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Life is a struggle, not against sin, not against Money Power . . But against hydrogen ions.

Dr. Mamta Khandelwal

Why acid base homeostasis is essential? How it is achieved ?

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The need for the existence of multiple mechanisms, involved in Acid-BaseAcid-Base homeostasis is important for the hydrogen ion (H+) concentration which is essential for the operation of many cellular enzymes and function of vital organs, most prominently the brain and the heart

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Acid-Base homeostasis involves chemicalchemical and physiologicphysiologic processes responsible for the maintenance of the acidity of body fluids at levels that allow optimal function of the whole individual

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The chemical processeschemical processes represent the first line of defense to an acid or base load and include the extracellular and intracellularintracellular buffers.buffers.

The physiologic processesphysiologic processes modulate acid-base composition by changes in cellular metabolism and by adaptive responses in the excretionexcretion of volatile acids by the lungslungs and fixed acids by the kidneyskidneys

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The task imposed on the mechanisms that maintain Acid-BaseAcid-Base homeostasis is large.◦Metabolic pathways are continuously consuming or producing HH++

◦The daily load of waste products for excretion in the form of volatile and fixed acids is substantial.

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Acid - BaseAcid - Base balance is primarily concerned with two ions:◦HydrogenHydrogen (H+) ◦BicarbonateBicarbonate (HCO3

- )

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H+ HCO3-

HH++ ion has special significance because of the narrow ranges that it must be maintained in order to be compatible with living systems

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Maintenance of an acceptable pH range in the extracellular fluids is accomplished by threethree mechanisms:◦1)1) Chemical BuffersChemical Buffers React very rapidly(less than a second)

◦2)2) Respiratory RegulationRespiratory Regulation Reacts rapidly (seconds to minutes)

◦3)3) Renal RegulationRenal Regulation Reacts slowly (minutes to hours)

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What is acid ? What are physiologically important acids?

What is base? What are physiologically important bases?

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Acids can be defined as a proton (HH++) donor

Many other substance (carbohydrates) also contain hydrogen but they are not acids because the hydrogen is tightly bound and it is never liberated as free HH+ +

Physiologically important acids include:◦ Carbonic acid (HCarbonic acid (H22COCO33))◦ Phosphoric acid (HPhosphoric acid (H33POPO44))◦ Pyruvic acid (CPyruvic acid (C33HH44OO33))◦ Lactic acid (CLactic acid (C33HH66OO33))

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Bases can be defined as:◦A proton (HH++) acceptor◦Give up OH- in solution. ◦Physiologically important bases include:

◦Bicarbonate (HCOBicarbonate (HCO33- - ))

◦Biphosphate (HPOBiphosphate (HPO44-2 -2 ))

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What is pH?What is normal blood pH ?What is the pH range compatible with life?

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pH refers to PPotential HHydrogen Expresses hydrogen ion concentration in water

solutions. Water ionizes to form equal amounts of HH++ ions

and OHOH-- ions

◦HH22OO HH++ + OH + OH--

Pure water is Neutral Neutral ( H+ = OH- ) pH = 7

AcidAcid ( H+ > OH- ) pH < 7

BaseBase ( H+ < OH- ) pH > 7

Normal blood pH is 7.35 - 7.457.35 - 7.45 pH range compatible with life is 6.8 - 8.06.8 - 8.0

◦

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The pH of the solution is defined as the negative logarithm ( base 10 )of the hydrogen ion (HH++) concentration

HH++ concentration in extracellular fluid (ECF)

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pH = log 1 / HH++ concentration

4 X 10 -8 (0.00000004)

Low pH values = high HH++ concentrations◦HH++ concentration in denominator of formula

Unit changes in pH represent a tenfold change in HH++ concentrations

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pH = log 1 / HH++ concentration

pH = 4 is more acidic than pH = 6 pH = 4 has 10 times more free HH++ concentration than pH = 5 and 100 times more free HH++ concentration than pH = 6

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ACIDOSIS ALKALOSISNORMAL

DEATH DEATH

Venous

Blood

Arterial Blood

7.3 7.57.46.8 8.0

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What is normal ratio of HCOHCO33--

to HH22COCO33 ?

What is acidosis ?

What is alkalosis?

What is compensation ?

What are the effects of pH

Change on cell functions?

Normal ratio of HCOHCO33-- to HH22COCO33 is 20:1

◦ HH22COCO33 is source of HH++ ions in the body Deviations from this ratio are used to identify

Acid-BaseAcid-Base imbalances

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BASE ACID

H2CO

3

H+

HCO3-

An increase in the normal 20:1 base to acid ratio so there is◦A decrease in the number of hydrogen ions(ex: ratio of 20:0.5)An increase in the number of bicarbonate ions (ex: ratio of 40:1)

Caused by base excess or acid deficit

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ACID

BASE

Acidosis is a decreasedecrease in pH below 7.35◦Which means a relative increase of HH++ ions.

◦A relative decrease in HCO3-

◦Both lead to a decrease in the ratio of 20:1

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H+ pH

=

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The body response to acid-base imbalance is called compensation

May be complete if brought back within normal limits

Partial compensation if range is still outside norms.

If underlying problem is metabolic, hyperventilation or hypoventilation can help by respiratory compensation.

If problem is respiratory, renal mechanisms can bring about normal pH--- metabolic compensation.

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pH changes have dramatic effects on normal cell function◦1)1) Changes in excitability of nerve and muscle cells

◦2)2) Influences enzyme activity◦3)3) Influences KK++ levels

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pH decrease (more acidic) depresses the central nervous system◦Can lead to loss of consciousness

pH increase (more basic) can cause over-excitability◦Tingling sensations, nervousness, muscle twitches

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pH increases or decreases can alter the shape of the enzyme rendering it non-functional

Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell

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When reabsorbing NaNa++ from the filtrate of the renal tubules KK++ or HH++ is secreted (exchanged)

Normally KK++ issecreted in muchgreater amountsthan HH++

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K+

K+K+K+K+K+K+Na+Na+Na+Na+Na+Na+

H+

If HH++ concentrations are high (acidosis) than HH++ is secreted in greater amounts

This leaves less KK++ than usual excreted The resultant KK++ retention can affect cardiac function and other systems

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K+K+K+Na+Na+Na+Na+Na+Na+

H+H+H+H+H+H+H+

K+K+K+K+K+

What are the different types of acidosis & alkalosis?

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Deviations from normal Acid-Base status are divided into fourfour general categories, depending on the source and direction of the abnormal change in HH++ concentrations◦Respiratory AcidosisRespiratory Acidosis◦Respiratory AlkalosisRespiratory Alkalosis◦Metabolic AcidosisMetabolic Acidosis◦Metabolic AlkalosisMetabolic Alkalosis

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◦Respiratory AcidosisRespiratory Acidosis and and Respiratory Respiratory AlkalosisAlkalosis

◦caused primarily by lung or breathing disorders.

◦Metabolic AcidosisMetabolic Acidosis and and Metabolic Metabolic AlkalosisAlkalosis caused by an imbalance in the production and excretion of acids or bases by the kidneys.

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What is respiratory acidosis?

What are the different causes of Rac ?

what is the Treatment of Rac?

Caused by hypercapnia( CO2) due to Hypoventilation Or Increased CO2 production Characterized by a decrease pH and an

increase in COCO22

High levels of COCO22 in the blood stimulate the parts of the brain that regulate breathing, which leads to faster and deeper breathing.

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Decreased COCO22 removal can be the result of:1)1) Obstruction of air passagesObstruction of air passages2)2) Decreased respiration (depression Decreased respiration (depression

of respiratory centers)of respiratory centers)3)3) Decreased gas exchange between Decreased gas exchange between

pulmonary capillaries and air sacs pulmonary capillaries and air sacs of lungs (emphycema,bronchitis)of lungs (emphycema,bronchitis)

4)4) Collapse of lungCollapse of lung

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Etiology :1) Alveolar hypoventilation Emphysema, Chronic bronchitis, Severe pneumonia Pulmonary edema Asthma Flail chest Diseases of the nerves or muscles of the chest . Over sedation from narcotics and strong sleeping

medications .

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2) Increased CO2 production Malignant hyperthermia Thyroid storm Intensive shivering Prolonged seijures

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Breathlessness Restlessness Lethargy and disorientation Tremors, convulsions, coma Respiratory rate rapid, then gradually

depressed Skin warm and flushed due to vasodilation

caused by excess CO2

Treat the under lying cause The treatment of respiratory acidosis aims to

improve the function of the lungs. Drugs to improve breathing may help people

who have lung diseases such as asthma and emphysema.

Ventilatory support.

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-metabolic balance before onset of acidosis-pH = 7.4

-respiratory acidosis-pH = 7.1-breathing is suppressed holding CO2 in body

-body’s compensation-kidneys conserve HCO3

- ions to restore the normal 40:2 ratio-kidneys eliminate H+ ion in acidic urine- therapy required to restore metabolic balance

- lactate solution used in therapy is converted to bicarbonate ions in the liver

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What is respiratory alkalosis?

What are the different causes of RaL ?

what is the Treatment of RaL?

Cause is Hyperventilation leads to elimination of excessive amounts of COCO2.2.

◦Increased loss of COCO22 from the lungs at a rate faster than it is produced.

◦There is increase in pH and decrease in HH++

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Can be the result of:◦1) pain,anxiety, emotional disturbances

◦2) Respiratory center lesions◦3) Fever◦4) Salicylate poisoning (overdose)◦5) Assisted respiration◦6) High altitude (low PO2)

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Kidneys compensate by:Retaining hydrogen ionsRetaining hydrogen ions

Increasing bicarbonate excretionIncreasing bicarbonate excretion Respiratory system Decreased COCO22 in the lungs will eventually slow the rate of breathing Will permit a normal amount of COCO22 to be retained in the lung

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HCO3-

HCO3-

HCO3-

HCO3-

HCO3-

HCO3-

H+

H+

H+

H+

H+

H+

H+

H+

Usually the only treatment needed is to slow down the rate of breathing

Breathing into a paper bag or holding the breath as long as possible may help raise the blood COCO22 content as the person breathes carbon dioxideback in after breathing it out

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-metabolic balance before onset of alkalosis-pH = 7.4

-respiratory alkalosis-pH = 7.7

- hyperactive breathing “ blows off ” CO2

- body’s compensation

- kidneys conserve H+ ions and eliminate HCO3

- in alkaline urine

- therapy required to restore metabolic balance

- HCO3- ions replaced by Cl- ions

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What is metabolic acidosis (mac) ?

What are the different causes of Mac ?

what is the Treatment of

mac ?

Decrease in blood pHpH and bicarbonate level (below 22mEq/L)

Excessive HH++ or decreased HCOHCO33--

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H2CO

3

HCO3-

1 20:= 7.4

H2CO

3

HCO3-

1 10:= 7.4

The causes of metabolic acidosis can be grouped into fivefive major categories◦1)1) Ingesting an acid (acetylsalicylic acid)

◦2) 2) Abnormal Metabolism (type I Abnormal Metabolism (type I DM,shock)DM,shock)

◦3) Kidney Insufficiencies(3) Kidney Insufficiencies(renal tubular renal tubular acidosisacidosis or uremic acidosisuremic acidosis )

◦4) Strenuous Exercise4) Strenuous Exercise◦5) Severe Diarrhea5) Severe Diarrhea

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Unregulated diabetes mellitus causes ketoacidosisketoacidosis◦Body metabolizes fat rather than glucose

◦Accumulations of metabolic acids (Keto Acids)(Keto Acids) cause an increase in plasma HH++

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This leads to excessive production of ketones:ketones:◦AcetoneAcetone◦Acetoacetic acidAcetoacetic acid◦B-hydroxybutyric acidB-hydroxybutyric acid

Contribute excessive numbers of hydrogen ions to body fluids

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Acetone

Acetoacetic acid

Hydroxybutyric acid

H+

H+

H+

H+

H+H+H+

As the blood pHpH drops,breathing becomesdeeper and faster as thebody attempts to rid theblood of excess acid bydecreasing the amountof carbon dioxide

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Eventually, the kidneys also try to compensate by excreting more acid in the urine

However, both mechanisms can be overwhelmed if the body continues to produce too much acid, leading to severe acidosis and eventually a coma

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◦If the acidosis is mild, intravenous fluids and treatment for the underlying disorder may be all that's needed.

◦control diabetes with insulin or treat poisoning by removing the toxic substance.

When acidosis is severe, bicarbonate may be given

(NaHCO3=BD X 30% X BODY WEIGHT◦Bicarbonate provides only temporary relief

and may cause harm.

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- metabolic balance before onset of acidosis- pH 7.4

- metabolic acidosis- pH 7.1

- HCO3- decreases because of

excess presence of ketones, chloride or organic ions

- body’s compensation- hyperactive breathing to “ blow off ” CO2

- kidneys conserve HCO3- and

eliminate H+ ions in acidic urine

- therapy required to restore metabolic balance

- lactate solution used in therapy isconverted to bicarbonate ionsin the liver

0.5 10

What is anion gap ?What is the normal value?What is the effect of albumin?

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To achieve electrochemical balance, the concentration of negatively-charged anions must equal the concentration of positively-charged cations.

Na+UC=(Cl+HCO3)+UA Rearranging: Na-(Cl+HCO3)=UA-UC The difference (UA - UC) is a measure of the

relative abundance of unmeasured anions and is called the anion gap (AG).The normal value of the AG was originally set at 12

± 4 mEq/L (range = 8 to 16 mEq/L)

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Unmeasured Anions Unmeasured Cations

Albumin (15 mEq/L)* Calcium (5 mEq/L) Organic Acids (5 mEq/L) Potassium (4.5 mEq/L) Phosphate (2 mEq/L) Magnesium (1.5 mEq/L) Sulfate (1 mEq/L) Total UA: (23 mEq/L) Total UC: (11 mEq/L) Anion Gap = UA - UC = 12 mEq/L *If albumin is reduced by 50%, anion gap = 4

mEq/L

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Increased anion gap Normal anion gap (hyperchloremic)

Renal failure Increased HCO3 loss by GIT

Ketoacdosis (DM,starvation) Diarrhea, fistula, ureterosigmoidostomy

Lactic acidosis Increased loss of HCO3 by kidneys

Ingestion of toxin-salicylate methanol, ethylene glycol

Renal tubular acidosis,hypoaldosteronism

rabdomyolysis Dilutional –large amt of HCO3 free fluids

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What is metabolic alkalosis (mal) ?

What are the different causes of Mal ?

what is the Treatment of

mal ?

Elevation of pHpH due to an increased 20:1 ratio◦May be caused by: An increase of bicarbonate A decrease in hydrogen ions

◦Imbalance again cannot be due to COCO22

◦Increase in pHpH which has a non-respiratory origin

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Can be the result of: 1)1) Ingestion of Alkaline Substances Ingestion of Alkaline Substances (NaHCONaHCO33) often used

as a remedy for gastric hyperacidity.

◦ 2)Vomiting ,gastric drainage( 2)Vomiting ,gastric drainage( loss of HCl )loss of HCl )

◦ 3)Certain diuretics

◦ 4)Endocrine disorders:◦ prim. hyperaldosteronism, Cushing synd.

◦ 5)Massive blood transfusion

◦ 6)Severe dehydration

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Reaction of the body to alkalosis is to lower pHpH by:◦Retain CO2 by decreasing breathing rate.

◦Kidneys increase the retention of HH++

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CO2 CO2

H+

H+

H+

H+

Treatment of metabolic alkalosis is most often accomplished by replacing water and electrolytes (sodiumsodium and potassiumpotassium) while treating the underlying cause

Occasionally when metabolic alkalosis is very severe, dilute acid in the form of ammonium chloride is given by IV

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- metabolic balance before onset of alkalosis- pH = 7.4

- metabolic alkalosis- pH = 7.7

- HCO3- increases because of loss

of chloride ions or excess ingestion of NaHCO3

- body’s compensation- breathing suppressed to hold CO2- kidneys conserve H+ ions and eliminate HCO3

- in alkaline urine

- therapy required to restore metabolic balance

- HCO3- ions replaced by Cl- ions1.2

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http://umed.med.utah.edu/MS2/renal/AcidBaseTables/img001.JPG

RESP ACIDOSIS

RESP ALKALOSIS

METAB ACIDOSIS

METAB ALKALOSIS

COMPENSATION

Kidneys eliminate hydrogen ion and retain bicarbonate ion

Kidneys conserve hydrogen ionExcrete bicarbonate ion

Increased ventilationRenal excretion of H ions.K+ exchanges with excess H+ in ECF( H+ into cells, K+ out of cells)

Alkalosis commonly occurs with renal dysfunction, so can’t count on kidneys.Respiratory compensation difficult – hypoventilation limited by hypoxia

TREATMENT Restore ventilation,IV lactate solution

Breathe into a paper bagIV Chloride containing solution – Cl- ions replace lost bicarbonate ions

IV lactate solution

Electrolytes to replace those lost,IV chloride containing solutionTreat underlying disorder

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disturbance response Expected changes

Respiratory acidosis

acute HCO3 1mEq/L/10 mm of Hg inc .in Paco2

chronic HCO3 4mEq/L/10 mm of Hg inc .in Paco2

Respiratory alkalosis

acute HCO3 2mEq/L/10 mm of Hg dec .in Paco2

chronic HCO3 4mEq/L/10 mm of Hg dec .in Paco2

Metabolic acidosis

Metabolic alkalosis

PPaco2

Paco2

1.2 x the decrease in HCO30.7 x the increase in HCO3

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Mechanisms protect the body against life-threatening changes in hydrogen ion concentration◦1) Buffering Systems in Body 1) Buffering Systems in Body FluidsFluids

◦2) Respiratory Responses2) Respiratory Responses◦3) Renal Responses3) Renal Responses◦4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions

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Buffering systems provide an immediate response to fluctuations in pHpH◦1) Phosphate1) Phosphate◦2) Protein2) Protein◦3) Bicarbonate Buffer System3) Bicarbonate Buffer System

A buffer is a combination of chemicals in solution that resists any significant change in pHpH

Able to bind or release free HH++ ions

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1) Phosphate buffer system1) Phosphate buffer system

Na2HPO4 + H+ NaH2PO4 +

Na+

Most important in the intracellular system.

Phosphate concentrations are higher intracellularly and within the kidney tubules.

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2) Protein Buffer System2) Protein Buffer System◦Behaves as a buffer in both plasma and cells.

◦Hemoglobin is by far the most important protein buffer.

Proteins are excellent buffers because they contain both acid and base groups that can give up or take up HH++

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As HH++HbHb picks up OO22 from the lungs the HbHb which has a higher affinity for OO22 releases HH++ and picks up OO22

Liberated HH++ combines with HCOHCO33--

HCOHCO33-- HH22COCO33 COCO22

(exhaled)

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HHbb

O2

O2 O2

H+

O2

Protein buffer system works instantaneously making it the most powerful in the body.

75% of the body’s buffer capacity is controlled by protein.

◦Bicarbonate and phosphate buffer systems require several hours to be effective

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3) Bicarbonate Buffer System3) Bicarbonate Buffer System◦Predominates in extracellular fluid (ECFECF)

HCOHCO33- - + H+ H++

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HH22COCO33

This system is most important because the concentration of both components can be regulated:◦Carbonic acidCarbonic acid by the respiratory system◦BicarbonateBicarbonate by the renal system

Neurons in the medulla oblongata and pons constitute the Respiratory Respiratory CenterCenter

Increases in CO2 and H+

stimulate the respiratory center.

◦The effect is to raise respiration rates, but the effectdiminishes in1 - 2 minutes.

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Respiratory centers

Chemoreceptors are also present in the carotidcarotid and aorticaortic arteries which respond to changes in partial pressures of O2 and CO2 or pH

Increased levels ofCO2 (low pHpH) ordecreased levels ofO2 stimulaterespiration ratesto increase

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Overall compensatory response is:◦HyperventilationHyperventilation in response to increased CO2 or H+ (low pHpH)

◦HypoventilationHypoventilation in response to decreased CO2 or H+ (high pHpH)

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81pH rises toward normal

rate and depth of breathing increase

CO2 eliminated in lungs

H+ stimulates respiratory center in medulla oblongata

H2CO3 H+ + HCO3-

H+ acidosis; pH drops

CO2 + H2O H2CO3

cell production of CO2 increases

The kidney compensates for Acid - Acid - BaseBase imbalance within 24 hours and is responsible for long term control

The kidney in response:◦To AcidosisTo Acidosis Retains bicarbonate ions and eliminates hydrogen ions

◦To AlkalosisTo Alkalosis Eliminates bicarbonate ions and retains hydrogen ions

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COCO22 + H + H22O HO H22COCO33 H H++ + HCO + HCO33--

Hyperventilation removes HH++ ion concentrations

Hypoventilation increases HH++ ion concentrations

Kidneys eliminate or retainHH++ or bicarbonate ions

HyperkalemiaHyperkalemia is generally associated with acidosis◦Accompanied by a shift of H+ ions into cells and K+ ions out of the cell to maintain electrical neutrality.

◦Acidosis may cause Hyperkalemia and Hyperkalemia may cause Acidosis

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H+

K+

HypokalemiaHypokalemia is generally associated with reciprocal exchanges of H+ and K+ in the opposite direction◦Associated with alkalosis

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H+

K+

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THANKS