Acid-base lecture notes

From Biol557

• started here on 04/07/10.

• moving some lectures around

Contents 1 Acid / Base homeostasis 1.1 Acid / base 101 1.2 Where do we get the acid equivalents? 1.3 types of acids 1.4 Compensation for acid production 1.5 Immediate buffering systems 1.6 Buffer systems 1.7 Chemical buffers 1.7.1 Proteins 1.7.2 Phosphate buffering 1.7.3 CArbonic acid / bicarbonate / CO2 system 1.8 Respiratory buffering 1.9 Renal buffering 1.9.1 Bicarbonate 1.9.2 Ammonia 1.9.3 Acid / base 1.10 Disturbances of acid / base balance 1.10.1 REspiratory acidosis 1.10.2 Respiratory alkylosis 1.10.3 Metabolic acidosis 1.10.4 Metabolic alkylosis

Acid / Base homeostasis

Acid / base 101

• There is a difference across the membrane: 7.4 blood and 7.0 in the ICF.
• Blood pH doesn't change much, only 0.1.
• The metabolic activity is what causes the low pH inside cells.

• acid can donate hydrogen ion, base can accept.
• There are weak and strong acids and bases.
• Dissociation can be measured by k_a; it is often expressed as the negative log.
  • The stronger the acid the lower the number.
  • We won't go over Kas for acids.
• We will look at pH.
• pH is the negative log of the hydrogen ion concentration.
• When using a negative log, something that is 10^-14 is much lower than -7.
  • Anything above pH 7 is basic, below is acidic.
• Increasing blood pH over 7.8, you have death from overexcitation of nervous system, muscle tetany, convulstions.
• Lower than 6.8 will put one in a coma from depression of nervous system.
• So pH maintenance is important. There are several systems that do this.

Where do we get the acid equivalents?

• Mostly from metabolism.
  • Breakdown of phosphoproteins generates phosphoric acid.
  • Brteakdown of sulfuric containing stuff => sulfuric acid.
  • Breakdown of cationic acids gives hydrochloric acids.
  • Anearobic meta = lactic acid
  • Fat metabolism generates ketone bodies.
• These are just a handful of the processes that generate the acids.

types of acids

• There are three generalized types; the different regulatory systems can handle one or more types.
• Types:
  • CO2
  • Fixed acids, cannot be ridden thorugh respiratory processes so kidney must excrete.
  • Organic acieds, respiration can compensate but not get rid of these.

Compensation for acid production

• How do we deal with wild swings in acid and base levels?
• First is the chemical buffers inside cells and the blood stream.
  • There is a bunch of buffering capacity.
  • Happens immediately.
• Repiratory center
  • Brain stem has center that can change breathing rate which determines how much CO2 there is in the blood.
  • This takes minutes.
• Renal compensation
  • This can take hours.
  • This is the getting rid of acids and bases through urine secretion.

Immediate buffering systems

• How good are they?
  • If you put 1 ml of 10mM of HCl into 10 ml of water, the pH goes from 7 to 3.
  • If you put 1 ml of 10mM of HCl into 10 ml of blood, the pH goes from 7.4 to 7.
• So, you're immediate response is really fairly phenomenal.

Buffer systems

• There are several common pairs of acids and buffers.
• All three systems (chemical, respiratory centers, kidneys) will be involved.
• Chemicals break down into:
  • proteins, phosphate buffers, bicarbonate / CO2.
• The respiratory system can only deal with bicarbonate / CO2.
• The kidneys can work through:
  • bicarbonate / CO2
  • titratable acids (these are fixed acids like sulfate, etc).
    • We call them titratable because they used to be titrated to measure their levels in the urine.
  • Amonnia, ammonium.

Chemical buffers

• The effectiveness is dependent on:
  • Strength of dissociation of acid / base
  • concentration of component

Proteins

• These are good because all the side groups can act as buffering units.
• They are also good because they are found in high concentration on the inside and outside of cells.
• Hb has 37 histidine residues which are good at absorbing hydrogen ions.
• Albumins are also good at buffering.

Phosphate buffering

• Phosphates have a pKA such that they are good at buffering at the pH of blood.
• However, they are not high enough in concentration to control buffering all alone.

CArbonic acid / bicarbonate / CO2 system

• This is important in chemical, respiratory, and renal buffering.
• Present in large quantities.
• Carbonic anhydrase must be present in order for this system to work.
• Recall that CA converts CO2 to H2CO3 and vice versa.
• The movement from H2CO3 to HCO3 does not require an enzyme.
• NaHCO3 can be used to store the HCO3.
  • This is called the bicarbonate reserve.

Respiratory buffering

• CO2 is exhaled at the same rate CO2 is being produced, so there is net balance.
• If you hypoventalate the CO2 is not given off so you become acidic because it pushes the reaction toward generation of HCO3.
• If you are getting rid of CO2 faster than it is being produced, it will drive the reaction to the left toward CO2 and thus the blood becomes alkaline.
• If the blood becomes acidic, then the peripheral receptors in the corotid and aortic vessels will sense the pH and signal the respiratory center that is in the brain to increase ventilation. That will decrease CO2 and increase the pH by forcing the reaction to the left.
• If the blood becomes basic, different peripheral receptors will sense it and decrease breathing.
• This sensing and changing of breathing will work for a short time and then sensors in the brain will sense the CO2 and override the peripheral receptors (CO2 receptors override the pH sensors).
• And this makes sense because if you stop breathing you'll die fast. It is more important that you keep breathing and hope that pH gets figured out therough other mechanisms.

Renal buffering

• The respiratory system can only regulate the CO2. So it can compensate for fixed acids and bases in the blood but cannot change their levels.
• So the renal system must do this.
• The renal system is going to work with the CO2 / bicarbonate system and with fixed acids but in a different manner.

Bicarbonate

• Renal can secrete H+ into the lumen, reabsorb bicarbonate from the filtrate, and produce bicarbonate.
  • note that this "reabsorbing" of the bicarbonate is not direct.
• The bicarbonate that is filtered is 4500 mEquivalents / day but cannot be reabsorbed because there is not apical mover on the ductal epithelium.
• But there is a mechanism for preserving bicarbonate.
• How is it done?
  • We have bicarbonate in the filtrate.
  • No transporter on epithelial surface.
  • We do have a membrane bound CA on the apical membrane, through.
  • So it changes bicarbonate into carbonic acid.
  • Then carbonic anhydrase can be broken down into CO2 and water.
  • CO2 moves into cell by diffusion.
  • Then an enzyme (CA) will use the H20 and CO2 and make it into HCO3.
  • Then an HCO3 transporter on the basal membrane moves it into the blood.
  • The extra H ion goes back into the fluid.
• Why do all this?
  • It is a mechanism for controlling acid / base.
  • If we just reabsorbed it all we would have no modulation.
• The hydrogen that leaves is important for keeping the cycle going and for use with fixed acids and bases.
• If we didn't have this system only about 1% of the acid could be secreted.
• so this is how "reabsorption" works.
• This whole process can be reversed, too:
  • Pretend the blood is basic.
  • intracellular CA genrates bicarbonate and H+
  • H+ goes into blood.
  • HCO3 can't get into fluid except by a cotransporter that is one way out.

Ammonia

• If necessary, if you need to acidify the urine, we can actually make ammonia in the proximal tubule cells.
  • Glutamine is broken downt of form the ammonai.
  • Thi si not normally active.
  • This is upregulated in severe acidosis, but it takes about a day.
• How does this work?
  • Glutamine is broken down into NH4 and HCO3.
  • HCO3 goes into the bllod to decrease acidosis.
  • NH4 or NH3 (ddepending on pH of cell) will be secreted to the urine.
  • This gets rid of acid and puts a base int eh blood.

Acid / base

• Under acidic conditions, kidney can secrete the hydrogen and can rais the plasma bicarbonate.
• Under basic conditions, the kidney simply secretes bicarbonate.
• Remember that CO2 is a gas that can diffuse.

Disturbances of acid / base balance

• If we say acidosis or alkylosis we must clarify whether it is a respiratory or metabolic acidosis / alkylosis.
• If the problem is with fixed acids or bases it is a metabolic disturbance.
• If the probelm is swith CO2 it is a respiroatry disturbanc.e

REspiratory acidosis

• Generally caused by a CO2 issue.:
  • Biggest cause is pulmonary disease where you cannot get rid of CO2 because you cannot exhale enough CO2.
  • There could be insufficient neural drive.
• Common causes:
  • Pneumonia, CF (scarring decreases gas exchange), emphasema, pulmonary adema.
  • All inhibit gas exchange.
  • Narcotic or barbituate overdose.
  • Brain stem injury.
• How can we treat it?
  • Dependson what causes the problem.
  • We can do artificial respiration if nerual or muscular issue. IV if a bicarbonate issue.
• How does the body deal with this?
  • Chemical buffering, we'll ignore this because it is always there.
  • Respiraotyr
    • Peripheral sensors will notice imbalance and increase breathing rate.
      • In pulmonary edema (where the lungs or breathing are the problme in the first place) this won't help much.
  • Renal reaction
    • Secretion of H ions (because of all that CO2 coming into epitheilial cell from both times).
    • Generates HCO3 which is screted, too.

Respiratory alkylosis

• Cuaseed by hyperventiallation:
  • Voluntary, could be crying for long periods of time
  • Anxiety
  • Stimulation of respiratory centers
    • Aspirion toxicity (don't take lots together, often)
    • High fevers can affect resp center.
  • Reflex action at high altitudes
    • Because pp of O is low, we start taking more and deeper breaths. This causes hyperventillation and causes CO2 to go down.
• So all-in-all this is a net loss of CO2.
• What does the body do about it?
  • Chemical system
  • REspiratory
    • Reduces breathing rate
  • Renal
    • Kidneys secrete bicarbonate (that is, don't reabsorb it).
• Treatment:
  • Breath in a paper bag which will increase pp of CO2 and decrease release of CO2.

Metabolic acidosis

• Causes:
  • Renal failure
    • If you can't get rid of fixed bases then you will end up acidotic.
  • Uncontrolled diabetes; ketone body formation causes acidosis.
  • Excess exercise
    • Generates transient acidosis state because of lactic acid.
    • Don't need to worry about this
  • Ingestion, think ammonium chloride
  • Loss of bicarbonate by diarrhea
    • We often put bicarbonate into the GI to get rid of acids so if we have diarrhea, it all goes out.
  • Excess alcohol consumption
    • Metabolites are acidotic.
• What does our body do?
  • Chemical buffers.
  • Respiratory centers
    • Peripheral notice low pH and increases ventilation to decrease CO2
  • Renal
    • Reclaims all the bicarbonate; turns it into CO2 in the lumen, puts it in the cell, turns it back into bicarbonate, put s it int eh blood.
    • If it goes on for a long ntime, kidney will start making ammonia to put even more (that is, new) bicarbonate into the blood.
• Treatment:
  • IV bicarbonate.

Metabolic alkylosis

• Caused by:
  • Ingestion of excess base; perhaps from overuse of antacids, don't use baking soda because it is sodium bicarbonate!
    • Better to use antacids so they are not so readily absorbed.
  • Vomiting
    • This happens because when you vomit you get rid of stomach acids to the stomach starts making more acids. It does this by secreting an H+ ion and putting HCO3 into the blood stream.
  • Some diuretics
    • Cause potassium depletion because they secondarily cause H+ secretion.
• What does the body do?
  • Chemical buffers
  • Respiratory system
    • Sensors see high pH and send the signal to hypoventilate. This will only last until CO2 builds up to trigger the brain to say "hey, start breathing, moron".
  • Renal
    • Stops reabsorbing bicarbonate.
• Treatment:
  • Administer ammonium chloride. In the liver, ammonium chloride will be broken down such that H+ ions are generated.

• end of acid / base.

• test on Monday

• We'll start with PKD then GI.

• stopped here on 04/07/10.