H+J. Lecture 28+29 Regulation of acid-base balance Flashcards
do acids accept or yield protons?
yield
do bases accept or yield protons?
accept
do strong acids/bases dissociate more or less in solution compared to weak acids/bases?
dissociate more
do strong or weak acids liberate more protons?
strong
do strong or weak acids buffer more protons?
weak
what is the equation for the dissociation constant?
(proton conc x conjugate base conc)/ (conc of undissociated acid)
what is the equation for pH?
-log10[H+]
what happens to [H+] as pH goes down/more acidic?
it increases
what is the [H+] in ECF?
around 4 x 10-8 M
what is the pH of arterial blood?
around 7.45
what is the pH of venous blood?
around 7.35
what is the pH range compatible with life?
6.8-8.0
what happens outside the pH range of 6.8-8.0?
death
what is pH less than 7.35 called?
acidosis
what is pH more than 7.45 called?
alkalosis
what 3 things can small changed in pH affect?
Nerve excitability
Enzyme activity
K+ homeostasis
what affects does acidosis have on CNS activity?
decreases it
what can acidosis lead to?
disorientation, coma, death
what affects does alkalosis have on CNS activity?
increases it
what can alkalosis lead to?
pins/needles, muscle twitch, death
what are enzymes?
proteins that are made from AAs
what are AA R-groups?
titratable side-chains
why is R-group charge vital?
to correct folding
why is the 3D shape of enzymes vital?
for functioning
are proton handling and K+ secretion linked?
yes
what effect does acidosis have on secretion of H+?
increases it
what does an increase in secretion of H+ result in?
decrease secretion of K+
what does a decrease secretion of K+ lead to?
hyperkalaemia
what does hyperkalaemia cause?
depolarisation of excitable cells
what are the 2 sources of acids and bases?
food and metabolism
how are proteins a source of acids?
contain phosphorus and sulphur, converted to phosphoric and sulphuric acid (strong acids)
what does fruit digestion yield?
release of bases
what is released from fat metabolism?
fatty acids
what type of acids are fatty acids?
Weak acids, yield protons
what is produced from anaerobic glycolysis?
lactic acids
what type of acid lactic acid?
Weak acid, yields protons
what is CO2 from respiring cells hydrated to form?
carbonic acid
is carbonic acid a strong or weak acid?
weak
what is the formation of carbonic acid catalysed by?
carbonic anhydrase
is the formation of carbonic acid reversible?
yes, at the lungs
what produces vast quantities of carbonic acid?
respiring cells
what are the 3 mechanisms of maintaining acid-base balance?
Blood buffers
Respiratory compensation
Renal compensation
how long do blood buffers take to work?
seconds
how long does respiratory compensation take to work?
minutes
how long does renal compensation take to work?
hours to days
what is a buffer?
weak acid or base
can buffers absorb protons?
yes
is blood buffering effective?
yes, very effective
what is the main blood buffer?
bicarbonate
is H2CO3 difficult to measure?
yes, very difficult to measure
what does the relationship of CO2 and H2CO3 in solution depends on?
partial pressure (Pco2) and its solubility
what is the equations for pK?
-log10K
what is the Henderson-Hasselbalch equation?
pH = pK + log10([HCO3-] /alphaPco2)
what does blood pH depend on?
HCO3- and CO2 concentration
what can be altered to regulate pH?
CO2
HCO3-
how is CO2 regulated?
by the lungs
how is HCO3- regulated?
by the kidneys
how can conditions be diagnosed clinically?
by measuring H-H equation parameters
what effect does respiratory acidosis have on CO2?
increases it
what affect does increased CO2 have on bicarbonate?
increases it
what affect does increased bicarbonate have on H+?
increases it
what affect does increased H+ have on pH?
decreases it
what effect does respiratory alkalosis have on CO2?
decreases it
what affect does decreased CO2 have on bicarbonate?
decreases it
what affect does decreased bicarbonate have on H+?
decreases it
what affect does decreased H+ have on pH?
increases it
what affect does metabolic acidosis have on pH and bicarbonate?
add acid, decreases them
what affect does metabolic alkalosis have on pH and bicarbonate?
add base, increases them
what are the 3 other buffering systems, apart from bicarbonate?
Haemoglobin
Plasma proteins
Phosphate
what does haemoglobin buffer metabolically to produce?
CO2
what are the H+ mopped up by?
reduced haemoglobin (Hb)
what happens to Hb after O2 delivery to cells?
it is reduced
is O2 low or high in the lungs?
high
what does high O2 in the lungs do?
liberates CO2, removing the excess acid
In ECF, what is made possible by proteins
small amount of buffering
what are proteins composed of
AAs which contain acidic and basic R groups and are amphoteric
are carboxyl R groups strong or weak acids or bases
weak acids
Amino R groups strong or weak acids or bases
weak bases
why do phosphate play a minor role in ECF
due to relatively low concentration
when is phosphate a good urinary buffer and why
under normal conditions as there is little reabsorption
what is the Henderson-Hasselbalch equation
pH = pK + log10([HCO3-]/αPco2)
what does the Henderson-Hasselbalch equation predicts in Respiratory compensation
predicts that if the pH decreases then it is likely that the Pco2 will be increased
is the CO2 solubility (α) high or low in Henderson-Hasselbalch equation
low (0.03)
what is increased Pco2 detected by
Central chemoreceptors
Peripheral chemoreceptors
where are Central chemoreceptors located
brainstem
where are Peripheral chemoreceptors located
aortic arch
what happens if the pH drops
CO2 is increased
what detects a pH decrease
Detected by brainstem/peripheral chemoreceptors
what occurs if the pH drops and CO2 is increased
Causes increased ventilation to blow off CO2
when ventilation occurs to blow off CO2, what then happens
increases blood pH
negative feedback
what does the Henderson-Hasselbalch equation predicts in Renal Compensation
predicts that if the pH decreases then it is likely that bicarbonate will be decreased
how can the kidney compensate by
by regulating bicarbonate reabsorption and proton secretion
what is Renal Compensation more efficient at
restoring pH balance
For every bicarbonate absorbed how many H+ secreted into urine
1
In respiratory compensation, how is pH regulated
by change in CO2
how happens to Plasma [H+] in acidosis Renal Compensation
Plasma [H+] is increased
why is less HCO3- filtered in acidosis Renal Compensation
filtered as it is buffering the increased H+
why does urine becomes more acidic in acidosis Renal Compensation
Renal H+ secretion increases
how happens to Plasma [H+] in alkalosis Renal Compensation
Plasma [H+] decreases
why is less HCO3- filtered in alkalosis Renal Compensation
as it is less required for buffering
why is not all HCO3- reabsorbed in alkalosis Renal Compensation
because H+ availability is rate limiting
what happens to urine in alkalosis Renal Compensation
urine becomes more alkaline
what must be maintained
to acidify urine during acidosis
gradient for H+ secretion
what helps to maintain the gradient of H+
If H+ is mopped up by buffers in urine
what is secreted H+ buffered by
Phosphate and Ammonia
what happens too Phosphate In acidosis
capacity is exceeded
what does ammonia + proton make
ammonium ion
where is ammonia secreted
in the kidney
is ammonia weak/strong acid/base?
Weak base
what is Ammonia produced from
glutamine metabolism
when is Production of Ammonia up-regulated
during acidosis
what does Ammonia in collecting ducts do
mops up urinary H+ during acidosis
what does an acid-base disturbance affects
pH, Pco2 and/or [HCO3-]
at least 2 out of 3 of them
when does Compensation comes into play in an acid-base disturbance
immediately
what does Compensation correct in an acid-base disturbance
Corrects pH change only
what is sacrificed in Compensation in an acid-base disturbance
Pco2 and HCO3- sacrificed to restore pH
what does Correction correct in an acid-base disturbance
Complete restoration of pH, Pco2 and HCO3-
4 types of of acid-base balance disorder
Respiratory acidosis
Respiratory alkalosis
Metabolic acidosis
Metabolic alkalosis
what is a change in pH that has a respiratory cause associated with
abnormal Pco2
what does an abnormal Pco2 gives rise to
gives rise to a change in carbonic acid-derived H+
what is a change in pH that has a metabolic cause associated with
altered [HCO3-] as a result of the participation of HCO3- in buffering abnormal [H+]
Respiratory Acidosis cause
Retention of CO2 (hypoventilation)
Respiratory Acidosis uncompensated result
pH decreases, HCO3- increases
Respiratory Acidosis compensated result
Increased reabsorption of HCO3-
Secretion of ammonium
HCO3- remains elevated
Acute intracellular buffering in Respiratory Acidosis time course
seconds or minutes
Chronic renal compensation in Respiratory Acidosis time course
days
3 Clinical causes of Respiratory Acidosis
Drug-induced depression of respiratory centres
Pulmonary oedema
Emphysema
Respiratory Alkalosis cause
Loss of CO2 (hyperventilation)
Respiratory Alkalosis uncompensated result
pH increases, HCO3- decreases
Respiratory Alkalosis compensated result
Decreased reabsorption of HCO3-
Decreased secretion of ammonium
HCO3- remains depressed
Acute intracellular buffering in Respiratory Alkalosis time course
seconds or minutes
Chronic renal compensation in Respiratory Alkalosis time course
days
4 Clinical causes of Respiratory Alkalosis
Anxiety, fear
Pain
Aspirin poisoning
High altitude
Metabolic Acidosis cause
Loss of HCO3- or addition of H+ to plasma
Metabolic Acidosis Uncompensated result
pH decreases, HCO3- decreases
Metabolic Acidosis compensated result
Respiratory compensation (increased ventilation) partially restores pH
Renal compensation completes the restoration of pH by increasing reabsorption of HCO3-
Acute respiratory of Metabolic Acidosis Time course
seconds or minutes
Chronic renal compensation of Metabolic Acidosis Time course
days
4 Clinical causes of Metabolic Acidosis
Diabetic keto-acidosis (abnormal fat metabolism)
Diarrhoea (loss of HCO3-)
Heavy exercise (addition of lactic acid)
Renal failure (reduced secretion of protons)
Metabolic Alkalosis cause
Addition of HCO3- or loss of H+ from plasma
Metabolic Alkalosis Uncompensated result:
pH increases, HCO3- increases
Metabolic Alkalosis compensated result
Respiratory compensation (increased ventilation) partially restores pH (C)
Renal compensation completes the restoration of pH by decreasing reabsorption of HCO3-
Acute respiratory in Metabolic Alkalosis Time course
seconds and minutes
Chronic renal compensation in Metabolic Alkalosis Time course
days
2 Clinical causes of Metabolic Alkalosis
Ingestion of antacids
Vomiting (loss of HCl)
what is respiratory compensation response limited by
hypoxaemia which counteracts response via chemoreceptors
what is the most effective at causing compensation
the renal response of in metabolic alkalosis