Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen

Medical Biotechnology Master’s Programmes

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

CHANGES OF

ELECTROLYTE/WATER AND ACID/BASE

HOMEOSTASIS

Erika Pétervári and Miklós Székely

Molecular and Clinical Basics of Gerontology – Lecture 12

Medical Biotechnology Master’s Programmes

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

Electrolyte/water homeostasis pH disturbances

AGING vs. …

• In the elderly the spontaneous water intake decreases.

Their regulation is insufficient e.g. their thirst

sensation is impaired. Following water deprivation fluid replacement is slower and incomplete.

(In old animals the angiotensin II-induced water intake is smaller than that seen in young animals.

Dypsogenic effects of ADH is weakened.)

SALT AND WATER BALANCE IN

THE ELDERLY 1

• Upon water deprivation or salt and water loss, severe hypovolemia and hypertonicity develops

(ADH refractoriness). This can also contribute to the development of orthostatic hypotension in the

elderly.

• Salt/water loss, diuretic therapy, inappropriate

excess of ADH (e.g. operation, pain), water intake (exceeding the decreased excretion capacity)

causes dangerous hypotonicity.

• On the other hand, upon salt and/or water load (due to decreased excretion capacity) a fast elevation of the blood pressure can also be observed.

SALT AND WATER BALANCE IN

THE ELDERLY 2

ADH effect decreases with age

U/P in ul in (u rin e/p la sma co nc . rati o)

Urine Collection Period

0 0 10 20 30 40 50 60 70 80 90 100 110 120

1 2 3 4 5 6 7 8 9 10

Young Middle Old

ADH

• The number of the nephrons decreases progressively with age.

• GFR also decreases progressively (the glomeruli become more and more sclerotic, the basal membrane gets thicker [degeneration]), by the age of 80 GFR may decrease to 50% – this results in azotemia.

• The decrease in the number of tubules (decrease in the function of the thick ascending limb of the loop of Henle where the reabsorption of Na-K-Cl without water takes place and impairment of the corticomedullary osmotic concentration gradient), – it leads to hyposthenuria. In

response to ADH the increase in the specific gravity of the urine is diminished.

Salt and water balance in the elderly:

kidney

Specific gravity of urine

Number of nephrons

1,000

2,000,000 1,500,000 1,000,000 500,000 0

1,010 1,020 1,030 1,040

Hyposthenuria

Development of hyposthenuria

Isosthenuria

Specific gravity of plasma

• Responsiveness to hormones playing a role in salt and water balance impairement.

• The same decrease in plasma volume elicits a

smaller RAAS activation than in young individuals.

The effects of aldosterone or angiotensin are

diminished compared to that in young adults, too.

Low EC volume induces ADH production that may lead to hypotonicity without completely normalizing the ECV.

ADH production may be maintained or even increased (but the efficacy decreases).

Salt and water balance in the elderly:

hormones

• Elderly patients cannot properly protect themselves against water overload either.

Suppression of baseline RAAS activity is delayed;

activation of natriuretic factors is inefficient

(atriopeptin level is high, but effects are blunted), suppression of renal ADH effects is also

unsatisfactory due to decreased nephron numbers and dysfunctional receptors.

Salt and water balance in the elderly:

hormones

Exsiccosis and dehydration: decrease of extracellular volume (ECV)

Exsiccosis: decreases of ECV due to salt/water, decrease of both plasma volume (hypovolemia) and interstitial volume.

Dehydration: loss of pure water (not followed by proportional loss of electrolytes), followed by proportionate decrease of

volume and increase of osmotic pressure (hyperosmolarity) in both extracellular and intracellular compartments.

IC

0 100 200 300

0 10 20 30 40

EC

Osmolarity (mOsm/liter)

liter

IC

0 100 200 300

0 10 20 30 40

EC

Osmolarity (mOsm/liter)

liter

Exsiccosis and dehydration in the elderly: causes

Decrease in thirst and kidney functions +

• low fluid intake (immobilization, changed mental status),

• diarrhea,

• overdose of diuretics,

• acute fever,

• diabetes mellitus.

Exsiccosis and dehydration in the elderly: clinical signs

Symptoms:

• lethargy,

• dizziness,

• fainting,

• signs of volume depletion such as decreased skin turgor,

• dryness of the mucous membranes,

• low blood pressure,

• tachycardia,

• oliguria-anuria.

Lab findings:

• increase in blood urea nitrogen (BUN), creatinine

Exsiccosis and dehydration in the elderly: management

Rehydration, either p.o. or i.v. depending on the severity.

The first half of the fluid should be administered in 12 hours, while the second half must be given at a slower rate to maintain adequate blood pressure and

circulation.

Too fast fluid replacement may result in acute heart

failure and pulmonary edema.

Hyponatremia (hypotonicity)

Common causes:

Reduced Na concentration while the water volume is normal or increased („water-intoxication”):

• low-sodium diet

• intravenous rehydration with hypotonic fluid

• syndrome of inappropriate ADH secretion (SIADH)

due to operation, stress, fear, pain, stroke, local

inflammation, adenoma, tumors, increased intracranial pressure etc.

Na loss > water loss:

• vomiting

• diarrhea

• overdose of diuretics

Signs and management of hyponatremia

Symptoms depend on the rate and severity of Na loss.

Characteristic signs appear at 120 mM/L or lower:

• edema,

• delirium,

• cerebral edema, nausea,

• convulsions, muscle cramps,

• Cheyne-Stokes respiration

• all-cause mortality (6-8×) . Management:

0.9 % saline solution is given to hypovolemic patients.

In SIADH: restriction of fluid intake.

Administration of hypertonic saline solution can lead to central pontine myelinolysis and therefore, its use is not allowed.

Hypernatremia (hypertonicity)

Na concentration >150 mM/L

It means usually either relative or absolute water loss and hypovolemia.

Hypertonicity is significant.

Common causes:

• restricted fluid intake

• exsiccosis (e.g. diabetic osmotic diuresis, sweating)

Signs and management of hypernatremia

Symptoms:

• coma,

• seizures,

• intracellular dehydration,

• hypovolemia,

• renal failure,

• decreased capacity of kidneys to concentrate urine.

Management:

• normal saline solution (0.9%)

• slow infusion! (fast infusion may cause hypertensive crisis)

Potassium disorders: hypokalemia

Hypokalemia: K< 3.5 mM/L Common causes:

• insufficient intake,

• increased loss due to diuresis,

• vomiting,

• primary or secondary hyperaldosteronism.

Signs:

• muscle weakness, muscle cramps

• paralytic ileus,

• metabolic alkalosis

• sleepiness, changes in the mental status,

• extrasystole, tachycardia, ventricular fibrillation,

• ECG: ST depression, T wave flattening, U waves, prolonged QT.

Treatment: potassium repletion (oral).

Potassium disorders: hyperkalemia

Hyperkalemia: K>5.5 mM/L Common causes:

• overdose on drugs containing potassium,

• renal failure,

• cell lysis,

• use of potassium sparing diuretics in renal failure,

• side-effect of NSAIDs

• hypoaldosteronism.

Signs:

• fatigue, muscle weakness,

• paresthesias in the lower limbs,

• metabolic acidosis,

• changes in the mental status,

• bradycardia, sinoatrial, atrioventricular, ventricular blocks,

• ECG: flattened P waves, ST depression, wide QRS, tall, peaked T waves, short QT

Management of hyperkalemia

• forced diuresis with 40-60 mg of furosemide,

• 0.9% NaCl solution,

• treat the underlying acidosis,

• cation-exchange resin p.o.,

• in case of abnormal ECG findings 10-20 ml of CaCl₂ should be given in about 10 minutes,

• Na-bicarbonate and/or 40% glucose + short-acting insulin can be administered,

• dialysis is appropriate for severe, refractory cases.

Electrolyte/water homeostasis 

pH disturbances:

The normal pH value does not change with age, but aging-associated alterations in its regulation may

contribute to development of disturbances in acid- base homeostasis.

AGING vs. …

Common causes:

• vomiting

• repeated removal of gastric fluid

• secondary hyperaldosteronism (e.g. chronic congestive heart failure with edemas)

• diuretics-induced hypokalemia and secondary

hyperaldosteronism (aggravating already existing secondary hyperaldosteronism of patients with heart failure)

• hypokalemia promotes:

- cellular H⁺ / K⁺ exchange (internal K⁺-balance) - bicarbonate reabsorption in the proximal tubules

- Na⁺ /H⁺ exchange in the distal tubules (external K⁺-balance)

 Hypokalemia and alkalosis are involved in a vicious circle.

Metabolic alkalosis in the elderly

Common causes:

• diabetic ketoacidosis

• lactic acidosis

• decreased erythropoietin production - anaemia

• salicylate-toxicosis (NSAID)

• diarrhea

• renal failure

• renal tubular acidosis (e.g. diabetic nephropathy) Compensation: generally weak in the elderly

• Compensation by hyperventilation is weaker, while:

sensitivity of the central and peripheral respiratory regulation (for CO₂, H⁺ and hypoxia) is decreased.

• The aging kidney shows an impaired reaction to acidosis, therefore, it takes longer to normalize pH.

Metabolic acidosis in the elderly

Common causes:

• hypoxia

• sepsis

• pulmonary embolism

• heart failure (enhanced sympathetic tone)

• liver failure (NH₃ accumulation)

• mild salicylate-toxicosis (regular use of NSAIDs for pain)

• frequent situations with anxiety

Respiratory alkalosis in the elderly

Common causes:

• the central and peripheral respiratory regulation is less sensitive to hypercapnia and hypoxia (by the age of 70

sensitivity to hypoxia decreases by 50%, to hypercapnia by 40-50%; arterial pO₂ decreases 0.3% per year)

• medications decreasing the sensitivity of the respiratory center (e.g. opiates)

• decreased vital capacity (VC) and FEV₁

• decreased chest wall compliance (kyphoscoliosis, obesity)

• neuromuscular diseases can worsen the function of the respiratory muscles

• decreased respiratory surface (severe emphysema)

• chronic bronchitis is more frequent (mucociliary clearance , longer exposition time to environmental pollutants, smoking)

Respiratory acidosis in the elderly

Compensatory capacity of both the kidneys and the lungs is narrowed.

In respiratory acidosis, oxygen therapy may be needed.

Its danger: due to decreased CO

-sensitivity hypoxia regulates ventilation – oxygen therapy may result in hypoventilation and CO

coma!

Assisted ventilation may be necessary.

Compensation of the respiratory pH-

disorders in the elderly

In the elderly mixed acid-base disturbances are very common.

• In acute respiratory insufficiency (pneumonia) combined with heart failure respiratory acidosis is mixed with metabolic

acidosis.

• In serious heart failure: decreased tissue perfusion leads to lactate (metabolic) acidosis, but diuretic therapy influences the balance towards metabolic alkalosis.

Mixed acid-base disturbances