diffusion

• Process by which a solute in solution moves

• Involves a gas or substance

• Movement of particles in a solution

• Molecules move from an area of higher concentration to an area of lower concentration

• Evenly distributes the solute in the solution

For eg: diffusion of CO2 and O2 at respiratory epithelia

Osmosis

• Movement of the solvent or water across a membrane

• Involves solution or water

• Equalizes the concentration of ions on each side of membrane

• Movement of solvent molecules across a membrane to an area where there is a higher concentration of solute that cannot pass through the membrane

Active transport system

• Moves molecules or ions uphill against concentration & osmotic pressure

• Hydrolysis of adenosine triphosphate (ATP) provides energy needed

• Requires specific “carrier” molecule as well as specific enzyme (ATPase)

• Sodium, potassium, calcium, magnesium, plus some sugars, & amino acids use it

Filtration

• Movement of fluid through a selectively permeable membrane from an area of higher hydrostatic pressure to an area of lower hydrostatic pressure

• Arterial end of capillary has hydrostatic pressure > than osmotic pressure so fluid & diffusible solutes move out of capillary

Hormones involved Fluid balance and electrolyte balance

Fluid balance and electrolyte balance are mediated by three hormones:

• Antidiuretic hormone (ADH)

• Aldosterone

• Renin

ADH (Antidiuretic Hormone)

• Produced in hypothalamus; water conservation hormone

• Stored in posterior pituitary gland

• Acts on renal collecting tubule to regulate reabsorption or elimination of water

• If blood volume decreases, then ADH is released & water is reabsorbed by kidney. Urine output will be lower but concentration will be increased.

Aldosterone

• Produced by adrenal cortex

• Released as part of RAA mechanism

• Acts on renal distal convoluted tubule

• Regulates water re absorption by increasing sodium uptake from the tubular fluid into the blood but potassium is excreted

• Responsible for re absorption of sodium & water into the vascular compartment

RENIN

• Released by kidneys in response to decreased blood volume

• Causes angiotensinogen (plasma protein) to split & produce angiotensin I

• Lungs convert angiotensin I to angiotensin II

• Angiotensin II stimulates adrenal gland to release aldosterone & causes an increase in peripheral vasoconstriction

Electrolyte Functions in general:

• Volume and osmotic regulation

• Myocardial rhythm and contractility

• Cofactors in enzyme activation

• Regulation of ATPase ion pumps

• Acid-base balance

• Blood coagulation

• Neuromuscular excitability

• Production of ATP from glucose

Normal plasma range of Electrolytes

Cations

Major cations inside the cell (ICF) include

• Sodium (Na)

• Potassium (K)

• Magnesium (Mg)

Major cations outside the cell (ECF) include

• Sodium (Na)

• Potassium (K)

• Calcium (Ca)

• The concentration of cations inside the cell and outside the cell differs as shown  in figure on the right e.g. there is much  higher concentration of potassium in the ICF than in the ECF,  there is much higher concentration of sodium in the ECF than in the ICF.

Anions

Major Anions inside the cell (ICF) include

• Chloride (Cl)

• Proteins

• Phosphates (HPO4)

• Bicarbonate (HCO3)

• SO4

Major Anions outside the cell (ECF) include

• Chloride (Cl)

• Proteins

• Phosphates (HPO4)

• Bicarbonate (HCO3)

• SO4

• The concentration of anions inside the cell and outside the cell differs as shown in figure on the right e.g. there is much higher concentration of proteins and Phosphate in the ICF than in the ECF,  there is much higher concentration of chloride in the ECF than in the ICF

Cations and Anions in Body Fluids

• Despite the differences in the concentration of specific substances, the ICF and ECF osmotic concentrations are identical

• If the cell membrane were freely permeable, diffusion would continue until these ions were evenly distributed across the membrane

Sodium (Na+)

• Range 135 - 145 mEq /L in serum

• Total body volume estimated at 40 mEq/kg

• 1/3 fixed to bone, 2/3 extracellular and available for Trans membrane exchange

• Normal daily requirement 1-2 mEq/kg/day

• Chief extracellular cation about 90%

Food Sources

High Sodium	Low Sodium
Bacon Corned beef Ham Catsup Potato chips Pickles Olives Soda crackers Tomato juice Beef cubes Dill Decaffeinated coffee	Fruit Fresh Frozen canned Unsalted grains Pastas Oatmeal Popcorn Shredded wheat Fresh meats

Sodium function

•Transmission and conduction of nerve impulses

•Responsible for osmolality of vascular fluids

•Regulation of body fluid levels

•Sodium shifts into cells and potassium shifts out of the cells (sodium pump)

•Assists with regulation of acid-base balance by combining with Cl- or HCO3 to regulate the balance

Clinical Features:

• IF serum sodium ions is < 135 mmol/L Hyponatremia

•Increased Na+ loss

• Aldosterone deficiency

• Addison’s disease (hypo-adrenalism, result in desearsed aldosterone)

• Diabetes mellitus

• In acidosis of diabetes, Na is excreted with ketones

• Potassium depletion

• K normally excreted, if none, then Na

• Loss of gastric contents

Clinical manifestations of Hyponatremia

• Neurological symptoms: Lethargy, headache, confusion, apprehension, depressed, reflexes, seizures and coma

• Muscle symptoms: Cramps, weakness, fatigue

• Gastrointestinal symptoms: Nausea, vomiting, abdominal cramps and diarrhoea

Hypernatremia: Serum Sodium exceeds 145 meq/liter

Clinical Features: Hypertonic IV solution

• Oversecretion of aldosterone

• Loss of pure water

• Long term sweating with chronic fever

• Respiratory infection → water vapor loss

• Diabetes – polyuria

• Insufficient intake of water ( hypodipsia hypodipsia)

• Cushing's syndrome - opposite of Addison’s

Clinical manifestations of Hypernatremia

• Thirst

• Lethargy (Lack of energy)

• Neurological dysfunction due to dehydration of brain cells

• Decreased vascular volume

Treatment of Hypernatremia

• Lower serum Na+

• Isotonic salt -free IV fluid

• Oral solutions preferable

Potassium ions( K+)

Potassium normal values

Serum (adults) – 3.5 - 5.3 mEq/L

Newborns slightly higher – 3.7 - 5.9 mEq/L

• Range 3.5 - 5.0 mEq mEq/L in serum

• Total body volume estimated at 50 mEq/kg

• 98% intracellular concentration of 150 mEq mEq/L

• Extracellular concentration of 70 mEq/L

• Normal daily requirement 0.5 – 0.8 mEq/kg/day

• Chief intracellular cation

Potassium Function:

• Most abundant intracellular cation

 Necessary for transmission and conduction of nerve impulses

• Maintenance of normal cardiac rhythm

 Necessary for smooth and skeletal muscle contraction

Food sources – veggies, fruits, nuts, meat

Causes of Hypokalemia

• Increased K+ loss

• Chronic diuretics

• Acid/base imbalance

• Trauma and stress

• Increased aldosterone

• Redistribution between ICF and ECF

• Hepatic disease

• Acute alcoholism

Clinical manifestations of Hypokalemia

• Neuromuscular disorders

• Weakness, flaccid paralysis, respiratory arrest, constipation

• Dysrhythmias: appearance of U wave

• Postural hypotension

• Cardiac arrest

Treatment: Increase K+ intake, but slowly, preferably by foods

Hyperkalemia

• Serum K+ > 5.5 mEq / L

• Check for renal disease

• Massive cellular trauma

• Insulin deficiency

• Addison Addison’s disease

• Potassium sparing diuretics

• Decreased blood pH

• Exercise causes K+ to move out of cells

Treatment of Hyperkalemia

If time, decrease intake and increase renal excretion

• Insulin + glucose

• Bicarbonate

• Ca++ counters effect on heart

Chloride Cl-

– The normal adult value for chloride is 97-107 mEq/L.

– Chloride is the major extracellular anion

– Moves relatively easily between ECF and ICF because most plasma membranes contain Cl

– Leakage channels and antiporters

– Can help balance levels of anions in different fluids

• Chloride shift in RBCs

– Regulated by

• ADH – governs extent of water loss in urine

• Processes that increase or decrease renal reabsorption of Na+ also affect reabsorption of Cl-

• Chloride is an important electrolyte

• Maintains body's metabolism

• Maintains water balance, acid-base balance, aids in digestion (hydrochoric acid) & osmotic pressure (with Na and H20) Combines with Na to form salts

• Regulated by kidneys

Source of foods – Citrus fruits, Salt

Clinical features: Hyperchloremia

Hyperchloremia (increased plasma Cl concentration)

• Serum level > 106mEq/

Causes of hyperchloremia

May include:

• Loss of body fluids from prolonged vomiting, diarrhea, sweating or high fever (dehydration).

• High levels of blood sodium.

• Kidney failure, or kidney disorders

• Diabetes insipidus or diabetic coma

• Drugs such as: androgens, corticosteroids, estrogens, and certain diuretics

Treatment: restore fluid & electrolyte balance

Symptoms of Hyperchloremia

•Many people do not notice any symptoms of hyperchloremia, unless they are experiencing very high or very low levels of chloride in their blood

•Dehydration, fluid loss, or high levels of blood sodium may be noted.

•Diarrhea, or vomiting when suffering from hyperchloremia

•Arrhythmias, decreased cardiac output, muscle weakness, LOC changes, Kussmauls’s respirations

Clinical features: Hypochloremia

Hypochloremia (decreased plasma Cl concentration)

 Serum level 96mEq/L

 Results from prolonged vomiting & suctioning

 Is observed in salt-losing nephritis as associated with chronic pyelonephritis

Treatment: diet/IV therapy

Causes of hypochloremia may include:

•Loss of body fluids from prolonged vomiting, diarrhea, sweating or high fevers

•Drugs such as: bicarbonate, corticosteroids, diuretics, and laxatives

Symptoms of Hypochloremia

• Dehydration, fluid loss, or high levels of blood sodium may be noted

• Diarrhea, or vomiting

• Metabolic alkalosis

• Nerve excitability

• Muscle cramps

• Twitching

• Hypoventilation

• Decreased BP if severe

Phosphate   PO^4-

• Principal anion of intracellular fluid compartment

• Plasma 1.7-2.6 mEq/liter

• Phosphate (H2PO^{4 -,} HPO4^2-, PO4 ^3-)

• Most (85%) is stored in bone as calcium salts

• Also combined with lipids, proteins, carbohydrates, nucleic acids (DNA and RNA), B vitamin synthesis

• High energy phosphate transport compound

• Important acid-base buffer in body fluids

Source of foods: Dairy product, meats, poultry, fish, egg, nuts.

Function of phosphate:

•Involved in acid–base buffering system, ATP production, and cellular uptake of glucose

•Maintenance requires adequate renal functioning

•Essential to muscle, RBCs, and nervous system function

Clinical features: Hypophosphatemia

• Serum level < 1.8mEq/L

• Results from decreased intestinal absorption and increased excretion

• S/S bone & muscle pain, mental changes, chest pain, respiratory failure

Treatment: Diet/ IV therapy

Management

– Oral supplementation

– Ingestion of foods high in PO4^3-

– IV administration of sodium or potassium phosphate

Clinical features: Hyperphosphatemia

• Serum level> 2.6mEq/L

• Results from renal failure, low intake of calcium

• S/S: neuromuscular changes (tetany), EKG changes, parathesia-fingertips/mouth

Treatment: Diet; hypocalcemic interventions   Medications: phosphate binding

• The body can tolerate hyperphosphatemia fairly well BUT the accompanying hypocalcemia is a larger problem!

Treatment:

– Identify and treat underlying cause

– Restrict foods and fluids containing PO4^3-

– Adequate hydration and correction of hypocalcemic conditions

Bicarbonate HCO^3-

• Bicarbonate 22-28 mEq/L

• Second most prevalent extracellular anion

• Principle buffer of body pH. (Extracellular)

• Neutralizes acids

• Plays important role in acid / base balance

• Acts as chemical sponge to soak up Hydrogen ions

• (Acidic metabolic waste) for every one Hydrogen ion twenty bicarbonate ions are released to maintain balance

Regulation:

 Bicarbonate is regulated by secretion / reabsorption of the renal tubules

Acidosis : ↓ renal excretion

Alkalosis : ↑ renal excretion

 Kidney regulation requires the enzyme carbonic anhydrase - which is present in renal tubular cells & RBCs carbonic anhydrase

Reaction: CO2 + H2O ⇋ H2CO3 → H⁺ + HCO^3–

Clinical Significance:

• Alterations of HCO^3- and CO2 dissolved in plasma are characteristic of acidbase imbalance

• When acid-base imbalance is suspected, evaluation of blood gases and pH is required

- Increase in CO2 occur in metabolic alkalosis due to:

eg: severe vomiting,hypokalemic states

- Decrease in CO2 are seen in: eg: renal failure

Calcium Ca++

• In body fluids mainly an extracellular cation ---4.5-5.5mEq/L

• Most abundant in body but: 99% in teeth and bones

• Needed for nerve transmission, vitamin B12 absorption, muscle contraction & blood clotting

• Inverse relationship with Phosphorus

• Vitamin D needed for Calcium absorption

• The most abundant mineral in the human body

Food sources for calcium ions

Dairy foods: Milk, yogurt, cheese

Leafy green vegetables: Broccoli, kale, spinach

Fruits: Oranges

Beans and peas: Tofu, peanuts, peas, black beans, baked beans

Fish: Salmon, sardines

Miscellaneous: Sesame seeds, blackstrap molasses, corn tortillas, almonds, brown sugar

How it functions in body metabolism

• 99% of total body calcium is stored in the bones and teeth

• 1% is found throughout the body in blood, muscle, and the fluid between cells

 45% circulates as free Ca ions

 40% bound to albumin

 15% bound to anions

• Ionized calcium is usually a more sensitive and specific for calcium disorders

Physiological function of calcium ions

• The normal transmission of nerve impulses

• Calcium flows into nerve cells and stimulates the release of molecules called neurotransmitters

• The role in muscle contraction

• Healthy blood pressure

• The initiation of blood clotting and

• The regulation of various hormones and enzymes

Physiological function of calcium ions

Can it be synthesized by the human body or must it come from other sources

• Body needs calcium to build and maintain strong bones and teeth

• Absorb calcium every day from dietary intake because body does not make calcium

Clinical Features: Hypocalcemia

• Serum Calicum < 4.3mEq/L

• Results from low intake, loop diuretics, parathyroid disorders, renal failure

• Treatment: diet/IV therapy

• What are some medical conditions that may cause hypocalcemia?

Hypoparathyroidism (low PTH levels = decreased release of Ca from bones)

S/P thryoid surgery (low Calcitonin = decreased release of Ca from bones)

Acute pancreatitis

Crohns Disease (inflammatory bowel disease)

Hyperphosphatemia (ESRF)

• What are some other conditions that might cause low Ca?

GI losses – nasogastric suctioning, vomiting, diarrhea

Long term immobilization

Lactose intolerance

• If hypocalcemia is prolonged, the body will utilize stored Ca from bones. What complication might arise?

Fractures (late sign)

Treatment of hypocalcaemia

Calcium, Vitamin D

Clinical Features: Hypercalcemia

• Serum Ca > 5.3mEq/L

• Results from hyperparathyroidism, some cancers, prolonged immobilization

• S/S muscle weakness, renal calculi, fatigue, altered LOC, decreased GI motility, cardiac changes

• Treatment: medication/ IV therapy

• What are some medical conditions that may cause hypercalcemia?

Hyperparathyroidism (high PTH levels = increased release of Ca from bones)

Paget ’s disease

Some Cancers – Multiple Myleoma

Chronic Alcoholism (with low serum phosphorus)

• What are some other conditions that might cause low Ca?

Excessive intake of Ca OR Vitamin D

Excessive intake of OTC antacids

If hypercalcemia is uncorrected, AV block and cardiac arrest may occur

Magnesium Mg ²⁺

• The eighth most abundant element in the earth’s crust

• Body concentration: 1.5-2.5mEq/L

• Most located within ICF

• Needed for activating enzymes, electrical activity, metabolism of proteins, DNA synthesis

• Regulated by intestinal absorption and kidney

• Magnesium plays important roles in the structure and the function of the human body

Food Sources for magnesium ion

• Green vegetables such as spinach because the center of the chlorophyll molecule (which gives green vegetables their color)

• Legumes (beans and peas)

• Nuts and seeds

• Unrefined grains

• Tap water (varies according to the water supply)

How it functions in body metabolism

• Activates more than 300 enzymes (energy related)

• Regulates (Ca, K, and Na) transmission of nerve impulses. Calcium contract muscles and magnesium relax muscles

• Ensures proper DNA and RNA formation and function

• Facilitates PTH secretion

• Helps to regulate blood sugar levels, promotes normal blood pressure

• Involve in energy metabolism and protein synthesis

Metabolism of magnesium ion in the body

• Healthy individuals absorbs 40-60% magnesium consumed

• Absorption enhanced by calcium, phosphorus and fat

• Long term storage in the bones

• Kidney is the organ regulate magnesium homeostasis

• 90% of filtered magnesium is reabsorbed by the kidneys in response to salt and H2O reabsorption

Can it be synthesized by the human body or must it come from other sources

• Magnesium is a mineral, so therefore just like calcium, magnesium must be absorbed through dietary intake

• 50% of total body magnesium is found in bone

• The other half is found predominantly inside cells of body tissues and organs

• Only 1% of magnesium is found in blood, but the body works very hard to keep blood levels of magnesium constant

Clinical Features: Hypomagnesemia

• Serum < 1.5mEq/L

• Results from decreased intake, prolonged NPO status, chronic alcoholism & nasogastric suctioning

• S/S: muscle weakness, cardiac changes, mental changes, hyperactive reflexes & other hypocalcemia S/S

• Treatment: replacement IV therapy restore normal Ca levels (Mg mimics Ca) seizure precautions

Clinical Features: Hypermagnesemia

• Serum>2.5mEq/L

• Results from renal failure, increased intake

• S/S: Flushing, lethargy, cardiac changes (decreased HR), decreased respiratory, loss of deep tendon reflexes

• Treatment: Restrict intake,diuretic

Concentration for expressing electrolytes:

The concentration of electrolytes in solution is expressed in terms of milli equivalents (mEq)

• Refers to the chemical activity of an electrolyte

• Is related to the total number of ionic charges in solution and considers the valence (charge) of each ion

• For a given chemical compound, the milli equivalents of cations equals that of anions

Example: a solution of NaCl will contain the same number of milliequivalents of Na+ (the cation) as it will Cl- (the anion)

• There is a trend to shift from using mEq to using mg of the given ion

• Beware that this can be confusing! They are not EQUIVALENT!!! And mg of a given ion is not equivalent to mg of the compound

For example:  mEq CaCl2 is not equal to mg CaCl2 which is not equal to mg Ca ion

Milli equivalents Formula:

• mEq = represents amount in milligrams, of a solute equal to 1/1000 of its gram equivalent weight taking into account the valence of the ions.

mEq = mg x valence / atomic, molecular or formula weight

mg = mEq x atomic, molecular or formula weight / valence

Equivalent weight = formula weight divided by the total valence

Equiv Weight (g) = atomic, molecular or formula weight / valence

Acids and Bases and Buffers

• Acids– Release H+ into solution

• Bases– Remove H+ from solution

• Acids and bases– Grouped as strong or weak

• Buffers: Resist changes in pH

– When H+ added, buffer removes

– When H+ removed, buffer replaces

• Types of buffer systems

– Carbonic acid/bicarbonate

– Protein

– Phosphate

Acid-base Balance

The importance of pH control

• The pH of the ECF remains between 7.35 and 7.45

– If plasma levels fall below 7.35 (acidemia), acidosis results

– If plasma levels rise above 7.45 (alkalemia), alkalosis results

– Alteration outside these boundaries affects all body systems

e.g. can result in coma, cardiac failure, and circulatory collapse

Regulation of blood pH

• The lungs and kidneys play important role in regulating blood pH

• The lungs regulate pH through retention or elimination of CO2 by changing the rate and volume of ventilation

• The kidneys regulate pH by excreting acid, primarily in the ammonium ion (NH4+), and by reclaiming HCO3- from the glomerular filtrate (and adding it back to the blood)

Mechanisms of pH control

• Buffer system consists of a weak acid and its anion

• Three major buffering systems:

– Carbonic acid-bicarbonate

• Buffers changes caused by organic and fixed acids

– Protein buffer system

• Amino acid

– Hemoglobin buffer system

• H+ are buffered by hemoglobin

Carbonic Acid-Bicarbonate Buffering System

• Carbonic acid-bicarbonate buffer system

– CO2 + H2O ßà H2CO3 ßà H⁺ + CO3^–

• Has the following limitations:

– Cannot protect the ECF from pH changes due to increased or depressed CO2 levels

– Only functions when respiratory system and control centers are working normally

– It is limited by availability of bicarbonate ions (bicarbonate reserve)

Carbonate buffer system

H2CO3 + H2O ↔ H3O⁺ + HCO3^-

• Excess acid (H3O+) in the body is neutralized by HCO3-

• H2CO3 + H2O ← H3O⁺ + HCO3^-

Equilibrium shifts left

• Excess base (OH-) reacts with the carbonic acid (H2CO3)

• H2CO3 + OH- → H2O + HCO3-

Equilibrium shifts right

Protein buffer system

• Proteins contain – COO^- groups, which, like acetate ions (CH3COO^-), can act as proton acceptors.

• Proteins also contain – NH3⁺ groups, which, like ammonium ions (NH4⁺), can donate protons.

• If acid comes into blood, hydronium ions can be neutralized by the – COO^- groups

- COO^- + H3O⁺ → - COOH + H2O

• If base is added, it can be neutralized by the – NH3⁺ groups

- NH3⁺ + OH^- → - NH2 + H2O

Phosphate buffer system

• The phosphate buffer system (HPO4^2-/H2PO4^-) plays a role in plasma and erythrocytes.

H2PO4^- + H2O ↔ H3O⁺ + HPO4^2-

• Any acid reacts with monohydrogen phosphate to form dihydrogen phosphate

H2PO4^- + H2O ← HPO4^2- + H3O⁺

• The base is neutralized by dihydrogen phosphate

H2PO4^- + OH^- → HPO4^2- + H3O⁺

Kidney excretion of H⁺

– Metabolic reactions produce nonvolatile acids

– One way to eliminate this huge load is to excrete H⁺ in urine

– In the proximal convoluted tubule, Na+ /H+ antiporters secrete H+ as they reabsorb Na+

– Intercalated cells of collecting duct include proton pumps that secrete H+ into tubule fluid

– Urine can be up to 1000 times more acidic than blood

– 2 other buffers can combine with H+ in collecting duct

• HPO4^2- and NH3

Acid-base imbalances

– Normal pH range of arterial blood 7.35-7.45

• Acidosis – blood pH below 7.35

• Alkalosis – blood pH above 7.45

– Major physiological effect of

• Acidosis – depression of synaptic transmission in CNS

• Alkalosis – overexcitability of CNS and peripheral nerves

Metabolic acidosis/alkalosis

• Results from changes in HCO3^- concentration

– Metabolic acidosis – abnormally low HCO3^- in systemic arterial blood

• Loss of HCO3^- from severe diarrhea or renal dysfunction

• Accumulation of an acid other than carbonic acid – ketosis

• Failure of kidneys to excrete H⁺ from metabolism of dietary proteins

• Hyperventilation can help

• Administer IV sodium bicarbonate and correct cause of acidosis

Clinical Features: Metabolic acidosis

– Abnormally high HCO3^- in systemic arterial blood

• Nonrespiratory loss of acid - vomiting of acidic stomach contents, gastric suctioning

• Excessive intake of alkaline drugs (antacids)

• Use of certain diuretics

• Severe dehydration

• Hypoventilation can help

• Give fluid solutions to correct Cl^-, K⁺ and other electrolyte deficiencies and correct cause of alkalosis

Monograph of Sodium chloride

Name: sodium chloride

Chemical formula: Nacl

Molecular weight: 58.4

Standards: Sodium Chloride contains not less than 99.0 per cent and not more than 100.5 per cent of NaCl, calculated on the dried basis

Synonyms: common salt

Method of Preparation:

Industrially, Laboratory

Industrially: By the evaporation of sea water

Laboratory: By neutralization process

Chemical reaction:

NaOH + HCl à NaCl + H2O

Properties of Sodium chloride:

Description:

 White or colourless crystals or a white crystalline powder

Solubility: Freely soluble in water

Test for purity

•Appearance of solution

•Acidity or alkalinity

•Bromide

•Iron

•Arsenic

•Loss on drying

•Calcium and magnesium

•Sulphates

• Heavy metals

• Barium

•Iodide

Assay Principle

Precipitation titration, Modified Volhards Method

Nitrobenzene /dilute HNO3

NaCL + AgNO3 -------------------------------------à AgCl + NaNO3 + AgNO3

                                            excess

NH4SCN + AgNO3 à  AgSCN + NH4NO3

                                                                                            Unreacted

NH4SCN + Ferric alum à Ferric thiocyanate

Storage: Store protected from light

Medicinal uses:

•Manufacturing dialysis fluid

•Electrolytic replenisher

•Common Salt

Monograph of Potassium chloride

Name: Potassium chloride

Chemical formula: KCl

Molecular weight: 74.6

Standards: Potassium Chloride contains not less than 99.0 per cent and not more than 100.5 per cent of KCl, calculated on the dried basis

Synonyms:  Sylvine, sylvite

Method of Preparation:

It is prepared by neutralization of potassium hydroxide and hydrochloric acid

KOH + HCl à KCl + H2O

Properties of Potassium chloride:

Description: Colourless, Elongated, Prismatic or Cubical crystals or White granular powder, Odourless

Solubility: Freely soluble in water; insoluble in ethanol

Test for purity

•Iodides

•Appearance of solution

•Bromides

•Heavy metals

•Iron

•Arsenic

•Calcium and magnesium

•Sulphates

• Barium

•Loss on Drying

•Acidity or alkalinity

Assay Principle

Precipitation titration, Mohr’s Method

KCL + AgNO3 à AgCl + KNO3

Indicator: Potassium chromate

Colour change: Yellow to Brick red

Storage: Store protected from moisture

Medicinal uses:

•Seasoning agent

•Electrolytic replenisher

•Gelling agent

•Yeast food

Monograph of Calcium Gluconate

Name: Calcium Gluconate

Chemical formula: C12H22CaO14. H2O

Molecular weight: 448.4

Standards: Calcium gluconate contains not less than 98.0 per cent and not more than 102.0 per cent of calcium gluconate, calculated on the dried basis

Properties of Calcium gluconate :

Description: Colourless or White granular powder, Crystalline, Odourless, Stable in air

Solubility: Freely soluble in boiling water; insoluble in ethanol, chloroform and ether

Assay of calcium gluconate

Buffer: Ammonia and ammonium chloride solution

Indicator: Modarant Black II

Colour change: Pink – blue

Storage: Store protected from moisture

Medicinal uses:

•Hypocalcaemia

•Electrolytic replenisher

Oral Rehydration Salts

Name: Oral Rehydration Salts

Standards: Oral Rehydration Salts contain not less than 90.0 per cent and not more than 110.0 per cent of the stated amount of Dextrose (anhydrous) or Dextrose Monohydrate (as appropriate) and of the requisite amounts of sodium, Na, potassium, K, chloride, Cl, and citrate, C6H5O7, calculated from the stated amounts of the relevant constituents.

ORS Powder

Oral Rehydration Salts are dry, homogeneously mixed powders containing Dextrose, Sodium Chloride, Potassium Chloride and either Sodium Bicarbonate or Sodium Citrate for use in oral rehydration therapy after being dissolved in the requisite amount of water

Storage:

•Store protected from moisture in sachets, preferably made of aluminium foil,

•containing sufficient powder for a single dose or for a day’s treatment or

•for use in hospitals, in bulk containers containing sufficient quantity to produce a volume of solution appropriate to the daily requirements of the hospital concerned

Labelling. The label states

(1) For sachets, the total weights, in g, of each constituent

(2) For bulk containers, the weights, in g, of each constituent in a stated quantity, in g, of the oral powder

(3)The molar concentration in millimoles per litre of sodium, potassium, chloride and citrate ions, and of dextrose as well as the total osmolar concentration in mOsmol per litre of the solution prepared from the oral powder

(4) The total weight of the contents of the container

(5) The directions for use

(6) That any portion of the solution prepared from the oral powder that remains unused for 24 hours after preparation should be discarded

(7) The storage conditions

Properties of ORS:

Description: white to creamy-white, amorphous or crystalline powder, odourless

Solubility: Freely soluble in water

Test for purity

•Uniformity of weight

•Seal test

•Other test as per oral powders

Medicinal uses:

•Maintaining acid base balance in body fluid

•Electrolytic replenisher

Summary

•The compositions of intracellular and extracellular fluids

•The movement of fluid that takes place within the ECF, between the ECF and the ICF, and between the ECF and the environment

•The hormones play important role in regulating fluid and electrolyte balance

Electrolytes play a major role in the body fluid compartments: Osmotic regulation, myocardial, acid base balance, blood coagulation

• The cations: Sodium, potassium, magnesium

• The anion: Chloride, phosphate, bicarbonate, sulphate

• Sodium: Major cat ion found in ECF

Function: Nerve impulses, sodium potassium pump.

Deficiency: Hyponatraemia - Sodium ions replacement

Hypernatraemia-Less sodium content

• Potassium: Higher concentration in the ICF

Maintains intracellular, functioning of excitable cells

Deficiency: Hypokalaemia -Replacement of potassium ions

Hyperkalaemia- Insulin + glucose, bicarbonate

• Chloride: The major extracellular anion, 97-107 mEq/L,regulated by ADH,maintains body metabolism, water and acid base balance, mainly with sodium ions

Deficiency: Hyperchloremia:Serum level > 106mEq/L

Treatment: restore fluid & electrolyte balance

Hypochloremia: Serum level > 106mEq/L

Treatment: restore fluid & electrolyte balance

• Phosphate PO4- : Plasma 1.7-2.6 mEq/liter, important acid-base buffer in body fluids

Deficiency:

Hypophosphatemia: Serum level < 1.8mEq/L

Treatment: Diet/ IV therapy

Hyperphosphatemia Serum level> 2.6mEq/L

Treatment: Diet; hypocalcemic interventions

Medications: phosphate binding

• Bicarbonate: Second most prevalent extracellular anion, 22-28mEq/L concentration, principle buffer of the body pH

• Change in the concentration of bicarbonate ions can form metabolic acidosis and metabolic alkalosis

• Calcium: Mainly an extracellular cation ---4.5-5.5mEq/L,99% of total body calcium is stored in the bones and teeth,1% is found throughout the body in blood, muscle, and the fluid between cells.

Function: Nerve impulses, releases neurotransmitters, muscle contraction, blood clotting, regulation of blood clotting

Deficiency: Hypocalemia: Serum calcium < 4.3mEq/L,

Treatment: diet and IV therapy

Hypercalcemic: Serum Ca > 5.3mEq/L,

Treatment: Medication / IV therapy

• Magnesium: 1.5-2.5mEq/L, located within ICF

– Function: For activating enzymes, electrical activity, metabolism of proteins, DNA synthesis

– Deficiency : Hypomagnesemia: Serum < 1.5mEq/L

Treatment: Replacement/ IV therapy

Hypermagnesemia: Serum>2.5mEq/L

Treatment: Restrict intake, diuretic 

• Milli equivalents: Represents amount in milligrams, of a solute equal to 1/1000 of its gram equivalent weight taking into account the valency of the ions

• Acids: Release H+ into solution

• Bases: Remove H+ from solution

• Buffers: Resist changes in pH

• Types of buffer systems

– Carbonic acid/bicarbonate

– Protein

– Phosphate

• Metabolic acidosis – abnormally low HCO3- in systemic arterial blood

• Metabolic alkalosis- Abnormally high HCO3- in systemic arterial blood

•Sodium chloride: Commonly known as common salt, is prepared by evaporation of sea water, assayed by modified Volhards method and medicinally used as electrolyte replenisher and in the preparation of isotonic solution

•Potassium chloride: Prepared by neutralising potassium hydroxide with Hydrochloric acid, assayed by Mohr’s method and medicinally used as electrolyte replenisher, gelling agent, adsorbent and yeast food

Calcium gluconate: Prepared by treating gluconic acid with calcium carbonate, used in the treatment of calcium deficiency

• ORS: Available in the form of sachets with different flavours, used for maintaining acid base balance