This document provides an overview of acid-base disorders, including normal acid-base homeostasis, types of acid-base disorders, diagnosis, and treatment approaches. It discusses various acid-base concepts and defines terms. The types of acid-base disorders covered are metabolic acidosis, respiratory acidosis, mixed disorders, and others. Causes, clinical presentations, and treatments are summarized for different conditions like diabetic ketoacidosis, lactic acidosis, and respiratory acidosis.

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