Transcript Changes of electrolyte/water and acid/base homeostasis

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
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
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
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Erika Pétervári and Miklós Székely
Molecular and Clinical Basics of Gerontology – Lecture
12
CHANGES OF
ELECTROLYTE/WATER
AND ACID/BASE
HOMEOSTASIS
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AGING vs. …
Electrolyte/water homeostasis
pH disturbances
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SALT AND WATER BALANCE IN
THE ELDERLY 1
• 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 IIinduced water intake is smaller than
that seen in young animals. Dypsogenic
effects of ADH is weakened.)
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SALT AND WATER BALANCE IN
THE ELDERLY 2
• 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
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ADH effect decreases with
age
120
U/P inulin
(urine/plasma conc.
ratio)
Young
Middle
Old
110
100
90
80
70
60
50
40
30
ADH
20
10
0
0
1
2
3
4
5
6
7
8
9
Urine Collection Period
10
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Salt and water balance in
the elderly: kidney
• 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
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Development of
hyposthenuria
Specific gravity of urine
1,040
Hyposthenuri
a
Isosthenur
1,030
ia
1,020
1,010
Specific gravity of
plasma
1,000
2,000,000
1,500,000
1,000,000
500,000
Number of nephrons
0
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Salt and water balance in
the elderly: hormones
• 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.
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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.
Exsiccosis and dehydration:
decrease of extracellular
volume (ECV)
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200
EC
IC
100
0
0
10
20
30
40
liter
Osmolarity (mOsm/liter)
Osmolarity (mOsm/liter)
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
300
300
intracellular compartments.
200
EC
IC
100
0
0
10
20
30
40
liter
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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
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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),
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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.
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Hyponatremia (hypotonicity)
Common causes:
Reduced Na concentration while the water
volume is normal or increased („waterintoxication”):
• 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.
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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.
Hypernatremia
(hypertonicity)
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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)
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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
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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
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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,
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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 + shortacting insulin can be administered,
• dialysis is appropriate for severe,
refractory cases.
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AGING vs. …
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.
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Metabolic alkalosis in the
elderly
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
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Metabolic acidosis 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
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Respiratory alkalosis 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
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Respiratory acidosis 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
Compensation of the
respiratory pH-disorders in
the elderly
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Compensatory capacity of both the
kidneys and the lungs is narrowed.
In respiratory acidosis, oxygen therapy
may be needed.
Its danger: due to decreased CO2sensitivity hypoxia regulates
ventilation – oxygen therapy may result
in hypoventilation and CO2 coma!
Assisted ventilation may be necessary.
Mixed acid-base
disturbances
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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.