• ACID – BASE BALANCE:
• Normal total body A-B balance is when the
arterial pH is between 7.35 - 7.45
• Large amounts of acid are added to the body
daily mainly in the form of CO2, by:
a) cellular metabolism,
b) energy generation,
& c) protein metabolism
*Some H ions & weak organic & inorganic
nonvolatile acids also are generated.
• The pCO2 is maintained within the normal range
because CO2 generated is continuously diffused
& eliminated across the lungs.
• The kidneys maintain serum[HCO3] within
normal by:
a) reabsorbing HCO3 ions from the glomerular
filtrate
& b) by generating new HCO3 ions in renal tubular
cells.
• Acid-base disturbances are caused by serum [CO2] or
[HCO3] changes.
• If the problem originates with CO2→ pH change is of
resp. origin.
• If it begins with HCO3 → pH change is of metabolic
origin.
• Plasma pH < 7.35 →acidosis ( respiratory or metabolic )
• plasma pH >7.45 →alkalosis (respiratory or metabolic)
• When plasma pH goes outside the normal range → lungs
& kidneys act to compensate & normalize the pH value.
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PRIMARY ACID-BASE DISTURBANCES
METABOLIC ACIDOSIS
plasma pH < 7.35 as a result of a low blood [HCO3]
Possible Causes:
1. losses from the body,
2. ↓’d renal regeneration of HCO3,
3. ↑’d amounts of acid added to the body by ingestion
or metabolic processes.
* As the [HCO3] ↓→ lungs try to ↓ pCO2 & maintain normal
pH by ↑’ing depth & rate of respiration
• SxS of metabolic acidosis are clinically sig. @ pH ≤ 7.1
• # of (+) charged ions in body must always =
# of ( - ) charged ions
* Electrical neutrality in plasma is achieved by
dissolved electrolytes & proteins
Na = Cl + HCO3 + Unmeasured anions
*Unmeasured ions: plasma proteins & small amounts
of SO4 & PO4 not measured by tests in clinical labs
• The usual amounts of these anions in the blood
have a combined ionic strength of 8-16 mmol/L
(8-16 mEq/L).
• This value is called the anion gap, & it rarely
changes.
• Assuming that Na remains constant, a change in
the number of any one of the anions necessitates
a change in one or both of the others to maintain
electrical neutrality.
• Because the # of unmeasured anions is fixed, the
Cl & HCO3 are alterable.
• Metabolic Acidosis:
A) Nonanion Gap Metabolic Acidosis:
• The # of unmeasured anions is the same as
usual, & so ↓’d [HCO3] may be due to:
*Cl loading (NS infusion, NaCl overload)
*actual HCO3 loss from the body (prolonged
diarrhea)
Or *↓’d HCO3 generation (renal failure)
• Important to determine which type of
Metabolic Acidosis before Tx is started.
• Treatment of Nonanion Gap Met. Acidosis:
1. Correct underlying cause
2. Replace HCO3 deficit
** The kidneys generate sufficient HCO3
& normalize pH when acidosis cause is
corrected, EXCEPT in Renal Failure
or profound & continuous GI loss.
• Acute HCO3 replacement is needed only when:
1. pH ≤ 7.1
or 2. Life-threatening SxS of acidosis
• Amount of HCO3 deficit:
• HCO3 deficit (mmol)=
[24-Measured HCO3(mmol/L)]Xbody wt(kg)X 0.5
• ½ the calculated dose is given →
(usually↑pH by 0.2)
• Goal of emergency HCO3 replacement:
to correct existing cardiac or CNS
disturbances by reaching pH ≥ 7.2
* Because acidosis onset is gradual →
CNS is slowly equilibrated to low pH→
Rapid changes in plasma pH relative to CNS
pH → may cause seizures & death because
CNS pH may lag behind
• In addition to the risk of alkalosis & hypernatremia
with rapid replacement with NaHCO3
• In Renal Failure:
• Due to the ↓’d ability of damaged kidneys to
generate HCO3 → Nonanion gap metabolic
acidosis is usually chronic, mild &
asymptomatic
• With severe renal failure → severe acidosis →
Require hemodialysis
• If diarrheal losses > ability of kidneys to
generate HCO3 → HCO3 must be given
(Na or K Bicarbonate or Acetate)
*Composition of the fluid lost must be
determined by lab
* Amount of base given must be enough to:
a. correct initial deficit
& b. maintain the daily loss
B. Anion Gap Metabolic Acidosis:
• ↑# of unmeasured anions (nonvolatile acids)
in plasma →↓[HCO3] to maintain electrical
neutrality
• Possible causes (Abnormal metabolic processes):
1. Diabetic ketoacidosis
2. Prolonged starvation
3. Hypoxia→ lactic acidosis
4. Anaerobic carbohydrate metabolism
5. Accumulation of ingested acids (salicylate/methanol poisoning)
6. Normally produced acid in the body that can not be eliminated
• Treatment of Anion-Gap Met. Acidosis:
1. Correct underlying cause
e.g. Diabetes → IV insulin
lactic acidosis → restoration of app.
circulating vol. or
plasma O2 carrying
capacity
poisoning → hemodialysis or gastric lavage
2. HCO3 Tx → *reserved for pH < 7.1
or *severe SxS of acidosis
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Metabolic Alkalosis:
Plasma pH > 7.45 by ↑’d blood [HCO3]
Anion gap: Never affected
Lungs compensate by↓’ing resp. depth & rate
to ↑ pCO2 & normalize pH
• Significant SxS seen @ pH≥ 7.6
• Most Common Causes:
1. Cl ion loss (NG suction, loop diuretics,
mineralcorticoid excess→Na
retention with K & H loss)
2. ECF depletion (↑[HCO3]→contraction
alkalosis)
3. Hepatic failure → 2⁰Hyperaldosteronism →
K & H losses
• Treatment of Metabolic Alkalosis:
1. From Volume Depletion:
NS →Tx of Choice:
• Na & Cl loss & ↑HCO3 with volume contraction → Saline
Responsive
• NS: a)Replaces Na →stops aldost.-stimulated
exchange of H & Na in
renal tubules
b)Replaces Cl →stops generation of HCO3
needed for elect. neutrality
c)Vol. expansion →↓[HCO3] in vascular space
2) Met. Alk. associated with TBW overload (i.e.
in hepatic failure) →can NOT tolerate NS
Tx →IV infusion of HCl acid
*Dosage HCl to replace H & Cl deficit:
HCl (mmol) = [103 - Measured Cl (mmol/L)]
Xbody wt(kg) X 0.2
*Give ½ HCl deficit IV over 12-24 hrs → ↓pH by 0.2
*This should not cause CNS pH gradient
* IV infusion in central venous catheter NOT peripheral
→ ↓phlebitis risk
3) Metabolic alk. From Hypokalemia 2⁰ to
ICF/ECF exchange of H for K &
mineralcorticoid excess→ Saline resistant
→Treatment: Potassium Replacement
4) Met. Alk. Caused by ↓’d aldosterone
degradation (i.e., in hepatic failure)
→Treatment: Spironolactone
5) Mineralcorticoid-producing tumors of
adrenal/pit. gland
→Treatment: Aminoglutethamide or surgery
• Respiratory Acidosis:
• Plasma pH < 7.35 from pCO2 > 40mmHg
• Slow HCO3 generation in kidney→↑[HCO3]
→ Normalize plasma pH
• CO2 excretion capacity of normal lungs →
always > metabolic production of CO2
→ Resp. Acidosis only results from severe
pulmonary disease
• Treatment of Respiratory Acidosis:
1) Correcting underlying Pulm. Dz.
(i.e. Antibiotics, broncodilators, steroids)
2) Intubation & mechanical ventilation if resp.
depression
**Avoid rapid correction of pH
3) HCO3: ONLY if pH≤7.1
4) Chronic Respiratory Acidosis with COPD:
develops slowly & rarely requires Tx ( many adapt)
Acute in ↓ pCO2 &↑pO2 →Not recommended due
to risk of apnea
• Respiratory Alkalosis:
• Plasma pH >7.45 from pCO2< 40mmHg
• Possible Causes:
1) Voluntary hyperventilation
2) Respiratory Stimulants & mechanical vent.
3) Hypoxemia → ↑ RR →↓pCO2
• Treatment of Respiratory Alkalosis:
• Correct disorder→↑[CO2] of inspired air by:
1. ↑inspired CO2 by a ventilator
Or 2. Rebreathe pt’s own expired air
(bag placed loosely over nose & mouth)
• Compensatory Responses to A/B disturbances:
• All 1⁰ A/B disturb. → compensatory response.
• May be difficult to determine 1⁰ if plasma pH is
within normal
• Two 1⁰ A/B problems can occur together
EXCEPT Resp. acidosis & Resp. Alkalosis
• Correct diagnosis with pt’s hx are important for
starting therapy
• Electrolytes ( Cont.):
• POTASSIUM (3.5-5 mEq/L), (3.5-5.0 mmol/L):
• Changes in acid-base status alter the distribution of K+
in the body.
• Serum [K] ↑’s with acidosis or ↓’s with alkalosis by 0.6
mEq/L for every 0.1 change in pH from 7.4.
• Hyperkalemia:
• may be a medical emergency manifesting as sudden
cardiac arrhythmias usually @ serum [K+] > 6 mEq/L.
• Treatment of Hyperkalemia:
• Any exogenous sources of K i.e., IV fluids or
drugs that contain K should be discontinued
immediately.
• Measures used to correct hyperkalemia act by:
a) normalizing neuromuscular membrane
potential,
b) shifting ions back into the intracellular space,
c) removing K from the body.
a) If the K-induced arrhythmia is life threatening:
*Give 2.5-5 mmol (5 to 10 mEq) Calcium over several minutes to
temporarily correct the K:Ca ratio & eliminate the cardiac problem.
*A constant IV infusion of Ca @ a rate determined by simultaneous
ECG monitoring may be necessary to maintain cardiac function
until measures that permanently normalize serum [K] take effect.
• Ca gluconate (2.3 mmol/g) or Ca Cl (6.8 mmol/g) is used
•
Therapy cannot be continued for long periods because hypercalcemia
may occur.
b) Shifting of K from ECF→ ICF through adm. of :
*Glucose & insulin: Potassium ions move with glucose across cell
membranes in the presence of insulin.
• 2 – 3 g glucose/ unit of insulin is needed to maintain a normal [BG]
• E.g., administered solutions include 25 - 30 U of R insulin/ L of 10%
dextrose solution
• Or 10 units in 50 mL 50% dextrose.
*Beta 2-agonists : A total of 10 - 20 mg of albuterol may be adm. by nebulizer,
in combination with glucose &insulin.
* NaHCO3 : A temporary alkalosis is caused,
• Recommended in combination with insulin & glucose because of its poor
efficacy when used alone
• Cannot be continued for long periods because Na overload & metabolic
alkalosis may occur.
• All these are temporary because they do NOT remove K from the body
• 3 Different treatments may be used to remove K from the body:
• Should be initiated as soon as possible,
• They may not correct cardiac arrhythmias soon enough
• Not considered acute treatment for hyperkalemia.
1) Cationic-anionic exchange resin Na polystyrene sulfonate (SPS):
*po or rectally ( po preferred due to longer contact time with GI mucosa)
*Binds K to itself through exchange with Na in GI tract (may cause Na
overload).
* 1Gm of SPS removes ~ 1mmol K & adds 2-3 mmol Na.
*Very constipating, so it is given with sorbitol, an osmotic cathartic, & water
to prevent fecal impaction.
*The initial dosage : 30-60 g resin in 20% sorbitol & can be repeated Q 1- 2
hrs if the serum [K] remains high.
2)Loop diuretics,(furosemide):
• Have been used as Tx for pts. with hyperkalemia
3)Hemodialysis:
• Can be used to remove K from the body.
• Immediate but very invasive
• Should be used only when the patient’s condition
is life threatening & other Tx methods have failed.
• Hypokalemia:
• Can also be a cardiac medical emergency, with rhythm disturbances
appearing at serum [K] < 3 mEq/ L. .
• Correction of underlying dz. or discontinuation of drug therapy that
contributes to hypokalemia is a basic part of the initial Tx.
* Hypokalemia 2⁰ to hyponatremia is almost always accompanied by
hypochloremic alkalosis.
* Renal reabsorption of Na→ K & H ions secretion
* The dissociation of Carbonic acid in renal tubular cells → H & HCO3.
* The H ion needed for exchange with Na is secreted into the urine, & HCO3 is
resorbed into the blood.
* HCO3 accumulation in serum → alkalosis
* Any concomitant hyponatremia & alkalosis must be corrected for
hypokalemia Tx to be successful.
* KCl salt : The Tx of choice because alkalosis must be corrected.
• Cl loading → ↑’s elimination & ↓’s generation of HCO3 by the kidneys →
alkalosis resolves.
• If a nonchloride salt of K is used → hypokalemia will not be corrected .
• Treatment of Hypokalemia:
• ICF deficit of K almost always precedes & accompanies an ECF deficit →
requires large amounts of K
• po or IV K shifts slowly into the ICF to correct that deficit → slow IV
infusion of KCl to avoid hyperkalemia.
• IV KCl @ 10 mEq/ hr in pts with serum [K] < 3.5 mEq/ L, & 30-40 mEq
given over 3- 4 hrs in D5W or NS is a common rate of K replacement.
• Serum [K] should be reassessed & K administered until normal (3.8 to 4.0
mEq/L).
• In profound hypokalemia & continued K wasting, replacing K deficit may
need to be given in very large doses → 20 - 40 mEq/ hr given centrally to
avoid pain & phlebitis @ infusion site.
• Oral administration of potassium chloride can cause GI irritation
→ IV replacement may be needed for large K
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CHLORIDE:(95-105 mmol/L)
• Major anion in the ECF,
• It usually ↑’s or ↓’s with total body sodium,
• A change in [Cl] → acid-base disturbance.
*Hyperchloremia:
• Results from: *metabolic acidosis,
*respiratory alkalosis,
* hypernatremia, or
*Cl loading.
• Treatment:
• Correcting the underlying disorder.
• If the cause is metabolic acidosis or respiratory alkalosis → correcting
them is the only Tx.
• Changing NS infusion to 0.45% saline infusion or replacing NaCl with Na
acetate may resolve it.
• If caused by overingestion of NaCl → Tx :free H2O replacement & diuresis.
* In hypernatremia caused by H2O loss → Tx: TBW fluid replacement
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Hypochloremia:
Hyponatremia → hypochloremia (to maintain electrical neutrality);
Cl normalizes with correction of the ECF [Na]
Most common causes: *NG suction,
*vomiting,
*diuretic therapy.
• Treatment:
• Replacing with high-Cl solutions i.e., NS or LR.
• Liberalizing sodium chloride intake, reducing the diuretic dose, &
correcting symptomatic hyponatremia and hypokalemia
with saline and KCL solutions.
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CALCIUM: (8.8-10.3 mg/dL or 2.2- 2.6 mmol/L )
Only 1% of the total is in the fluid spaces.
50% is protein bound
PTH, vit. D, & calcitonin regulates GI absorption,
renal excretion, & skeletal deposition or
resorption of Ca & determine its serum [Ca]
• An inverse relationship occurs between serum
[Ca] & [PO4]
•
Corrected, measured total serum Ca can be calculated by accounting for a
patient’s ↓’d albumin on the basis of a normal value of 4 g/dL.
Corrected serum Ca = [4 g/dL - Measured albumin(g/dL)] X 0.8
+ Serum calcium measured
• Either monitor the reported ionized Ca or the corrected measured total
serum Ca
• Acid-base disturbances affect the ionized:bound Ca ratio but not the total
serum Ca.
• In acidosis, hydrogen ions displaces Ca ions from their protein binding
sites, & ↑’s free Ca in the blood.
• The converse is true in alkalosis.
• For each 0.1 change in pH, the ionized Ca changes by 0.42 mmol/ L in the
opposite direction.
• Hypercalcemia: (corrected total serum Ca > 2.6 mmol/L (10.3 mg/dL) or
ionized Ca > 1.15 mmol/L).
• *Any sources of exogenous Ca should be discontinued immediately.
• Treatment:
•
1) Shifting Ca ions into the bone
• Or 2) Eliminating Ca from the body.
1) Therapies administered to remove Ca from the body are given first
because they work faster & are generally more effective in acute situation.
• Loop diuretics, such as furosemide and bumetanide, ↑ renal Ca excretion.
• The initial furosemide dosage is 1mg/ kg & is given with of NS to maintain
normal body H2O & [Na]
• Electrolytes must be carefully monitored & K & Mg administration may be
needed to prevent hypokalemia & hypomagnesemia .
• This washout therapy may need to be continued for extended periods if
the cause of the hypercalcemia is severe or if abnormally large amounts of
Ca continue to appear in the vascular compartment.
2)
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Treatments that shift Ca back into bone are slow & may become ineffective because of
tachyphylaxis.
Parenteral Calcitonin:
Rapidly ↑’s bone uptake of Ca
Rapid onset but short duration, and tachyphylaxis develops within days.
The initial parenteral dose 4 IU/ kg Q 12 hrs SQ or IM .
Etidronate disodium:
a bisphosphonate that inhibits osteoclastic bone resorption by binding hydroxyapatite.
Initial treatment 7.5 mg/kg/day IV QD X 3days
The infusion time: @ least 2 hrs to avoid renal damage (renal disease)
Once serum [Ca] is normalized, po therapy 20 mg/kg/d
Pamidronate disodium:
May be > effective than etidronate
Faster onset & longer duration of action than etidronate
Dose: 60-90 mg given IV over @ least 2 hrs.
May be repeated as often as every 7 days if needed
Calcitonin in combination with bisphosphonates is used in the acute management of
hypercalcemia.
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Steroids i.e. prednisone:
useful in managing chronic mild hypercalcemia.
Initial prednisone dose15-100 mg/d
Onset of action 3-10 days.
Steroids antagonize activation of vit.D in the liver
& reduce bone resorption.
• For these reasons, steroids are not effective in
hypercalcemia secondary to hyperparathyroidism
• Oral phosphate:
• Not Tx option in this type of hypercalcemia because the
amount of serum Ca falls when [P] rises usually is small &
because of the risk of soft tissue calcification exceed
benefit of this therapy.
• Mithramycin:
• Cancer chemotherapeutic agent that acts by inhibiting
DNA-dependent bone osteoclast RNA synthesis → slows or
stops bone resorption.
• An effective but potentially toxic therapy for hypercalcemia
• Indicated only when other therapies fail.
• Doses smaller than those used in cancer but hematologic &
GI toxicity remain
• OA 12-48 hrs, DA 3-7 days
• Hypocalcemia: Corrected [Ca] < 8.8 mg/dL (2.20 mmol/L)
or an ionized [Ca] <1 mmol/L.
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Acute Tx: IV Ca.
Ca chloride contains 6.8mmol/gm (13.5 mEq Ca/gm),
Ca gluconate & gluceptate 2.3 mmol/gm (4.6 mEq Ca/gm)
The initial dose 2.5-5 mmol Ca followed by an infusion of
0.075-0.1 mmol Ca/kg/hr
• Monitor [Ca], BP, & ECG
• If hypocalcemia SxS do not resolve, evaluate for
hypomagnesemia
• Treatment of Chronic hypocalcemia:
• Correct the underlying cause.
• Mostly, the cause of chronic hypocalcemia is a low concentration
of biologically active vit. D in advanced hepatic or renal dz. because
of ↓’d transformation of cholecalciferol (D3) → active 1,25dihydroxycholecalciferol (1,25-DHC).
• The serum [Ca] will not normalize until conc. of 1,25-DHC is normal.
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Therapy: Ca & vit. D supplements.
Ergocalciferol (D2) 1.25-5 mg (50,000-200,000 IU/d)
Dihydrotachysterol (DHT) 0.25-1 mg/day (30,000-120,000 IU of D2)
The onset of action can take several weeks &
effect may be prolonged because of the long t1/2 of vit. D.
• Activated forms of vit. D must be given when renal or hepatic
failures.
• 25-Hydroxycholecalciferol (calcifediol) or 1,25-DHC (calcitriol)
• Active forms of vit D OA 3-7 days and are preferred because
their shorter half-lives reduce the risk of prolonged
hypercalcemia.
• Ca supplements 25-100 mmol/ day (1 to 4g) elemental Ca is
begun simultaneously.
• Ca carbonate contains the highest amount of elemental Ca
400 mg/ 1,000 mg
• Other salts: Ca lactate contains, Ca gluceptate & Ca gluconate
• Ca carbonate is preferred because lower # of tablets used.
• When hypocalcemia is caused by hypoparathyroidism →
parathyroid hormone replacement is indicated & is the only
therapy that raises [Ca]
• MAGNESIUM: 1.6-2.4mEq/L(0.8-1.2 mmol /L)
• 99% in bone & intracellular & 1% in vascular
space ( 25% is PB & 75% ionized)
• Hypermagnesemia is rarely seen without severe
renal dysfunction.
* Mg-containing antacids are often a contributing
factor in this situation.
• All sources of exogenous Mg should be
discontinued.
• Treatment of Hypermagnesemia:
Treatment of Hypermagnesemia:
• Similar as Tx of hyperkalemia
• Hypomagnesemia
• usually appears with hypokalemia,
hypocalcemia, & hypophosphatemia.
• Concentrations of these electrolytes should be
measured
• Therapy of hypomagnesemia:
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IV MgSO4 or oral MgO or Mg gluconate salts.
IV MgSO4 dose 1 mEq/kg/day if [Mg] < 0.6 mmol/L, &
0.5 mEq/kg/day if [Mg] is 0.7-1.2 mmol /L.
IV MgSO4 is administered slowly @ 0.5-1 g/hr.
Serum [Mg] may take up to 48 hrs to equilibrate with
intracellular shifting.
• The oral replacement of large deficits can be difficult (may
cause diarrhea)
• MgO capsules are most commonly given (6.2 mmol/250 mg
MgO) because of pt. convenience, but solutions of
magnesium sulfate & gluconate are also available.
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PHOSPHORUS: 2.5-5 mg/dL ( 0.8-1.6 mmol/ L)
99.99% in bone & the intracellular space.
Hyperphosphatemia:
Almost always from ↓ excretion in the presence of
severe renal dysfunction
• Treatment of Hyperphosphatemia:
a) ↓ P intake
Or b) ↓P absorption from the GI by binding it with
Ca salts, or Al-containng antacids, or
sevelamer (polymeric compound).
**Careful from accumulation of Ca or Al in renal failure
• Hypophosphatemia:
• Abnormality usually is the result of starvation & appears
• with simultaneous deficits in other intracellular ions.
• Therapy:
• Replacement with Na or K salts of PO4.
• Initial PO4 dose 0.64 mmol/kg/day if serum [P] < 0.5 mmol /L (1.5 mg/dL)
0.32 mmol/kg/day if [P] is 0.5 -0.7 mmol/L (1.6-2.2 mg/dL).
• Therapy should be given over @ least 6 hrs to allow for equilibration into
• the intracellular space.
• Oral Na & K PO4 replacement (as capsules, packets, or solution)
• Large oral dosages → not recommended.
• Dosages of 8-16 mmol PO4 (250-500 mg) 4X/day after meals &
@ bedtime are usually tolerated
* Large doses may be given IV