week 4 Flashcards
H+ donator
acid
H+ acceptor
base
why is regulation of [H+] important
proteins eg enzymes are influenced by pH
at physiological pH most biosynthetic and metabolic pathways involve precursors which are ionised - degree of ionisation determines location of molecules in cells and organelles
deviation of pH hugely impairs cellular and metabolic function
acid-base disorder examples
cardiovascular - BP, cardiac rhythm respiratory - ventilation, resp rate metabolic - protein wasting, bone renal - electrolytes GI neurological - confusion, seizures
what can alter homeostasis and the acid-base balance
generation of CO2 from aerobic respiration
metabolism of foods generating acid or alkali
incomplete respiration producing lactic acid or keto-acids
loss of alkali in stool or loss of acid in vomiting
3 major components of acid-base regulation
buffering
ventilation - control of CO2
renal regulation of HCO3 and H+ secretion and reabsorption
how could [H+] be normal in an acid-base disturbance
happens at the expense of other blood chemistry eg [HCO3-] or pCO2
what are buffers and how do they work
buffers are weak acids, partially dissociated in solution
buffers react poorly with water and are available to react with either H+ or OH-
CO2 - HCO3 equation
CO2 + H2O H2CO3 HCO3 + H+
can simplify
CO2 + H2O HCO3 + H+
CO2 - HCO3 system
CO2 + H2O H2CO3 HCO3 + H+
CO2 is highly diffusible and is regulated by respiration so [CO2] is held constant
addition of H+ consumes HCO3 which generates CO2 and water - CO2 exhaled - little free H+
loss of H+ leads to the opposite
at physiological pH, [HCO3-]:[H2CO3] = 20:1 so the system effectively buffers H+
does not buffer CO2a
buffers other than HCO3
haemoglobin - buffers CO2 in blood
proteins - important intracellular buffer
bone - long term buffer
PO4 - intracellular and urinary buffer
volatile acid v fixed acid
volatile acid can be eliminated from the body as a gas
buffering a fixed acid
consumes HCO3
although CO2 will be ventilated, this will be at the expense of lowered [HCO3] - to remove the H+ effectively more HCO3 must be generated
how do the kidneys regulated acid-base balance
reabsorb filtered HCO3
secrete fixed acid: (two below - these remove volatile acid from body)
titrate non-HCO3 buffer in urine - primarily PO4
secrete NH4 into urine
all achieved by using selective permeability of the luminal and baso-lateral cell membranes to match transport of H+ and HCO3 in opposite directions
describe the reabsorption of filtered HCO3
active process largely in PCT with small contributions from TALH and DCT - consumes large amount of energy
maintaining acid-base homeostasis requires that virtually all filtered HCO3 is reabsorbed
inability to reabsorb filtered HCO3 is a cause of metabolic acidosis
no net loss of H+ or gain of HCO3
excretion of acid in kidneys
require to eliminate fixed acid
tubular cells generate a new HCO3 which is absorbed along with a H+ that binds to a base other than HCO3 - or is fixed with NH3
this takes form of either titration of filtered PO4 or secretion of NH4 into urine
titration of PO4 is dependent on delivery of filtered buffer and is relatively fixed
mechanism of NH4 excretion is complex but is able to be up-regulated in acidosis
failure to secrete H+ is a cause of acidosis
titration of phosphate in the excretion of acid
PO4 is the major non-HCO3 buffer in urine
delivery of PO4 is not amenable to much regulation but completeness of titration depends on urine pH
accounts for excretion of ~40mmol H+/day
excretion of ammonium in the excretion of acid
regulated by metabolism of glutamine
acidosis stimulates glutamine transport and oxidation
in normal conditions, generation of NH4+ accounts for 50-100mmol H+/day but can be increased
[H+] in acid-base disorders
primary disturbance which tends to make [H+] abnormal
acute change will be buffered - compensatory response so that [H+] remains in the normal range but will be at the expense of HCO3 or CO2
how do metabolic disorders alter [HCO3]
metabolic acidosis - decrease in [HCO3] and so a decrease in pH
metabolic alkalosis - increase in [HCO3] and so an increase in pH
how do respiratory disorders alter [CO2]
respiratory acidosis - increase in [CO2] so decrease in pH
respiratory alkalosis - decrease in [CO2] so an increase in pH
which disorders can increase H+
metabolic acidosis and respiratory acidosis
which disorders can decrease H+
metabolic alkalosis and respiratory alkalosis
approach to diagnose an acid-base disorder
initial clinical assessment - from history and examination and initial investigations make a clinical decision on what it is most likely to be
acid-base diagnosis - systemic evaluation of the blood gas and other results and make an acid-base diagnosis
synthesise info to make overall diagnosis
respiratory acidosis and link to COPD
condition where pCO2 rises due to increased generation of CO2 and reduced ventilation of CO2
in COPD;
reduced central sensitivity to hypoxia and hypercapnia
destruction of lung tissue causes ventilation/perfusion mismatch
respiratory muscle fatigue
how does the body compensate in respiratory acidosis
cause is respiratory so compensatory response is metabolic
acute phase - buffering
chronic phase - compensation
buffering respiratory acidosis
CO2 + H2O H2CO3 HCO3 + H+
addition of CO2 drive reaction to right generating H+
acute rise in H+ is buffered by protein (Hb and phosphate) leaving behind HCO3 which rises slightly
Compensating respiratory acidosis
effect of increased arterial pCO2 is to promote renal retention of HCO3
increase in ammonium excretion
causes of metabolic acidosis
addition of extra acid: generation of organic acid through metabolism eg lactic acidosis or keto-acidosis ingestion of acid failure to excrete acid: renal tubular acidosis loss of HCO3: in stool (diarrhoea) or urine compensatory response is fall in pCO2 due to respiratory drive
systemic effects of metabolic acidosis
specific symptoms relating to cause
CVS - arrythmias, increased cardiac contractility, vasodilation
respiratory - increased ventilation
metabolic - protein wasting, resorption of Ca from bone
lactic acidosis
lactic acid produced through glycolytic metabolism of pyruvate
buffered by HCO3 to lactate and then metabolised in liver (and kidney)
production of lactic acid is vastly greater than renal excretion of H+
acidosis usually results results from hypoperfusion and reduced hepatic clearance - occurs in sepsis
can occur due to drugs, liver failure, poisoning