3. Regulation of Acid-Base Balance

Less critical because the kidneys have more time to provide for ongoing compensation -Renal compensation, which works over a longer period, includes increased excretion of H+ and restoration of HCO3-. -Other renal buffer system such as the use of ammonium (NH4) will also provide a secondary response.

Chronic respiratory acidosis

will provide data needed to evaluate acid-base status and begin steps toward intervention.

ABG measurements

Affect concentration of electrolytes in both ECF (extracellular fluid) and ICF (intracellular fluid)

Acid-base changes

Changes in potassium (K+), Chloride. (Cl-), and sodium (Na+) may accompany

Acid-base disorders

The buffer system is not adequate to control the acidosis, respiratory rate and depth will increase (hyperventilation). This allows large amounts of CO2 to be expired.

Acidosis

The kidney regulatory system do not have time to compensate, since these only begin to react within 12-24 hours

Acute respiratory acidosis

H+ + HCO3- <-> H2CO3 <-> CO2 + H2O the bicarbonate-carbonic acid buffer system

As the buffer system reacts with fixed acids, H2CO3 is produced. H2CO3 readily dissolves to CO2 and H2O. Therefore, the lungs will accommodate the increased load of acids by increasing rate and depth of breathing and by expiring the CO2. The kidney helps with this buffer system by either reabsorbing HCO3- or regenerating additional HCO3- from CO2 and H2O

Symptoms of respiratory alkalosis

Cardiovascular system symptoms: cardiac arrhythmias Respiratory system symptoms: frequent yawning and deeper breaths Central nervous system symptoms: lightheaded ness, mental confusion, anxiety, and seizures. Other symptoms: cold and clammy extremedied

ongoing metabolic acidosis relies on carbonate from bone to buffer the acid load. This results in growth failure in children and renal osteodystrophy in adults.

Chronic renal disese symptoms in metabolic acidosis

the disease caused by either the absence or inefficient use of the hormone insulin

Diabetes mellitus

-must be treated quickly and accurately to prevent coma and death - providing adequate insulin, fluids, and electrolytes allows the correction of the metabolic acidosis and prevents these complications

Diabetic keto acidosis treatment

one of the most common causes of lactic acidosis results in metabolic acidosis due to both increased production of and inability to metabolize ketones

Diabetic ketoacidosis

typically develops as a result of infections or because the patient does not take adequate amounts of insulin

Diabetic ketoacidosis

Most common cause of metabolic acidosis

Diarrhea

The kidney cant use bicarbonate as a buffer since it cannot be excreted at the same time as the hydrogen ions. It uses ___ and ____ to prevent damage from acidic urine

Dibasic phosphate and ammonium

Both function to accept H+ in order to control acid-base balance -in a situation where large load of fixed acids is produced, the kidneys will respond by increasing formation of acids within the buffer system.

Dibasic phosphate and sulfur

Important buffer system within red blood cells and tubules of the kidney - excretion of H+ could potentially make urine acidic that excretion would by physically damaging to the kidney - phosphate helps with this buffer system by either reabsorbing HCO3- or regenerating additional HCO3- from CO2 and H2O

Disodium/monosodium phosphate (Na2HPO4)

Hydrogen ions and bicarbonate

Electrolytes

Lab values in acute respiratory failure: compensatory mechanisms or secondary responses allow the pH to remain normal but serum bicarbonate and arterial pCO2

Elevated

Lab values in acute respiratory failure: pCO2

Elevated

HCO3- levels in metabolic alkalosis

Elevated >26mEq/L

this may occur in a patient who is respiratory-compromised and is unable to respond to a situation producing a metabolic disorder. This could also occur in situations of drug overdose where different medications cause both respiratory and metabolic responses.

Ex of when a mixed acid-base disorder may occur

Henderson-Hasselbalch equation

Explains the interrelationship between H2CO3, HCO3-, and pH. In humans, the pH, or the ratio of acids to bases, is 1 part H2CO3 to 20 parts HO3-. For pH to remain within normal range, the ratio has to be maintained. Any change in H2CO3 must be accompanied by a proportional change in HCO3-. If one part of the equation changes without the other and the ratio is not maintained, pH will move out of the normal range.

As renal function declines, other mechanisms to correct acid-base disturbance such as production of NH4+ may

Fail

In chronic kidney disease the ability to restore bicarbonate may

Fail

The largest source of base is ______ which is regulated primarily by the kidneys.

HCO3,

May be lost from an ileostomy or from pancreatic, biliary, or intestinal fistulas

HCO3-

Kidney responds by reducing the amount of HCO3- reabsorbed

Kidneys respond to alkalosis

Controlling both H+ and HCO3- ions

Kidneys role in maintenance of pH homeostasis

deep and labored respirations

Kussmaul's respirations.

When NAD concentration is decreased compared to NADH + H*, the scale leans in the direction of lactic acid production and not pyruvic acid production. Conditions that result in decreased concentrations of NAD include decreased oxygenation of the tissues, excessive ketone body production (as in diabetes), and metabolism of ethanol.

Lactic Acid Production

occurs as a result of increased production of lactate or ketoacids

Lactic acidosis

Have ability to change respiratory rate and depth of breathing to control either release or retention of CO2, and hence assist in acid-base balance -this control system is very sensitive and can respond spontaneously

Lungs

Evaluation of pH in humans

Measures that ratio of acids to bases - If both acids and bases increase or decrease in same proportion pH remains the same - when one changes out of proportion, then there is a pH change

All types of acidosis that are not caused by excessive CO2 -results from either excessive loss of base (HCO3-) or an excessive gain of fixed (nonvolatile) acids -can be acute or chronic -uses AG calculation to determine the origin of the disorder

Metabolic acidosis

Conditions that result in excess loss of bicarbonate from the gastrointestinal system or from renal excretion of bicarbonate can result in

Metabolic acidosis

occurs when there is retention of fixed acids or excessive loss of bases.

Metabolic acidosis

result of excessive loss of fixed acids or retention of bases.

Metabolic alkalosis

-lasting longer than 24 hours -a secondary renal response (compensation) occurs -kidneys reduce their secretion of H+ (which also reduces regeneration of HCO3-) and increase their excretion of bicarbonate (HCO3-)

Pathophysiology for chronic respiratory alkalosis

Allow the person to replace the carbon dioxide "blown off" while hyperventilating

Rebreathing into a paper bag

Renal regulatory control is slower than respiratory regulation and may take up to several days to fully respond to imbalances

Renal vs regulatory control responses

Occurs when there is an excess of acid in relationship to base caused by retention of carbon dioxide. -generally occurs when the lungs are not able to expire CO2 - as CO2 levels rise hypercapnia occurs (more carbonic acid H2CO3 is formed) and pH shifts towards acidosis

Respiratory acidosis

Respiratory conditions such as pneumonia, acute pulmonary edema, or pneumothorax can result in

Respiratory acidosis

is a result of retention of CO2

Respiratory acidosis

Four major types of simple acid-base disorders

Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis (Combinations and mixes of these disorders can occur) (The only combination not possible is respiratory acidosis and respiratory alkalosis because hypoventilation and hyperventilation cannot happen together)

-the major cellular buffering defense available is expiration of CO2 by the lungs, but this buffering system is typically insufficient -Body stores of HCO3- are released in order to maintain appropriate ratio of CO2 to HCO3-, keeping pH in a normal range.

Respiratory acidosis pathophysiology

Characterized by a relative excess amount of base (HCO3-) as a reduction of CO2 -the acid-base disturbance is generally a result of conditions causing hyperventilation - rapid breathing results in a decreased PaCO2

Respiratory alkalosis

Result in an inability to maintain adequate oxygenation or release of carbon dioxide.

Respiratory diseases such as chronic obstructive pulmonary disease

Major cause of respiratory acidosis

Respiratory dysfunction (this is why the buffering system is typically insufficient

include deep labored breaths which are referred to as Kussmaul breathing.

Respiratory symptoms in metabolic acidosis

Respiratory: high levels of H+ in the blood stimulate respiratory centers in the brain. Lungs: respond by increasing reate and depth of breathing Kidneys: behin their compensatory response by increasnig their excretion of H+ and retention of HCO3- Renal: comensation is much slower than respiratory, and if the kidney disease is present, effectiveness of the compensaiton is decreased

Responses of different systems to meabolic acidosis

-situations that increase the amount of acid, such as administration of ammonium chloride (used for treatment of metabolic alkalosis) and rapid administration of IV saline -accidental poising with substances such as salicylate (aspirin), ethylene glycol (anti-freeze), or formaldehyde

Result in metabolic acidosis

By conserving bicarbonate (HCO3-) urinary excretion of positively charged cations (Na*, K*, NH,*) increases

Second, the renal system compensates by

-no specific -determined by condiotons of volume deficit or electrolyte abnormalities

Signs and symptoms in metabolic alkalosis

Lab values in acute respiratory failure: bicarbonate levels

Slightly elevated if renal composition just began

with its reliance on fat stores, can also increase synthesis of ketoacids and result in acidosis

Starvation

are not as clear as those of other acid-base disturbances.

Symptoms of metabolic acidosis

Acid bases disturbances are difficult to assess and figure out the origin because

The body attempts to self-correct changes in pH by compensatory or secondary responses

Changes in pH (specifically CO2 levels) are detected in

The cerebrospinal fluid by respiratory center in the brain.

Direct stimulation of respiratory center in the brain malignancy Stroke Hyper metabolic state (like fever and sepsis) Drugs (theophylline, salicylates, progesterone, doxapram, and catecholamines, and anxiety and other emotions distress) As an adaptive response to high oxygen demands during strenuous physical activity

Things that cause hyperventilation

Without adequate insulin, there is an increased dependence on lipids as the primary fuel source. The increased rate oflipolysis results in the production of ketones: aceto-acetic acid and hydroxybutyric acid. These ketone bodies are acids that lower serum pH. The kidney reacts by excreting the ketone bodies in the urine (ketonuria). The increased levels of hydrogen ions are buffered by plasma bicarbonate.

This combination of events results in metabolic acidosis.

A healthy, normally functioning kidney will reabsorb the majority of all HCO3- that is needed. This function requires the kidney to secrete H+ which combines with HCO3- forming H2CO3. H2CO3 dissolves to form CO2 and H2O which then forms HCO3- and free H+. This allows for constant regeneration of bicarbonate, which is needed to buffer the fixed acids being continuously released

To maintain a pH (kidneys)

focuses on correcting the underlying conditions causing respiratory changes

Treatment for respiratory acidosis

Correction of the underlying cause is the only significant treatment -correction of hypoxemia by providing oxygen therapy would be 1st step -if the cause if psychological hyperventilation, rebreathing of CO2 can correct the symptoms

Treatment for respiratory alkalosis

focused on the underlying cause of the acidosis. Correcting pH too quickly can cause additional complications. The goal is to raise systemic pH to a safe level.

Treatment of metabolic acidosis

In chloride-responsive metabolic alkalosis, correcting volume imbalance with isotonic saline with added KCL will correct alkalosis. Metabolic alkalosis that does not involve a fluid deficit requires treatment of underlying causes before alkalosis can be corrected. In severe conditions, use of a carbonic anhydrase inhibitor will enhance HCO, excretion.

Treatment of metabolic alkalosis

The largest source of acid within the body is

carbonic acid.

There will be no change in pH if the ratio remains stable, but

changes in either portion of the ratio will result in changes in pH.

Stored blood contains _____ as a perservitive

citrate

Increased secretion of aldosterone causes the kidney to increase reabsorption of sodium. This is accompanied by secretion of H*, which increases regeneration of HCO3.

example of non-volume-related alkalosis is in the condition of primary or secondary hyperaldosteronism.

a result of hyperventilation and a subsequent decrease in CO, levels

respiratory alkalosis

- primary buffer system in extracellular fluid (ECF) - accommodates more than 80% of the required buffering in the ECF - H+ + HCO3- <-> H2CO3 <-> CO2 + H2O

the bicarbonate-carbonic acid buffer system

serve as compensatory or secondary mechanisms in acid-base imbalance.

the respiratory and renal systems

Common Causes of Metabolic Alkalosis

• Loss of acid • Vomiting • Nasogastric suctioning • Hypokalemia • Excessive base • Intravenous therapy • Blood transfusion • Excessive or chronic use of antacids

How pH works in humans

-if both acids and bases increase or decrease In the same proportion then pH will remain steady -if one changes out of proportion then there is a change in pH - just because pH is in normal range, it does not exclude the possibility of an acid-base disturbance

High levels of ketoacids lead to an increase in the

plasma anion gap.

Symptoms of respiratory acidosis

-alteration in respirations include increased respiratory rate (hyperventilation) and an increase in depth of respirations -other symptoms result from the change in oxygenation in the brain and/or a decrease in neurotransmission these include restlessness, apprehension, lethargy, muscle twitching, tremors, convulsions, and finally a coma

Labs for both chronic and actuate respiratory alkalosis

-electrolyte imbalances -low serum levels of K+ and Ca+ as well as high levels of CL-

Physiological means of accommodating all the hydrogen ions it constantly produces

1) chemical buffers 2) respiratory regulation of pH 3) kidney regulation of pH

Effectiveness or the power of the particular buffer is determined by

1) its association with a cellular salt (pK) 2) its overall concentration in the fluid compartment

The pH is maintained in a ratio of

20:1 base to acid within body fluids.

Minimum pH of urine in humans

4.5

Normal pH in humans is

7.35-7.45.

Reference range for calculus AG is

8-16 mEq/L

pH levein in metabolic alkalosis

>7.45

pH level in acute respiratory alkalosis

>7.45 and PaCO2 is decreased

pH level in chronic respiratory alkalosis

>7.45 and plasma HCO3- is low

Cannot cross back across the cell membrane so H+ is trapped and exerted back into the urine

Ammonium (NH4+)

Fistula

An abnormal connection between organs

Injury or trauma to the chest wall can potentially result in

An inability to expire adequate amounts of carbon dioxide

Represents the difference between unmeasured anions and cations

Anion gap

Affect ventilation and thus the ability to release CO2

Any factor that inhibits the medullary respiratory center

Common labs to asses acid-base balance

Arterial blood gases (ABGs) and serum chemistries

Hydrogen ions secretion coupled with bicarbonate reabsorption in a kidney tabular cell

Because the disappearance of a filtered HCO3- from the tubular fluid is coupled with the appearance of another HCO3- in the plasma. HCO3- is considered to have been reabsorbed

Why are both base excess and HCO3 are measure but both values are not evaluated

Because they both directly correlate

Carbonic acid dissociates to

Bicarbonate and free H+

Reacts with free H+ ions in order to maintain acid-base equilibrium -present in all body fluids (extracellular and intracellular)

Buffer

The lab values for acid-base balance include arterial measures of

CO2 and O2 (PaCO2 and PaO2)

The lungs are the primary regulators of

CO2 levels.

Transport and Exchange of Carbon Dioxide and Oxygen

CO2 picked up at the tissue level is transported in the blood in three ways: 1) physically dissolved 2) bound to the hemoglobin (Hb), and 3) as bicarbonate ion (HCO3-). Hemoglobin is present only in the red blood cells, as is carbonic a hydrate, the enzyme that catalyzes the production of HCO3-. The H+ generated during the production of HCO3- also binds to Hb. Bicarbonate moves by facilitated diffusion down its concentration gradient out of the red blood cells into the plasma, and chloride (CL-) moves by means of the same passive carrier into the red blood cell down the electrical gradient created by the outward diffusion of HCO3-

Chronic conditions such as sleep apnea or acute events such as cardiac arrest

Can affect normal ventilation

Medications such as opiates or sedatives

Can inhibit respirations

Disease that affect musculature of the respiratory system and chest wall such neurological conditions such as myasthenia gravis or extreme obesity seen in Pickwickian syndrome

Can result in poor ventialtion

Diffuses into the blood as it is produced through out the body

Carbon dioxide

CO2 will combine with water forming

Carbonic acid

Oxygenated hemoglobin gives up the H+ to HCO3- to generate

Carbonic acid (HCO3)

Can result in excessive loss of base while inhibiting production of carbonic acid in the kidney. In the condition fo renal tubular acidosis, ability to reabsorb bicarbonate is decreased

Carbonic anhydride inhibitors such as the drug acetazolamide/ diamoz (used as an anti seizures medication)

affected by decreased contractility and response to catecholamines. Vasodilation may cause hypotension and dysrhythmias.

Cardiovascular symptoms in metabolic acidosis

can be categorized as either those conditions involving fluid imbalance (alka- losis with volume decrease) or those without fluid imbalances (alkalosis without volume contraction).

Clinical situations resulting in alkalosis

would include hyperaldosteronism, excessive use of corticosteroids, blood transfusions, chronic use of antacids, and excessive administration of sodium bicarbonate.24

Conditions leading to alkalosis that do not involve fluid imbalance

include prolonged vomiting, nasogastric (NG) suction, or use of diuretics.

Conditions that involve fluid imbalance

In the condition of renal tubular acidosis, the ability to absorb bicarbonate is

Decreased

Lab values in acute respiratory failure: pH

Decreased

one of the most serious acute complications of type 1 diabetes mellitus

Ketoacidosis

may result when the kidney or liver fails to convert lactate to pyruvate.

High levels of lactate

Commonly a result of a reduction in serum oxygen levels (hypoxemia)

Hyperventilation

Can be a result of respiratory diseases such pneumonia, asthma, pulmonary embolism, or pulmonary edema, or of exposure to high altitudes

Hypoxemia

it is possible the body will convert the citrate to bicarbonate. This potentially could lead to metabolic alkalosis.

If an individual receives a large amount of transfused blood

Electorlyte levels in metabolic alkalosis

Imblanced K+ <3.5mEq/L Cl- <98mEq/L

The chemical buffer system Phosphate Buffer System function

Important urinary buffer; also buffers ICF

Respiration's will slow, CO2 concentrations will increase, and pH will normalize.

In a situation where PaCO2 has decreases (alkalosis)

hypoxemia is present; this reduced level of oxygen is responsible for most symptoms associated with acidosis - a more acute onset will result in increased severity of symptoms

In both acute and chronic repiratory acidosis

as pH lowers, respiratory ventilation changes to accommodate the need to reduce pCO,, Respirations are deep and labored

In diabetic ketoacidosis

The kidney will increase secretion of H+ and increase the amount of HCO3- reabsorbed.

Kidney response to acidosis

there is both a fluid loss and a subsequent decrease in K* levels. To maintain serum K+ levels within a safe range, the kidney will excrete H* in exchange for K*. Even though K* may increase, the loss of H results in generation of more bicarbonate. This further contributes to alkalosis.

In situations where there is also volume depletion, such as in use of diuretics,

Lab values in acute respiratory failure: serum electrolytes

Increase in serum Ca+, K+, and possibly CL- due to changes in renal control

A pH of <7.35 or >7.45

Indicates acidosis or alkalosis

may be seen in post- operative patients who are experiencing ileus. It removes gasric secretions in prevention of vomitting or aspiration

NG suction

-a base -formed in renal tubular cells from the amino acid glutamine. -free H+ combines with it to form ammonium (NH4+)

NH3 (ammonia)

AG calculation

Na+ - (CL- + HCO3-)

Disodium/monosodium phosphate (Na2HPO4) buffer system

Na2HPO4 + H+ <-> NaH2PO4 + Na+

will affect the ability of the respiratory system to respond to changes in pH. The second line of defense is a secondary response "compensation"; this is coordinated by the kidneys

Nervous system controls respiration, or muscles that assist in breathing

lethargy and stupor with eventual coma are observed as the pH falls in cerebrospinal fluid.

Neurological symptoms in metabolic acidosis

Overall schema of maintenance of acid-base balance

On the usual mixed diet, pH us threatened by production of strong acids (ex. Sulfuric, hydrochloric, and phosphoric), which result mainly from protein metabolism. These strong acids are buffered by chemical buffers in the body. Removal of extra H+s and the accompanying anions from the body is accomplish by renal excretion. When the kidneys excrete H+s, they add new bicarbonate to the blood, thereby restoring depleted body buffer bases. The respiratory system eliminates CO2 produced by metabolism. CO2 is not a threat to acid-base balance, provided its partial pressure in arterial blood is kept at a normal value.

Stoma

Opening in the body

-within first 24 hours -is a shift of acid from the ICF to the ECF with an accompanying movement of bicarbonate into cells in exchange for chloride -Additional H+ is synthesized by an increase in lactic acid derived from pyruvate within cells. - Shifts in H+ are generally not adequate to handle a continued decrease in PaCO2

Pathophysiology of acute respiratory alkalosis

When H levels increase, the bicarbonate- carbonic acid buffer system is stimulated. This shift of H into ECF reduces serum K+ at the same time in order to maintain equilibrium between the ECF and ICF.

Pathophysiology of metabolic acidosis

begins with the underlying event that causes either an excessive loss of acid or accumulation of base. This could be, for example, prolonged vomiting that results in decreased concentration of HCI". Normally, the kidney will compensate for the decrease in nonvolatile acid by generating Ht and decreasing reab- sorption of bicarbonate. In order for metabolic alkalosis to progress, other events need to occur that prevent adequate compensation by the kidney.

Pathophysiology of metabolic alkalosis

Other lab values for acid-base balance include

Ph, CO2, HCO3, base excess, and anion gap

Focus treatment on increasing oxygenation through administration of oxygen or provision of mechanical ventilation -It's crucial to realize that hypoxemia may be providing the stimulus for ventilation -If oxygen therapy reduces hypoxemia, ventilation may acutely decline without this stimulus

Presence of hypoxemia treatment for respiratory acidosis

The chemical buffer system Bicarbonate-carbonic acid buffer system function

Primary ECF buffer against non-carbonic-acid changes

The chemical buffer system Protein Buffer system function

Primary ICF buffer; also buffers ECF

The chemical buffer system Hemoglobin Buffer System function

Primary buffer against carbonic acid changes

- Protein present in the plasma can act as buffers; their contributions are most important intracellularly - acts in the same fashion as the bicarbonate-carbonic acid buffer system in that protein accepts the H+. - Many proteins can also release the H+ if alkalinity increases - the proteins' ability to act in both situations increases the effectiveness of this buffer system

Protein buffer system

a mixed disorder should be suspected when PaCO, and HCO3 are not consistent with the measured pH. Or it may be present when the compensatory/secondary response is exaggerated. For example, metabolic alkalosis and respiratory acidosis may occur when a patient with chronic obstructive pulmonary disease receives diuretics.

When examining ABGs for a mixid acid-base disorder

We measure concentration of CO, as an indirect measure of acidity. Concentration of CO2 is expressed

as PaCO2.

pH is the ratio of

bases to acids.

Most important buffer in the blood

hemoglobin

In both starvation and chronic alcoholism, synthesis of ketoacids is

increased

Presence of an excessive amount of base (HCO3) results in -genrally, this acid-base distrubance is caused by a loss of nonvolatile acids or the excessive administration of bicarbonate transfusion within whole blood

metabolic alkalosis

The scale for measuring acidity or alkalinity ofa fluid is the measurement

of pH.

The levels of CO2 in the blood controls the

pH of the cerebrospinal fluid