Acid-base balance Flashcards
Types of acid
Strong acid: completely dissociates in solution, releasing large amounts of H+. Protein metabolism generates strong acids.
Weak acids only partially dissociate and is in equilibrium with its conjugate base. Forms a buffering pair that can respond to changes in [H+]
What is acid-base homeostasis?
Regulation of [H+]
Balance of intake, production and excretion required to maintain homeostasis. Important because H+ are small charged particles which can alter protein function and activity
Sources of H+ ions in the body
Volatile acids generated from aerobic metabolism and CO2 production by tissues. These leave solution and enter teh atmosphere to be excreted by the lungs
Non-volatile acids are generated from metabolic processes e.g. lactic acid, sulphuric acid. These are quenched by binding to HCO3- and are secreted by the kidneys
Three main mechanisms to minimise changes in pH
Buffer systems:
Rapid chemical reactions that reversibly bind to H+ ions at equilibrium to minimise sudden changes in pH. Unable to change overall [H+] in the body.
Lungs: rapidly adjust the excretion of CO2
Kidneys: Slowly adjust the excretion of H+ into the urine and alter HCO3- levels in the body
Three main buffer systems in the body
Phosphate: H2PO4- ► HPO42- + H+ (intracellular and urine)
Protein: Pr- + H+ ► HPr (intracellular)
Bicarbonate: H+ + HCO3- ► H2CO3 (extracellular)
Name two protein buffers
Albumin
Haemoglobin
How does the HCO3- system prevent changes in pH?
HCO3-/CO2 buffer system is controlled by the lungs and kidneys. Its components can be added or removed from the body at controlled rates.
Allows the body to respond to changes in pH by increasing ventilation or excretion via the kidneys (compensation).
Lungs respond rapidly, kidneys have a slower response (alter HCO3- production and H+ exceretion)
How to the lungs prevent changes in blood pH?
CO2 produced in metabolism enters the capillary blood where it reacts with water to form HcCO3. This dissociates instantly to yield H+ and HCO3-. The reaction is catalysed by carbonic anhydrase. In the lungs, the reactions reverse and H2CO3 is converted to CO2 which is expired.
A fall in blood pH (high H+) stimulates ventilation by acting on chemoreceptors in the medulla. This increases expiration and thus CO2 release, making the blood less acidic.
What are teh two main processes by which the kidneys regulate extracellular fluid pH
Synthesis and reabsorption of filtered HCO3-
Excretion of H+ via urine
How is HCO3- reabsorbed in the PCT?
Glomeruli filter HCO3- ions into the nephron. Urinary loss of these ions would lead to an increase in blood pH and impair the body’s ability to buffer H+ ions produced by metabolism.
90% of filtered HCO3- is reabsorbed in the PCT. H+ is secreted into the tubule via a Na/H+ exchanger on the luminal membrane. This binds to HCO3- to form H2CO3. Carbonic anhydrase type IV on the luminal membrane catalyses dehydration to CO2 and H2O.
CO2 diffuses back into the tubular cells and is converted to H2CO3 by type II carbonic anhydrase which dissociates into H+ and HCO3-.
The HCO3- is transported into the interstitial fluid by a Na-exhanger and H+ is pumped into the lumen.
How is HCO3- reabsorbed in the distal and collecting tubules?
Collecting duct cells have principal cells and intercalated cells (alpha and beta).
Principal cells secrete H+ via an H+ATPase (stimulated by aldosterone)
Water and CO2 is converted to H+ and HCO3- by carbonic anhydrase in the alpha intercalated cells.
The alpha cells have a H+ATPase which removes H+ from the cells into the lumen of the tubule and a H+/K+ATPase which pumps K+ into the cell to balance the charge.
HCO3- is pumped out of the cell via a HCO3-/Cl- anion exchanger.
How is H+ secreted in the distal tubules and collecting ducts?
The distal nephron secretes H+ ions via an H+ATPase or H+/K+ATPase. It is lined by tight epithelia so that secreted H+ ions diffuse out of the tubule which maintains a steep concentration gradient.
CO2 produced by metabolism diffuses into the cell and is converted to HCO3- and H+ ions. HCO3- is removed from the cell by a HCO3/Cl exchanger and H+ is pumped out by the ATPase.
The ATPase produces a minimum urinary pH of 4.5, once the luminal pH is below 4.5 the ATPase will not function. Urinary buffers (PO4 and NH3) help maintain a higher pH that enables the ATPase to function.
What are the two main urinary buffers?
Phosphate: has two forms, HPO42- and H2PO4- which form a buffer pair in the tubular fluid. Excess H+ in the lumen is bound and excreted in the urine.
Ammonia: Synthesised from breakdown of glutamine in PCT forms a buffer pair as NH3 and NH4+. Secreted mainly in the collecting duct and picks up excess H+ which is excreted in the urine.
Describe the how phosphate buffers aid urinary excretion of H+ ions
When urine is being formed there is more HPO4 than phosphoric acid (H2PO4).
Addition of H+ ions bind with HPO4 to form H2PO4 and H+ is excreted
Describe the production and exretion of ammonia by the nephron
Glutamine is metabolised to NH4+ and HCO3- in the PCT.
NH4+ is secreted into the lumen, and HCO3- enters the blood. The NH4+ ions are reabsorbed in the loop of Henle by the thick ascending loop and accumulated in the medullary intersitium where is forms a buffer pair (NH3>NH4+).
NH3 diffuses into the tubular fluid of the collecting but, and binds to H+ that has been secreted to form NH4+. This accumulates in the lumen and is excreted in the urine.
The ammonia buffer system can respond to the body’s acid-base status. A decrese in pH stimulates renal glutamine metabolism, increasing H+ excretion and HCO3- production and reabsorption. This is why renal respones are slower than the lungs.
