Acid Base Balance Flashcards
What is the significance of acid base balance?
Very important for normal body functions that [H+]/pH of body fluids is kept relatively constant
Why is pH significant to enzyme function?
Enzymes function at particular pH within a narrow range
What are the consequences of pH disturbances on enzyme function?
Enzymes have lots of functions in body, so disturbances in pH may result in abnormal respiratory and cardiac function, derangements in blood clotting and drug metabolism etc.
What is the normal body pH?
Normal [H+]/pH of body fluids (7.35-7.45)
What is the normal plasma [H+] ?
(40nM)
What is the main source of acid in the body?
metabolism of carbs & fats produces CO2
CO2 + H2O ↔ H2CO3 (volatile acid) ↔ H+ + HCO3-
Why does CO2 production not cause an increase in pH?
CO2 produced as a result of carb metabolism doesn’t usually result in increase in plasma H+ as it is excreted from body via lungs – hence the H2CO3 produced is known as a volatile acid
What is the product of protein metabolism?
Metabolism of proteins generates non-volatile (fixed) acids
S-containing amino acids (cysteine, methionine) ⇒ H2SO4
Lysine, arginine and histidine ⇒ HCl
What is the product of sulphur containing amino acids?
Sulphur containing aa produce sulphuric acid, which is non-volatile – these non-volatile acids need to be removed otherwise will get a net gain of H+
How is pH regulated in the body?
Presence of buffers are effective in controlling changes in pH in vivo
How does the body compensate for pH disturbances?
Disturbance in [H+]/pH compensated for:
- ICF & ECF buffering systems
- Respiratory system
- Kidney
What is the first line of defence against pH disturbance?
ECF and ICF
What is the major extracellular buffer system?
CO2-HCO3- buffer system
CO2 and HCO3- can be regulated independently via this system
How does the respiratory system compensate for pH alterations?
Regulates plasma PCo2 by controlling excretion / retention of metabolically produced CO2 (which is acid component of CO2 - HCO3- buffer system) in response to pH changes
What are the 2 ways the kidneys compensates for pH changes?
Regulates excretion or retention of HCO3- (the basic component of CO2-HCO3- buffer system)
Also regulates regeneration of HCO3-
What are the buffering systems of the blood?
the bicarbonate system
H+ + HCO3- ⮀ H2CO3 ⮀ CO2 + H2O
the phosphate system
H+ + HPO42- ⮀ H2PO4-
the protein buffers (inc haemoglobin)
H+ + Pr- ⮀ HPr
What are the advantages of CO2-HCO3 buffer system
CO2 and HCO3- can be regulated independently
Excretion / retention of CO2 is controlled by lung and reabsorption and regeneration of HCO3- is controlled by the kidney
There’s a readily available supply of CO2 from cellular metabolism
How many buffers are present in the body?
While buffering is the first, and immediate, defense against changes in H+ concentration, the buffers are present in limited quantities
How is the availability of buffer systems maintained?
As buffer capacity is used, less is available to control pH
Respiratory + renal systems eliminate excess H+ or base to restore buffer capacity to normal
Describe the bicarbonate buffer system
Most important is the [HCO3–]:[CO2] ratio
Plasma [CO2] proportional to partial pressure of CO2 (pCO2) in plasma
Constant to convert pCO2 (mmHg) to [CO2] mmol/L is 0.03, hence
How do we measure blood pH?
» measure pH with arterial blood gases (ABG)
What is the pK?
equilibrium constant of reaction
i.e. numerically existing to pH when the concentration of acid=base of that buffer
When are buffers most effective?
Buffer solutions resist change in pH when [base]=[acid]
Buffer is most effective 1pH on either side of pK
what controls PCO2?
Alveolar ventilation controls PCO2
What controls [HCO3-]?
Kidneys control [HCO3–]ECF
Independent regulation
How do kidneys control acid-base balance?
Kidneys control acid-base levels by excretion of acidic or basic urine
What are the primary renal mechanisms involved in acid-base control?
“Reabsorption” and secretion of HCO3-
Formation of “new” HCO3-
Secretion of [H+] into tubular fluid
Buffer systems within tubule that react with secreted [H+]
NH3: NH4+, HPO42-:H2PO4-, HCO3-:H2CO3
How do the kidneys buffering systems work?
HCO3- reabsorbed from tubule
Kidney regenerates new HCO3-; released into plasma
Kidney produces NH3
Protein remains in plasma
Phosphate ions reabsorbed from tubule
How are HCO3- filtered?
Like Na+ and other small solutes, bicarbonate ions are freely filtered by the glomeruli
What is the significance of HCO3- conservation?
If even a small proportion of HCO3- was excreted in urine, normal stores of this important buffer would be quickly exhausted
How is HCO3- excretion prevented?
Prevented by avid tubular reabsorption of HCO3- (>99.9%) sot only 2mmol of HCO3- are excreted in urine each day
Explain renal control of [H+] and [HCO3-]?
- Kidney tubule cells - CO₂ + H₂O = H₂CO₃ via carbonic
anhydrase - Carbonic acid dissociates into H+ and HCO3-
- Na+ moving down it’s conc gradient from tubular fluid →
cell provides energy for secondary active secretion of
H+ into tubule lumen. ATP provides energy for primary
active secretion of H+ from cell into lumen - With each H+ that’s secreted, one HCO3- enters blood
accompanied by Na+ which is swapped for H+ -
buffering in ECF
When is new HCO3- generated?
Only when H+ derived from intracellular H2CO3 is secreted into the tubule and buffered in the tubular fluid by a non-bicarbonate buffer
What is the role of Acetazolamide?
Acetazolamide inhibits H+ formation so tubular fluid acidification doesn’t occur
Leads to inhibition of HCO3- reabsorption leading to acidosis, loss of Na+ which is obligated to the unreabsorbed HCO3- and diuresis
Where does reabsorption of filtered HCO3 occur?
Occurs in the proximal tubule
85-90% of filtered HCO3- “reabsorbed”
Great capacity to secrete [H+]
How is HCO3 reabsorbed?
- Filtered HCO3⁻ combines with secreted H+ =>
H2CO3 - H2CO3 –> CO2 + H2O catalysed by carbonic
anhydrase in luminal brush border of PCT cells - CO2 diffuses into tubular cell down [ ] gradient
- Inside cell, CO2 + H2O due to carbonic anhydrase, to
form H2CO3 - H2CO3 –> HCO3⁻ and H+
- HCO3⁻ passes back into bloodstream
- H+ passes back into tubular fluid in exchange for Na+.
In this way, virtually all the filtered HCO3⁻ is reabsorbed in the healthy individual
Where is urine acidified?
Occurs in Intercalated cells of late Distal tubule and Collecting duct
H+-ATPase pump more important in this part of nephron
Describe the [HCO3-] in the DCT
In distal part of nephron [HCO3-] is low and H+ react with other buffers
What is the significance of the H+/ATPase pump in the distal nephron?
Allows H+ secretion against [H+] gradient acidifying the urine
What is a buffer?
a solution that minimizes change in [H+], usually a base that can accept H+
How can we determine the most effective pH of a buffer system?
Using titration curves
- linear portion = most effective pH (1 pH unit either side of the pK)
How is acidity of the blood recorded clinically ?
as 20;1 ratio of [HCO3-]:[CO2}
What is the activity of the enzyme Carbonic anydrase dpeendent upon?
Carbonic anhydrase activity depends on [H+] in ECF
Where is carbinic anhydrase located in the body?
Only in the luminal epithelial membrane of the proximal tubule
What is the role of the phosphate buffer?
During the acidification of urine, as majority of HCO3- has been used up other buffer systems are used to buffer the H+
Why is the phosphate buffer so effective?
Very effective buffer because pK = 6.8 (close to pH of filtrate)
Describe the sequence of events of the phosphate buffer system
- H2CO3 dissociates
- H+ pumped out via aldosterone sensitive ATPase pump
- H+ reacts with phosphate in lumen
H+ + HPO₄²⁻ → H₂PO₄⁻ maintains a single -ve charge
so is excreted in urine as polar molecules cannot cross
membrane - HCO3- exchanged for Cl- (HCO3-/Cl- exchanger in
intercalated cells) into ECF
Outline how the ammonia buffers work
- Tubular epithelium produces NH3 from glutamine via
enzyme glutaminase - Produces α-ketogluterate + 2NH₃
- α-ketogluterate → 2H₂CO₃ → 2H+ + 2HCO₃-
- H+ + NH₃ → NH₄ which is exchanged with Na via
antiporter - 2HCO₃- reabsorbed into blood via Na driven symporter
Summarise the 3 buffer systems in the kidneys
Reabsorption of HCO3-
Formation of titratable acid phosphate
NH4 secretion creating new HCO3-
How are disturbances in acid-base balance cayegorised?
Acidosis (plasma pH<7.4) or Alkalosis (plasma pH>7.4) Either respiratory (PaCO2) or metabolic (HCO3⁻) > depends on the event which initiates the disturbance
What 3 mechanisms are responsible for correcting changes in pH?
Intra- and extra-cellular buffering
Respiratory adjustment of ECF PCO2
Renal adjustment of ECF [HCO3-]
What is respiration controlled by?
Chemosenstive area in medulla regulates respiration
Monitors [H+] of plasma via CSF indirectly
Why is p not monitored directly by the brain?
Charged ions can not cross Blood Brain Barrier (spinal fluid and brain can’t adjust pH directly so do so indirectly via CO2 (indirectly responds)
Whatcauses metabolic acidosis?
Characterised by low pH as a result of
🡩ECF [H+] or 🡫ECF [HCO3-]
Explain how the regulation of respiration resolves acidosis
- inc. Plasma PCO2
- Detected as 🡫CSF pH and 🡫plamsa pH
- inc. respiratory ventilaton
- dec. Plasma PCO2
- Returning to normal ECF pH
What detects change sin CSF pH?
The medulla
What detects change sin CSF pH?
The medulla
What causes metabolic acidosis?
severe sepsis or shock ⇒ lactic acid
uncontrolled diabetes ⇒ overproduction of 3-OH-butyric acid & other ketoacids
diarrhoea ⇒ loss of HCO3- from GI tract
Explain how the lungs and renal circulation integrate to reduce acidosis
- ICF and ECF buffering
- less [HCO3-] used up to buffer H+
- [H+] remain high
- Lungs
- increased Ventilation
- decreased pCO2 (compensates 🡫ECF pH)
- kidneys
- more H+ secretion into urine
- more NH4- secretion
- more New HCO3- formation
- more HCO3- reabsorption
- (compensates low ECF pH)
What is metabolic alkalosis?
Characterised by high pH caused by
high ECF [HCO3-] or low ECF [H+]
What is metabolic alkalosis caused by?
Excessive diuretic (thiazide) use ⇒ chronic loss of Cl-,Na+ & K+ ⇒ increase H+ secretion
Vomiting ⇒ loss of H+ from GI tract
Ingestion of alkaline antacids
Hypokalemia
How does alkalosis effect urine?
During alkalosis urine = alkaline due to presence of HCO3-
Normally urine = acidic as HCO3- is destroyed
How do diuretics lead to alkalosis of the urine?
Diuretics such as frusemide and thiazides interfere with reabsorption of Cl- and Na+ in renal tubules
Outlin ehow renal and lund lung compensate in response to alkalosis
- ICF and ECF buffering
- less [H+] as its used up
- inc. [HCO3-] remains high
- Lung
- dec. ventilation
- high pCO2 (compensates for inc. ECF pH)
- Kidneys
- less H+ secretion into urine
- less NH4- secretion
- less HCO3- formation and reabsorption
- more HCO3- excretion
- (compensates for increased ECF pH)
What causes respiratory acidosis?
Hpoventilation due to actions of drugs (anaesthetics/barbiturates)
Chronic emphysema
Bronchitis
Why do lung conditions cause acidosis?
These conditions impair CO2 removal from lungs, causing a build up in plasma
CO2 enters cells rapidly and they contain CA so get rapid rise in H+
How is respiratory acidosis resolved?
↑[H+] buffered by proteins in plasma
(within hours) ⇒ ↑[HCO3-]
Within days kidney compensates by stimulating H+ secretion & increasing HCO3- reabsorption
Explain why respiratory alkalosis occurs
Less CO2 enters cells and less HCO3 diffuses out into plasma so [HCO3] is reduced
How is respiratory alkalosis resolved?
Within days kidney compensates by reducing H+ secretion & decreasing HCO3- reabsorption
