Acid-base balance Flashcards
Why is it important to keep the pH in a narrow range?
→ The body has a lot of enzymes which only function at a particular pH
What is the normal pH of body fluids?
→ 7.35-7.45
What are the sources of acid in the body?
→Metabolism of carbohydrates and fats produces CO2
→ CO2 + H2O → H2CO3 → H+ + HCO3-
→ can be removed by the lungs
→ Metabolism of proteins
What does metabolism of proteins generate?
→ Non-volatile (fixed acids)
→ S- containing amino acids → H2SO4
→ Lysine,arginine,histidine → HCl
How do we know that we can control our pH?
→ 156 ml of HCl infused IV into a dog
→ 156 ml of HCl added to 11.4 l of water ( same as body water of dog)
→ Dogs arterial plasma decreased gradually from 7.44 to 7.14 (severe acidosis but survival is possible)
→ pH of water dropped to 1.84 (fatal if in vivo)
What is it about plasma that controls pH?
→ Presence of buffers that are effective in vivo
What is the first line of defense when there is a change in pH?
→ Buffer system in the blood (ICF and ECF)
What is disturbance in H+ compensated for?
→ ICF & ECF buffering systems
→ Respiratory systems
→ Kidney
What is the equation for the bicarbonate system?
→ H+ + HCO3- ⇌ H2CO3 ⇌ CO2 + H2O
What is the equation for the phosphate system?
→ H+ + HPO4 2- ⇌ H2PO4-
What is the equation for protein buffers?
→H+ + Pr - ⇌ HPr
What is pK?
→ The equilibrium point of a buffer
→ Where it most strongly resists changes in pH
→ Near where [acid and base] are equal
What is the range over which a buffer is effective?
→ 1 pH on either side of the PK
If the pK of the phosphate buffer is 6.8 what are the pH ranges over which it is effective?
→ 5.8
→ 7.8
Which buffer is theoretically better and why?
→ Phosphate
→because the PK lies within the body pH ranges
Which buffer is biologically better and why?
→ Bicarbonate
→lungs control PCO2
→ Kidneys control HCO3-
→ Independent controlled regulation of both variables
What is the henderson hasselbach equation used for?
→ Measuring the pH of a buffer system
What is the ratio of [HCO3-]: [CO2]?
→ 24 : 1.2
How do you calculate the concentration of CO2 in the blood if it is a gas?
→ Plasma CO2 is proportional to the partial pressure of CO2
How do kidneys control acid base levels?
→ Excrete acidic or basic urine
What are the primary mechanisms involved in excretion of urine?
→ Reabsorption and secretion of HCO3-
→ Formation of new HCO3-
→ Secretion of [H+] into tubular fluid
→ Buffer systems within the tubule that react with secreted [H+]
What happens to proteins at the glomerulus?
→ They are not filtered and remain in the plasma
What happens to bicarbonate at the glomerulus?
→ Freely filtered
→bicarbonate is reabsorbed from the tubule
→ Kidney generates new HCO3-
→ Released into plasma at a controlled rate
What happens to phosphate at the glomerulus?
→ freely filtered
→ Reabsorbed from the tubule
What does the kidney produce that contributes to buffering other than bicarbonate?
→ HCO3-
What do kidney tubule cells form?
→ carbonic acid from CO2 and water
→ via carbonic anhydrase
What happens to the carbonic acid produced by kidney tubule cells ?
→ dissociates into H+ and HCO3-
→ Na+ moves into the cell down the concentration gradient
→ provides the energy for active secretion of H+ into lumen
How does H+ get into tubular fluid?
→ Na+ moves into the cell down the concentration gradient
→ provides the energy for active secretion of H+ into lumen
What are the 2 ways H+ gets into urine?
→ H+ ATPase
→ while Na+ moves in H+ moves out
What happens to the HCO3- in tubular cells?
→ diffuses out and goes back into blood
→ Via a symporter with Na+ ions
What can carbonic anhydrase be inhibited by?
→ acetazolamide and other thiazide diuretics
Where is most HCO3- reabsorbed?
→ 85-90% at the proximal tubule
→ Secrete H+
What is the balance of bicarbonate?
→for every 1 bicarbonate ion that is filtered
→1 is returned back into plasma
Where is carbonic anhydrase present in the kidney?
→ ONLY in the luminal brush border of the PCT
Flowchart of fate of bicarbonate in PCT
Bicarbonate is freely filtered
↓
Filtered HCO3- combines with H+ to form carbonic acid
↓
Carbonic acid dissociates to form CO2 and H2O this is catalyzed by carbonic anhydrase
↓
CO2 crosses into the tubular cell down a gradient
↓
CO2 recombines with H2O (carbonic anhydrase) to form carbonic acid
↓
Dissociates into H+ and HCO3-
↓
HCO3- passes into the blood stream while H+ is exchanged for Na+
What can the bicarbonate reabsorption also be stimulated by?
→ angiotensin II
What is the pH like in the DCT and why?
→H+ ATPase pumps out the H+
→ DCT has a lower pH
→
What is the pH like in the DCT and why?
→H+ ATPase pumps out the H+
→ DCT has a lower pH
→ HCO3- is low because it has been reabsorbed and H+ needs to react with other buffers
what does HPO4 2- buffer and why is it effective?
→ further H+ secreted into the lumen
→ PK is close to pH of filtrate
Flowchart for fate of H+ with phosphate in intercalated cells
Carbonic acid dissociates into H+ and HCO3-
↓
H+ is secreted via ATPase (aldosterone sensitive)
↓
reacts with phosphate
↓
becomes H2PO4-
↓
excreted into urine because it has a charge
↓
HCO3- reabsorbed with a HCO3- / Cl antiporter
Flowchart for fate of H+ in tubular epithelium, Creation of new Bicarbonate:
Ammonia + a ketoglutarate is produced from glutamine metabolism p
↓
a ketoglutarate is metabolized to form two H2CO3
↓
dissociates to form 2x H+ and 2x HCO3-
↓
H+ combined with ammonia to form ammonium
↓
ammonium is exchanged for Na+ in an antiporter and ammonium is excreted in the blood
↓
HCO3- is reabsorbed into blood
What does the tubular epithelium produce?
→ NH3 from glutamine with glutaminase
Describe the summary of the ion flow through the tubules?
1) reabsorption of bicarbonate
2) formation of titratable acid phosphate
3) ammonia secretion which creates new bicarbonate
What are changes in acid base balance called and what are the two types?
→ acidosis or alkalosis
→ respiratory or metabolic
What are the correction mechanisms for changes in pH?
1) intra and extra cellular buffering
2) respiratory adjustment of ECF PCO2
3) renal adjustment of ECF [HCO3-]
What area regulates respiration and how?
→ chemosensitive area in medulla
→ monitors H+ of plasma via CSF indirectly
→ charged ions cannot cross blood brain barrier but CO2 does
What happens if plasma pH decreases?
→ Plasma PCO2 increases
→ CSF pH decreases
→ Respiratory ventilation increases to remove CO2
How is the change in plasma pH monitored?
→ peripheral chemoreceptors in aortic arch and carotid body
What is metabolic acidosis characterized by?
→ low pH
→ High ECF H+
→ Low ECF HCO3-
What is metabolic acidosis caused by?
→ sepsis or shock - lactic acid increases
→ Uncontrolled diabetes - overproduction of 3OHbutyric acid or ketoacids
→ diarrhoea - loss of HCO3- from GI tract
What happens if there is an increase in H+?
1) ICF and ECF buffers bind to H+ to try and get rid of it
2) if H+ is still high the lungs increase ventilation to remove CO2
3) this compensates for decreased ECF pH
4) kidney increases H+ secretion
5) NH4+ secretion increases - forms new HCO3- ions
What is metabolic alkalosis characterized by?
→ Increase in ECF HCO3-
→ Decrease in ECF H+
What is metabolic alkalosis caused by?
→ Excessive diuretic use → Chronic loss of Cl-, Na+, K+, increase of H+ → Vomiting - loss of H+ → Antacids → Hypokalemia
What happens if there is an increase in HCO3-?
1) ICF and ECF bind to HCO3- to get rid of it
2) if HCO3- is still high the lungs decrease ventilation to increase CO2
3) compensates for increased ECF pH
4) Kidneys decreases H+ secretion
5) decreased HCO3- formation and reabsorption
6) Increased HCO3- excretion
