by mtoom


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What is normal pH?
7.4
What is significant vs life-threatening alkalosis?
  • Significant: 7.5-7.6
  • Life-threatening: >7.7
What is significant vs life-threatening acidosis?
  • Significant: 7.1-7.3
  • Life-threatening: Less than 7
Name the 3 methods that regulate pH and the time frame that these mechanisms work in.
  • 1. Buffers (sec)
  • 2. Removal of CO2 (min-hr)
  • 3. Excretion of acid/alkaline urine (hr-day)
In terms of pH, what is alkalosis?
>7.45
In terms of pH, what is acidosis?
Less than 7.35
When you have acidosis, how do you know if it is metabolic or respiratory?
  • Metabolic Acidosis:
    Low HCO3-
     
  • Respiratory Acidosis:
    High CO2
When you have alkalosis, how do you know if it is metabolic or respiratory?
  • Metabolic Alkalosis:
    High HCO3-
     
  • Respiratory Alkalosis:
    Low CO2 
What is the shorthand method to remember the determination of metabolic or respiratory acidosis/alkalosis? *
If the HCO3- is abnormal in the same direction as pH, it is metabolic. (If CO2 is abnormal in the same direction, then respiratory compensation)

If the CO2 is abnormal in the opposite direction as pH, it is respiratory. (If HCO3- is abnormal in the same direction, then metabolic compensation).
How is the PCO2 determined, in terms of a physiological equation?
PaCO2 is proportional to VCO2 (rate of CO2 production) divided by VA (rate of alveolar ventilation)
What are the 3 steps of regulating pH?
  • 1. Secreting H+
  • 2. Reabsorption HCO3-
  • 3. Producing HCO3-
What are the 3 steps in responding to acidosis?
  • 1. Reabsorb all filtered HCO3-
     
  • 2. Secrete/combine excess H+

    -NaHPO4- to NaH2PO4
    -NH3 to NH4+

  • 3. Produce new HCO3-

    -via Glutamine metabolism
    -via secretion of H+ 
What are the 2 steps in responding to alkalosis?
  • 1. Reabsorb less HCO3-
     
  • 2. Secrete more HCO3-
What do we know about the charge of a solution, like the serum? How is this information useful in interpreting the anion gap?
It is neutral in charge. Thus, the anion gap identifies the presence of so-called "unmeasured anions".
Describe 6 things that cause an elevated anion gap. Also, use an acronym to describe 8 letters.
  • Lactic acid
  • Ketoacids
  • Renal failure
  • Ingestion of aspirin
  • Methanol
  • Ethylene glycol

MUDPILES
  • M= Methanol
  • U= Uremia
  • D= Diabetic ketoacidosis
  • P= Propylene glycol
  • I= Isoniazid, Inborn errors, Iron, Infection
  • L= Lactic acidosis
  • E= Ethylene glycol
  • S= Salicylates
Can you have a metabolic acidosis with a normal anion gap?
Yes, for example hyperchloremic acidosis
Describe 2 mechanisms that lead to metabolic alkalosis
  • Loss of H+
    -Vomiting 
  • Gain of HCO3-
    -Volume contracting
    -Diuretics
Where do Carbonic (Volatile) acids come from? What happens to them?
  • Carbonic acids (eg. H2CO) come from fat/carb metabolism

  • They are exhaled by the lungs, (because they are volatile)
Where do non-carbonic (non-volatile) acids come from? What happens to them?
  • Non-carbonic acids (eg. sulphuric acid, HCl) produced by proteins, sulphates, phosphates

  • These constitute the daily acid load that must be excreted by the kidneys
Describe 3 extracellular acid buffer systems
  • 1. Bicarbonate (HCO3-)
  • 2. Plasma proteins
  • 3. Inorganic phosphates
Describe 3 intracellular acid buffering systems
  • 1. Cellular proteins
  • 2. RBCs (Hemoglobin)
  • 3. Phosphates
Bone acts as a buffer to H+, how does it do this?
  • Takes up H+
  • Dissolves bone mineral to release buffer
What 2 organs function in concert to deal with acid in the blood? How?
  • Lungs → Control PCO2
  • Kidneys → Control HCO3-
What are the 3 things that kidneys do to defend against addition of non-volatile acids in the body fluids? (This question is a repeat.)
  • Don't lose any HCO3- to urine (ie. reabsorb all bicarbonate)
  • Excrete the daily acid load (via titratable acids and Ammonium ion NH4+)
  • Regenerate any HCO3- consumed
What are the 3 steps of acid-base handling? (This question is a repeat.)
  • H+ secretion
  • HCO3- reabsorption
  • Excrete daily acid load and regenerate HCO3-
Are H+ filtered by the kidney as free ions? Describe how they are secreted.
  • H+ NOT filtered by kidney as free ions
  • They are secreted from the proximal tubule and collecting tubule cells into the lumen
What happens to H+ in the tubule lumen? (ie. what 2 things might it bind to?)

It binds to one of these 2 things:
  • Filtered bicarbonate (HCO3- reabsorption)
  • Titratable acids and ammonium
All the HCO3- reabsorption is a conseuqence of what?
H+ secretion

(CO2 diffuses into cell, combines with H2O to give H+ and HCO3-, and H+ leaves the cell)
How much HCO3- is reabsorbed and where does this occur?

100% reabsorbed, as follows:
  • 80-90% of HCO3- is reabsorbed in the Proximal Tubule (PT)
  • ~10% in TAL
  • ~6% in DCT
  • ~4% in CCD
What is a key point about HCO3- reabsorption and H+ secretion?
1mmol of HCO3- is returned to systemic circulation for every 1mmol H+ that is secreted
Name 2 places in nephron where bicarbonate (HCO3-) is created?
  • PT: H+ is secreted in exchange for Na+
  • CCD: H+ is secreted by ATPase
In generation of new bicarbonate, what accepts the H+ (2) so as not to increase H+ in the lumen?
(ie. create bicarbonate; if you don't bind it with another negative molecule, it binds HCO3- in lumen and there is no net increased in HCO3-)
  • H2PO4-
  • NH3
What is the major adaptation to an increasing acid load?
  • Major adaptation is to increase NH3 (and subsequently NH4+) production (by metabolizing Glutamine)
  • Titratable acids get used up quickly and don't adapt to an acid load

But note: Normally NH4+ is responsible for removing less than half of the acid
Describe the 3 steps to NH4+ excretion (not really necessary to understand these steps)
  • 1. Ammonium formation (proximal tubule)
  • 2. Ammonium reabsorption and recycling (TAL-LOH)
  • 3. Ammonium trapping (collecting tubule)
Where is Ammonium (NH4+) produced?
Lots of ammonium is produced in the PT.
If Ammonium (NH4+) is reabsorbed at the TAL, how does this occur?
It rides the Na/K/2Cl transporter into the cell in place of K+
Describe one key, necessary step for Ammoniagenesis to be effective in creating bicarbonate?
The NH4+ must be excreted! If not, it is being re-absorbed and metabolized at the cost of 2 HCO3-
Can NH3 diffuse from lumen to blood?
Can NH4+ diffuse from lumen to blood?
  • Yes (problem, because we don't want to lose NH3 back into the blood)
  • No
What happens to NH4+ in early parts of nephron (before Collecting Duct)?
It is reabsorbed by kidney, into the interstitium, and later secreted back into the lumen at the Collecting Duct.

(It would be bad if it went back to NH3 and was absorbed into the blood by diffusion. Since the collecting duct is very acidic, when NH4+ is secreted back into tubule there, it stays trapped in tubule lumen because NH4+ cannot diffuse back into cell)
Name 4 causes of Metabolic Acidosis? Which 2 are types of Renal Tubular Acidosis?
  • Overproduction of fixed acids
  • Increased extra-renal loss of base
  • Inability of kidney to reclaim filtered bicarbonate (RTA)
  • Inability of kidney to secret enough H+ ions (RTA)

The last two are types of Renal Tubular Acidosis (RTA), which can result from any of the following things:
  • Secreting H+
  • Reclaiming HCO3-
  • Excreting acid and generating new bicarbonate 
What are 3 types of Renal Tubular Acidosis (RTA)? Describe them.
  • Proximal (Type 2)
    -Impaired HCO3- reabsorption in the Proximal Tubule (PT)
    -Lose HCO3- in the urine (every HCO3- lost is H+ gained)

  • Distal (Type 1)
    -Defective H+ ion secretion in the distal tubule
    -Less excretion of acid with titratable acids and NH4+

  • Aldosterone Deficiency/Resistance (Type 4)
    -Impairs H+ secretion, K+ secretion
    -Impairs NH4+ production 
Describe 4 things used to diagnose Renal Tubular Acidosis (RTA)
  • Metabolic acidosis
  • Normal anion gap
  • Serum K+, HCO3-
  • Urine test (urine pH, urine anion gap, urine osmolar gap, urine NH4+, fractional excretion of HCO3-)
Give an equation for Net Acid Excretion

Say something about each of the 3 components of the equation.
Net Acid Excretion = Titratable acids + NH4+ - urinary HCO3-
  • Titratable acids → Can't be regulated
  • NH4+ → Kidneys respond to an acid load
  • Urinary HCO3- → Means that H+ is added to the body
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