Acid base physiology Flashcards
What are acids?
Strong acids rapidly dissociate releasing large amounts of H+
E.g. HCl
Weak acids partially dissociate, releasing less H+
E.g., carbonic acid (H2CO3)
What are the types of bases?
Strong bases react rapidly and strongly to neutralize H+
-e.g. hydroxyl (OH-)
Weak bases
Weak bases bind H+ much more weakly
E.g. bi arbonate (HCO3-)
What is the acid dissociation constant?
The ratio of the concentrations of conjugate base and conjugate acid to the acid in question, in an aqueous solution, is called the dissociation constant (Ka)
The higher the acid dissociation constant the more an acid is ionized in aqueous solution and the greater is its strength
Weak acids (Ka)-lactic acid, carbonic acid, ammonium ions
Strong acids- HCl, H2SO4, H3PO4^-
What is the logarithmic expression of Ka?
The value of pKa, depends on the concentrations of acid and conjugate base in solution after the acid dissociation has achieved equilibrium. Thus value is converted to a long form because the acid dissociation constants can vary widely and can be very small numbers
pKa= -log (Ka)
In any aqueous solution the pKa of an acid can vary with temperature and with ionic strength of the solution. There is an inverse relationship between the pKa and the acid strength
A strong acid has a high Ka but a low pKa
A weak acid has a low Ka but a high pKa
What are the two forms of acid from metabolism?
Volatile and non-volatile/fixed
What are volatile acids?
E.g. carbonic acids (H2CO3^-)
This acid is in equilibrium with CO2 (300 mL produced daily from metabolism)
-concentrations of this acid can be controlled by the respiratory system
What are non-volatile/fixed acids?
E.g. lactate, acetoacetate, phosphoric acid, sulfuric acid non-carbonic
Cannot be directly affected by respiratory activity
- These are produced from incomplete oxidationof carbohydrate and fat metabolism
- These are therefore buffered by the body and excreted via the kidney
What is optimal pH?
6.8-7.8
What is acidosis?
Decreased pH or increased protons
What is alkalosis?
Increased pH/. decreased protons
What is pH determined by?
So pH is determined by the ratio of acid and base
E.g. Plasma pH is a simple function of the HCO3^-: PCO2
(Carbonic acid -H+ and HCO3^- CO2 and H2O
Discuss how chemical buffers regulate pH
A mixture of a weak ac8d and its conjugate base or weak base and its conjugate acid makes up a chemical buffer
A pH buffer is any substance that minimizes the change in pH produced when an acid or base is added
Note: it DOES NOT prevent the pH change
Buffers only promote the stability of pH
What are the buffer systems?
- HCO3^-/CO2 pH= 6.1 24 mEq
- H2PO4/HPO4^2-
- Proteins- most Importent is hemoglobin
HCO3^- is the better buffer because
- The pK is lower than H2PO4
- it is more abundant in the body
- The conjugate acid is CO2 which is volatile and can be expired by the lungs
Explain acid handling
- Cells: buffers bind to the proton and prevent them from entering cell. Cells also uses transporters to regulate intracellular pH
- Lungs(respiratory): CO2 produced diffuses from intracellular into vasculature. Transported bound to Hb. RBCs convert CO2 and H2O into HCO2^- and H+. Pulmonary epithelia converts it back to CO2 and H2O
- Kidneys (renal): H+ from protein metabolism is pumped into the renal tubule lumen and excreted in urine. Buffers protect renal epithelium. Renal epithelium generates HCO2^- and releases it back to vasculature to be transported to the sites of increased H+. H+ formed is excreted
What are the 3 primary systems for regulating acid handling?
- Buffer response- Found in Extracellular and intracellular fluid and bone. First line of blood pH defense. IMMEDIATE RESPONSE. Minimizes change but does not remove acid or base from the body
- Respiratory response- 2nd line of defense. Breathing as a means of removal of CO2 very quickly (respiratory compensation). This lowers arterial carbonic acid levels and thus increases pH. FEW MINUTES RESPONSE.
- Renal response-3rd line of defense. H+ ions are excreted with urinary buffers. At the same time, the kidneys add new HCO3^- used to buffer strong acids. DAYS TO RESPOND, BUT IS THE MOST POWERFUL
What is respiratory response?
Allows for reflex changes in ventilation to help defend blood pH
Changes in PCO2 and hence H3CO2 in the blood
-A fall in blood pH(increased arterial blood PCO2)
- Stimulates increased ventilation via action on central and peripheral (primary one) chemoreceptors
- When ventilation is stimulated, the lungs blow off more CO2 making the blood less acidic. One the other hand, a rise in blood pH inhibits ventilation.
Respiratory responses to disturb blood pH begins within minutes and are maximal in about 12-24 hours
Explain the respiratory regulation
The second line of defense against acid base changes up is control over ECF CO2 concentration by the lungs. Normal pulmonary function balances CO2 excretion with metabolic CO2 production. Increased ventilation decreases ECF [H+] (raises pH]
, whereas decreased ventilation increases ECF [H+] (lowers pH). These changes occur rapidly through the bicarbonate buffering equilibrium
Explain the ventilation rate responds strongly to acidemia
Not only does the alveolar ventilation rate influence pH by changing PCO2 but the pH in turn affects the rate of ventilation. The figure shows that an acid stimulus is especially effective at increasing the rate of ventilation and CO2 elimination. Recall that the presence of H+ sensors in peripheral chemoreceptors should prevent acidemia resulting from volatile acid (CO2) accumulation, assuming there is normal pulmonary function
Summarize renal response
They remove excess H+ or excess HCO3^-
HCO3^- buffer string acids produced by metabolism. The kidne6s then remove excess H+ via the urine and it also restores the depleted HCO3^- that was used to buffer the acids.
Most of the H+ ions are not excreted in their free form. But are combined with urinary buffers to be excreted as titratable acids and as ammonium (NH4)
Regulate ECF H+ concentration through 3 mechanisms:
- secretion of H+
- Reabsorption of filtered HCO3^-
- production of new HCO3 ^- (via ammonia/titratable acid excretion)
What are titratable acids?
This represents the amount of H+ ions that are excreted through combination with urinary buffers e.g. phosphate, creatinine, etc.
Largest component is phosphate (H2PO4)
-Ammonia(NH4)- accepts free hydrogen ions in the urinary tubules and is excreted as (NH4+) ammonium
(Not measured. As a titratable acid but use another method to measure- calorimetric /enzymatic)
Describe the ammonium buffer
H+ ions are added to the filtrate as it flows along the nephron. (Urinary acidification)
- Filtered HCO3^- is reabsorbed
- Titratable acid is formed
- Ammonia is added to the tubular fluid (NH3+ H+= NH4+)
- At th3 end of PCT tubular pH falls to about 6.7
- Most of the H+ ions secreted by the nephron occurs in the PCT and are used to bring about the Reabsorption of filtered HCO3^-
Explain secretion of H+ in the tubules of the nephron
PCT- Na+/H+ exchanger, H+/ATPase (luminal side), also produce ammonia from amino acid glutamine
Loop of Henle- descending limb- pH rises (H2O reabsorbed and bicarb left in the tubule). Ascending limb-Na+/H+ exchanger (thin). Na-K- 2Cl cotransport (thick ascending)
Distal nephron- fewer H+ ions secreted via electro genie H+-ATPase or electro neutral H+/K+-ATPase
Collecting duct- alpha -intercalated cells secrete H+ ions
Explain how aldosterone stimulates tubular H+ secretion
- Alpha intercalated cells of collecting duct -it directly stimulates H+ ATPase
- Collecting duct- enhances sodium Reabsorption which promotes H+ secretion by the electro genic H+ ATPase
- It promotes K+ secretion. Hypokalemia will result and renal H+ secretion will increase (K+/H+. antiport)
Summarize Renal HCO3^- resorption
Kidney recover filtered HCO3^- and return it to the blood.
Reabsorbed indirectly via H+ secretion
Proximal convoluted tubule
Luminal side: 90% HCO3^- is reabsorbed via conversion by carbonic anhydrase when the H+ ions are secreted (luminal side)
Basolateral side: HCO3^- /Na+ transport and HCO3^-/Cl- exchanger
What is the normal arterial blood plasma?
Mean- 7.4
Range- 7.35-7.45
What is normal arterial blood plasma H+?
Mean-40
Range- 35-45
What is normal blood arterial plasma PCO2( mmHg)?
Mean- 40
Range- 35-45
What is the normal arterial blood plasma [HCO3^-] (mEq/L)?
Mean- 24
Range- 22-26
What is the three question method?
What is this oasis?
If pH is below 7.35, then acidosis
If pH is above 7.45, then alkalosis
What is the cause of the osis?
There are 4 primary disturbances
Each can be an acidosis or alkalosis caused by either a respiratory or metabolic problem
Super acid-base disorder-only one disorder present
Mixed acid base disorder- more than one dis9rder present
Was there a compensation?
Respiratory disturbances- Renal system responds over time alter HCO3^-
Metabolic disturbances- Respiratory system responds quickly to alter CO2
What is metabolic acidosis ?
Decreased HCO3^- in blood
Acute values- pH below 7.4, PCO2- normal, HCO3^- below 24
What is respiratory acidosis ?
Increased CO2 in blood
Acute value- pH below 7.4, PCO2 above 40, HCO3^- is normal
What is metabolic alkalosis?
Increased HCO3^- in blood
Acute values- pH> 7.4, PCO2 normal, HCO3^- > 24
What is respiratory alkalosis?
Decreased CO2 in blood
Acute values- pH> 7.4, PCO2< 40, HCO3^-= 24(normal)
Can the body over compensate ?
The body never overcompensates- If it appears that a patient “overcompensate” for a primary disorder, there is a second disorder.
-If CO2 and HCO3^- go in opposite directions, in the acute phase, there is a combined disturbance - (mixed respiratory and metabolic acidosis; and mixed respiratory and metabolic alkalosis)
Too much CO2 is a respiratory acidosis
Too much CO2 is a respiratory alkalosis
What is the compensatory mechanism of metabolic acidosis?
Increased ventilation
Decreased pH, decreased HCO3^-, decreased CO2
Whatis the compensatory mechanism of respiratory acidosis. ?
Increased renal absorption of HCO3^- in the proximal tubule
Increased renal excretion of H+ in the distal tubule
decreased pH, increased HCO3^-, increased CO2
What is metabolic alkalosis ?
Decreased ventilation
Increased pH, increased HCO3^-, increased CO2
What is respiratory alkalosis compensatory mechanism?
Decreased renal excretion of H+ in th3 distal tubule
Increased pH, decreased HCO3^- and decreased CO2
Describe the 4 quadrants of the Davenport diagram
Values within shaded area: 1 acid base disorder present
Values outside shaded area: More than one disorder present(mixed)
Metabolic disorders: Each has 1 range of values since respiratory compensation occurs within minutes
Respiratory disorders: Each has 2 ranges of values:
- Acute disorder - Chronic disorder
Acute respiratory: disorder present before any renal compensation; has occurred
-pH= abnormal but [HCO3^-] = normalish
Chronic Respiratory: Disorder present after renal compensation has occurred (after several days)
-pH= normalish but [HCO3^-] = abnormal