5 Flashcards
(33 cards)
At what range should plasma pH be maintained at, and what about concentration of H+ ions?
- pH: 7.35-7.45
- concentration H+ ions is tightly regulated: 44.5-35.5 nmol/L
Is alkalosis or acidosis more dangerous?
-alkalosis because losing calcium as well
What is alkalaemia/alkalosis?
- when plasma pH > 7.45
- is more dangerous than acidosis since it lowers free calcium by causing Ca ions to come out of solution which increases to neuronal excitability
- Ca is a divalent cation that binds to excitable cells to protect them and make them less excitable
- with low Ca, these cells become more excitable such as muscle cells and nerves
- leads to paraesthesia (abnormal tingling) and tetany (muscle contracting); especially harmful if resp muscles
- 45% mortality if pH rises to 7.55
- 80% mortality if pH rises to 7.65
What is acidaemia/acidosis?
- when plasma pH < 7.35
- increases plasma potassium ion concentration
- affects excitability (particularly cardiac muscle)
- may lead to arrhythmia
- increasing [H+] affects many enzymes
- denatures proteins
- affects muscle contractility, glycolysis, hepatic function
- effects are severe below ph 7.1
- life threatening below 7.0
- affects enzyme function
- can lead to hyperkalemia
What is pCO2 and [HCO3] determined by?
- pCO2 determined by respiration
- controlled by chemoreceptors
- disturbed by respiratory disease
- [HCO3] determined by kidneys
- controlled by kidney
- disturbed by metabolic and renal disease
How do the kidney and lungs work together to control plasma pH?
Kidneys
-control pH: variable recovery of hydrogen carbonate and active secretion of hydrogen ions
Lungs
- alveolar ventilation allows diffusion of O2 into blood and CO2 out of blood (control pO2 and pCO2)
- rate of ventilation controlled by chemoreceptors
How come acid production does not deplete HCO3?
-body produces acid due to metabolism (lactic acid)
-Western diet also contains lots of H+ ions
Does not deplete HCO3 because:
-kidneys recover all filtered HCO3
-PCT makes HCO3 from amino acids, putting NH4+ into urine
-DCT makes HCO3 from CO2 and H2O, the H+ is buffered by phosphate and ammonia in the urine
Explain the recovery of HCO3 in the PCT
- HCO3 filtered at glomerulus
- 80% recovered in PCT
- mainly recovered through Na/H anti-porter
- Na/K ATPase created sodium gradient from basolateral membrane allowing Na/H anti-porter on apical membrane to work
- H+ reacts with HCO3 in lumen to form CO2 which enters cell
- converted back to HCO3 which enters ECF
- apical embrace of cell is rich in carbonic anhydrase
How is HCO3 created in the PCT?
- breakdown of glutamine
- glutamine in cell breaks down into a-ketoglutarate and ammonium (NH4+)
- a-ketoglutarate becomes 2 HCO3- which go into ECF through Na/HCO3 symporter
- NH4+ splits into NH3 and H+
- NH3 is uncharged so goes out to lumen and combines with H+ from Na/H anti-porter to make NH4+
- NH4+ is charged so cannot be reabsorbed and is excreted through urine
How is HCO3 controlled in the DCT and CD?
- secrete H+ produced from reactio of CO2 with H2O
- H+ ions are ACTIVELY secreted
- H+ buffered by NH4+ and H2PO4 which are both excreted
- No CO2 is formed to re-enter the cell which allows HCO3 to enter plasma
- occurs specifically in a-intercalated cells
- H+ ATPase pump on apical membrane sends H+ from buffering system out to lumen
- H+ combines with HPO4 to make H2PO4 which is excreted
- HCO3 goes to ECF through Cl/HCO3 anti-porter
- HPO4 buffer is more effective as pH of urine falls
What is the major adaptive response to an increased acid load in healthy individuals?
- excretion of ammonium
- ammonium generation from glutamine in PCT can be increased in response to low pH
- NH3 freely moves into lumen through interstitium b/c uncharged so it can be created in PCT and move and buffer in the DCT
- H+ actively pumped into lumen in DCT and CT
- H+ combines with NH3 to make NH4+
- NH4 can also be taken up in TAL and transported to interstitum and dissociate to H+ and NH3 into lumen of CD
How much acid must be excreted per day?
- total acid excretion: 50-100mmol H+ per day
- needed to keep [HCO3] normal
- if you dont excrete that amount of acid then HCO3 concentration will deplete
- pH doesn’t lower due to the ammonium/ammonia buffering system
How does acidosis lead to hyperkalaemia?
- K+ ions move out of cells
- decreased potassium excretion in distal nephron
- too much H+ ions in ECF so goes into cell
- hyperkalaemia makes Intracellular oH of tubular cells more alkaline
- favours HCO3 excretion (metabolic acidosis)
- non-renal causes of metabolic acidosis cause increased reabsorption of K+ by kidneys
How does alkalosis lead to hypokalaemia?
- K+ ions move into cells
- enhanced excretion of potassium in distal nephron
- reciprocal cation shifts
- too much H+ ions in cell, so goes into blood
- hypokalaemia makes intracellular pH of tubular cells more acidic
- H+ ions move into cells
- favours H+ excretion and HCO3 recovery
- metabolic alkalosis
How does ventilation disturb the acid base balance?
- Hyperventialtion leads to hypocapnia
- hypocapnia leads to rise in pH
- results in respiratory alkalosis
- characterized by: low pCO2, normal HCO3, raised pH
How does compensation work for acid-base balance?
- plasma pH depends on ratio of [HCO3] to pCO2, not on their absolute values
- changes in pCO2 can be compensated by changes in [HCO3]
- kidneys increase [HCO3] to compensate for respiratory acidosis
- kidneys decrease [HCO3] to compensate for respiratory alkalosis
- takes time though, 2-3 days
What are the characteristics of compensated respiratory acidosis?
- high pCO2
- raised [HCO3]
- relatively normal pH
What are the characteristics of compensated respiratory alkalosis?
- low pCO2
- lowered [HCO3]
- relatively normal pH
What is the anion gap?
-difference between MEASURED cations and anions
-can be used to determine the cause of a metabolic acidosis
([Na+] + [K+]) - ([Cl-] + [HCO3-])
-normal difference: 10 to 18 mmol/L because other anions may not be measured
-gap is increased if HCO3 is replaced by other anions that are not measured
-if a metabolic acid (i.e. lactic acid) reacts with HCO3, the anion of the lactic acid replaces HCO3
-so lactate will form and gap will increase since lactate isn’t measured
-in renal cause of acidosis, anion gap will be unchanged because not making enough HCO3, but that is replaced by Cl- which IS measured
What are the characteristics of metabolic acidosis?
- normal pCO2
- low HCO3
- low pH
- increased anion gap if HCO3 is replaced by another organic anion from an acid
- normal anion gap if HCO3 is replaced by Cl-
What are the characteristics of compensated metabolic acidosis? How is it detected?
- low HCO3
- lowered pCO2
- nearer normal pH
- detected by peripheral chemoreceptors (carotid bodies)
- they stimulate ventilation which leads to decrease in pCO2
What are the characteristics of metabolic alkalosis?
- raised HCO3
- normal pCO2
- increased pH
- cannot normally be compensated to a great extent by reducing breathing since you need to maintain pO2
- should be easy for kidney to correct by recovering less HCO3
What conditions lead to respiratory acidosis?
Type 2 respiratory failure
- low pO2 and high pCO2
- alveoli cant be properly ventilated
- severe COPD, severe asthma, drug overdose, neuromuscular disease
- can be compensated for by increase in [HCO3]
- chronic conditions can be well compensated such that pH is near normal
What conditions lead to respiratory alkalosis?
Hyperventilation -anxiety/panic attacks (acute setting) -low pCO2 -rise in pH Hyperventialtion in response to long-term hypoxia (Type 1 respiratory failure) -low pCO2 with initial rise in pH -chronic hyperventilation can be compensated for by fall in [HCO3] -can restore pH to near normal
