acid base

Acid-Base Balance in the Body

Course Information

• Course Title: VPHY 3100/3107

• Instructor: Aleksandra Pawlak

• Contact: aleksandra.pawlak@uga.edu

Learning Objectives

• Learning Objective 1: Outline how carbon dioxide is transported in blood.

• Learning Objective 2: Understand the role of the lungs in acid-base balance.

• Learning Objective 3: Describe the processes by which acid–base balance is regulated by the kidneys.

• Learning Objective 4: Understand basic mechanisms of how acid-base balance is monitored by the body.

Overview of Key Concepts

Interaction Between Physical and Biological Principles

• Flow-Down Gradients (Flux): Movement based on gradients of concentration or energy.

• Energy and Mass Balance: Essential for maintaining life and biological processes.

• Homeostasis: Mechanism to maintain stable internal conditions in the body.

• Cell Theory: Fundamental concept in biology that explains the structure and function of cells.

• Cell Membrane: Barrier that separates the inside of the cell from the external environment.

• Cell-Cell Communication: Mechanisms that allow cells to communicate with each other.

• Scientific Reasoning: Methodology based on observation, hypothesis, experimentation, and analysis.

Bicarbonate Buffer System

Key Characteristics

• Main Chemical Buffer: Regulates pH in blood and body fluids.

• Balance Between Carbonic Acid (H₂CO₃) and Bicarbonate (HCO₃⁻): Prevents harmful acidity changes.

• Reversible Reaction: Essential for buffering capacity, enhanced by carbonic anhydrase (CA).

Carbonic Anhydrase (CA)

• Enzyme facilitating reaction between carbon dioxide and water to form bicarbonate.

• High Expression: Found in red blood cells (RBCs), gastric mucosa, pancreatic exocrine cells, and renal tubules.

• Concentration Information: Free H+ typically in nmol/L; free HCO₃⁻ in mmol/L concentrations.

Transport of CO₂ in Blood

Forms of CO₂ Transport

1. Dissolved CO₂ (10%): Contributes to PCO₂.

2. Carbaminohemoglobin (20%): CO₂ binds to hemoglobin; does not bind to heme directly.

3. Bicarbonate (70%): Major form of transport.

Mechanism of Transport

• CO₂ Movement: Readily crosses plasma membranes, while HCO₃⁻ requires transport mechanisms.

• Antiporter Mechanism: Exchanges chloride (Cl⁻) for bicarbonate across plasma membranes.

Chloride-Bicarbonate Exchanger

• Transport Dynamics: Cl⁻ and HCO₃⁻ move in opposite directions, coupling one in concentration gradient (facilitated) and the other against (secondary active transport).

• Extracellular vs. Intracellular: Higher levels of Cl⁻ and HCO₃⁻ extracellularly than intracellularly.

Acid-Base Balance Concepts

pH Definition

• pH: Measure of H+ ion concentration in an aqueous solution.

• Formula: $pH = - ext{log} [H^+]$

• pH Impact: Change of one pH unit reflects a tenfold change in H+ concentration.

Acid and Base Definitions

• Acid: A substance that donates H+ ions.

• Base: A substance that accepts H+ ions.

Normal Blood pH

• Normal Range: 7.40 (7.35 – 7.45)

• Acidosis: Occurs if pH < 7.35 (increased H+)

• Alkalosis: Occurs if pH > 7.45 (decreased H+)

• Regulated By: Lungs and kidneys adjusting CO₂ and H+/HCO₃⁻ levels.

Henderson-Hasselbalch Equation

• Normal blood pH Ratio: The ratio of HCO₃⁻ to CO₂ ideally maintained at 20:1.

• Equation: $pH = 6.1 + ext{log} rac{[HCO<em>3^-]}{[CO</em>2]}$

Acid Production in the Body

Two Major Acid Classes

1. Volatile Acids:

   • Can convert to gas, examples being CO₂ which can be exhaled.

   • Exists through the reaction: $H<em>2O + CO</em>2 <br>ightleftharpoons H<em>2CO</em>3 <br>ightleftharpoons H^+ + HCO_3^-$

2. Nonvolatile Acids:

   • Cannot leave blood and include lactic acid, fatty acids, and ketone bodies.

   • Bind with buffer molecules including HCO₃⁻, phosphate ions, and proteins (e.g., Hemoglobin).

Role of the Lungs in Acid-Base Balance

• H+ from CO₂ forms carbonic acid influencing blood pH.

Responses to Acidic or Alkaline Conditions

Acidosis Response

• Increased H+: Respond through increased respiratory rate to lower PCO₂.

Alkalosis Response

• Decreased H+: Respond through decreased respiratory rate to retain CO₂.

Role of the Kidneys in Acid-Base Regulation

Mechanisms of pH Regulation by Kidneys

Acid-Base Reaction by Kidneys

• $CO<em>2 + H</em>2O <br>ightleftharpoons H<em>2CO</em>3 <br>ightleftharpoons HCO_3^- + H^+$

• Removal or retention of bicarbonate and H+ can adjust pH.

Renal Handling of HCO₃⁻ and H+

• Proximal Convoluted Tubule (PCT):

  • Function: Main site for HCO₃⁻ reabsorption and Na+ reabsorption via Na+/H+ antiporter.

  • Role of Carbonic Anhydrase: Necessary since HCO₃⁻ cannot cross membranes.

  • H+ Cycling: Small amounts may be secreted for excretion.

• Distal Convoluted Tubule (DCT) / Collecting Duct (CD):

  • Mechanism: Active transport of H+ ions into filtrate using H+ ATPase and H+/K+ ATPase.

  • Bicarbonate Creation: Bicarbonate created and returned to the plasma, combining with phosphate and ammonia buffers for excretion.

Responses to Acidosis or Alkalosis by Kidneys

• In Acidosis:

  • Reabsorb HCO₃⁻ in PCT, generate bicarbonate in CD, and secrete H+ into filtrate.

• In Alkalosis:

  • Downregulation of acidosis responses, reduced HCO₃⁻ reabsorption, and H+ secretion.

Monitoring Changes in Blood Composition

Chemoreceptors Involved

Central Chemoreceptors

• Location: Found in the medulla, function to detect changes in blood PCO₂ primarily due to blood-brain barrier permeability.

Peripheral Chemoreceptors

• Location: Positioned in carotid and aortic bodies, they detect blood PO₂ changes directly and PCO₂ changes indirectly through pH modifications.

Transport Dynamics Equation

• Chemical balance equation: $H<em>2O + CO</em>2 <br>ightleftharpoons H<em>2CO</em>3 <br>ightleftharpoons H^+ + HCO_3^-$

Regulation of Breathing

Homeostasis Mechanisms

• Sensors: Chemoreceptors for chemical changes and mechanoreceptors for mechanical changes.

• Integrator: The brain, notably the medulla oblongata and pons, regulates both voluntary and involuntary respiratory actions.

  • Actions: Voluntary controlled by the cerebrum, hypothalamus, and limbic system; involuntary responses managed by brainstem respiratory centers.

Effectors

• Respiratory Muscles: Engage to facilitate breathing alterations based on metabolic needs.

Acid-Base Imbalances from Respiratory System

Respiratory Acid-Base Disorders

Respiratory Acidosis

• Causes: Hypoventilation due to CNS depression, neuromuscular disorders, lung disease, or obstruction leading to CO₂ accumulation and increased PCO₂, lowering blood pH.

Respiratory Alkalosis

• Causes: Hyperventilation, possibly from CNS issues, asthma, or psychogenic factors, leading to decrease PCO₂ and increased blood pH.

Summary of Respiratory Responses to Imbalances

• Acidosis: Leads to hyperventilation, causing loss of H+, which raises pH.

• Alkalosis: Leads to hypoventilation, causing retention of H+, which lowers pH.

Non-Respiratory Causes of Acid-Base Imbalance

Metabolic Conditions

Metabolic Acidosis

• Definition: Excess of nonvolatile acids due to increased acid intake/production or decreased renal excretion.

• Characteristics: Results in a decrease in the ratio of [HCO₃⁻] to [CO₂], leading to lower pH. Examples include ketoacidosis, lactic acidosis, and loss of HCO₃⁻ in diarrhea.

Metabolic Alkalosis

• Definition: Occurs due to excess HCO₃⁻ or loss of nonvolatile acids (e.g., vomiting stomach acid).

• Characteristics: Increases the ratio of [HCO₃⁻] to [CO₂], resulting in increased pH.

Summary of Renal Responses to Acid-Base Imbalances

• In Acidosis: Kidneys reabsorb HCO₃⁻ and secrete H+ leading to more buffering and less H+.

• In Alkalosis: Decreased reabsorption of HCO₃⁻ and less H+ secretion leads to less buffering and more H+.

Conclusion and Questions

• Final Remarks: Acid-base balance is essential for homeostasis, influenced by respiratory and renal systems as well as monitoring mechanisms.

• Questions?: Engage for further clarification on any presented concepts.