ACID-BASE DISORDERS

BY

DR I O MBAH (MB;BS,FWACP)

Chief Physician/ Nephrologist

DEFINITIONS

• • Acids are compounds that are capable of donating H+ ions; when an acid (HA) dissociates, it yields an H+ ion and its conjugate base or anion (A−).
• • Bases are compounds that are capable of accepting H+ ions.
• • Valence is the net electrical charge on a compound or an element. HA ⇌ H + + A −

PHYSIOLOGY OF PROTON

• From a chemical perspective, H+ is the smallest ion (atomic weight 1) and its concentration in body fluids is tiny (a million-fold lower than that of its major partner, HCO− 3 ).

• Nevertheless, H+ ions are extremely powerful because they are intimately involved in the capture of energy from oxidation of fuels by driving regeneration of adenosine triphosphate (ATP4−).

• In this context, the electrical charge on the protons is far more important than their chemical concentration

• The concentration of H+ ions in body fluids must be maintained in a very narrow range.
• If their concentration rises, H+ ions will bind to intracellular proteins, and this changes their charge, shape, and possibly their functions, with possible dire consequences.

• Hence, a system is needed to remove H+ ions, even if their concentration is not appreciably elevated.
• This function is achieved by the bicarbonate buffer system (BBS).

• The special feature that allows the BBS to function as an effective buffer is that a low PCO2 drives the reaction of H+ ions with HCO− 3 anions

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• H+ + HCO3 −↔ CO2 + H2O

• Because a small increase in H+ ion concentration in plasma stimulates the respiratory center and causes hyperventilation,
• the concentration of CO2 in each liter of alveolar air and hence in the arterial blood will be lower.

• Removal of H+ ions by the BBS leads to a deficit of HCO− 3 ions.
• Accordingly, one must have another system that adds new HCO− 3 ions to the body as long as acidemia persists.
• This task is achieved by the kidneys, in the metabolic process of excretion of ammonium ions (NH+ 4 ) in the urine

• A high rate of excretion of NH+ 4 ions must be achieved while maintaining a urine pH that is close to 6.0
• To avoid precipitation of uric acid.
• Base balance is maintained by excreting an alkali load in the urine as a family of organic anions rather than HCO− 3 ions

• . This avoids having a high urine pH and the risk of precipitation of calcium phosphate in the luminal fluid

Base Balance

• 1. Input of alkali:
• This occurs primarily when fruit and vegetables are ingested because they contain the K+ salts of organic acids that are metabolized to yield HCO− 3 anions.
• 2. Elimination of alkali: This is achieved in a two-step process:

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• (1) the alkali load stimulates the production of endogenous organic acids

(e.g., citric acid), the H+ ions of which eliminate HCO− 3 anions, and

• (2) the kidneys excrete organic anions (e.g., citrate anions) with K+ ions in the urine

ACIDEMIA Vs ACIDOSIS

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• • Acidemia describes an increased concentration of H+ ions in plasma.
• • Acidosis is a process in which there is an addition of H+ ions to the body; this may or may not cause acidemia.

ACID-BASE TERMS

• • Concentration of H+ ions: The normal value in plasma is 40±2 nmol/L, which is 0.000040 mmol/L.
• • pH is the negative logarithm of the [H+] in mol/L, its normal value in plasma is 7.40±0.02.

• • HCO − 3 ions:
• the conjugate base of carbonic acid is the “H+ ion remover” of the BBS;
• its concentration in plasma is close to 25 mmol/L,
• but there are large fluctuations throughout the day (22 to 31 mmol/L).

• • PCO2:
• The major carbon waste product of fuel oxidation is carbon dioxide.
• Its concentration is reflected by its partial pressure (PCO2).
• The normal arterial PCO2 is 40±2 mm Hg.
• The PCO2 in blood-draining skeletal muscles is ∼6 mm Hg greater than the arterial PCO₂ at rest

INTRODUCTION 1

• The chemical rxns that sustain life depend on a delicate balance bw acids and bases in the body
• Even a slight imbalance in homeostasis can profoundly affect metabolism and essential body fxns, enzymes, muscle contractn etc
• Several conditions such as trauma or infection and medications can affect this balance

INTRODUCTION 2

• However to understand this balance u need to understand some basic chemistry
• pH: Understanding acids & bases requires an understanding of pH, a calculation based on the %age of H⁺ in a soln as well as the amount of acids and bases
• Acids consist of molecules that can donate H⁺ to other molecules while bases accept it

INTRODUCTION 3

• Carbonic acid is an acid that occurs naturally in the body while HCO₃⁻ is an example of a base.
• A soln that contains more base than acid has fewer H⁺ and so higher pH.
• A soln with pH >7 is a base or ALKALINE while soln of pH <7 is acidic
• You can access a pt’s acid-base if you know the blood pH

INTRODUCTION 4

• The art blood is usually used to measure this pH And is normally slightly alkaline ranging from 7.35-7.45
• Generally pH is MAINTAINED IN A RATIO of 20parts of HCO₃⁻ to 1part of Carbonic acid
• A pH of <6.8 OR >7.8 is usually fatal
• Acidosis is a condition in which pH <7.35
• Alkalosis is pH > 7.45

REGULATING ACIDS & BASES

• A person’s well being depends on his ability to maintain normal pH
• Therefore when pH rises or falls, 3 regulatory systems come into play
• CHEMICAL BUFFERS (HCO₃⁻, PO₄⁻, Prot⁻), act immediately to protect tissues & cells instantly combining with the offending acid or base neutralizing their harmful effects until other regulators take over

OTHER REGULATORS ARE:

• THE RESP SYSTEM: Which uses hypo or hyperventilation as needed to regulate excretion or retention of acids within minutes of this pH change
• THE KIDNEYS: They kick in by excreting or retaining acids and bases as needed. Renal compensation kicks in after 6hrs if the other two systems fail to restore the pH. This may take hours to days

• The kidneys assist the HCO₃⁻ buffer syst by regulating the production of HCO₃⁻
• The lungs assist by regulating the production of Carbonic acid, which results from combining CO₂ & H₂O
• The normal PaCO₂ LEVEL IN THE BODY IS 35-45mmHg
• The normal HCO₃⁻ = 22-26mmol/l

Henderson-Hasselbalch Equation

• The metabolic and Respiratory components that regulate systemic pH are described by this equation:

HCO₃

pH = 6.1 + log ----------------

PaCO₂ X 0.0301

• Usual steady state of PaCO₂ is at 40mmHg
• Under excretion of CO₂ → Hypercapnia ; Overexcretion → Hypocapnia

• HENDERSON EQUATION
• • This equation has three parameters; if two are known, the third can be calculated.
• If all three are measured, the equation can be useful to detect whether there may be a laboratory error in the measurements.

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• [ H + ] (nmol/L) =
• 24 × PCO2 (mm Hg)/PHCO3 (To make the mathematics easier, one can use 24 or 25 as the constant in this equation.)

HYPERCAPNIA

• PaCO₂ is regulated by neural respiratory factors and not subject to the rate of CO₂ prod
• Hypercapnia usually results from hypoventilation rather than ↑CO₂ prod
• So ↑ or ↓ in PaCO₂ represents derangement in neuro-respiratory control or
• Alteration in HCO₃ regulation by way of compensatory mechanism

REGULATION of Plasma HCO₃⁻

• This is the job of the kidneys
• By 3 main processes;

-Re-absorption of filtered HCO₃⁻

-Formation of titrable acid

-Excretion of NH₄⁺ in the urine

The kidney filters = 4000mmol of HCO₃⁻ / day

So to re-absorb this filtered load of Bicarb the renal tubules must secret 4000mmol of H⁺

80-90% of Bicarb is reabsorbed in PT, the rest in DT

SIMPLE DISORDERS OF ACID-BASE

• Metabolic Acidosis

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• Metabolic Alkalosis

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• Respiratory Acidosis

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• Respiratory Alkalosis

METABOLIC ACIDOSIS (Causes)

• It can occur due to increase in endogenous acid production (Lactate & Ketoacids)

-DKA

-Renal Failure (Acute & Chronic)

-Alcohol

-Toxins ; Ethylene glycol, Methanol, Salicylates

• It can also occur due to loss of HCO₃ ⁻ (Diarrhea)

Clinical Presentation

• The fall in pH leads to KUSSMAUL respiration
• CNS fxn is depressed

-Headache

-Lethargy

-Stupor

-Coma

• Glucose intolerance

Pathophysiology

• Pry metabolic disturbance like DKA elicit predictable compensatory respiratory responses.
• Kussmaul breathing results from low exra-cellular fluid HCO₃⁻ + ↓ extra-cellular pH → stimulating medullary chemoreceptors → ↑Ventilation to normalize PaCO₂ & HCO₃⁻
• KUSSMAUL (= the causes) of…

EXPECTED RESPONSES TO PRIMARY ACID–BASE �DISORDERS�

• DISORDER EXPECTED CHANGE
• Metabolic acidosis For every mmol/L fall in PHCO3 from 25, the arterial
• PCO2 falls by ∼1 mmHg from 40.

LAB Parameters (Met Acidosis)

• ↓ pH
• ↓HCO₃⁻
• ↓PaCO₂
• Where everything is low

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TREATMENT

• Identify & correct the underlying cause
• If DKA (insulin, N/S inf, GKI, Ca-gluconate)
• If Renal failure (Conservative & Dialysis)
• Ethylene / methanol intoxication Dialysis
• Salicylate poisoning; activated charcoal after gastric lavage with N/S , HD with bicarb dialysate

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MIXED ACID-BASE Disturbance

• DKA & COPD can give rise to metabolic acidosis & Respiratory acidosis →↑ acidemia
• A DKA pt may present with Renal Failure both giving metabolic acidosis (x2) → acidemia
• Metabolic acidosis / metabolic alkalosis = normal pH
• Triple acid base disorder is more complex eg Alcohol (acidosis) + vomiting (alkalosis) ₊ Hyperventilation (Resp alkalosis)

ANION GAP 1

• The strength of cations (+vely charged ions) and anions (-vely charged) must be equal in the blood to maintain proper balance of electrical charges.
• The anion gap result helps one differentiate among various acidic conditions
• Normal anion gap ranges from 8-14mmol/l
• If Na⁺ (140) – [HCO₃⁻ (25) + Cl⁻ (105)] = 10

Anion Gap 2

• AG represents those unmeasured anions in plasma (10-12mmol/l) & is calculated thus;
• AG = Na⁺ - (Cl⁻ + HCO₃⁻)
• The unmeasured anions = proteins (Alb⁻), PO₄⁻, SO₄⁻ (In N/Syndr →↓AG due to low Alb), Organic acids like ketones, lactic acids.
• But when acid anions (acetoacetate & lactate) accumulate in ECF , the AG increases →↑ AG (it ↓ HCO₃) acidosis (not due ↓cations Ca⁺⁺, Mg⁺ or K⁺)

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ANION GAP 3

• Normal anion gap is found in hyperchloremic acidosis, Renal Tubular acidosis and severe HCO₃⁻ wasting conditions like biliary & pancreatic fistulas or poorly fxning ileal loops
• A Decreased anion gap is rare but can occur in
• Hypermagnesemia & paraproteinemia (MM) and Waldenstrom’s Macroglobulinemia

METABOLIC ALKALOSIS (Causes)

• GI Origin

-Vomiting

-Gastric Aspiration

-Villous Adenoma

• Renal diuretics
• Milk Alkali syndrome
• Alkali administration (Bicarb)

• Metabolic alkalosis For every mmol/L rise in PHCO3 from 25, the arterial
• PCO2 rises by ∼0.7 mmHg from 40.

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Pathogenesis

• Usually occurs due to net gain of HCO₃⁻ or loss of non-volatile acid from ECF ( HCl esp from vomiting)
• For HCO₃⁻ to be added to ECF it must be by exogenous route or endogenously generated by the kidneys
• It is not usual for alkali to be added to the body so it is most likely to be made available by the kidneys
• Following acid loss→ alkalosis, the kidneys should compensate by excreting HCO₃⁻, BUT

Clinical presentation

• Usually presents with hypocalcemic symptoms
• CNS : Mental confusion, Obtundation, Seizures, Paraesthesia, Muscular cramping, Tetany & Arrythmia

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Work up

• Measure BP (RECUMBENT & Standing)
• Serum K⁺, ↑pH, ↑HCO₃⁻, ↑PaCO₂ (All high). (compensatory hyperventilation)
• Measure Ald level (Pry Hyperaldosteronism)
• If HBP + ↓K⁺ = Mineralocorticoid Xs, or hypertensives on diuretics
• ↓K⁺ + Normal BP = Barter’s syndr (↓calciuria) or Gitleman’s syndr (↓Mg⁺ )

Treatment

• Treat underlying cause ( hyper-Ald, surgery)
• Cushing’s syndr
• DC Diuretics
• Correct K⁺ def
• If ECF is contracted, Give N/S
• Impaired renal fxn, dialyse with acetate dialysate

RESPIRATORY ACIDOSIS

• Due to severe pul dse,
• Resp muscle fatique or
• abnormality in resp control
• ↑PaCO₂, ↓pH
• Compensatory mech to buffer the acid comes from the kidney to conserve HCO₃⁻

�Respiratory Acidosis�

• Acute For every mmHg rise in the arterial PCO2 from 40, the
• plasma [H+] rises by ∼0.8 nmol/L from 40.
• Chronic For every mmHg rise in arterial PCO2 from 40, the
• plasma [H+] rises by ∼0.3 nmol/L from 40 and the
• PHCO3 rises by ∼0.3 mmol/L from 25.

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AETIOLOGY

• CNS; -- Drugs (Sedatives, Anaesthetics, Morphine)

-- Stroke

--Infections

• Airway : COPD, Asthma, Emphysema, Bronchitis
• Neuromuscular: Myasthenia, Polio, muscular dystophy

CLINICAL

• Anxiety
• Dyspnoea
• Confusion
• Psychosis, Hallucination, Loss of memory
• Impairment of coordination, tremor, myoclonic jerks
• Day time somnolence
• Asterixis, headache (signs that mimick ↑ICP

INVESTIGATION

• PaCO₂
• pH
• Spirometry
• O₂ saturation (Pulse oxymeter)
• Diffusion of CO

TREATMENT

• Could be life threatening ,
• Reverse underlying cause /Tracheal intubation
• Mechanical Adequate alveolar ventilation
• Use O₂ with care,
• No rapid correction of hypoxemia esp in COPD bcos rapid falling of PaCO₂ will ppt arrhythmias, reduced cerebral perfusion & seizures

RESPIRATORY ALKALOSIS

• Alveolar hypoventilation →↓PaCO₂ &↑HCO₃⁻/PaCO₂ ratio
• ↑ pH

Respiratory Alkalosis�

• Acute For every mmHg fall in arterial PCO2 from 40
• The plasma [H+] falls by ∼0.8 nmol/L from 40.
• Chronic For every mmHg fall in arterial PCO2 from 40,
• The PHCO3 falls by ∼0.5 mmol/L from 25.

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Aetiology

• CNS; Pain, Anxiety, CVA, Meningitis, Psychosis, Encephalitis, Tumour, Trauma, Fever
• Hypoxemia or Tissue hypoxia
• High Altitude, severe anaemia
• Pneumonia, Sepsis
• Pul oedema, aspiration,
• Drugs eg salicylates, Hormones (progesterone), Pregnancy,

CLINICAL

• Reduced CBF → dizziness, mental confusion, seizures
• Hypocapnia too → Arrythmia in cardiac pts, chest tightness or pain

TREATMENT

• Reassure pt with hyperventilation syndr
• Re-breathing from a paper bag during symptomatic attacks
• Attention to underlying cause (psychological)
• Antidepressants & sedatives to be avoided

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