IMED1003 - Buffers + Acid Base Balance (L24)

pH chemistry and in the body

DIAGRAM ON SLIDE 4

Acid Base Chemistry

DIAGRAM ON SLIDE 5 (WHOLE SLIDE)

The most important acid to human physiological homeostasis is CO2

- CO2 + H2O <--> H2CO3 <-> H+ + HCO3-

- CO2 is a lewis acid (accepts electron pair from H2O, liberating H+)

Acid-Base Homeostasis

- ECF [H+] = 0.00004 mEq/L = 40 nEq/L

- normal [H+] variation = plus minus 3-5 nEq/L (probs wont die unless <10 or >160)

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- pH = -log[H+]

- pH = -log (0.00000004) = 7.4

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mEq/L means milli equivalents per L, aka millimoles per litre

Acidosis (process), Acidaemia (state)

- increase in acidity ([H+]) of body fluids

- Reduction in arterial pH <7.35

Alkalosis (process), Alkalaemia (state)

- reduction in acidity ([H+]) of body fluids

- increase in arterial pH >7.45

-aemia

blood

pH effects on Metabolism

- practically every step of every metabolic process is pH dependent

- Deviate from optimal pH - decreased reaction efficiency

- this is because of enzymes

pH effects on neuromuscular system

- acidosis -> inhibitory (inhibits signalling)

- alkalosis -> excitatory (too much excitation of signalling)

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WHY?

Acidosis increases free [Ca2+]

- Ca2+ binding to albumin is pH dependent

- Ca2+ blocks vNa+ channels -> raises AP threshold

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K+ Balance:

- Acidosis -> increase in serum [K+]

- Alkalosis -> decrease in serum [K+]

Consequences of Acidosis

- headaches, confusion, lethargy, tremors, sleepiness

- Cerebral dysfunction -> coma

- Cardiovascular dysfunction

- hyperventilation

Consequences of Alkalosis

- muscular weakness, pain, cramps, spasms (smooth and skeletal muscle) -> tetany

- hypoventilation

Consequences

IMPACT DEPENDENT ON SEVERITY OF ILLNESS

- Anaesthesia

- Intensive care (exercise)

- Emergency medicine

- Respiratory medicine

- Nephrology

Normal physiology promotes acidosis

- whie living, eating and drinking there is production of 1mmol of acid/kg body weight per day (70kg = 70mmol/day)

- most acid comes from CHO/fat metabolism (generates 15000 to 20000 mmol of CO2 daily

Acid Base Balance

- we can either breathe out CO2 or excrete it in the urine to get rid of acids

Defense Mechanisms

CHEMICAL BUFFERING (IMMEDIATE - BUT EXHAUSTIBLE)

- Solutions that resist changes in pH

- intracellular and extracellular buffers provide an immediate response to acid-base disturbances (bone also buffers acid loads)

- they can't get rid of acid from the body, they can only temporarily reduce its impact short term

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Pulmonary regulation (minutes-hours - limited question)

- [CO2] is regulated by changes in breathing frequency and depth

- as CO2 is exhaled -> blood pH increases

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RENAL REGULATION (HOURS-DAYS, VERY POWERFUL, INFINITE CAPACITY):

- Kidneys control adjust the amount of HCO3- and/or H+ that is excreted

- Excreting HCO3- -> decrease blood pH, excreting H+ -> increase blood pH

Buffer Systems

- Buffer = substance that reversibly consumes or releases H+ to decrease changes in pH

- made up of a weak acid and its conjugate base (conjugate base can accept H+ and the weak acid can donate H+ -> minimising changes in free [H+]

- Buffer- + H+ <--> H-Buffer

Henderson-Hasselbach equation

- Relationship between the pH of a buffer system and the concentration of its components:

- pH = pKa + log (whatever on diagram)

- pKa is the dissociation constant of a weak acid

- So ... pKa determines optimal pH for max. buffering capacity (a buffer system works best to minimise pH changes near its pKa)

- and the relative [cj.base]:[acid] determine how much acid or base can be buffered -> i.e acid-buffering capacity, base-buffering capacity

Buffer Power

- buffer power is determined by the "pH appropriateness" of the system (does pKa match pH?)

- capacity determined by: total [buffer] and relative [H-B] and [B-]

Phsyiologically-Relevant Buffer Systems

- there are certain physiologicla situations where we need different buffers

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BICARBONATE: HCO3- (pKa = 6.37)

- Dominant ECF buffer

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AMMONIA: NH3 (pKa = 9.25)

- ECF too, but mostly in renal tubules

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PHOSPHATE: HPO4 2- (pKa = 7.21)

- ICF buffer

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PROTEINS (many close to pKa of around 7.4, Hb around 6.8)

- ICF buffer (ie - Hb in RBCs), 60-70% of total buffering capacity

Bicarbonate Buffer System

- carbonic anhydrase is the enzyme

- bottom parts shows it being driven in both directions (buffering against acid and buffering against base)

The Others

- dont need to memorise these equations (probably have to considering IMED)

Respiratory Control

- ventilation rates control pH balance (increased ventilation removes CO2)

- hyperventilation drives reaction to the left (decreased H+, increaesd pH)

- hypoventilation drives reaction to the right (increased H+, decreased pH)

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- we would call abnormal loss of CO2 respiratory alkalosis since its coming form respiratory and its alkalopsis

- respiratory acidosis is more profound then alkalosis since there is a stimulus to breathe when CO2 is high but no stimulus when its low

Effect of ventilation on pH

- increase Va x2 --> increased pH by 0.23 (7.4 -> 7.63)

- decreased Va to 1/4 --> decreased pH by 0.45 (7.4 -> 6.95)

Renal Control

- kidneys constantly remove (filter) HCO3- (base) from blood

- to maintain balance, we must reabsorb enough HCO3- back into blood

- BUT kidneys cannot reabsorb HCO3- it must first b e converted:

HCO3- + H+ <--> H2CO3 <--> H2O + CO2

- To do this, kidneys must secrete H+ (1:1 ratio with HCO3-)

- Quantitative H+ secretion determines HCO3- reabsorption

Renal Control EXPLAINED DIAGRAM

- basically the kidney cell uses carbonic anhydrase to make HCO3- and H+.

- the bicarbonate goes back into the blood, the H+ is excreted

Renal Control and H+ secretion

- Result: excretion of acidic or basic urine

- Balance between: H+ secretion / HCO3- filtration

- H+ secretion = HCO3- filtration = no change

- H+ secretion > HCO3- filtration = acid loss

- H+ secretion < HCO3- filtration = base loss

Respiratory and Metabolic Control

- Respiratory control changes blood [CO2] (PCO2)

- Metabolic control (renal) changes blood [HCO3-]

Acid Base Disorders

Cause - metabolic or respiratory? (we can determine whether or not its metabolic or respiratory by looking at the following factors):

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METABOLIC:

- due to production, ingestion or loss of acids/bases

- change plasma [HCO3-]

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RESPIRATORY:

- due to hyper/hypoventilation

- change in PCO2 (ventilation)

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- basically we can determine the source of error. is the kidney having trouble excreting?

- it can be metabolic or respiratory acidosis or alkalosis

Homeostatic Compensation

RESPIRATORY DISORDER -> Metabolic Compensation

- Primary change in PCO2 -> change in pH -> change in HCO3-

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METABOLIC DISORDER -> Respiratory Compensation

- Primary change in HCO3- -> change in pH -> change in PCO2

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METABOLIC COMPENSATION (KIDNEYS):

- Acidosis: increased H+ excretion, total HCO3- reabsorption

- Alkalosis: decreased HCO3- reabsorption -> excreted in urine

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RESPIRATORY COMPENSATION (LUNGS):

- Acidosis: increased ventilation -> decreased PCO2 -> increased pH

- Alkalosis: decreased ventilation -> increased PCO2 -> decreased pH

Simple AB Disorders

DIAGRAM ON SLIDE 31

Summary

DIAGRAM ON SLIDE 33

QUESTION

DIAGRAM ON SLIDE 34