pH Flashcards
what does pH depend on?
pH depends on the
ratio of [HCO3-] to pCO2
what is the normal range of plasma pH ?
if pH is below this range then it is called?
if pH is above this range then it is called?
7.35 – 7.45
which is a concentration of between 44.5 and 35.5 nmol/L of H+ ions
- below this range, condition is known as acidaemia.
- above this range, condition is known as alkalaemia.
how do the kidneys and lungs work together to control plasma pH ?
Kidneys
• Control pH – variable recovery of hydrogen carbonate and active secretion of hydrogen ions
Lungs
- Alveolar ventilation allows diffusion of O2 into blood and CO2 out of blood – control pO2 and pCO2
- Rate of ventilation controlled by chemoreceptors
effect of alkalemia on Ca+
in alkalosis, there is less H+ available, so the albumin is left with COO- ends,
this attracts Ca+ to leave their solution and binds to it, therefore u get less free Ca+ available!
HYPOCALCEMIA
effects of hypocalcemia
normally resting state of Na+ ions is stabilized by Ca+ ions (preveting free spontaneous depolarization)
paresthesia and tetany
If the pH rises above ______, 45% of patients die
7.55
why does acidaemia cause hyperkalemia?
why is this dangerous?
to compensate for the high levels of acid H+ in the blood,
cells EXCHANGE their K+ with H+, causing high K in blood!
high K+>> arrythemias!
what can increasing H+ ions cause?
can effect enzymes>> binds to proteins & denatures proteins!
this effeects muscle contractility, gylcolysis, hepatic functions!
In acidemia, since the H+ ion concentration in ECF is so low, if we add very small amounts of acid this would change the concentration & pH dramatically.
but this is not the case in our body….why?
bc H+ ions are buffered by binding to various sites.
In acidosis, how is pCO2 is lowered?
what pH does acidosis become fatal?
by increasing ventilation
below 7.0
what is the most important ECF buffer?
The most important ECF buffer is the
CO2/HCO3-
Describe the CO2/ HCO3 buffer system
determined by?
controlled by?
disturbed bh?
how do H+ ions that r produced metabolically, effect the concentration of HCO3-
If H+ ions are produced metabolically ,
they react with HCO3- to produce CO2 in venous blood,
which is then breathed out through the lungs,
leaving a directly proportional deficit of [HCO3-] in arterial blood :(
in alkalosis, when pCO2 may be slightly raised, why is compensation limited?
compensation is limited by hypoxia resulting from hypoventilation.
what does correction of the acidosis or alkalosis depends upon?
the kidney variably excreting or creating HCO3-.
Describe the cellular mechanisms for reabsorption of HCO3- in the proximal tubule of the nephron
Na-K pump, when NA is pumped out> NA inside the cell is LOW> this creates a gradient where Na+ from lumen can now come in!
THIS IS WHAT DRIVES the Na+-H+ exchanger!
ok…moving on to HCO3-….
it is filtered in considerable quantities at the glomerulus – about 180 mmol/hour.
recovering HCO3- on it own isnt enough cuz weyre using it all up in metabolism due to producing acid!!
so reabsorption of all filtered HCO3- is still not enough to restore plasma HCO3-!
SHIIIIIITTT
so HCO3- will have to be created within the kidney.
where is final site for HCO3- absorption and H+ excretion.
what type of cell does this occur in?
Describe the cellular processes
H+ buffered by ammonia and phosphate (‘titratable’)>> bc we dont want our tubules to be too acidic
– Produce NH4+ and H2PO4- which are excreted
A -intercalated cell
how do we produce acid?
how come this does not deplete HCO3-
Normally we produce acid due to metabolism (breakdown if proteins)
This does not deplete HCO3- because:
– The kidneys recover all filtered HCO3-
– Proximal tubule makes HCO3- from amino acids, putting NH4+ into urine
– Distal tubule makes HCO3- from CO2 and H2O; the H+ is buffered by phosphate and ammonia in the urine
How does the kidney make new HCO3-?
where in the kidney does this happen?
PROXIMAL
Break down of a.a> glutamine (Glut):
- alpha-ketoglutorate yields>> 2 HCO3-, which enters the blood , (in effect, this is indirect excretion of H+ attached to ammonia).
- Ammonium is made & dissocites into ammonia and free H+ ions (this must happen cuz we cant have free H+ ions in the blood)
the ammonia ions can cross the membrane & into the lumen & bind to free H+ ions to form AMMONIUM!> IS CHARGED AND TRAPPED IN THE LUMEN!
This process takes place largely in the proximal tubule, but is supplemented distally.
Describe the mechanism of buffering H+ in the urine and explain the concept of titratable acid and the role of NH4+
- free H+ r like little snakes that bite anyone if not captured!*
- so we need to cage them!*
so most of the excreted H+ reacts with buffers and remains in the urine.
One such buffer – monobasic phosphate (HpO-4) becomes more effective as the pH of urine falls (acidic).
ALSO, H+ can bind to ammonia ions in the lumen to make>> AMMONIUM!>>we pee it out!
Overall,
the kidney is able to both recover the filtered HCO3- and replace any, which has been removed from the blood by the buffering of metabolic acid.
cool
In respiratory acidaemia or alkalaemia, how is renal tubular pH probably affected ?
- by changes in the rate of diffusion of CO2 into the cells as pCO2 alter.
- Plasma K+ concentration also influences HCO3- reabsorption and ammonium excretion, so that as [K+] rises, the capacity of the kidney to reabsorb and create HCO3- is reduced.
Hypokalaemia can lead to metabolic alkalosis or acidosis?
metabolic alkalosis
- Hypokalaemia makes the intracellular pH of tubular cells more acidic
- H+ ions move into the cells
- This favours H+ excretion and HCO3- recovery
• Metabolic alkalosis
Describe the Renal Responses to Respiratory acidaemia (acidosis)
u get a fall in renal tubular pH bc of the diffusion of extra CO2 into the cells > leads to increased excretion of H+> with more production and reabsoption of HCO3-,
restoring the ratio of HCO3- to pCO2 nearer to normal
so remember for each H+ secreted, a HCO3- is reabsorbed!
Describe the Renal Responses to Respiratory alkalaemia (alkalosis):
how can Metabolic Acidosis occur
why is it not due to an increase of CO2 levels?
- excess metabolic production of acids, (lactic acidosis, ketoacidosis) > this reacts with and removes HCO3-
- HCO3- is lost
- or there is a problem with renal excretion of acid.
bc that extra Co2 levels is breathed off at the lungs!
what is the anion gap?
how do u calculate it?
The value normally ranges from 8-14 mmol/L and
the reason for this difference is bc not all the anions r measured, there r also other things with negative charges (anions) present (ex: protiens)
Difference between measured cations and anions
([Na+] + K+]) – ([Cl-] + [HCO3-])
exaplain the effects on the kidney if excess acid is produced .
what would happen to the anion gap?
if excess acid is produced, the associated anion (e.g. Lactate) will replace HCO3- in plasma, which will influence the anion-gap.
If HCO3- is replaced by another anion which is not included in the calculation >> the gap will increase.
if u get acidosis bc of a renal cause, what happens to the anion gap?
no change,
cuz if theres somthing wrong with the kidneys, that means theyre not making enough HCO3-, and in this case it is replaced with Cl ions!
& remember lalls, Cl- is one of the measured anions in the anion gap!
Proximal tubule makes HCO3- from _________putting NH4+ into urine
Distal tubule makes HCO3- from________ the H+ is buffered by phosphate and ammonia in the urine
amino acids,
co2 and h20
The main classes of metabolic acidosis and the role of anion-gap in distinguishing between them.
- If HCO3- is replaced by another anion which is not included in the calculation the gap will increase.
- If the problem lies with the renal excretion of H+ ions this will change the [HCO3-] directly without replacement by an unmeasured ion, so the anion- gap is less likely to change.
common causes of metabolic alkalosis,
• In metabolic alkalosis HCO3- is retained in place of Cl-
• Stomach is a major site of HCO3- production
– Severe prolonged vomiting - loss of H+
– Or mechanical drainage of stomach
what if u get metabolic Alkalosis & volume depletion?
why would compensating be difficult in this stage?
in order to maintian blood V. the Na-H exchanger would still keep working (in order to try to reabsorb more Na)
- this will make it difficult to lose the HCO3-,*
- bc it keeps getting reabsorbed!*
common causes of metabolic Acidosis w/ increased anion gap
If anion gap is INCREASED – indicates a metabolic production of an acid
– Keto-acidosis
• diabetes
– Lactic acidosis
• Exercising to exhaustion
• Poor tissue perfusion
– Uraemic acidosis
• Advanced renal failure – reduced acid secretion, build up of phosphate, sulphate, urate in blood
common causes of metabolic Acidosis w/ normal anion gap
If anion gap is normal, it means HCO3- is replaced by Cl-
• Renal tubular acidosis (This is a rare condition)
– Problems with transport mechanisms in the tubules
– Type 1 (distal) RTA – inability to pump out H+
– Type 2 (proximal) RTA (very rare) – problems with HCO3- reabsorption
• Severe persistent diarrhoea can also lead to metabolic acidosis due to loss of HCO3-
– Replaced by Cl-
– Therefore anion gap unaltered
how does DKA cause metabolic Acidosis?
the H iions then use up the HCO3- and uve got ketones left instead of the HCO3- and theyre acting as the anions!
and therefore theyre not measured.
so u get an increase in the anion gap!
conditions that lead to respiratory Acidosis?
• Type 2 respiratory failure
– Low pO2 and High pCO2
– The alveoli cannot be properly ventilated
– Severe COPD, severe asthma, drug overdose, neuromuscular disease
conditions that leads to respiratory Alkalosis?
• Hyperventilation
– Anxiety / panic attacks – acute setting – Low pCO2, rise in pH
• Hyperventilation in response to long-term hypoxia – Type 1 respiratory failure
– Low pCO2 with initial rise in pH
what is the major adaptive response to an increased acid load in healthy individuals ?
Excretion of ammonium
when NH4+ is fromed it is trapped in lumen…why?
cuz its charged, it cant get out!
NH4+ can also be taken up in TAL and transported to interstitium and dissociates to H+ and NH3 lumen of collecting ducts
which one is more life threatening? alkalemia or acidemia?
Acidemia!
where is HCO3- made? controlled?
normal range in blood?
Made in RBC
but controlled in by kidneys!
Normal concentration in arterial blood ~ 25 mmol.l-1
– Range 22 – 26 mmol.l-1
– But can be changed to maintain pH
what controls PCO2 levels?
central chemorecepters!
how many ammonium ions is made fromt he breakdown of glutamine?
2!
H+ ions r buffered by 2 things, name them
H+ buffered by ammonia and phosphate (‘titratable’)
– Produce NH4+ and H2PO4- which are excreted
In the distal tubule (intercalated cells)
why can’t we use the Na-H+ exchanger to get H+ ions into the lumen?
bc we’ve passed the diluting segment of nephron, & lumen now diluted> therefore Na+ gradient in the lumen aint so good
so we use the H+ ATPASE!
which strucutre formed process of breakdown of Glutamine, can freely move across cells? how can it do that?
ammonia!
cuz its uncharged!
what is the minimum PH of urine?
total acid excretion per daY? why is this amount excreted crucial to us?
The minimum pH of urine is 4.5
Total acid excretion = 50 – 100mmol H+ per day
it is needed to keep [HCO3-] normal !
how long does kidney compensation take place
2-3 days!
how do u compensate for metabolic acidosis?
Peripheral chemoreceptor (carotid bodies) detect pH drop
– Stimulate ventilation
– Leading to decrease pCO2
(remember, peripheral can detect pH changes, while the central chemorecpeters detect change in C<span>o2</span> directly)
how do u compensate for metablic alkalosis?
u’d have to reduce breathing …..
but that can be a problem
- Cannot normally be compensated to a great extent by reducing breathing – bc we need to maintain pO2*
- but that should be a problamo for the kidneys, cuz all ut has to do is stop recovering the HCO3-…easy peasy*
how does stomach play a role in making HCO3-?
via alkaline tide!
HCO3- exchanged with CL
so it can make HCL from the H and CL
In DKA, there can be a total depletion of K+
why?
u have lots of glucose in ur urine>> causing osmotic diuresis>> meaning u can loose K+ in the urine!
so if u give a patient insulin>> (insulin casues K+ to move into cells!) tootah likes her king ;P
K can move into cells>> then u would cause HPOKALEMEIA
