Acid-Base Balance and pKa

• pKa is the negative logarithm of the ionization constant

• pKa is linked to the ionization constant, which indicates the strength of acids and bases

• pKa is the pH at which protonated and unprotonated ions are present in equal concentrations

• pKa indicates acid strength; high pKa indicates a weak acid, while low pKa indicates a strong acid

• An equilibrium state is reached when pH and pKa are equal

• A buffer is a combination of a weak acid or base with its salts that resists changes in pH

• A buffer's effectiveness depends on its pKa and the environment's pH

Acid-Base Balance: Maintenance of H+

• Normal extracellular fluid H+ concentration is 36-44 nmol/L

• The ideal blood pH ranges from 7.35-7.45

• Lungs and kidneys are vital for maintaining pH homeostasis

• The body controls hydrogen ion levels to maintain homeostasis through lung and kidney mechanisms

• Values outside the normal pH range can cause alterations in consciousness, neuromuscular irritability, tetany, coma, or death

Control System of Arterial pH

• Buffers, the respiratory center and lungs, and kidneys regulate arterial pH
• Kidneys regulate the production and retention of acids and bases

Definition of Terms

• Acid (H+) yields hydrogen or hydronium ions when dissolved in water and donates hydrogen ions
• Base (OH-) yields hydroxyl ions, accepts hydrogen ions, and has a dissociation constant (K)
• The strength of acids and bases depends on their dissociation ability in water, described as the dissociation constant or ionization constant
• pH is the negative logarithm of hydrogen ion concentration
• A decrease of one pH unit equals a tenfold increase in hydrogen ion concentration

Blood Buffers

• Bicarbonate and carbonic acid (HCO-3 and H2CO3) and plasma proteins function as blood buffers
• Plasma proteins have charges that affect testing

Regulation of Acid-Base Balance: Lungs and Kidneys

• Lungs and kidneys work to regulate acid-base balance
• Lungs regulate pH by retaining or eliminating CO2
• Kidneys regulate pH by excreting acid (ammonium ion) and reclaiming bicarbonate from the glomerular filtrate

Regulation of Acid-Base Balance: Peripheral Tissues

• Carbon dioxide, a product of aerobic metabolism, diffuses from tissues to plasma and RBCs
• In plasma, carbon dioxide dissolves, combines with proteins to form carbamino compounds
• Carbonic anhydrase aids the majority of carbon dioxide in the blood's combination with water to form carbonic acid
• Carbonic acid then forms hydrogen and bicarbonate.
• Carbonic anhydrase is found in red cell membranes

Hemoglobin

• Hemoglobin carries and unloads oxygen and maintains homeostasis
• Inorganic PO4 has involvement in the exchange of sodium ions in the urine

Chloride Shift

• In peripheral tissues, bicarbonate concentration increases
• Increased bicarbonate in RBCs diffuses into the plasma, initiating the chloride shift
• The chloride shift involves bicarbonate diffusing into plasma and chloride diffusing into RBCs
• This process ensures electroneutrality by maintaining equal cation and anion numbers on each side of the RBC membrane
• Plasma proteins and buffers mediate the chloride shift.

Regulation of Acid-Base Balance: Lungs

• In the lungs, oxygen inhaled diffuses from alveoli into blood and binds to hemoglobin to form oxyhemoglobin
• Hydrogen ions carried on reduced hemoglobin in venous blood are released and recombine with bicarbonate to form carbonic acid
• Carbon dioxide diffuses into alveoli for elimination through ventilation
• Lung function alters the bicarbonate-carbonic acid ratio by expelling carbon dioxide
• Respiratory control of carbon dioxide excretion allows sensitive pH adjustment.

Respiratory Acidosis

• Respiratory acidosis is caused by slow or non-removal of carbon dioxide in the lungs, which increases H+ concentration

Respiratory Alkalosis

• Respiratory alkalosis is caused by removing carbon dioxide faster than it is produced, which decreases H+ concentration

Regulation of Acid-Base Balance: Kidneys

• The kidneys regulate acid-base balance, the equivalent of alkali generation refers to the reabsorption of HCO-3 from the glomerular filtrate, returning it to the bloodstream

Kidney Function

• In the glomerular filtrate, bicarbonate levels are the same as in plasma
• The proximal convoluted tubules reabsorb acid but if not reabsorbed, bicarbonate is lost in urine, leading to acidity
• Hydrogen ions are excreted directly, as ammonium ions, or indirectly
• Bicarbonate: urine loss results in excess acid gain

Renal Control

• The kidneys regulate HCO-3 concentration
• The kidneys regulate bicarbonate ions generation and urinary excretion
• Normally, urine is acidic to excrete acid, maintaining a minimum urine pH of 4.6
• Inorganic phosphates in blood buffer for greater hydrogen ion excretion
• Hydrogen ions in glomerular filtrate bind either to monohydrogen phosphate or ammonia
• The result is producing and excreting dihydrogen phosphate and ammonium ions in the urine

Plasma and Urine Bicarbonates

• Bicarbonate increase is due to IV infusion of lactate, acetate, and HCO3
• Decreased bicarbonate is due to diuretics, and reduced reabsorption
• With HCO3 below 25 mmol/L, or plasma CO2 above normal range, the tubule reabsorbs all glomerular filtrate HCO3
• In this process bicarbonate is reabsorbed by tubules, resulting in no excretion through urine
• Urinary excretion of HCO3 occurs when plasma levels reach 26-30 mmol/L, with a small amount (10 mEq/day) excreted to maintain acid-base regulation

Henderson-Hasselbalch Equation

• This equation expresses acid-base relationships, and calculates pH using weak acid dissociation properties
• The pH depends on the ratio of bicarbonate to pCO2, and requires normal kidney and lung function

Parameters in Assessment of Acid-Base Balance

• Tests measuring pH, pCO2, HCO3, and pO2 assess acid-base balance
• Normal arterial blood pH is 7.35-7.45
• pH is optimum at a level of 7.40
• The effectiveness of acid-neutralization from short-term buffering capacity is immediate
• Organic acidosis, diarrhea (bicarbonate loss), and exogenous toxins can generate extrarenal acidosis

Assessing Ventilation

• Normal pCO2 levels are 35-45 mmHg
• Low pCO2 indicates respiratory alkalosis
• High pCO2 indicates respiratory acidosis
• pCO2 measures gas exchange, regulated by the retention or elimination of CO2

Assessing Metabolic Processes

• Normal HCO3 levels range from 21-28 mEq/L.

Oxygenation

• Normal pO2 ranges from 81-100 mmHg which means the patient has adequate oxygenation
• Levels below 81 mEq/L indicate metabolic acidosis, whereas values exceeding 100 mEq/L indicate metabolic alkalosis

Hypoxemia

• Hypoxemia can be mild (61-80 mmHg), moderate (41-60 mmHg), or severe (40 mmHg or less)

Partial Pressure

• It reflects gas availability in blood
• Venous blood registers 60-70% lower due to tissue oxygen release
• Partial pressure changes more rapidly than pCO2 and pH
• Determination measures oxygen association or dissociation with Hb
• Low pressure indicates MI, interstitial pneumonia, and severe CHF, or is found at higher altitudes
• Lower inspiration happens if there is low oxygen

Terms

• "-emia" refers to blood, while "-osis" refers to a body process, where acidosis/alkalosis causes academia/alkalemia
• Acidemia increased hydrogen ions in the blood, with decreased pH
• Alkalemia caused by decreased hydrogen, increased blood pH
• Respiratory acidosis or alkalosis results from ventilation/ventilator dysfunction (based on CO2 levels)
• Non-respiratory/metabolic disorders involve problems with bicarbonate levels and kidney function relating to secretion or acid reabsorption

Metabolic Acidosis

• Metabolic acidosis is a bicarbonate deficit, which results in excess acid in the blood
• DKA, lactic acidosis, and normal chloride occur with low anion gaps (diabetic ketoacidosis)
• Kidney failure, renal tubular acidosis, and diarrhea all lead to increased loss of bicarbonate ions

Potassium

• The release of Potassium is greater than in respiratory acidosis
• Potassium, the major cation inside the cell, diffuses into the ECF

Compensation

• Increased breathing rate occurs along with hyperventilation to eliminate carbon dioxide
• The bodies breathing rate will quicken as a compensation
• Low HCO3/pCO2 and pH 4 occur, completing within 12-24 hours
• Hyperkalemia, potassium levels rise, chloride increases, and decrease with sodium gradually

Metabolic Alkalosis

• Metabolic Alkalosis is the presence of a bicarbonate excess
• Observed in vomiting, there is a loss of chloride in the stomach, causing a slight decrease in breathing rate
• Compensation indicates increased HCO3 + pCO2 and pH >7.4
• Sodium increases in order to compensate

Respiratory Acidosis

• Respiratory Acidosis is due to excessive CO2 accumulation from reduced respiratory operation. This condition is usually observed in chronic conditions such as COPD from airway obstruction

Myasthenia Gravis

• Partial paralysis of the accessory muscles for breathing so that CO2 is inefficiently excreted

CNS Problems

• CNS disease and drug overdose slow the respiratory center, causing hypoventilation that increases CO2 levels

Pneumonia

• Stroke, myxedema, pneumonia, congestive heart failure, emphysema, and asthma occur

Compensation

• The kidneys retain HCO3 , maximal compensation, and restrictions of NaCl
• Bicarbonate rises; high PCO2 and HCO3 results while arterial pH remains less than 7.4

Respiratory Alkalosis

• With excessive CO2 loss, there will be seen or observed with anxiety in patients
• Physical injury in patient as well
• Decrease in concentration of arterial PCO2, increasing respiratory rate causing hyperventilation
• Extreme elevations in pH happens when the patient has psychogenic over-stimulation
• Severe pain and asprin overdoses occur

Alkalosis Medications

• High preogesterione levels and salicylates are likely to cause it
• The blood pH gets dangerously high when a patient has increased respiratory alkalosis
• Chronic respiratory alkalosis is present during pregnancy

Actions taken to fix imbalance

• The body tries to compensate for any imbalance and return the pH to normal
• Cellular and metabolic processes depend on a steady and balance pH
• Sometimes, if the pH of the blood is unable to return back to its natural state, then the patient is considered " Fully compensated"

Lung Functions

• Lung Compensation is an immediate response and Renal Compensation is the action more gradual.

Assessment for Balance

• Look for parameters that signal or lead to unbalance, assess pH, level of arterial carbon, also use to evaluate for ventilation status of lung
• Asses evaluation of metabolic processes

Evaluation of pH

• One should check the partial of the CO2 and the carbonic acid present, these readings help determine if a patient has unbalance or not

Acid Excretion

• Acid excretion equals generating alkali by reabsorbing HCO3 from the glomerular filtrate, adding it to the blood
• The glomerular filtrate has the same bicarbonate level as plasma
• Proximal convoluted reabsorb acids, and if they are not reabsorbed, leads to great loss of bicarbonate the leads to acid build up
• Urine loss that contains amounts of HCO-3 contribute to acid building

Kidney Actions

• Kidneys excrete acids via NH4+ and titrable acids as well

Hydrogen Release

• A release of hydrogen is excreted by direct excretion and forms of ammonium ions
• The kidneys work to regulate the levels of the bicarbonate.

Erythrocytes

• Erythrocytes participate in the transport of blood gases
• Oxygen is used in energy production and status is measured by pO2, pH, and PCO2

Measurement

• Most oxygen in arterial blood gets to cells through hemoglobin
• Hemeoglobin has four conditions of note: O2Hb, HHb (oxy bind when available), COHb, and MetHb where the iron cannot bind because it cannot bind due to oxidized state

Transport

• Oxygen delivery to tissues is mostly through hemoglobin in arterial blood
• Hemoglobin exists in several states, including O2Hb, HHb, and MetHb
• HHb can bind oxygen, COHb strongly binds carbon dioxide, and MetHb cannot bind oxygen
• There occurs a dissociation where if the oxygen is in a lower tension, it would also have affect and be affected with the hB

Sigmoid shape

• This has a cooperativity to the effect of the molecule that may be needed

Acid-Base Analysis

• Arterial blood specimen is collected with use of Heparin.
• Best samples are using aterial blood in green tubes
• Use self- filling disposable syringe with pre-heparinized needle
• One cannot mix butterfly set it will compromise results of the syringe,
• Examine right away to check that blood count levels are optimal and not out of range.

Hypoxia

• It is best if one does not leave sample in open air, this will increase the oxygen which causes it to shift
• Examining it any later causes issues with the the red blood count number and pH count, this compromise the accuracy of the sample