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(1)

WATER-ELECTROLYTE BALANCE

Serkan SAYINER, DVM PhD. Assist. Prof.

Near East University, Faculty of Veterinary Medicine, Department of Biochemistry serkan.sayiner@neu.edu.tr

(2)

Water

■ Water is an indispensable factor in life.

■ There is a living thing that can sustain a lightless or oxygen-free existence, but there is no living creature that can protect its life without water.

■ In adult living organisms, 60-70% of body weight differs by the amount of water in individual organs and

tissues.

Organ Water Ratio %

Total Body Water Share %

Eye 98 0.1

Blood 79 5

Muscle 77 50

Skin 72 7

Skeleton 22 12

Fat 15 2

Teeth 10 < 0.1

(3)

Functional Distribution of Water

■ Intracellular Fluid (ICF)

■ Extracellular Fluid (ECF)

– Intercellular (Interstitial) – Intravenous (Intravasal)

■ A horse of about 500 kg,

– 300 L water = 200 L ICF + 75 L intercellular + 25 L intravasal

■ Approximately 65-70% of total body weight in mammalians is water.

(4)

Water Availability

■ Free Water (Unbound water)

– Blood, lymph, CSF (cerebrospinal fluid), body fluids.

■ Bound Water

– Hydrate Water

• Water bound to macromolecules like proteins, carbohydrates by H bridges.

– Intermolecular Water

• It is found in fibers and membranes (connective tissue) and lost its fluidity.

(5)

Biological importance and functions of water

1. It is the building block of macromolecules.

– Many complex compounds, such as polysaccharides, proteins and nucleic acids, have the ability to hold water regularly. The macromolecule and the water molecule are linked by hydrogen bonds.

2. A good building block for small molecules.

– It is a solvent in which many metabolism events occur in the water, where the substrates are transported, and metabolism events are the result of eliminating many residual products.

3. A substrate and co-substrate.

– Water participates in many reactions of metabolism. Hydrolase and hydratase group enzymes require water as co-substrate;

Oxidases, respiratory enzymes produce water as a reaction product (oxidation water).

(6)

Biological importance and functions of water

4. Regularly manages energy.

– Hydrogen bonds can change to covalent bonds when hydrated, or vice versa.

5. It is a good body temperature regulator.

– The water has a high melting point and evaporation heat.

– The evaporation of a small amount of water in the organism causes a lot of heat loss.

– This is the cooling effect of the body. The emergence of water vapor through the skin and lungs constitutes an important mechanism of body temperature regulation.

(7)

Biological importance and functions of water

■ Total amount of body water is fixed for every living thing.

– There are regulatory mechanisms that provide protection for this constant.

– There is an inverse relationship between water fluctuations and the organizing grade of living being.

• The fluctuation is high in primitive life (procaryote), and low in advanced life.

■ Body water and solute electrolytes resembles a solution to form a functional unit.

– A change in one of these is often reflected in the other.

(8)

■ ECF;

– Primary cation is Na+

– Primaray anions are HCO3- and Cl-

• Found as NaCl and NaHCO3

■ ICF;

– Primary cations are K+ and Mg++

– Primary anions are proteinat and H2PO4- ;HPO4-

Electrolyte distribution

(9)

Water and Water intake

■ What is the organism's water requirement?

■ How are the water requirements met or what are the water resources?

■ What losses can be compensated for?

(10)

Water Intake

■ Water intake and discharge are affected by a number of factors.

– Age, nutrition, physiological status, body weight, climate and activity etc.

■ For this reason it is quite difficult to determine the daily water requirement.

■ All data reported in this area should be considered as approximate values.

■ For example;

– 7,6 L/day for Rams

– 49-59 L/day for Jersey cows

– 30-57 L/day for a 500 kg horse living in hot climate – 50 mL/kg Live Animal Weight for dogs.

– Disease conditions change daily requirements.

(11)

Water Sources

■ EXOGENOUS WATER

– It is the water that is ingested with the foodstuff and drinks.

• Dry foods: 6-10%

• Semi-wet: 24-60%

• Wet: 68-84%

– Exogenous water was made isotonic in the digestive tract.

– Most of them are absorbed from the small intestine, the remaining large intestine (colon).

– The water taken into the bloodstream is transported to the tissues and stored in the interstitial fluid.

(12)

Water Sources

■ ENDOGENOUS WATER (Metabolic Water)

– It is the water obtained by metabolic events. It also called as Metabolic water.

– It is obtained from the oxidation of hydrogen in organic materials. The amount of water synthesized in this way depends on the nature of the foodstuffs. Number of

hydrogen atoms are directly proportional with the amount water produced (more hydrogen, more water).

– I.e. Glucose = 0.6 mL/g ; Stearic acid = 1,14 mL/g

■ When sheep are fed with wet grasses, they can live without drinking water. Horses require an additional 40-50 liters of water per day, despite the water they receive and/or water produced in metabolism.

(13)

Water Losses

■ Insignificant Water Losses

– Ordinary, inevitable.

– I.e. In large breed dogs, 40 mL/kg

■ Significant Water Losses

– Can be regulated.

■ Water Losses related to a special condition

– Physiological and healthy

(14)

Insignificant Water Losses

■ Losses due to evaporation

– Skin loss

• Very little perspiration (salt water, air arrest weakens thermal conductivity)

– Respiratory losses (pure water)

– Frequent breathing (+++ dog + cat)

■ Saliva losses

– Lots of eating (+/0 dog < +++ cat)

(15)

Significant Water Losses

■ Urinary Losses

– Source; Renal Infiltration – It can be regulated.

– Cat = 15-20 ml/kg/day – Dog = 24-40 ml/kg/day

– Ability to concentrate the urine;

• Cat > Dog

• Density; Cat 1035-1060, Dog 1015- 1045

– Amount of absorbet water – Dissolved molecules

• I.e. 1 g NaCl need 30 ml water, 1 g urea need 100 ml water.

Nephrone

Filtrated volume (>4xH2O total)

Vena

Collecting Duct

TCP

Descending Limb

Ascending Limb Loop of Henle

AA EA

Absorbtion

(16)
(17)

Significant Water Losses

■ Faecal Losses

– Mandatory but less.

– Sources

• Faecal humidity: 60-80% for normal life.

• Normal or pathological digestive secretions.

– Change factors

• The amount of salt, the level of nutrition

• Moisture level of food

• The nature and proportion of fibers (non-digestible residues and fermentation products)

(18)

Water Losses related to a special condition

■ Lactation

– For example, in dogs there are 77.2 grams of water in 100 milliliters of milk and 81.5 grams of water in cats.

■ Diarrhea

– Functional: Motor malfunction, impairment of permeability – Osmotic: Digestive insufficiency, dietary overload,

malnutrition

– Infectious or inflammatory.

(19)

Effective Forces on Water-Electrolyte Balance

1. Cell permeability

– Cell membranes have large

permeability to water and a large number of dissolved nutrients (glucose, amino acid, etc.).

2. Capillary permeability and isotonia

– Changes in the amount of electrolyte in any sector will cause the osmotic pressure to change and this will

cause inter-sectoral water movement.

– In regular;

• ICFosm. Pressure > ECFosm. pressure

(20)

Daily water balance of an adult human

■ Physiological water losses are about 50 mL/kg/day.

■ Water Loss Ways

– Skin : 500 mL – Lung : 400 mL – Intestine : 100 mL – Kidney : 500 mL

■ Water Intake Ways

– Metabolic Water : 400 mL – Water taken with foods : 1100 mL

(21)

Regulation of Water-Electrolyte Balance

1. Effective circulating volume (ECV) 2. ADH (Vazopressin)

3. Renin-Angiotensin-Aldosteron System (RAAS)

4. Atrial-Natriuretic Factor/Peptide

(ANF/ANP)

(22)

Renin-Angiotensin-Aldosteron System (RAAS)

* Hypovolemia

* Decrease in efferent arteriole pressure

* Increase of Na value of tubular urine in macula densa

(23)

Filtrated Volume (> 4 x H2O

total)

3-100 0,5-5

URINE

99,5%

absorbed

33

20

100 5 15

0,5 40

Collec ting Duc t

AA

AE Passive NaCl

Transport

Na+ change with K+,H+,NH+ 4 Active Na+

transport

(Cl-, HCO32- follows) Su

30

10 20-30

K absorbtion+ K+

Passive ure transport 100 100

100 10

50

(24)

Filtrated Volume (> 4 x H2O

total)

URINE

99,5%

geri emilir

> 119 ml/dak

AA

EA

100

0,5%

< 1 ml/dak

Water

Active Resorption (ADH)

33

20

15

5

Water Filtration and Resorption

Collec ting Duc t

Approx. 120 ml/dak

(25)

Sodium Filtration and Resorption

Filtrated Volume (> 4 x H2O

total)

3-500

URINE

AA

AE Na+ change

with K+,H+,NH4+

K absorption+

K+ 100

20-30

10

Collecting Duc t

(26)

Urea Filtration and Resorption

Filtrated Volume (> 4 x H2O

total)

40

URINE

AA

EA Urea

Passive transport

100

50

100

Collec ting Du ct

(27)

Atrial-Natriuretic Factor/Peptide (ANF/ANP)

■ It is especially synthesized by heart and released to circulation.

■ It extends the atrial wall. It is a given response to increased venous blood pressure.

■ It reduces systemic blood pressure.

■ It triggers diuresis and natriuresis in kidneys

■ It blocks aldosterone release.

(28)

Water- Electrolyte Imbalances

■ DEHYDRATION

– Loss of fluid by 5-7% of body weight causes the following symptoms to appear:

– Skin wrinkles

– Migration in the eye pits – Pulse increase

– Suspension Dryness in mucous membranes

– Hyperthermia

– Weight loss Fatigue

– → 12-15% ends with SHOCK.

■ HYPERHYDRATION

– There is a total increase in total liquid and it is accompanied by water as well as Na.

– Main symptoms are

Nausea,

Vomiting

Disgusting beverages

(Water intoxication)

(29)

Water- Electrolyte Imbalances

Water loss, more than intake

Water and electrolyte inadequacy

DEHYDRATION

(30)

Dehydration

Isotonic Hypertonic Hypotonic

• Water and salt loss together.

• Na+, Cl and osmolality... Normal

• Hemoconcentration

• PCV and plasma proteins increase.

• Skin wrinkles, tiredness, ring

around eyes, no thirst, pulse weak and fast, frequently kidney failure

• Water loss = Salt loss

isonatremic dehydration

Diarrhea, renal diseases

• Isotonic salt and glucose solution recommended.

• (0.9% NaCl + 5% Dextrose)

• ECF water loss > Na+loss

• Na+, Cl and osmolality... High

• Hemoconcentration

• PCV and plasma proteins increase.

• Water loss from cells (get out)

• Severe thirst, dryness in tongue and mucous membranes, fever, general impairment and nervous symptoms

• Water loss > Salt loss

Hypernatremic dehydration

D. insipidus, Hypodipsia, diarrhea,

pulmonary losses due to hyperventilation and temperature

• Hypotonic salt and glucose solution is recommended.

• (0.4% NaCl + 5% Dextrose)

• Serum Na is not dropped quickly.

• Edema in brain cells!!!

• ECF water loss < Na+loss

• Na+, Cl and osmolalitye... Low

• PCV and plasma proteins increase.

• Water enters in the cells and

swells, nausea and vomiting, loss of thirst sensation, disgust from water, moist tongue, loss of appetite and convulsions

• Salt loss > Water loss

Hyponatremic dehydration

Secretary diarrhea, vomiting, 3rd spacing losses

• Hypertonic salt and glucose solution recommended

• (4.5% NaCl + 30% Dextrose)

* PCV and plasma protein do not increase if there is simultaneous protein loss or anemia.

(31)

Source: Wiki

(32)

Hypertonic Dehydration

ECF 350 mEq

ICF 350 mEq ICF

310 mEq ECF

600 mEq Hypotonic

losses

1 2 3

Hypotonic Dehydration

ECF 310 mEq

ICF

310 mEq ECF

280 mEq

ICF 280 mEq ICF

310 mEq ECF

200 mEq Hypertonic

losses

1 2 3

Isotonic Dehydration

ECF 310 mEq

ICF

310 mEq ICF

310 mEq ECF

310 mEq Isotonic

losses

1 2

1. Normal 2. Change due to dehydration 3. Compensation

ECF 310 mEq

ICF 310 mEq

(33)

Degree of water loss and clinical symptoms

Mild 3-5%

Moderate 6-9%

Severe

>10%

General symptoms

Pulse

Blood pressure Urine

Thirst, Restless,

Decline in food intake

Plump Normal Oliguria

Thirst, Incoordination, Respiratory Strength, Hemoconcentration

Fast

Normal-low Oliguria

Sweating, Comatose, Nervous disorders

Weak

Can notmeasured Anuria

(34)

Hyperhydrations

Isotonic Hypertonic Hypotonic

• Na+ and osmolality... Normal

• Water and Na+ retention

• GFR decreases

• Weight gain, edema, pleuro- peritoneal transudates

• Causes

• Hypovolaemia

• Hypoproteinemia

• Malnutrition

• Cirrhosis

• Renin-angiotensin- Aldosterone system (RAAS) is activated.

• Water > Na+ retention

• Na+ and osmolality... Low

• Nausea, vomiting

• Causes

• Therapeutic failure (Liquid support in an oligo-anuric patient)

• Increase in ADH release (contrast to diabetes insipidus)

• The blood dilution system is activated.

• Na+ Cl - and osmolalitye... High

• Apart from intracellular

dehydration, an extracellular hyperhydration develops, but hyperosmolarity is dominant in both sectors

• Severe thirst

• Causes

• Hypertonic NaCl administration

• Low NaCl diet and plenty of water intake are recommended.

(35)

Hypertonic Hyperhydration

1. Normal 2. Change due to hyperhydration

Isotonic Hyperhydration

Saline ECF 420 mEq

ICF 310 mEq

ECF

342 mEq ICF 342 mEq

1 2

Hypertonic NaCl solution

Hypotonic Hyperhydration

ECF 236 mEq

ICF 310 mEq

1 2

Water

ECF 310 mEq

ICF 310 mEq

ECF 287 mEq

ICF 287 mEq

(36)

Clinical Evaluation

■ What is the degree of fluid loss?

■ Is there osmolar imbalance?

■ Is there acid-base disturbances?

■ How is potassium metabolism?

■ How are kidney functions?

(37)

Clinical Laboratory Examination

■ History and Clinical Observation

– General status of animal

– Skin turgor (distensiton-rigidity) – Color of mucous membranes – Capillary refill time

– Pulse and heart rhythm – Respiratory frequency – Urinary flow

■ Hematological and Biochemical Assessments

– Hematocrit (PCV) – Plasma total protein

– Blood urea (or BUN-Blood Urea Nitrogen) – Blood glucose

– Ionogram and osmolality (pH, Na,K,Cl,HCO3-) – Urinanalysis

(38)

Sodium (Na)

■ Sodium has many important functions, including

maintaining normal blood pressure and volume and maintaining normal function of muscles and nerves.

■ These functions are dependent on keeping plasma sodium concentrations within a narrow range.

■ The concentration of sodium in the blood is

predominantly a balance between what is consumed in food and drink and what is excreted in urine.

– Only a small amount is normally lost through stool and sweat, but these routes can become more important in certain disease or physiological states, depending on species.

(39)

Sodium (Na)

■ The regulation of sodium cannot be discussed without also discussing water balance since these substances are intricately tied together.

■ Water balance between different compartments is

dependent on osmotic pressures. As the most abundant cation of plasma, sodium, along with its associated

anions, is the major determinant of extracellular osmolality.

■ Water and sodium regulation is associated with maintaining normal blood volume and osmolality.

■ Sensors of osmolality and vascular pressure result in

changes of sodium and/ or water handling by the kidney.

(40)

Sodium (Na)

■ As little as a 1–2% increase in plasma osmolality will be

detected by osmoreceptors in the hypothalamus, resulting in vasopressin (antidiuretic hormone) secretion from the posterior pituitary.

– Alternatively, a perceived deficit in blood volume of 10% will result in vasopressin release regardless of osmolality.

■ Vasopressin enhances water reabsorption in the renal

collecting duct to replenish vascular water. Osmoreceptor cells are also involved in the sensation of thirst.

■ If arterial and atrial baroreceptors sense elevated blood pressure or blood volume, impulses are sent to the

hypothalamus to inhibit vasopressin release.

(41)

Sodium (Na)

■ They also act to decrease sodium reabsorption in the distal nephron.

■ The juxtaglomerular cells of the kidney are

baroreceptors that detect low blood pressure. These cells activate the renin- angiotensin-aldosterone

system (RAAS) by secreting renin.

– Angiotensinogen II causes the release of aldosterone from the adrenal glands, increases secretion of vasopressin, and

stimulates thirst centers.

– Aldosterone acts on the renal cortical collecting tubules to reabsorb sodium.

– The reabsorption of sodium is coupled with either the secretion of potassium (another very important function of aldosterone) or the absorption of chloride to maintain electroneutrality.

(42)

Sodium (Na)

■ When evaluating serum sodium concentration, the animal’s total body water must be taken into

consideration.

■ Is there clinical or biochemical evidence of low body water (dehydration) or does it appear normal or,

possibly, increased?

– An increase in serum sodium concentration can be due to more sodium, less water, or a combination of causes.

– A decrease in serum sodium concentration can be due to less sodium, more water, or a combination of causes.

(43)

Excess salt?

Did the

animal get into

something salty?

Was the

animal given hypertonic fluids I.V.?

Hyperaldosteronism (Rare)

Water deficit

Decreased intake Water loss > Na

Frozen or Spilled Water

source Monitor water intake

(Neurological Deficit,

Weakness)

Renal GI

Fever Panting

Hyperventilation

Serum Na+

(Hypernatremia)

(44)

Endogenous Shifts

Sodium Deficit (Na Loss > Water)

Serum Na+

(Hyponatremia)

Excess Water?

(Water Retention > Na)

lnappropriate Secretion of

ADH (Rare)

Excess Sodium-

Poor Fluids l.V.?

Hypovolemia/Edema

-Congestive Heart Failure -Hepatic Fibrosis

-Nephrotic Syndrome

Plasma

Hyperosmolality from Substance Other Than Na

(Water shifts from lCF to ECF)

Renal Loss Third-

Spacing of Body Fluids

Sweating in horses

GI Loss

(45)

Chloride (Cl)

■ Chloride is the major anion in the ECF and, similar to sodium, chloride is important in the transport of electrolytes and water.

Chloride also serves as a conjugate anion in acid base metabolism.

■ To maintain electroneutrality chloride either moves in the same direction of the positively charged sodium or exchanges with the negatively charged bicarbonate ions.

■ When evaluating an abnormality in serum chloride concentration, it is important to compare chloride levels with sodium levels and to the animal’s acid base status.

– If abnormalities in chloride concentration appear to be in pro- portion to abnormalities in sodium concentration, differentials to consider are similar to those given for hyponatremia or hypernatremia above.

If the change in chloride concentration appears greater than a

change in sodium concentration, bicarbonate concentration should be evaluated and a blood gas analysis may be indicated.

(46)

Chloride (Cl)

■ Hyperchloremia

– Hyperchloremia is usually associated with a water deficit.

– Alternatively, hyperchloremia can be related to hypobicarbonatemia.

– Loss of bicarbonate can occur from the GI tract with diarrhea, loss of saliva in cattle which contains a high

bicarbonate concentration, or vomiting intestinal contents as can occur with intestinal obstruction.

– Renal loss of bicarbonate occurs with proximal or distal tubular acidosis. In response to a respiratory alkalosis, there is decreased renal conservation of bicarbonate, resulting in retention of chloride.

(47)

Chloride (Cl)

■ Hypochloremia

– If chloride is decreased to a greater degree than sodium,

differentials related to metabolic alkalosis must be considered.

– In the process of secreting HCl into the stomach, serum chloride is decreased and serum bicarbonate is increased. These

changes are normally reversed when hydrogen and chloride ions and water are reabsorbed in the intestines.

– If gastric fluid is lost due to vomiting or sequestered due to a displaced abomasum, pyloric obstruction, or functional

obstruction, serum chloride will remain low and bicarbonate will remain elevated.

– Serum chloride levels decrease when bicarbonate

concentrations increase in the compensatory response to chronic respiratory acidosis.

(48)

Potassium (K)

Thrall ve ark. 2012

■ Potassium is a major intracellular cation that plays an important role in resting cell membrane potential.

■ Clinical signs associated with abnormal serum

potassium concentrations manifest as cardiac and skeletal muscle dysfunction and hyperkalemia can have life-threatening effects on cardiac conduction.

Therefore, it is important to maintain serum potassium

concentrations within narrow limits.

(49)

Potassium (K)

■ Total body potassium is a balance between what is

ingested (100%) and what is excreted from the kidneys (normally ∼90–95%) and colon (normally ∼5–10%).

■ The concentration of ECF (serum) potassium is also reliant on the translocation of potassium between the ECF and ICF.

■ Less than 5% of total body potassium is present in the

ECF; therefore serum potassium concentration is an

unpredictable representation of total body potassium

content.

(50)

Increased K+ Load

Serum K+

(Hyperkalemia)

Decreased Renal Excretion

Translocation between ICF & ECF

• Metabolic Acidosis

• Insulin Deficiency

• Severe Tissue Injury Hypoadrenocorticism

Oliguric/Anuric Renal Failure Urethral Obstruction

Ruptured Urinary Bladder

Decreased Renal Tubular Flow from Hypovolemia

• Gastrointestinal Disease

• Body Cavity Effusions

In vitro artifacts

• Hemolysis

• Thrombocytosis

• Delayed Serum Removal

• EDTA Contamination

(51)

Serum K+

(Hypokalemia)

Decreased Intake or

K-Poor Fluids I.V.?

• Gastric Vomiting

• Small Intestinal Diarrhea

• Chronic Renal Failure

• Distal Renal Tubular Acidosis

• Post-Obstruction Diuresis

• Diabetic Ketoacidosis

• Diuretics

• Hyperinsulinism

• Alkalosis

Loss

Translocation between ICF & ECF

Renal Gastrointestinal

(52)

Sodium:Potassium Ratio (Na:K)

■ Hypoadrenocortisism

■ Na:K < 27:1 ??

– Na:K ratios <15 are more commonly associated with hypoadrenocorticism in dogs.

■ Absolute or relative K increase or Na decrease or combination.

– Increased K is the most common reason.

■ It is important in differential diagnosis.

– It may decrease in renal/urinary tract disorders, GI diseases, parasites (dogs), body cavity effusions, D.

insipidus, pancreatitis, pyometra, ocular diseases.

(53)

Anion Gap

■ We measure several anions and cations in the blood, but there are many others that are not routinely

measured.

■ Thepredominant cations of ECF are sodium, potassium, calcium, and magnesium and the

predominant anions are chloride, bicarbonate, plasma proteins, organic acid ions, phosphate, and sulfate.

■ The number of unmeasured anions is greater than the number of unmeasured cations, and the difference

between these is called the anion gap.

(54)

• Definition: Anion gap is the difference between UA and UC.

• Calculation: Anion gap is the difference between Na&K and Cl&HC03.

(55)

Anion Gap

■ An indirect method is used to calculate the anion gap.

The calculation is based on the law of electroneutrality (The number of positive charges need to equal the

number of negative charges in the body).

■ Anion Gap = {[Na

+

] + [K

+

]} - {[Cl

-

] + [HCO

3-

]}

■ The anion and cation concentrations measured in the serum to calculate anion gap. Ions are measured in mEq/L or mmol/L.

■ Reference value = 10-25 mEq/L – 8-25 mmol/L

– It may vary depending on species, methods and equipments.

(56)

Anion Gap

■ The greatest change in the anion gap is when an

elevation occurs due to an increase of organic acids in the circulation. The anion gap, therefore, is

important in determination of the acid-base status of an animal.

– The anion gap is essentially used to determine the cause of decreased blood bicarbonate concentrations (metabolic

acidosis) or to detect metabolic acidosis during a mixed acid-

base disorder in which bicarbonate may be normal or increased.

■ Since cations rarely change enough to affect the anion gap, a decrease in bicarbonate has to be

accompanied by either an increase in unmeasured

anions or a decrease in chloride to keep the equation

equal and to maintain electroneutrality.

(57)
(58)

Anion Gap

■ Unmeasured anions that have the most affect on anion gap are the endogenous products lactate, ketones, and uremic acids, as well as the exogenous substances

salicylate and the metabolites of ethylene glycol toxicity.

– Lactic acidosis is produced during hypoxia and anaerobic metabolism.

– Keto acids are produced when there is a negative energy balance and metabolism switches from primarily glycolysis to lipolysis.

– Uremic acids are phosphates, sulfates, and organic acids that are no longer adequately filtered because of decreased glomerular filtration rate (GFR).

(59)

Calcium (Ca)

■ Alterations in blood calcium concentrations can result in severe clinical problems, including death. Another reason is that recognizing and pursuing the cause of calcium abnormalities often aids in diagnosing the underlying disease process.

■ When measuring serum concentrations of calcium, it is important to understand the difference between the

measurement of total calcium and free, ionized calcium.

– Free (unbound) ionized calcium (iCa) is the biologically active, hormonally regulated fraction that comprises approximately 50% of total calcium.

(60)

Predominant Hormone Actions on Serum

Calcium and Phosphorus

(61)

Calcium Fractions

(62)

Calcium (Ca)

■ Hypercalcemia differentials (Total calcium)

– Granulomatous inflammation – Osteolytic lesions

– Spurious results

– Hyperparathyroidism (primary) – Dvitamin toxicity

– Addison’s disease

– Renal disease (chronic) – Neoplasia

– Idiopathic – Transient

(63)

Calcium (Ca)

■ Hypocalcemia differentials (Total calcium)

– Magnesium deficiency – Injury to tissues (severe) – Lactation/pregnancy

– D vitamin deficiency – Pancreatitis

– Renal disease

– Albumin deficiency

– Intake from GI decreased – Sepsis

– Ethylene glycol

(64)

Phosphorus (P)

■ Phosphorus is required for energy metabolism, nucleic acid synthesis, and cell signaling.

■ It is an important buffer in blood and urine and an

important component in structural plasma membrane phospholipids and phosphoproteins and in bone.

■ Abnormalities in serum phosphorus concentrations can be due to abnormalities in hormonal balance, intestinal

absorption, renal excretion, or tissue or cell distribution.

Serum concentrations of phosphorus may not reflect total body levels.

– If there is a concurrent abnormality in serum calcium, pursuing and determining the cause of the calcium abnormality will often provide explanation for an abnormality in phosphorus.

Examining the pattern of change between calcium and phosphorus can provide important clues.

(65)
(66)
(67)
(68)
(69)

Magnesium (Mg)

■ Magnesium is primarily an intracellular ion and is a cofactor of many enzymatic reactions, including all

reactions involving the formation and utilization of ATP and many mitochondrial reactions.

■ It is also required for protein and nucleic acid synthesis.

Vitamin D and PTH influence, but do not regulate magnesium metabolism.

■ Homeostasis is primarily a balance between intestinal absorption and renal excretion.

■ Magnesium has a similar charge as calcium and, as does calcium, exists in free ionized, protein-bound

(approximately 30%), and complexed forms in serum.

– Serum magnesium contains only approximately 1% of total body magnesium and therefore is not necessarily an accurate

representation of total body magnesium.

(70)

Magnesium (Mg)

■ Hypomagnesemia is more commonly associated with morbidity than hypermagnesemia.

– Neuromuscular signs occur with hypomagnesemia, including hyperexcitability, muscle tremors, spasms, and fasciculations, and ataxia.

– Other complications associated with hypomagnesemia include the development of hypokalemia or hypocalcemia. These

deficiencies may not be able to be corrected unless hypomagnesemia is corrected first.

– Hypomagnesemia is typically associated with either increased loss or decreased intake.

– Losses, the most common cause of hypomagnesemia in small animals, are through the renal or gastrointestinal systems.

• Renal loss occurs with diuresis and renal disease. Renal reabsorption can also be inhibited by hypercalcemia. Malabsorption and diarrhea are causes of gastrointestinal magnesium loss.

(71)

Magnesium (Mg)

– Decreased intake is a common cause of hypomagnesemia in ruminants. Grass tetany is a disease that is associated with ruminants eating lush green pastures that are high in potassium and low in magnesium content.

• Elevated potassium ingestion blocks normal magnesium absorption in the rumen.

– Prolonged intravenous fluids or parenteral nutrition can also lead to hypomagnesemia if magnesium

supplementation is not included.

– Other causes of hypomagnesemia include redistribution and hypoalbuminemia (if total magnesium is measured instead of free, ionized magnesium).

(72)

Magnesium (Mg)

■ Hypermagnesemia is typically a less significant clinical problem, unless it develops acutely.

– It can result in cardiac or neurological problems and cause nausea and vomiting.

– Hypermagnesemia can occur iatrogenically or due to

decreased renal excretion, primarily associated with acute renal failure or urethral obstruction.

(73)

■ W% = (TPH - TPS) x 100/TPH

– W%: Fluid loss in blood plasma as a percentage – TPH: Patient total protein (g/dL)

– TPS: Total protein of healthy animal (g/dL)

■ ECF Loss (L)= (W% x LW x 0,4)/100

– LW: Live Animal Weight

Calculation of Fluid Losses in Blood

Plasma

(74)

Dehydrations and Hyperhydrations

Syndromes Osmolality ECF ICF Causes

Hypertonic Dehydration

(Fluid depletion) Increase Decrease Decrease Water loss > Salt loss Hypotonic Dehydration Decrease Decrease Increase Water loss < Salt loss

Isotonic Dehydration Normal Decrease Water loss = Salt loss

Hypertonic Hyperhydration Increase Increase Decrease Water retention < Salt retention Hypotonic Hyperhydration

(water intoxication) Decrease Increase Increase Water retention > Salt retention Izotonic Hyperhydration Normal Increase Water retention = Salt retention

(75)

Your Questions?

Send to serkan.sayiner@neu.edu.tr

(76)

References

■ Karagül H, Altıntaş A, Fidancı UR, Sel T, 2000. Klinik Biyokimya. Medisan, Ankara.

■ Prof. Dr. Arif ALTINTAŞ, Ders notları.

■ Sink CA, Weinstein NM, 2012. Practical Veterinary Urinanalysis, 1st ed.

Wiley-Blackwell.

■ Thrall MA, Weiser G, Allison RW, Campbell TW, 2012. Veterinary Hematology and Clinical Biochemistry, 2nd edi. Wiley-Blackwell.

(77)

Next topic;

ACID-BASE BALANCE

(78)

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