This presentation has been made by a resident doctor in kandahar regional hospital - Afghanistan.

1. 786
ACID-BASE DISORDES
Presentator: Dr. S. BESMELLAH (AFGHAN)
Instructor: Dr. M. YONUS (ZAHEER)
Year: 2019

2. Contents:
 Basic concepts
 Normal Acid-Base homeostasis
 Diagnosis of Acid-Base disorders
 Types of acid-base disorders
 Approach to acid-base disorders

3.  Basic concepts:
 pH: Signifies free H+ ion concentration
 pH = – log [H+]
 H+ plasma concentration (10- 1 to 10- 14 )
 Acid: A substance that can “donate” H+ ion or when added to solution raises H+ ion (lowers pH).
 Base: A substance that can “accept” H+ ion or when added to solution lowers H+ ion (raises pH).
 Anion: An ion with negative charge (HCO3
- & Cl- )
 Cation: An ion with positive charge (Na+, K+, Mg+)
 Acidosis: Abnormal process or disease, which reduces pH due to increase in acid or decrease in
alkali.
 Alkalosis: Abnormal process or disease, which increases pH due to decrease in acid or increase
in alkali.
 Compensation: The body response to acid-base imbalance
 Buffer: The chemical system that take up H+ or release H+ as conditions change
 Volatile acids: Acids which can be excreted from body as gases by the lungs (breathed off)
 Fixed acids (non-volatile): Acids which must be excreted in the urine (Not by breathed off)
 Anion gap: The charge difference between unmeasured anions and cations
 Unmeasured anions: Anionic proteins (albumin), Phosphate, sulphate & organic anions
 Unmeasured cations: (Ca+2, Mg+2, K+)
 (AG) = Na+ – (Cl- + HCO3
-) = 12±2 mEq/L (Normalvalue)

4.  Normal acid-base homeostasis:
 Homeostasis of pH is tightly controlled
 Extracellular fluid pH = 7.4
 Blood pH = 7.35 – 7.45
 pH< 7.35: Acidosis (Acidemia)
 pH> 7.45: Alkalosis (Alkalemia)
 pH< 6.8 or > 8.0: death occurs
 Normal range of Paco2 = 35-45 mmHg
 Normal range of HCO3
- = 22-26 mEq/L
 Respiratory compensation range (PaCO2= (1.5 × [HCO3
-]) + 8 ± 2)
 Three lines of defense to regulate the body’s acid-base balance
 Blood buffers (Bicarbonate – carbonic acid systems, Plasma proteins, Hemoglobin, Phosphates)
o Act fastest but have least buffering power
 Respiratory mechanism (by excreting volatile acids, lung regulates Paco2 ) 50-75% efficacy rate
o Acts rapidly (seconds to minutes) & has double buffering power
 Renal mechanism (the role is to maintain plasma HCO3
- concentration) 100% efficacy rate
o Starts within hours and takes 5-6 days for the peak effect & is the most powerful buffering

5.  Types of acid-base disorder:
 Simple acid-base disorders
 Metabolic acidosis
o High-AG
o Non-AG (Hyperchloremic)
 Metabolic alkalosis
 Respiratory acidosis
o Acute
o Chronic
 Respiratory alkalosis
o Acute
o Chronic
 Mixed acid-base disorders
 Metabolic acidosis + Respiratory acidosis or alkalosis
 Metabolic alkalosis + Respiratory acidosis or alkalosis
 Respiratory acidosis + Metabolic acidosis or alkalosis
 Respiratory alkalosis + Metabolic acidosis or alkalosis
 Metabolic acidosis + Metabolic alkalosis
 Metabolic acidosis + Metabolic acidosis

6.  Steps of acid-base diagnosis
Step 1: Determine the primary (main) disorder whether, it is metabolic or respiratory from blood pH,
HCO3
- and Paco2 values
Step 2: Determine the presence of mixed acid-base disorders by calculating the range of
compensatory responses
Step 3: Calculate the anion gap (AG)
Step 4: Calculate the corrected HCO3
- concentration, if the AG is increased
Step 5: Examine the patient to determine whether the clinical signs are compatible with the acid-base
analysis

7.  Compensatory responses:
Disorder pH HCO3
- Paco2
Metabolic acidosis ↓ ↓ ↓
Metabolic alkalosis ↑ ↑ ↑
Respiratory acidosis ↓ ↑ ↑
Respiratory alkalosis ↑ ↓ ↓

8.  Metabolic acidosis
• pH (Low)
• HCO3
- (Low)
• Paco2 (Low)
 Causes:
 High-AG (Increased unmeasured anions rather decrease unmeasured cations)
• Lactic acidosis
• Ketoacidosis
o Diabetic
o Alcoholic
o Starvation (Low carbohydrate diet)
• Toxins
• Renal failure (Renal acids and Albumin retention & increased anionic charge of albumin)
 Non-AG
• GIS HCO3
- loss (Diarrhea, drugs such us CaCl2, Mg2so4 & Cholestramine)
• Renal acidosis (Hyperkalemia, Hypokalemia & Normokalemia)
• Others
 Low-AG:
 Increased unmeasured cations
 Add external cations (Lithium intoxication)
 Reduced plasma albumin (Nephrotic syndrome) & decrease anionic charge of albumin
 Hyper viscosity and severe hyperlipidemia
 Clinic:
 CNS: Headache, Lethargy, Stupor, Coma
 CVS: Cardiac function due to catecholamine release may be normal
 Pulmonary edema
 Hyperventilation (Kussmaul respiration)
 Glucose intolerance

9.  Medical treatment:
o The alkali therapy should be reserved for severe acidemia (pH<7.10)
o The pH should be slowly increased
o Except when the pt has no potential HCO3
- in plasma
o In the first determine delta-AG (pt AG – 10)
o Delta-AG determines wethere the anion acids are:
• Metabolizable (β-hydroxybutyrate, acetoacetate, lactate)
• Non-metabolizable ( CRF, Toxins ingestion)
o The pH should not to be increased to normal (Keep pH = 7.2)
o The K+ level must to be monitored during treatment (Risk of Hypokalemia)
o P/O (NaHCO3 or Shohls solution)
o IV (NaHCO3 50-100 meq 30-45 mins)

10.  Lactic acidosis:
 L-Lactate:
 Type A: Poor tissue perfusion
 Circulatory insufficiency (shock & HF)
 Severe anemia
 Mitochondrial enzyme defects & inhibitors (CO & Cyanide)
 Type B: Aerobic disorders
 Malignancies
 HIV
 DM
 Renal or hepatic failure
 Thiamine deficiency
 Severe infections (Cholera & Malaria)
 Seizures
 Drugs/Toxins
 Unknown bowel ischemia/infarction in pts with Cardiac decompensation receiving vasopressors (most common)
 Pyro glutamic acidemia (Depletion of glutathione)
 D-Lactate (formed by gut bacteria):
 Jejunoileal bypass
 Short bowel syndrome
 Intestinal obstruction

11.  Treatment of L-Lactate acidosis:
 Correct underlying conditions
 Restore tissue perfusion
 Avoid vasopressors
 Alkali therapy reserved for acute severe acidemia (pH<7.15)
 HCO3
- disturbs cardiac function & enhance lactate production paradoxically
 Because (HCO3
- stimulates phosphofructokinase)
 The use of alkali in moderate acidemia is controversial
 Infuse adequate NaHCO3 over 30-40 mins
 NaHCO3 causes volume overload & HTN
 After underlying conditions relapsed, lactate will be converted to HCO3
- & leads to alkali overshoot

12.  Diabetic ketoacidosis (DKA):
 Increased fatty acids metabolism
 Accumulation of ketoacids (acetoacetate & β-hydroxybutyrate)
 Often in IDDM
 insulin cessation
 Intercurrent illness which acutely increase insulin requirements (Infection, AGE,
Pancreatitis, MI)
 Elevated-AG
 Glucose> 300mg/dL
 Volume depletion
 HCO3
- therapy reserved for severe academia (pH< 7.1)
 Insulin prevents production of ketones
 Fluid restoration (N/S)
 Hyperchloremic acidosis is common during fluid administration
 IV insulin regular

13.  Alcoholic ketoacidosis (AKA):
 Abrupt alcohol cessation
 Poor nutrition
 Binge drinking, vomiting, abdominal pain, starvation & volume depletion
 Ketones are elevated (β-hydroxybutyrate)
 The mixed acid-base disorders are common
 After volume correction (β-hydroxybutyrate shifts to acetoacetate) Ketosis & Ketonuria occurs
 Normal renal function
 Normal AG
 Treatment:
 IV (N/S & D5%)
 Correct hypophosphatemia (12-24 hrs. after add), hypokalemia & hypomagnesaemia if existed
 Hypophosphatemia exacerbated by D5% & if became severe leads to Rhambdomyolysis & Respiratory
arrest
 Upper GIB, Pancreatitis & pneumonia also may accompany

14.  Renal failure:
 Hyperchloremic acidosis converted in high-AG acidosis
 Pathogenesis made by poor filtration and reabsorption of organic anions
 Disturbed net acids production by renal disease progression
 Uremic acidosis made by reduced rate of ammonium production & excretion
 In CKD, Retained acids buffered by bone alkaline salts (calcium carbonate)
 Serum bicarbonate not decreased despite significant acids retention
 Buffers participated out side the ECC (Extracellular compartment)
 Significant bone mass loss
 Increased urinary calcium excretion
 Treatment:
 Administrate Oral alkali 1-1.5 mmol/kg to maintain HCO3
- >22mmol/L
 Shohl’s solution (sodium citrate) is equally effective NaHCO3
 Citrate must never be given by aluminum-containing antacids (aluminum intoxication)

15.  Non-AG Metabolic acidosis:
 Alkali loss (Diarrhea & RTA)
 Reciprocal changes in Cl- & HCO3
-
 The absence of reciprocal changes suggest mix disorders
 The acidosis due to volume depletion
 Urine pH>6 because of NH4
+ high synthesis & excretion
 NH4
+ low (RTA) & high (Diarrhea)
 UAG = [Na+ + K+] u ̶ [Cl-] u estimate NH4
+ Levels
 When [Cl-]u > [Na+ + K+]u the UAG (–) suggests extra-renal cause (High urine NH4
+)
 If UAG (+) suggests renal cause
 Types of RTA:
 Classic distal RTA (Type 1):
 Hypokalemia, low urine NH4
+ ,
 Urine pH>5.5
 Hypocitraturia, Hypercalciuria (Nephrolithiasis, Nephrocalcinosis & bone disease)
 Proximal RTA (Type 2) the most often:
 Manifested by hypokalemia, glycosuria, generalized aminoaciduria & phosphaturia (Fanconi syndrome)
 Urine pH<5.5
 Therapy by NaHCO3 causes hypokalemia (because HCO3
- not reabsorbed normaly by proximal tubules)
 Generalized proximal RTA (Type 3):
 Generalized distal RTA (Type 4):
 Hyperkalemia (Reduced GFR)
 Acommpany with Renal failure (Diabetic nephropathy, Obstructive uropathy & chronic tubulointerstitial disease)
 Concurrent HTN & CHF

16.  Metabolic alkalosis:
 pH (High)
 HCO3
- (High)
 Paco2 (High)
 Hypoventelition
 Hypochloremia & Hypokalemia
 Associated with respiratory acidosis or alkalosis or metabolic acidosis
 Causes:
A. Exogenous HCO3
- loads
 Acute alkali admistration
 Milk-alkali syndrome
B. ECFV contraction (Normotemsion + Potassium deficiency)
 GIS
 Vomiting
 Gastric aspiration
 Renal
 Diuretics
 Recovery from lactic acidosis or ketoacidosis
C. ECFV expansion (Normotemsion + Potassium deficiency)
 High renin
 RAS
 Accelerated HTN
 Renin-secreting tumor
 Estrogen therapy
 Low renin
 Primary aldosteronism
 Adrenal enzyme defects

17.  Clinic:
 CNS:
 Confusion
 Obtundation
 Seizurae
 Paresthesia
 Muscular cramping
 Tetany
 CVS
 Arrythmia (Hypokalemia)
 Hypoxemia (COPD)
 Treatment:
 Correct underlying stimuluses' for HCO3
- generation
 Correct underlying causes reverse alkalosis
 PPI
 D/C diuretics (Thiazides & Loop diuretics)
 Repair K+ deficiency that increase HCO3
- reabsorption
 N/S if ECFV contraction is present
 Acetazolamide a CAI (Accelerate HCO3
- secretion) but may accelerate K+ depletion

18. Respiratory acidosis:
 HCO3
- (High)
 Paco2 (High)
 pH (Low)
 Types:
 Acute:
 Immediate cellular buffering response
 Chronic (>24 hrs.):
 Renal buffering response
 Causes:
 Central (Drugs, Stroke & infection)
 Airway (Obstruction & Asthma)
 Parenchyma (Emphysema, Bronchitis, ARDS & Barotrauma)
 Neuromuscular (Poliomyelitis, Kyphoscoliosis, Myasthenia & Muscular dystrophies)
 Miscellaneous ( Obesity, Hypoventilation & Permissive hypercapnea)

19.  Clinic:
 Acute:
 Hypercapnea (Tachypnea)
 Anxiety
 SOB
 Confusion
 Psychosis
 Hallucinations
 Coma
 Chronic:
 Sleep disturbance
 Loss of memory
 Daytime somnolence
 Personality changes
 Impairment of coordination
 Motor disturbances (Tremor, Myoclonic jerks & Asterixis)
 Headaches, Papilledema, abnormal reflexes & focal muscle weakness (secondary loss of co2
vasodilator effects)
 Treatment:
 Restore adequate alveolar ventilation (Oxygen 2-4Lit/min, Intubation & Mechanical ventilation)
 Avoid rapid ventilation correction (Oxygen > 4Lit/min)
 Overcorrection leads to Alkalosis (Arrhythmias, Cerebral hypo perfusion & Seizures)
 Chronic type is difficult to correct

20.  Respiratory alkalosis:
 HCO3
- (Low)
 Paco2 (Low)
 pH (High)
 Types:
 Acute:
 Hypocapnea (Hypoxemia)>2-6 hrs. till renal compensation activates
 Full renal adaptation takes several days
 Intracellular shifts of (Na+, K+ & PO4
-2)
 Reduce free Ca+2 (increase protein-bound fraction)
 Hypocapnea- induced hypokalemia is usually minor
 No increased HCO3
- renal excretion
 DDx with APE, CAD & Hyperthyroidism
 Chronic:
 Most common in (ICU) & during mechanical ventilation
 Occurs in many cardiopulmonary disorders (early to intermediate stages)
 Rapid respiratory failure
 Hypocapnea (No hypoxemia)
 Causes:
 CNS stimulation: (Pain, Anxiety/Psychosis, Fever, CVA, Meningitis/Encephalitis, Tumor & Trauma)
 Tissue hypoxia/Hypoxemia: (High altitude, Pneumonia/Pulmonary edema, Aspiration & Severe anemia)
 Drugs/Hormones: (Pregnancy/Progesterone, Salicylates the most common & HF)
 Chest receptors stimulation: (Hemothorax, Flail chest, HF & APE)
 Miscellaneous: (Septicemia, Hepatic failure, Mechanical hyperventilation, Heat exposure & Recovery from metabolic acidosis)

21.  Clinic:
 Dizziness, Confusion & Seizures (Rapid decline in Paco2 )
 Arrhythmia occurs due to oxygen unloading in patients with cardiac disease (Bhor effect )
 Paresthesia, circumoral numbness, Chest tightness/pain, dizziness, SOB & Tetany (Hyperventilation syndrome)
 Thyrotoxicosis, High caloric load & exercise (Precipitants)
 Common feature of pregnancy
 Prominent in Hepatic failure
 Often in gram-negative septicemia
 Treatment:
 Correct underlying disorder
 Reassurance, Rebreathe from a paper bag (Hyperventilation syndrome)
 Avoid Antidepressants & Sedatives
 To ameliorate hyper adrenergic states use β-blockers

22.  Mixed acid-base disorders:
 Mixed Metabolic & Respiratory:
 Metabolic acidosis-Respiratory acidosis: (Severe pneumonia & Pulmonary edema)
 Metabolic acidosis-Respiratory alkalosis : (Lactic acidosis & Sepsis in ICU)
 Metabolic alkalosis-Respiratory alkalosis: (Liver disease & Diuretics)
 Metabolic alkalosis-Respiratory acidosis: (COPD & Diuretics)
 Mixed Metabolic disorders:
 Metabolic acidosis-Metabolic alkalosis: (Uremia & Vomiting)
 Metabolic acidosis-Metabolic alkalosis: (Diarrhea, Lactic acidosis & Treatment of DKA)

23.  References:
 Harrisons principles of internal medicine (20th)
 Current medical diagnosis (2019)
 Emedicine-medescape