What are the three fixed sources of hydrogen?
Anaerobic breakdown of glucose
Metabolism of cystine
Oxidation of phosphoproteins
What two proximal tubule transporters are responsible for carrying bicarbonate through the basolateral membrane?
Bicarbonate exits the cells of the proximal tubule via a bicarbonate sodium symporter, or a bicarbonate chloride antiporter.
What are the four buffer systems discussed in this lecture?
Phosphoric acid (H2PO4)
Plasma proteins (albumin)
What are the symptoms of respiratory alkalosis?
Often tachypnea (the cause) is the only sign.
Peripheral and circumoral paresthesias,
What are the causes of high anion gap metabolic acidosis?
Renal Failure (Uremia)
What causes chronic respiratory acidosis?
Anything that makes breathing difficult chronically.
(COPD is a good example)
How does phosphate buffering in the tubular lumen help reclaim bicarbonate?
It is possible for carbonic anhydrase to break carbonic acid down into a bicarbonate and hydrogen, but then for that hydrogen to leave the apical surface via the sodium/hydrogen exchanger, and bind to sodium phosphate. That sodium phosphate allows us to clear the hydrogen, resulting in a net gain of one bicarbonate.
What is the general pathological mechanism of type II renal tubular acidosis?
Impaired bicarbonate reabsorption the proximal tubule
How does ammonia clear hydrogen ions from the nephron?
It sits in an equilibrium between ammonia and ammonium in the medullary interstitial fluid. The uncharged ammonia is capable of entering the intratubular fluid by passing through the cells of the collecting duct. This ammonia binds there with hydrogen, and drags it out to be excreted in the urine.
What is the general pathological mechanism of type IV renal tubular acidosis?
Low plasma aldosterone, or a failure to respond to it.
This increases intracellular potassium, which for some reason decreases ammonia synthesis in the cells of the proximal tubule. This decreased ammonia synthesis means less ammonia is available to bind hydrogen and create bicarbonate. This results in metabolic acidosis.
How does the body compensate for metabolic acidosis?
In the short-term, we hyperventilate – decreasing carbon dioxide.
In the long-term, the kidneys increase production of ammonia and phosphate – which can clear hydrogen ions, and (thereby) create bicarbonate.
What is the response from the kidneys to respiratory acidosis?
The kidneys want to create more bicarbonate, so they increase production of ammonia and phosphate.
What is the general pathological mechanism of type I renal tubular acidosis?
The alpha intercalated cells of the distal tubule and collecting duct failed to secrete hydrogen appropriately. This all decreases the amount of available bicarbonate by decreasing the amount of hydrogen available for phosphate and ammonia buffering.
What is the typical pH of the intracellular compartment?
How do we calculate carbonic acid concentration (HA)?
.03 x partial pressure of CO2 in mmHg
What is the Henderson Hasselbalch equation?
pH = pK + log ([A -] / [HA])
Compare the rates of the four slow mechanisms of pH balance.
Lungs: minutes to hours
Ionic shifts: 2-4 hours
What transporter is responsible for the reabsorption of ammonium from the thick ascending limb into the medullary interstitial fluid?
NKCC2 receptor – ammonium takes the place of the potassium
What are the primary causes of respiratory acidosis?
Severe pneumonia, embolism, edema
(They sell acidic air in CANS)
What are the two volatile sources of hydrogen?
Oxidation of glucose
Oxidation of fat
What helps make type IV renal tubular acidosis more common than the other types?
ACE inhibitors decrease angiotensin II formation, which can decrease aldosterone.
Toxic levels of ACE inhibitors can therefore cause type IV renal tubular acidosis.
What is the typical pH range for urine?
4.5 to 8.0 pH
What are the causes of metabolic alkalosis?
Post-hypercapnia, Diuretics, Contraction, Licorice, Endo, Vomiting, Excess alkaline, Re-feeding alkalosis.
People who are basic think they are Pretty Darn CLEVER
What are the causes of the non-anion gap acidosis?
Hyperalimentation, Acetazolamide, Renal tubular acidosis, Diarrhea, Ureteropelvic shunt, Post-hypocapnia, Spironolactone
(The not-high are HARDUPS)
Where are principal cells, alpha intercalated cells, and beta intercalated cells found?
In the collecting ducts
What is the pK of the bicarbonate/carbonic acid buffer reaction?
What are the symptoms of chronic respiratory alkalosis and acidosis?
Usually these are well tolerated.
What four organs/mechanisms are responsible for “slow” regulation of blood pH?
Lungs (elimination of CO2)
Ionic shifts (exchange of hydrogen for potassium and sodium through cell membranes)
Kidneys (bicarbonate reabsorption, phosphate buffering, ammonia formation)
Bone (exchanges of calcium, phosphate, and carbonate)
In terms of hydrogen and bicarbonate clearance, what are the responsibilities of the alpha-intercalated cells and the beta-intercalated cells, respectively?
Alpha-intercalated cells excrete acid (hydrogen)
Beta-intercalated cells excrete bicarbonate
What causes symptoms of metabolic alkalosis?
Increased bicarbonate in the bloodstream binds calcium, causing hypocalcemia.
Also, less hydrogen ions in the bloodstream allows more calcium to bind albumin, also causing hypocalcemia.
Hypocalcemia results in neuromuscular excitability, headache, lethargy, delirium, tetany, and seizures.
What should you expect if the patient has acidemia, a normal anion gap, normal serum creatinine, and no diarrhea?
Renal tubular acidosis
What are the causes of respiratory alkalosis
Diarrhea causes a loss of what substance?
will see normal anion gap and hyperchloremia
In type two renal tubular acidosis, there is a loss of what?
nomal anion gap and hyperchloremia
In type 1 renal tubular acidosis, there is a loss of what?
a decrease in excretion of H ions as titratable acid and NH4
decreased ability to make acidic urine
normal anion gap
In type 4 renal tubular acidosis, what condition is associated with this?
decrease excretion of NH4
hyperkalemia inhibiting NH3 synthesis
normal anion gap