Lecture 22-24: Acid:Base Part One Flashcards
What is a strong vs weak acid:
- A strong acid is an acid that completely dissociates in solution i.e the [H+] equals the intial acid concentration. i.e fully ionised HCL-> H+ and Cl-
- A weak acid is an acid that only partially dissociates in solution i.e H2CO3-> H+ and HCO3 (only a small amount of carbonic acid exists as H+ in solution
Describe pH in normal homeostasis
7.35-7.45 for cellular and enzyme function (tightly controlled)
This corresponds to a [H+] ranging from 35-45nMol/L
Where is the acid sources in the body?
Oxidative metabolism: Volatile acid i.e CO2 production
Protein catabolism: Non-volatile / fixed acids that MUST be excreted. Massively increased amounts i.e Lactic acid production (exercise), keto-acidosis = aceto-acetic acid and b-hydroxybutyric acid.
What are the bodies buffering systems?
- Bicarb, instant but limited long term (ECF mainly and most important)
- IC proteins, phosphates
What is acidaemia and alkalaemia?
Acidaemia = pH\<7.35 Alkalaemia = pH\>7.45
Write some notes on acidosis:
pH < 7.35
- pH < 7.2 = severe acidosis
- pH < 6.9 = Usually incompatible with life
Write some notes on alkalosis
pH < 7.45
- pH < 7.6 = severe alkalosis
- pH < 7.9 = Usually incompatible with life
What are the components of acid base balance?.
- Diet
- Blood
- Liver
- Lungs
- Kidneys
i.e Many facets
What are the three mechanisms in which the body prevents dangerous changes in pH?
- Buffers
- Respiratory control of ventilation
- Excretion of acids (or bases) by the kidneys
** Every change of 0.3pH represents a change in [H+] by a factor of 2
What is a buffer?
Buffers are a solution consisting of a weak acid and its conjugate base
- A buffer is a chemical in solution that resits changes in pH i.e mopping up H+
How does a buffer work?
- H+ is added, increasing H+ and lowering pH
- Equilibrium is right shifted
- H+ are consumed by the buffer conjugate base/anion, forming the buffer conjugate weak acid
- [H+] reduces, restoring pH to(wards) normal
What are the four buffers of blood?
Bicarbonate
Haemoglobin
Phosphate (also celllular)
Proteins (also cellular)
Describe how bicarbonate acts as a buffer:
H+ (+) HCO3- H2CO3 H2O (+) CO2
- Carbonic acid only exists in very small amounts
Describe how Hb acts as a buffer:
Hb
- Dissolved CO2 enters RBC, some binds Hb
- Rest becomes HCO3 and H, the H produced is buffered by the Hb whilst HCO3 diffuses into the plasma in exchange for chloride
Describe how phosphate acts as a buffer
H + HPO4 H2PO4
Both phosphate and proteins contribute relatively little to buffering by blood and ECF due to their relatively low concentrations in plasma
Describe how proteins act as a buffer:
H + i.e albumin HA
Both phosphate and proteins contribute relatively little to buffering by blood and ECF due to their relatively low concentrations in plasma
What are other buffers aside from the ones in blood and ECF?
Muscle + liver (H+Cl enter cell and exchanged for cation)
Bone (Usually only in chronic acidosis, but CaCO3 accepts H+ and forms Ca and HCO3)
What equation determines the pH
Henderson-hasselbach equation
pH = 6.74 + log (HCO3/CO2)
Describe the contribution of respiration to acid-base regulation
- CO2 is removed via ventilation
- Oxidative metabolism produces CO2 which forms HCO3 + H in the blood.
- Low pH stimulates ventilation
- Increased ventilation blows off CO2
Increased pCO2 causes acidosis
Decreased pCO2 causes alkalosis
Describe the role of the kidneys in acid- base balance
Metabolism produces H+ and these are excreted into the kidney to balance non-volatile acid generated through metabolism
Kidneys also reabsorb HCO3 and produce HCO3 .
Excess H is buffered by:
- > Phosphate buffers
- > Ammonia buffers
What are the two main renal processes in acid-base balance
- Reabsorption of filtered bicarbonate (includes generation of ‘new’ bicarbonate
- H+ Secretion in distal nephron (DT and CD), principally via ammonia, phosphate
Refer to previous lecture for detailed notes // explain this here
Describe the response of the kidney to an acid load:
- Increased HCO3 and H+ transport along the nephron
- Increased ammoniogenesis
- Increased availability of urinary buffers (mainly via ammonia)
Describe in detail the generation of new bicarb production in the kidney and H secretion:
PCT: CA present on microvilli convert bicarb and acid into CO2 and water. CO2 crosses and in cell is converted back by CA. HCO3+Na symporter on basaloteral reasborbs these into blood. Na/H exchanger pump H back into tubule. (PCT+DCT and CD do this) [reabsorbed]
Production of new HCO3 comes from cellular CO2 production: H is secreted. into tubule lumen. HCO3/Cl exchanger on basolateral membrane. (DCT and CD)
H in tubule combines with HPO4 and NH3.
NH3 is produced by renal cells from glutamine.
What is the rate of HCO3 reabsorption related to?
VIP
Related to arterial PCO2 and is increased by increased adrenal corticosteroids.
i.e in cushings, HCO3 is inversely related to plasma K and Cl.
What is the rate of acid secretion by the kidney influenced by?
- Availability of urinary buffers
- Dissociation constants for those buffers and degree of acidosis
What is the mantra of acid base physiology
Acidity = Bicarbonate / Carbon Dioxide
What happens with respiratory disturbance in acid/base:
Respiratory acidosis = CO2 retention
Respiratory alkalosis = Hyperventilation
What happens in metabolic disturbances acid base physiology
Metabolic acidosis: Increased acid production (low pH) (Low HCO3 as it buffers it)
Metabolic alkalosis: Loss of acid due to vomiting (stomach acid = HCl) (high pH and high HCO3 (from CO2, limitless supply))
If the disorder is respiratory where does compensation occur?
- Compensation is by the kidneys
- This takes days
If the disorder is metabolic where does compensation occur?
- Compensation is by the lungs (+/- kidneys)
- This takes hours
ECF buffering corresponds to the HCO3 bicarb buffer system
Describe the compensation for respiratory disorders:
Ventilatory failure -> Inc. pCO2 -> Dec. pH -> Inc. H+ secretion and NH3 synthesis (Inc. HCO3)
Results in: Acid excretion as NH4
NB: Immediate effect of buffers has been omitted as these would have already occurred
(Process reversed for metabolic alkalosis)
Describe compensation for (non-renal) metabolic disorders:
H+ accumulation via addition of acid or loss of HCO3 (i.e from gut)
Decreased pH, (HCO3 buffers and blunts this) this results in:
-> Inc. ventilation, decreasing pCO2 (develops over hours)
–> Renal compensation develops over days (inc. H+ secretion, inc NH3 secretion = acid excretion as NH4)
= pH return towards normal
(Process reversed for metabolic alkalosis)
Describe compensation for renal metabolic disorders
Loss of HCO3 from kidneys results in H+ accumulation
Decreased pH (HCO3 buffers and blunts this)
=
Increased ventilation (dec. pCO2), pH returns towards normal
RENAL COMPENSATION LIKELY ABSENT FOR RENAL METABOLIC DISORDERS
(Process reversed for metabolic alkalosis)
What is it called be low pH stimulates breathing?
Acidotic breathing
In metabolic acidosis, how does the respiratory compensation function?
Reduction in pCO2 (hours)
Restores the pCO2/HCO3 ratio
In respiratory acidosis, how does the renal compensation function?
Increase in bicarbonate (days)
Restores the pCO2/HCO3 ratio
Summarise the changes in HCO3 and pCO2 in:
- Metabolic alkalosis
- Acute respiratory acidosis
- Acute respiratory alkalosis
- Metabolic acidosis
- Mixed resp and metabolic acidosis
Describe the compensation and pH changes of:
Metabolic acidosis
Resp. alkalosis
Resp. acidosis
Metabolic alkalosis
Whats the role of aldosterone in acid base physiology?
Aldosterone acts on intercalated cells to promote H secretion
This is balanced by greater HCO3 reabsorption. (Cl loss to balance)
It also: ROMK (secretion) and ENAC (Na reabsorption) but these are principle cells
