Water and electrolytes balance in chemical pathology.

1. WATER AND ELECTROLYTE
BALANCE
BY
DR G.O AYOADE

2. General principles
• Osmolarity : number of osmoles per liter of solution
• Osmolality: number of osmoles per kilogram of solvent
• Measurement: depression of freezing point
• Calculation (plasma): 2x(Na)+glucose+BUN (mmol/l)
• Tonicity: effective osmolality of a solution relative to
plasma
• Colloids: high molecular weight particles (> 20000 D)
• Oncotic pressure (colloid osmotic pressure): the pressure
necessery to prevent diffusion of solvent molecules
(water) into region in which there is a higher
concentration of a colloid to which the membrane is
impermeable

3. Intracellular space
Extracellular space
Interstitial space
Intravascular
space
Capillary wall
Oncotic pressure
Colloids
Electrolytes
Water
Cell membrane
Osmotic pressure

4. Body Fluid Volumes
Compartment Fluid Vol.
(l)
% Body
Fluid
% Body
Wgt.
Total Body
Fluid
42 100 60
Intracellular
Fluid
(ICF)
28 67 40
Extracellular
Fluid (ECF)
14 33 20
Plasma 2.8 6.6
(20% ECF)
4
Interstitial
Fluid
11.2 26.4
(80% ECF)
16
Lymph &
Transcellular
Fluid
Neg. Neg. Neg.

5. Daily Water Balance (liters)
• FLUID INTAKE 1.5
• IN FOOD 0,8
• METABOLIC 0.3
• Total 2,6
• INSENSIBLE 0.8
• SWEAT 0,1
• FECES 0.2
• URINE 1.5
• Total 2.6
INPUT OUTPUT

6. Introduction
• The maintenance of normal volume and normal composition of the
extracellular fluid is vital to life.
• Three types of homeostasis are involved in this maintenance:fluid
balance, electrolyte balance, and acid-base balance.
• The ICF contains nearly2/3rd of total body water;the ECF contains the
rest.
• Exchange occurs between the ICF and ECF.

7. Distribution of Body Fluids
• Water is the most abundant constituent in the body
• 50% of weight in women;
• 60% of weight in men
• Difference due to adipose tissue composition
• Total Body Water divided into 2 compartments
• Extracellular : 25 – 45%
• Intravascular – plasma water (25%)
• Extravascular – interstitial fluid(75%)
• Intracellular : 55 – 75%

8. Distribution of Body Fluids
• Movement of fluids between Extracellular and
Intracellular
• Determined by Osmolality (solute or particle
concentration of a fluid)
• Fluids cross cell membranes to achieve osmotic
equilibrium (ECF osmolality = ICF osmolality).
• Major ECF solutes – Sodium, Chloride,
Bicarbonate
• Major ICF solutes – Potassium, Organic
Phosphates (ATP, creatine phosphate,
phospholipids)

9. Distribution of Body Fluids
Movement of fluids between Intravascular and Interstitial
Starling’s Forces
• Capillary hydraulic pressure – from blood pressure
• Colloid osmotic pressure – oncotic pressure (proteins)

10. Water Balance
• For steady state, water intake must equal water excretion
• Water intake
• Primary Stimulus is thirst
• Thirst is induced either by an increase in
effective osmolality or a decrease in ECF
volume or blood pressure.
• Osmoreceptors located in the anterolateral
hypothalamus, are stimulated by a rise in
tonicity.

11. Water Balance
• Water Excretion
• Normal individuals have an obligate water loss
consisting of urine, stool, and evaporation
from the skin and respiratory tract.
• principal regulation of water excretion is by
arginine vasopressin (AVP) synthesized in the
supraoptic and paraventricular nuclei of the
hypothalamus and secreted by the posterior
pituitary gland.

12. Water Balance
• AVP binds to the V2 receptors on the basolateral
membrane of principal cells in the collecting duct leads to
the insertion of water channels into the luminal
membrane.
• The net effect is passive water reabsorption along an
osmotic gradient from the lumen of the collecting duct to
the hypertonic medullary interstitium.

13. Water Balance
• The major stimulus for AVP secretion is increased
osmolality
• Effective osmolality is primarily determined by the plasma
Na concentration because major ECF solutes are Na salts
• Nonosmotic factors that regulate AVP secretion include
effective circulating (arterial) volume, nausea, pain, stress,
hypoglycemia, pregnancy, and numerous drugs.

14. Water Balance and ECF Osmolality
• To remain properly hydrated, water intake must equal water output
• Water intake sources
• Ingested fluid (60%) and solid food (30%)
• Metabolic water or water of oxidation (10%

15. • Water output
• Urine (60%) and feces (4%)
• Insensible losses (28%), sweat (8%)
• Increases in plasma osmolality trigger thirst and release of antidiuretic
hormone (ADH)

16. Regulation of Water - Homeostaisis
• Intake - Hypothalmic Thirst Center
• Thirst is quenched as soon as we begin to drink water
• Feedback signals that inhibit the thirst centers include:
• Moistening of the mucosa of the mouth and throat
• Activation of stomach and intestinal stretch receptors

17. Influence and Regulation ofADH
• Water reabsorption in collecting ducts is proportional to ADH release
• Low ADH levels produce dilute urine and reduced volume of body fluids
• High ADH levels produce concentrated urine
• Hypothalamic osmoreceptors trigger or inhibit ADH release
• Factors that specifically trigger ADH release include prolonged fever; excessive sweating,
vomiting, or diarrhea; severe blood loss; and traumatic burns

18. Fluid Balance
• Angiotensin II and aldosterone reduce urinary loss of Na+ and Cl- and
thereby increase the volume of body fluids.
• ANP promotes natriuresis, elevated excretion of Na+ (and Cl- ), which
decreases blood volume.
• The major hormone that regulates water loss and thus body fluid
osmolarity is ADH.

19. • An increase in the osmolarity of interstitial fluid draws water out of
cells and they shrink slightly.
• A decrease in the osmolarity of interstitial fluid also causes cells to
swell.
• When a person consumes water faster than the kidneys excrete it or
renal fn. is poor-water intoxication,cells swell

20. Disorders of Water Balance
• Dehydration
• Hypotonic Hydration
• Edema

21. Sodium Balance
• 85 to 90% of all Sodium is extracellular, actively
pumped out of the cell by the Na–K ATPase
pump
• ECF volume is a reflection of total body Sodium
content
• Regulatory mechanisms ensure that Sodium loss
balances Sodium gain.
• Excess Na in diet  ECF expansion  increased
renal excretion

22. Sodium Balance
• Filtered Sodium
• About 60% is reabsorbed in PCT
• 25 to 30% in the thick ascending limb of the loop
of Henle (Loop diuretics)
• 5% in the DCT (thiazide-sensitive)
• Final Na reabsorption in the cortical and
medullary collecting duct (Aldosterone)

23. Disorders of Water and Sodium Balance
HYPOVOLEMIA – combined salt and water loss exceeding
intake leading to ECF volume contraction
Causes
Extrarenal –
•Gastrointestinal (vomiting, nasogastric suction,
drainage, fistula, diarrhea).
• About 9L of fluids enter GIT/24hrs (2L ingestion, 7L
secretion). Almost 98% is reabsorbed, faecal loss is
100 – 200ml/day.
•Enhanced secretion or impaired reabsorption

24. Disorders of Water and Sodium Balance
Causes
•Skin/respiratory (insensible losses, sweat, burns)
•Insensible water loss typically about
1500ml/24hr
•Increased during febrile illness, prolonged heat
exposure,
•Increased water /salt loss through sweat
•Hyperventilation, mechanically ventilated
persons, neonates

25. Disorders of Water and Sodium Balance
• Third space loss (burns, peritonitis, pancreatitis)
“ECF”, not in equilibrium with ECF or ICF, effectively
lost
burns – subcutaneous tissue
retroperitoneal space in acute pancreatitis
peritoneal cavity in acute peritonitis
•Severe Hemorrhage

26. DISORDER OF NA BALANCE
• Disorders of Na+ homeostasis can occur because of excessive loss, gain, or
retention of Na+, or as the result of excessive loss, gain, or retention of H2O. It is
difficult to separate disorders of Na+ and H2O balance because of their close
relationship in establishing normal osmolality in all body water compartments.
• In the proximal tubules, 70 to 80% of filtered Na+ is actively reabsorbed, with
H2O and Cl− following passively to maintain electrical neutrality and osmotic
equivalence.
• In the descending loop of Henle, H2O, but not electrolytes, is passively
reabsorbed because of the high osmotic strength of interstitial fluid in the renal
medulla. In the ascending loop of Henle, Cl− is reabsorbed actively, with Na+
following.
• At the level of the distal tubule, the first of the two primary Na+/H2O regulating
processes occurs. Here, aldosterone stimulates the cortical collecting ducts to
reabsorb Na+ (with water following passively) and secrete K+ (and to a lesser
extent, H+) to maintain electrical neutrality.

27. • Hyponatremia
• Hyponatremia is defined as a decreased plasma Na+ concentration
• (<130 to 135 mmol/L).
• Hyponatremia typically manifests clinically as nausea, generalized
weakness, and mental confusion at values <120 mmol/L, ocular palsy at
<110 mmol/L, and severe mental impairment at between 90 and 105
mmol/L
• The rapidity of development of hyponatremia influences the Na+
concentrations at which symptoms develop [i.e., clinically apparent
symptoms may manifest at higher Na+ concentrations (≈125 mmol/L) when
hyponatremia develops rapidly]

28. • Hyponatremia can be hypo-osmotic, hyperosmotic, or
• isosmotic. Thus, measurement of plasma osmolality is an
• important initial step in the assessment of hyponatremia. Of
• these, the most common form is hypo-osmotic hyponatremia.

30. Hypernatremia
• Hypernatremia (plasma Na+ >150 mmol/L) is always hyperosmolar.
• Symptoms of hypernatremia are primarily neurologic (because of neuronal
cell loss of H2O to the ECF) and include tremors, irritability, ataxia,
confusion, and coma.
• As with hyponatremia, the rapidity of development of hypernatremia will
determine the plasma Na+ concentration at which symptoms occur.
• Acute development may cause symptoms at 160 mmol/L, although in
chronic hypernatremia, symptoms may not occur until Na+ exceeds 175
mmol/L

31. • In many cases, the symptoms of hypernatremia may be masked by underlying
conditions. Indeed, most cases of hypernatremia occur in patients with altered
mental status or in infants, both of whom may have difficulty in rehydrating
themselves despite a normal thirst reflex.
• Thus, hypernatremia rarely occurs in an alert patient with a normal thirst
response and access to water.
• Hypernatremia arises in the setting of
• (1) hypovolemia (excessive water loss or failure to replace normal water losses),
• (2) hypervolemia (a net Na+ gain in excess of water gain),
• (3) normovolemia.
• Again, assessment of TBW status by physical examination and measurement of
urine Na+ and osmolality are important steps in establishing a diagnosis

33. POTASSIUM DISORDERS
• The total body potassium of a 70 kg subject is ≈3.5 mol (40 to 59 mmol/kg),
of which only 1.5 to 2% is present in the ECF.
• Nevertheless, plasma K+ is often a good indicator of total K+ stores, unless
abnormal K+ is due to abnormal cellular shifts.
• Disturbance of K+ homeostasis has serious consequences. For example, a
decrease in extracellular K+ (hypokalemia) is characterized by muscle
weakness, irritability, and paralysis.
• Plasma K+ concentrations less than 3.0 mmol/L are often associated with
marked neuromuscular symptoms and indicate a critical degree of
intracellular depletion.
• At lower concentrations, tachycardia and cardiac conduction defects are
apparent by electrocardiogram (flattened T waves) and can lead to cardiac
arrest

34. POTASSIUM DISORDERS
• High extracellular K+ (hyperkalemia) concentrations may produce
symptoms of mental confusion, weakness, tingling, flaccid paralysis of
the extremities, and weakness of therespiratory muscles.
• Cardiac effects of hyperkalemia include bradycardia and conduction
defects evident on the electrocardiogram as prolonged PR and QRS
intervals and “peaked” T waves.
• Prolonged severe hyperkalemia >7.0 mmol/L can lead to peripheral
vascular collapse and cardiac arrest.
• Symptoms are almost always present at K+ concentrations >6.5
mmol/L. Concentrations >10.0 mmol/L in most cases are fatal, but as
with Na+, symptoms vary with the rapidity of onset.

35. HYPOKALEMIA CAUSES

36. HYPERKALEMIA CAUSES

37. SIADH
• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is
defined by the hyponatremia and hypo-osmolality resulting from
inappropriate, continued secretion or action of the antidiuretic hormone
arginine vasopressin (AVP) despite normal or increased plasma volume,
which results in impaired water excretion.
• Etiology
• SIADH is most often caused by either inappropriate hypersecretion of ADH
from its normal hypothalamic source or by ectopic production. The causes
of SIADH can be divided into four broad categories:
• nervous system disorders, neoplasia, pulmonary diseases, and drug
induced (which include those that [1] stimulate AVP release, [2] potentiate
effects of AVP action, or [3] have an uncertain mechanism).

38. SIADH Causes
• SIADH may be due to:
• 1. Intracranial pathology (head injury, haemorrhage, meningitis, encephalitis, or
brain tumor), where there is direct stimulation of hypothalamic ADH release.
• 2. Pulmonary pathology (pneumonia, TB, assisted ventilation), where volume
receptors in the pulmonary vascular bed falsely report a message of vascular
depletion to the hypothalamus.
• 3. Ectopic production of ADH by tumors, particularly bronchial carcinomas.
• 4. Cortisol deficiency – since these hormones antagonize ADH, a deficiency of
either will result in unopposed ADH action.
• 5. Pain, from trauma or surgery, stimulates ADH release.
• 6. Drugs, including psychoactive drugs (antidepressants, narcotics,
carbamazepine), sulphonylureas, oxytocin for labour induction, vincristine for
chemotherapy

39. • In the absence of a single laboratory test to confirm the diagnosis, the syndrome of
inappropriate antidiuretic hormone secretion (SIADH) is best defined by the classic
criteria introduced by Bartter and Schwartz in 1967, which remain valid today. The
criteria can be summarized as follows [2] :
• Hyponatremia with corresponding hypoosmolality
• Continued renal excretion of Na+
• Urine less than maximally dilute
• Absence of clinical evidence of volume depletion - Normal skin turgor, blood pressure
within the reference range
• Absence of other causes of hyponatremia - Adrenal insufficiency (mineralocorticoid
deficiency, glucocorticoid deficiency), hypothyroidism, cardiac failure, pituitary
insufficiency, renal disease with salt wastage, hepatic disease, drugs that impair renal
water excretion
• Correction of hyponatremia by fluid restriction

40. • Serum Na+, potassium, chloride, and bicarbonate
• Plasma osmolality
• Serum creatinine
• Blood urea nitrogen
• Blood glucose
• Urine osmolality
• Serum uric acid
• Serum cortisol
• Thyroid-stimulating hormone
• Plasma AVP

41. DIABETES INSIPIDUS
• Diabetes insipidus (DI) is defined as the passage of large volumes (>3
L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major
forms:
• Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized
by decreased secretion of antidiuretic hormone (ADH; also referred to
as arginine vasopressin [AVP])
• Nephrogenic DI, characterized by decreased ability to concentrate
urine because of resistance to ADH action in the kidney

42. • Decreased secretion or action of AVP usually manifests as DI, a
syndrome characterized by the production of abnormally large
volumes of dilute urine.
• The 24-h urine volume is >50 mL/kg body weight and the osmolarity
is <300 mosmol/L. The polyuria produces symptoms of urinary
frequency, enuresis, and/or nocturia, which may disturb sleep and
cause mild daytime fatigue or somnolence.
• It is also associated with thirst and a commensurate increase in fluid
intake (polydipsia). Clinical signs of dehydration are uncommon unless
fluid intake is impaired

43. • Pituitary diabetes insipidus
• Acquired
• Head trauma (closed and penetrating)
• Neoplasms
• Primary
• Craniopharyngioma
• Pituitary adenoma (suprasellar
• Nephrogenic diabetes insipidus
• Acquired
• Drugs
• Lithium
• Demeclocycline
• Methoxyflurane
• Amphotericin B
• Aminoglycosides

44. • In a patient whose clinical presentation suggests diabetes insipidus
(DI), laboratory tests must be performed to confirm the diagnosis. A
24-hour urine collection for determination of urine volume is
required. In addition, the clinician should measure the following:
• Serum electrolytes and glucose
• Urinary specific gravity
• Simultaneous plasma and urinary osmolality
• Plasma antidiuretic hormone (ADH) level

45. • A urinary specific gravity of 1.005 or less and a urinary
osmolality of less than 200 mOsm/kg are the hallmark of DI.
Random plasma osmolality generally is greater than 287
mOsm/kg.
• Suspect primary polydipsia when large volumes of very dilute
urine occur with plasma osmolality in the low-normal range.
Polyuria and elevated plasma osmolality despite a relatively
high basal level of ADH