Flashcards in Session 6 - Acidosis and Alkalosis Deck (79):
1
How do the kidneys control plasma volume?
• Filtering and variably recovering salts
2
How do the kidneys control plasma osmolarity?
• Filtering and variably recovering water
3
How do the kidneys variably control plasma pH?
• Filtering and variably recovering hydrogen carbonate and active secretion of hydrogen ions
4
What is normal pH range?
• 7.38 - 7.42
5
When does alkalaemia occur?
>7.42
6
When does acidaemia occur?
• <7.38
7
What is normal conc of H+?
37-43 nmol/l
8
Outline what occurs in alkalaemia
• Lowers solubility of Ca2+ salts, free Ca2+ binds to proteins. Results in hypocalcaemia
○ Increases excitability of nerves
• Paraesthesia
• Tetany
9
What is % mortality at pH 7.55?
45%
10
What is % mortality at pH 7.65?
80%
11
Outline what occurs in acidaemia
• Hyperkalaemia (heart arrythmias and arrest)
• Affects many enzymes
○ Reduces cardiac and skeletal muscle contractility
○ Reduced glycolysis in many tissues
○ Reduced hepatic function
• Effects severe under 7.1
• Life threatening below pH 7.0
12
How much HCO3- is required for accurate pH maintenance?
• 20x as much HCO3- as there is CO2
• pH = pK + log (HCO3-/pCO2 x 0.23)
• Log 20 (20x higher) = 1.3
• pK - 6.1 + 1.3 = 7.4
13
What is CO2 determined by?
• Controlled by chemoreceptors
• Disturbed by respiratory disease
14
What is HCO3- conc determined by?
• Controlled by kidney
Disturbed by metabolic and renal disease
15
What is HCO3- largely created by?
• Red blood cells
16
What is respiratory acidaemia (acidosis)?
• Hypoventilation leads to hypercapnia
• Hypercapnia causes plasma pH to fall
• Less than 20x amount of HCO3-
• pH <7.35
17
What is respiratory alkalaemia (alkalosis)?
• Hyperventilation leads to hypocapnia
• Fall in pCO2 causes pH to rise
• More than 20x amount of HCO3- than CO2
18
What is normal pH?
7.38 - 7.42
19
What is normal HCO3-
• 22 - 29 mmol/l
20
What is normal pO2?
• 9.8 - 14.2 kPa
21
What is normal pCO2?
• 4.2 - 6.0 kPa
22
How is pH corrected in respiratory alkalosis/acidosis?
• Central chemoreceptors normally control pCO2 within tight limits
• Peripheral chemoreceptors enable changes in respiration driven by changes in plasma pH
• This is CORRECTION - Changing the factor at hand
23
How is pH compensated in respiratory acidosis/alkalosis
• changes in pCO2 compensated by changes in HCO3-
• Kidney control HCO3-
• Respiratory acidosis is compensated by kidneys increasing HCO3-
• Respiratory alkalosis is compensated by kidneys decreasing HCO3-
24
What is metabolic acidosis?
• Tissues produce acid (or acid in blood - amino acids)
• H+ reacts with HCO3-, leading to fall in pH
Metabolic acidosis
25
How is metabolic acidosis compensated (acidosis means alteration in buffer base!)?
• Compensated by changes in ventilation
○ Peripheral chemoreceptors increase ventilation
○ This lowers pCO2
Restores pH towards normal
26
What is metabolic alkalosis caused by?
• Plasma HCO3- rises (after vomiting for instance)
• Plasma pH rises
• Metabolic alkalosis
27
How is metabolic alkalosis compensated?
• Partially compensated by decreased ventilation
28
How are respiratory changes in pH changed? (use correct terminology)
• Compensated by kidney
• Corrected by breathing
29
How are metabolic changes in pH modified? (use correct terminology)
• Compensated by breathing (changing factor than other directly changes)
• Corrected by kidney
30
What is produced in metabolic acidosis?
• H+ ions which react with HCO3- to produce CO2 in venous blood
• CO2 breathed out, proportionally reducing HCO3-
31
Why can metabolic alkalosis only be partially compensated?
• Because can only slightly reduce respiratory to increase CO2
• At risk of hypoxia
32
How much HCO3- filtered per day?
• 4500 mmol
33
How can HCO3- be increased?
• Recover all filtered HCO3-
Make new
34
Give two ways in which kidneys synthesise HCO3-
• Amino acids
CO2
35
How do the kidneys make new HCO3- from CO2?
• Kidneys produce a lot of CO2
• Combined with water to produced H2CO3-
• H+ excreted into water, HCO3- into blood
36
How do the kidneys make new HCO3- from amino acids?
• Glutamine
• Produces NH4- to enter urine, HCO3- excreted into blood
37
Where is HCO3- recovered in kidney?
• 80-90% in PCT
• Remainder in thick ascending limb of loop of henle
38
How is HCO3- recovered in PCT of kidney?
• H+ exported from cell into lumen via Na-H antiporter
○ Up conc grad
○ Energy from movement of Na+ down Conc grad (Na/K+ ATPase on basolateral membrane
• H+ reacts with HCO3- in lumen, making CO2 + H20
• CO2 enters cell, reacts with H20 to make HCO3-
• HCO3- exported with K+ into ECG
39
How is HCO3- created from amino acids in the PCT?
• Glutamine broken down to produced
○ A-ketoglutarate (HCO3-)
○ Ammonium (NH4+)
○ HCO3- into ECF
○ NH4+ into lumen
40
What does HCO3- reabsorption look like in PCT?
• DRAW IT NOW
41
What has happened to HCO3- by the time of the DCT?
Has almost all been filtered and recovered
42
How is HCO3- recovered in distal tubule cells?
• CO2 produced and combined with H20 to make H2CO3-
• Na+ gradient insufficient to drive H+ secretion
• H+ actively transported out of cell via H+ ATPase and H+/K+ antiporter
• H+ bound to HPO42- + H+ -> H2PO4- in lumen
43
What happens to K+ when cells export H+?
• K+ is absorbed into blood
44
Why may you end up absorbing a large amount of K+?
• If a large amount of HCO3- needs to be reabsorbed due to respiratory acidosis, large amount of K+ will be reabsorbed with it. May cause hyperkalaemia
45
What is minimum urine pH
4.5
46
What is a titratable acid?
• One which can freely gain H+ ions in an acid/base reaction
47
How is H+ buffered in urine?
• HP04 2- -> H2PO4-
• NH3 -> NH4+(ammonia -> ammonium)
48
What is daily acid secretion?
• 50-100mmol H+
49
How is H+ excretion controlled?
• pH detected by intracellular pH of tubular cells
• Change in rate of HCO3- export to ECF produced by changes in ECF (H+ automatically excreted)
50
How is respiratory acidosis associated with K+?
• Causes hyperkalaemia
• HCO3- being generated, H+ being expelled
K+ taken in in exchange for H+
51
How is metabolic alkalosis associated with hypokalaemia?
• Hypokalaemia
52
How does hyperkalaemia cause metabolic acidosis?
• As K+ rises, kidneys ability to reabsorb and create HCO3- reduced.
• Hyper kalaemia makes intracellular pH alkaline, favouring HCO3- excretion
53
How does hypokalaemia cause metabolic alkalosis?
• Hypokalaemia makes intracellular pH acidic, favouring H+ excretion and HCO3- recovery
54
Draw activities of DCT
NOW
55
Give 4 cellular responses to acidosis
• Enhanced H+/Na+ exchange
○ Full recovery of all filtered HCO3-
○ Enhanced ammonium production in PCT
○ Increased activity of H+ ATPase in distal tubule
○ Increased activity of H+ ATP-ase from tubular cells to ECF
56
What is metabolic acidosis due to?
• Fall in HCO3-
• A gain in H+
57
What is metabolic alkalosis due to?
• Due to rise in HCO3-
• A fall in H+
58
Give an outline of metabolic acidosis
• Acids produced metabolically
• Produced from H+ and an anion (lactate, ketones)
• H+ reacts with HCO3-, producing CO2 which is breathed out
Some HCO3- replaced by anion from acid
59
What happens to HCO3- after vomiting?
• Large increase in HCO3- and as replacement H+ produced
• Kidneys cannot excrete HCO3- as they are trying to compensate for dehydration
• HCO3- and Na+ recovery is favoured to increase osmolarity of plasma and cause osmotic movement of water
• Metabolic alkalosis ensues
60
How can you treat metabolic alkalosis after vomiting?
• Rehydration
• Post rehydration HCO3- will be excreted quickly
61
Why does HCO3- increase after persistent vomiting?
• H+ decreased in stomach
• More H+ produced, releases HCO3- into blood
• Hypokalaemia ensues
62
Why does hypokalaemia occur as a result of vomiting?
• H+ secretion in kidney stops, so does K+ reabsorption (Antiporter, intercalated cells)
63
Why do side effects of vomiting include hypokalaemia?>
• H+ secretion in kidney stops, so does K+ reabsorption
• More K+ lost in urine
• Hypokalaemia
64
Give three causes of metabolic acidosis
• Excess metabolic production of acids
• Acids are ingested (amino acids)
• Problem with the renal excretion of acid
65
What is the anion gap?
• Indicates whether an HCO3- has been replaced with something other than Cl-
66
How is the anion gap calculated?
• Difference between (Na+ + K+) and (Cl- + HCO3-)
67
What is the normal value of the anion gao?
• 10-15 mmol/l
68
When is the anion gap increased?
• If anions from metabolic acid has replaced plasma HCO3-
69
hen can renal problems reduce HCO3- without increasing the anion gap?
If HCO3- replaced with Cl-
70
Give four causes of an increased anion gap metabolic acidosis
• Lactate
• Ketoacids
• Toxic alcohols
• Aspirin
71
What is renal correction of low pH?
• Fall in tubular cell intra-cellular pH stimulates acid secretion and HCO3- recovery, thus raising plasma HCO3-
72
How can metabolic alkalosis occur?
• HCO3- increases after persistent vomiting
• Should be very easy to correct
73
What is the issue with a HCO3- infusion?
• Excreted in kidney immediately
74
Why does vomiting compromise ability to excrete HCO3-?
• Vomiting also causes dehydration
• Volume depletion. Capacity to lose HCO3- is less, because high rates of recovery favour HCO3- recovery and H+ secretion
75
How do you treat metabolic alkalosis?
• Rehydrate
76
What is a dangerous effect of metabolic acidosis?
• Hyperkalaemia
○ K+ moves out of cells, in order to control intracellular pH
More K+ reabsorbed in distal nephron, as a result of H+ excretio
77
What is a dangerous effect of metabolic alkalosis?
• Hypokalaemia
○ K+ moves into cells
Less K+ reabsorption (less H+ excreted in distal nephron
78
How does hypokalaemia cause metabolic alkalosis?
• Make intracellular pH of tubule cells acidic
○ Favours H+ excretion and HCO3- recovery
○ Therefore metabolic alkalosis occurs
79