Welcome To Seminaron

Acid – Base disorder

Dr. Tareq Rahman

(Resident phase – B , year 4)

Dr. Bipin Karki

(Resident phase – B , year 5)

Bangabandhu Sheikh Mujib Medical University,Dhaka , Bangladesh.

Concerning matter ?

• Acid-base balance is one of the body’s most important homeostatic mechanisms –

- It represents equilibrium, balance, and a steady state.

- Without acid-base balance, the cells cannot function properly. - The body can tolerate slight deviations in balance for short

periods of time - Chronic imbalances can result in pronounced, potentially fatal

changes in metabolic activity and essential body functions. - Structural shapes of proteins and/or protein functions are

altered. - Enzymatic activity is diminished. - Chemical reactions may cease.

Neonatal status

• Due to higher metabolism, production of acid is three times more than adult.

• Respiratory and renal function can not maintain acid base balance properly like adult.

• In the premature or sick newborn, buffers may be blunted or insufficient.

Terminology

Acid

Any substance that can yield a hydron (proton or hydrogen ion H+)when dissolved in water

Base

Substance that can yield hydroxyl ions (OH-)

Accept proton or H+

Acid Production

• Volatile acid –

- CO2 is produced from aerobic metabolism of cells.

- CO2 combines with H2O to form the weak acid H2CO3 , which dissociates into H+ and HCO3 by the following reaction –

CO2 + H2O – H2CO3 - H+ + HCO3-

• Non-volatile acid –

- Sufuric acid ( a product of protein metabolism).

- Phosphoric acid ( a product of phospholipidmetabolism ).

- Ketoacid , lactic acid and salicyclic acid are other acids , are overproduced in disease or may be ingested.

pH

Negative log of the hydrogen ion concentration

Measure of acidity

pH= pK + log([base]/[acid])

Represents the hydrogen concentration

Normal pH of body fluid is 7.35-7.45

pK

Negative log of the ionization constant of an acid

The pH at which a buffer is 50% dissociated is it’s pK.The best physiologic buffers have pK close to 7.4.

Henderson–Hasselbalch equation

• Henderson–Hasselbalch equation describes the derivation of pH as a measure of acidity.

• The equation is given by:

pH = pKa + log ([A-]/[HA])

• [A-] = molar concentration of a conjugate base

• [HA] = molar concentration of a undissociatedweak acid (M)

Estimating blood pH

pH = pKa + log ([HCO3−]/[H2CO3])

= 6.1 + log ([HCO3−]/[H2CO3])

= 6.1 + log ([HCO3−]/0.03x pCO2)

where:

• pKa is the logarithm of the acid dissociation constant of carbonic acid. It is equal to 6.1.

• [HCO3−] is the concentration of bicarbonate in the blood

• [H2CO3] is the concentration of carbonic acid in the blood

• 0.03 is the solubility factor of CO2

• pCO2 - Partial pressure of CO2 in blood

Acidemia -

Blood pH less than 7.35 ( < 7.4 is acidotic)

Alkalemia -

Blood PH greater than 7.45 ( > 7.4 is alkaline)

Acidosis: pathological process that causes an increase in hydrogen ion concentration.

Alkalosis: pathological process that causes a decrease in hydrogen ion concentration.

• Base Excess (BE) :

- It refers to the change in the concentration of buffer base ( BB ) from it’s normal value . Base excess refers principally to the [ HCO3- ].

BE are only influenced only by metabolic process.

Normal range : -5 to + 5 mEq/L in arterial blood.

Increase HCO3- : positive base excess ( metabolic alkalosis)

Decrease HCO3- : negative base excess ( metabolic acidosis )

Regulation of pH

Mechanism :

- Buffers 1st line defense.

- Respiratory Center and Lungs

2nd line defense.

- Renal system

Buffer -

Combination of a weak acid and /or a weak base and its salt

What does it do?

Resists changes in pH

• Extracellular buffers –- HCO3 is major extracellular buffer produced from CO2 and

H2O

- Phosphate is a minor urinary buffer and most important

urinary buffer .• Intracellular buffers – Proteins

- Hemoglobin is a major intracellular buffer.- Imidazole and alfa amino groups

Organic acid - AMP , ADP , ATP , 2,3-diphosphoglycerate .

• Bone –

- Bone represents an important site of buffering acid load.

- An acid load, is associated with the uptake of excess H+ ions by bone which occurs in exchange for surface Na+ and K+ and by the dissolution of bone mineral

- It has been estimated that at least 40% of the buffering of an acute acid load takes place in bone.

- Chronic acidosis can have very adverse effects on bone mineraliz can result in bone diseases such as rickets, osteomalacia and osteopenia.

Mechanism of Buffer

• Buffers combine with the strong acids replacing them with weaker acids, and vice versa.

-Buffers do not actually rid the body of H+ or CO2 but combine with them until another system can excrete them from the body.

-Depending on whether an acid or base state exists, chemical buffer reactions are reversible.

Bicarbonate buffer

• Is a mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3) and the reversible reaction catalyzed by carbonic anhydrase

• If strong acid is added-

-Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak acid)

- The pH of the solution decreases only slightly

• If strong base is added –

- It reacts with the carbonic acid to form sodium bicarbonate (a weak base)

- The pH of the solution rises only slightly

Hemoglobin buffer

• In RBC CO2 binds with Hbto form carbamino-Hb

• CO2 also converted into H2CO3 which dissociates to HCO3

- and H+ .

• HCO3- exchanged for

chloride ions (Cl-) into plasma called chloride shift.

• H+ combines with oxyhemoglobinstimulating the release of the oxygen

Renal Regulation System :• The renal buffer system uses bicarbonate,

phosphate and ammonium buffers.

• It takes hours to days

• Kidney maintain acid-base balance in three ways:

- secrete H+,

- reabsorb bicarbonate,

- produce new bicarbonate.

Cont…

• The renal responses to abnormal acid load are – increases secretion of H+

increases HCO3- reabsorption and HCO3

- generation increases excretion of titrable acid and NH4+ ( mainly )

• The renal responses to abnormal alkali load are – increases HCO3

- excretion in urine increases excretion of phosphate buffer base Suppression of ammonia secretion

Reabsorption of bicarbonate

Excretion of titrable acid

Excretion of ammonium

Respiratory system regulation

• Acts within min to hours maximal within 12-24 hrs.• H2CO3 produced converted to CO2, and excreted by

the lungs.• Powerful, but works with volatile acids• Exhalation / accumulation of carbon dioxide.• Body pH can be adjusted by changing rate and depth

of breathing.• CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3

-

• Metabolic acidosis – hyperventilation – exhalation of CO2

• Metabolic alkalosis – hypoventilation –accumulation of CO2

Anion gap

The anion gap is the difference in the measured cation ( Sodium and potassium) and the measured anions ( Bicarbonate and chloride) in plasma.

Anion gap= ([Na+] + [K+]) − ([Cl−] - [HCO3−])

Normal value: 8-16 mmol/L

It is also the difference between unmeasured anions and unmeasured cations.

Anion gap is increased when there is increase in unmeasured anions.

Acid- Base disorders

Metabolic acidosis

Metabolic alkalosis

Respiratory acidosis

Respiratory alkalosis

Mixed disorder

Metabolic acidosis

Bicarbonate deficit - blood concentrations of bicarbonate drop below 24 mmol/L

3 basic mechanisms:

1. Loss of bicarbonate from body

2. Impaired ability to excrete acid by kidney

3. Addition of acid to the body

Causes:

1. Normal anion gap

2. Increased anion gap

Metabolic alkalosis

\ Metabolic alkalosis is elevation of arterial pH , an increase in serum {HCO3-} .

RESPIRATORY ACIDOSIS

• Caused by hypercapnia due to hypoventilation

• Characterized by a pH decrease and an increase in CO2

30

CO2 CO2

CO2

CO2

CO2

CO2CO2

CO2CO2

CO2

CO2 CO2

CO2

pH

pH

RESPIRATORY ALKALOSIS

• Cause is Hyperventilation

– Leads to eliminating excessive amounts of CO2

– Decrease in H+

31

CO2 CO2 CO2CO2CO2

CO2

CO2

CO2CO2

CO2CO2

Mixed Acid-Base Disorders• Mixed- when compensation is inappropriate

• Mixed respiratory alkalosis & metabolic acidosis

– Sepsis

• Mixed respiratory acidosis & metabolic alkalosis

– Excessive use of diuretics , BPD

Metabolic acidosis

Increased anion gap metabolic acidosis (Normal Chloride) Lactic acidosis associated with clinical evidence of

decreased tissue perfusion• Asphyxia• Hypoxia • Respiratory distress syndrome (RDS)• Sepsis• Anemia• Hypothermia/cold stress• Patent ductus arteriosus• Necrotizing enterocolitis

Inborn errors of metabolism

Renal failure

Toxins and medications

• Maternal use of salicylates acetaminophen, cocaine, nitroprusside, ibuprofen, iron, isoniazid, paraldehyde, sulfasalazine, valproicacid.

Normal or non–anion gap metabolic acidosis

Renal loss of bicarbonate

(a) Immature kidneys

(b) RTA

(c) Renal failure

(d) Medications Carbonic anhydrase inhibitors (acetazolamide)

GI loss of bicarbonate

(a) Diarrhea (usually secretory)

(b) Urologic and GI procedures

Surgery for NEC, ileostomy, Enterocutaneous or bowel fistula

Effects of metabolic acidosis

• Hyperventilation (Kussmaul respiration)

• Depression of myocardial contractility (PH≤7.2)

• Resistance to the effects of catecholamines

• Vasoconstriction of pulmonary arteries

• Shift of K+ out of cells causing hyperkalaemia

Management

Metabolic acidosis.

• The primary treatment is to treat the underlying cause. Correct hypoxia, hypovolemia, low cardiac output, and anemia.

• Fluid therapy for metabolic acidosis Volume expansion should not be used to treat acidosis unless there are signs of hypovolemia.

• Treatment with bicarbonate is not recommended as a supportive therapy and its use is very controversial.

• Cochrane review states there are insufficient data to make a recommendation on using sodium bicarbonate during resuscitation. (Beveridge et al 2006)

• There is insufficient evidence from randomisedcontrolled trials to determine whether infusion of base or fluid bolus reduces morbidity and mortality in preterm infants with metabolic acidosis. (Cochrane review 2005)

• Some institutions treat acidosis if severe with an alkali infusion if the base excess is > –5 to –10 or if the pH is ≤7.25

• Total requirement=0.4× wt in kg× base excess

• 1 st1/3rd mixed with same amount of distilled H2O IV stat

• 2 nd 1/3rd mixed with 24 hrs IV fluid

• Rest 1/3rd : Auto-correction, if renal functions is in normal limit

ARF: If pH is ≤ 7.2 bicarbonate ≤ 18: Sodium

Side effect of Sodium Bicarbonate• Hypernatremia• IVH• Alkalosis• Hypocalcaemia• Extravasation cause tissue injury• ability to generate CO2 and actually lower the

intracellular pH and cerebrospinal fluid pH. (HCO3-+H+→H2CO3→H2O+CO2)

PrerequisiteAdequate ventilation

• Tromethamine (THAM) can be used in infants who have a severe metabolic acidosis but have a high serum sodium (>150 mEq/L) or high Pco2 (>65 mm Hg) despite aggressive assisted ventilation.

• Use only in infants with good urine output (hyperkalemia risk) and monitor for hypoglycemia

• Polycitrate (Polycitra) (oral solution). Chronic renal insufficiency intrinsic renal disease RTA Each 1 mEq citrate equals 1 mEq bicarbonate. Dose adjust

to maintain a normal pH.

Metabolic alkalosis

Common causes of metabolic alkalosis in the newborn

• Prolonged NG/OG suction

• Pyloric stenosis (persistent vomiting)

• Diuretic therapy (especially Lasix in patients with bronchopulmonary dysplasia)

• Excess alkali administration (eg, sodium bicarbonate, citrate, acetate, or lactate infusion)

• Potassium depletion

Effects of metabolic alkalosis

• Decreased myocardial contractility

• Decreased cerebral blood flow(cerebral vasoconstriction)

• Pulmonary vasodilation

• Confusion

• Mental obtundation

• Impaired peripheral oxygen unloading (due shift of oxygen dissociation curve to left).

Management of metabolic alkalosis

• Mild or even moderate alkalosis may not require correction.

• Because volume depletion is common so, infusion of isotonic saline (0.9% sodium chloride) is the most common method of chloride replacement in this condition.

Management of metabolic alkalosis

a. Excess administered alkali. Adjust or discontinue the dose of THAM, sodium bicarbonateb. Hypokalemia. The infant’s potassium level should be corrected c. Prolonged nasogastric suction. Treated with IV fluid replacement, usuallywith 1/2 normal saline with 10–20 mEq KCl/L, replaced mL/mL each shift.d. Vomiting and loss of chloride from diarrhea. Give IV fluids and replace deficits.e. Diuretics. Stop the dose temporarily, or decrease the diuretic dose if necessary, or add a potassium-sparing diuretic such as spironolactone.

Respiratory acidosis

• Increasing respiratory failure; lung diseases such as RDS, pneumonia, transient tachypnea (TTN), BPD/CLD, pulmonary hypoplasia, atelectasis.

• Obstructed ETT (eg, mucus plug).• Improper ETT position. An endotracheal tube positioned in the

oropharynx, down the right main stem bronchus, or at the carina.• Pneumothorax.• Hypoventilation or poor respiratory effort from maternal

anesthesia, PNA, medications, neuromuscular disorders, sepsis, intracranial hemorrhage, hypoglycemia.

• PDA with pulmonary edema• Others: Congenital diaphragmatic hernia, phrenic nerve paralysis

Effects of respiratory acidosis

• Acidemia, no matter the etiology, affects the cardiovascular system. An arterial pH <7.2 impairs cardiac contractility

• Hypercapnia causes cerebral vasculature vasodilation

• Hypercapnia produces vasoconstriction of the pulmonary circulation

• Central depression at very high levels of pCO2

Respiratory alkalosis

• Overventilation by the ventilator. Most common cause in NICU.

• Air bubble in the blood gas collection syringe. This can falsely lower the Pao2 and Paco2

• Hyperventilation therapy. As used in persistent pulmonary hypertension.

• Central hyperventilation. Central nervous system (CNS) stimulation of the respiratory drive caused by a CNS disorder or transient hyperammonemia

• Hypoxemia can cause a low CO2. Respiratory centers are stimulated through chemoreceptors.

• Hyperventilation. Seen in a spontaneously breathing infant secondary to sepsis, fever.

Effects of respiratory alkalosis

• Decreased intracranial pressure (secondary to cerebral vasoconstriction)

• Inhibition of respiratory drive via the central & peripheral chemoreceptors

• Decreased myocardial contractility

• Shift of the haemoglobin oxygen dissociation curve to the left (impairing peripheral oxygen unloading)

• Slight fall in plasma [K+]

Management of Respiratory acidosis and alkalosis

• ETT problem

• Ventilator issues

• Treatment of underlying disease

Sudden respiratory acidosis in MV

• D – Dislodged

• O – Obstructed

• P – Pneumothorax

• E – Equipment

Three-step process for interpreting acid–base disturbances.

• Step 1: Determine whether the pH is low (acidemia) or high (alkalemia).

• Step 2: Establish an explanation for the acidemia or alkalemia.

• Step 3: Calculate the expected compensation and determine whether a mixed disturbance is present

Quiz 1

• Baby boy, 28 wks GA, admitted 3 hrs ago, intubated initially, given surfactant, then extubated immediately to nasal CPAP, pressure 5 cm H2O, FiO2 0.5.

• ABG now: pH=7.20, PCO2=68, PO2=40, HCO3=22, SaO2=85%• Interpret above blood gas

AcidosisRespiratoryExp Hco3: 29Metabolic AcidosisHypoxemia

Quiz 2

• Baby girl, born at term by emergency CS, because of cord prolapse and severe fetal distress. She was flat, needed thorough resuscitation (intubation, UVC, 2 doses of epinephrine)

• Now she is 6 hrs old, ventilated, FiO2 0.3, and had focal seizure.

• ABG: pH=7.15, PCO2=30, PO2=60, HCO3=6, SaO2=92%• Interpret above blood gas• Acidosis• Metabolic • Exp Pco2 15-18• Respiratory acidosis

Quiz 3

• Hundred day-old baby girl, was born at 27 wks GA, had stormy course.

• Now she is on NC 1 LPM, FiO2 0.3• ABG: pH=7.34, PCO2=65, PO2=60, HCO3=35, SaO2=92%• Interpret above blood gas

AcidosisRespiratoryExp Hco3: 32.5Metabolic alkalosis

Quiz 4• Seven day-old, baby boy, born at 29 wks GA.• He had large PDA, led to pulmonary

hemorrhage, which treated conservatively.• Indomethacin cannot be given because of Lt

side grade 4 IVH, TFI was restricted to 120 ml/kg/d and furosemide was given 1.2 mg q12 hrs.

• ABG: pH=7.47, PCO2=40, PO2=60, HCO3=30, SaO2=92%

• Alkalosis• Metabolic • Exp Pco2: 44• Respiratory alkalosis

Thank you all