Acid and base balance - Renal 4 Flashcards
1
Q
Learning outcomes
* Acid-base disturbance
* H+ handling secretion
* Bicarbonate buffering
* Acidosis and alkalosis – metabolic and respiratory
A
2
Q
Arterial pH if it is?
A
Less than 6.8 / greater than 8 this is not compatible with life and death occurs
3
Q
Optimal pH in the body?
A
7.4 is equivalent to 40nMols/L [H+]
Arterial and venous pH differ
4
Q
What pH is acidosis?
A
Exists when blood pH falls below 7.35
5
Q
What is Alkalosis?
A
Occurs when blood pH is above 7.45
6
Q
Why is maintaining pH in the body so important? 3
A
- pH changes cause conformational changes in
proteins and can alter functions
e.g. enzyme activity is pH dependent - Nervous system function is v sensitive to pH changes, can lead to seizures, coma
- Cardiac arrhythmia: change in H+ ions can have domino effect on other ions and cause detrimental effects
7
Q
While reabsorbing Na+ from the filtrate, renal tubular cells secrete?
Predominantly?
Changes in K+ leads to?
A
Either H+ or K+
Predominantly K+ but H+ secretion increases to
compensate for acidosis.
Changes in [K+] ECF can lead to cardiac abnormalities
8
Q
SEE SLIDE 5
A
Antiport via same carrier proteins or other carrier proteins
Movement of K,H+Na ions is interlinked across membrane
Thus if pH changes this will have knock on effects -> Disturbingly wise
9
Q
Sources of H+ gain? 4
A
- CO2 in blood (combine with H2O via carbonic anhydrase)
- Non-volatile acids from metabolism (e.g. lactic)
- Loss of HCO3 - in diarrhoea or nongastric GI fluids
- Loss of HCO3 - in urine
10
Q
Sources of H+ loss? 3
A
- Loss of H+ in vomit
- Loss of H+ in urine
- Hyperventilation (blow off CO2)
11
Q
What is an acid - Brønsted-Lowry definition?
A
An acid is a substance that donates protons
and a base is a substance that accepts
protons
12
Q
A strong acid is?
A
An acid which is completely ionised in an aqueous solution
Completely dissociates from rest when in water
13
Q
A weak acid is?
A
Is an acid that ionises only slightly in an aqueous solution
Not complete dissociation in every instance when acid is in water
14
Q
What are buffers?
A
Buffers are balanced mixtures of a weak
acid and its conjugate base: substance that is formed when weak acid gives up its proton
15
Q
Chemical buffer systems minimise changes in pH how?
A
By binding or yielding free H+
First line of defence
16
Q
H2CO3: HCO3 buffer system major function?
A
Primarily ECF buffer against non-carbonic acid changes
17
Q
Protein buffer system major functions?
A
Primary ICF buffer but also buffers ECF
18
Q
Haemoglobin buffer system major function?
A
Primary buffer against carbonic acid changes
19
Q
Phosphate buffer system major functions?
A
Important urinary buffer, also buffers ICF
20
Q
Intracellular pH regulation occurs via what system?
See slide 9
A
Phosphate buffer system
21
Q
Phosphate buffer system - in a test tube:
Add a strong acid to a mixture of these two substances (for example HCl): H+ is accepted by HPO4 2- producing H2PO4–
What is the result?
A
The strong acid is replaced by a weak acid, ‘buffering’ the decrease in pH.
22
Q
Phosphate buffer system - in a test tube:
Add a strong base to a mixture of these two substances (for example NaOH) : H2PO4– donates a proton to OH– to form HPO4 2- + H2O.
What is the result?
A
The strong base is replaced by a weak base, ‘buffering’ the increase in pH.
23
Q
ICF pH regulation: Phosphate buffer system
1. In acid solution what happens?
2. In basic solution what happens?
A
- In acidic solution: (HPO4)^2- accepts H^+ and caused an increase in pH.
- In basic solution: H2PO4 donates H+ and causes a decrease in pH.
24
Q
Phosphate buffer system is important for buffering what?
What is this system made up of?
A
Within cells
Monohydrogen phosphate ions: (HPO4)^2-
Dihydrogen phosphate ions H2PO4-
25
HPO4^2- and H2PO4^- are what in terms of acids+ bases?
HPO4^-2 is conjugate base
H2PO4^- is a weak acid
26
Why does weak acid not have a huge effect on pH?
What is the net effect of taking strong acid and getting a weak one?
This weak acid made doesn't cause such a lowering of pH compared to HCL as weak acid remains partially undisocsaited in ICF
Net effect is taking strong acid and getting a weak acid so we limit its effect on pH and buffered the effects of adding the strong acid
27
Intracellular protein
What are 2 examples of amino acids with acidic side chains?
What are they in terms of protons?
Glutamic acid and Aspartic Acid
Proton donors at pH 7.4 - They give up H+ion
28
ICF Protein
What are 3 examples of amino acids with basic side chains?
What are they in terms of protons?
Arginine, Lysine, and Histidine
Proton acceptors at pH 7.4 - They accept H+ ion
29
What can amino acids act as in terms of pH?
See slide 11
Amino acids in proteins can act as buffer to pH change
30
ECF pH regulation - major system for this is?
see slide 12 equation
Bicarbonate
31
To maintain a normal pH of 7.4 in the blood what ratio of bicarbonate to carbonic acid must be maintained?
20:1
32
ECF pH regulation is via?
Regulated by the medulla oblongata of the brainstem (which regulates breathing) and the kidneys
33
ECF pH is regulated by the medulla oblongata of the brainstem (which regulates breathing) and the kidneys: through what 2 compensation mechanisms?
Respiratory and renal compensation
34
Explain respiratory compensation for ECF pH regulation?
Respiratory compensation: The rate and/or depth of breathing can be changed to compensate for changes in the blood concentration of CO2
Release of CO2 from the lungs pushes the reaction above to the left, causing carbonic anhydrase to form CO2 until excess acid is
removed.
35
Symptoms of acidosis: ph < 7.45 in CNS, Respiratory system, Heart, Muscular system and digestive system
CNS: Headache, sleepiness, confusion, loss of consciousness, coma
Respiratory system: Shortness of breath, coughing
Heart: Arrhythmia, increased heart rate
Muscular system: Seizures and weakness
Digestive system: nausea, vomiting, diarrhea
36
Symptoms of alkalosis: pH > 7.45 in CNS, Respiratory system, PNS, Muscular system and digestive system
CNS: Confusion, light-headedness, stupor, coma
PNS: Hand tremor, numbness/tingling in the face, hands or feet
Muscular System: Twitching, prolonged spasms
Digestive system: Nausea, vomiting
37
Explain renal compensation for ECF pH regulation?
Bicarbonate concentration can be regulated by
the kidneys by secreting H+ into urine and reabsorbing HCO3 - into the blood, or vice versa
38
SLIDE 13 SEE
With decreased pH
1. Buffer systems other than carbonic acid-bicarbonate system do that?
2. Renal compensation what effect on ions?
3. With decreased pH it causes increased pCO2 what compensates this?
1. Absorb H+ ions
2. Increased H+ secretion and increased HCO3- generation
3. Increased pCO2 causes respiratory compensation thus increased respiratory rate that decreasing pCO2.
39
SLIDE 13 SEE The response to acidosis
With decreased pH
1. Buffer systems other than carbonic acid-bicarbonate system do that?
2. Renal compensation what effect on ions?
3. With decreased pH it causes increased pCO2 what compensates this?
1. Absorb H+ ions
2. Increased H+ secretion and increased HCO3- generation
3. Increased pCO2 causes respiratory compensation thus increased respiratory rate that decreasing pCO2.
40
What do kidneys require to compensate for changes in body-fluid pH?
Hours to days to do this
41
Kidneys control the pH of body fluids by adjusting what? 3
1. H+ excretion
2. HCO3 excretion
3. Ammonium (NH3) secretion
42
The kidneys vary the extent of H^+ secretion via?
H+ATPase pumps and Na+-H+antiporters
43
Why is all filtered H+ excreted via the kidneys?
Most H+ enters the urine via?
Because it cannot be reabsorbed
Via secretion
44
What secretes H+?
Is urine normally acidic or basic and what is the pH
Proximal, distal and collecting tubules all secrete H+
Acidic - pH is 6
45
H+ secretion begins - in (1) what cells and (2) with what and (3) how many sources?
H+ secretion begins in the tubular cells with the CO2
from 3 sources
46
CO2 diffuses into tubular cells from? 3
1. Plasma
2. Tubular fluid
3. CO2 metabolically made in tubular cells
47
Bicarbonate is freely filtered at the glomerulus but how much of this is reabsorbed by the proximal tubule?
~80%
48
HCO3- Reabsorption and H+ secretion in PCT
See slide 18 diagram
1. What exchanger is on the apical membrane?
2. What is on the basolateral membrane?
1. Na+ /H+ exchanger 3 (NHE3) on the apical membrane
2. Electrogenic sodium bicarbonate cotransporter 1-A on the basolateral membrane
49
Slide 20 see diagram:
1. Type A intercalated cells - H+ is?
2. HCO3-?
3. K+?
4. Type A have what effect on acidisosis?
H+ Secreting
HCO3–reabsorbing
K + reabsorbing cells
Type A intercalated cells increase activity in
acidosis
50
CO2+ HCO3 + H+ secretion
SLIDE 18
How bicarbonate ions can be reabsorbed in conjugtion with proton secretion:
Looking at glomerulus, bicarbonate ions and sodium ions enter the tubular component of nephron in the glomerular filtrate.
Sodium passes down its concentration gradient on the apical side of the tubule epithelial lining and as it goes down then this concentration gradient that was made by the Na/K pump - the anti-porters enables protons to be moved into the tubular lumen
These protons can react with filtered bicarbonate ions to make water + CO2
That CO2 can pass back across the cell membrane into cytosol of tubule wall cells and can react with water to make protons and bicarbonate ions.
The protons can be excreted and these bicarbonate ions can be reabsorbed across membrane facing the peritubular capillaries via symport with sodium ions
Any excess protons that don't react can be excreted
51
Mechanism of renal H+ secretion in the DCT and collecting tubules:
1. Remainder of HCO3- is reabsorbed where?
2. Final urine is composed basically free of?
3. Urine acidification can be fine tuned where?
4. Intercalated cells can be detected all the way where?
5. Intercalated cells are found where?
6. Intercalated cells are the most abundant where?
7. They are dispersed among?
8. K+?
9. Na+?
10. Water is reabsorbed via what
1. The remainder of HCO3- is reabsorbed in the ascending limb of LoH, the distal convoluted tubule & the collecting duct.
2. The final urine is nearly free of bicarbonate
3. DCT and collecting duct: Urine acidification can be fine-tuned
4. They can be detected all the way from the cortex to the initial part of the inner medulla
5. Intercalated cells - in the late distal convoluted tubule
6. Most abundant in the collecting duct
7. Dispersed among principal cells
8. K+ secretion - ROMK
9. Na+ reabsorption
10. Water reabsorption - ADH
52
Type B intercalated cells have what effect on alkalosis?
Increase activity in alkalosis
53
Type B intercalated cells - what happens to HCO3-, H+ and K+?
HCO3 – Secreting
H+ reabsorbing
K+ secretion cells
54
Type A intercalated cells slide 20
At apical membrane express H+ATPase that use ATP to provide energy to pump H+ into tubular lumen and they express H+K+ ATPases which use ATP to pump K+ into cell and H+ protons out
Protons react with filtered bicarbonate ions in tubular lumen to make carbonic acid
Carbonic anhydrase or Ca can catalyse the breakdown of carbonic acid into water and CO2 which can pass across the apical membrane into the cytosol of the intercalated cell where the water+CO2 can be broken down or converted into H+ which cab be pumped out and bicarbonate ions which has been catalysed by Ca and bicarbonate ions can be pumped out of the cell at basolateral membrane due to expression of anti-porter which pumps bicarbonate ions out of cell to the interstitial space where it can pass into peritubular capillary plasma while Cl^- ions are passed into the cytosol
=> Important to note this is referred to as HCO3^- reabsorption even though the specific bicarbonate ion within the tubule has undergone a series of actions it is not directly transported into the plasma but since 1 HCO3^- ion has been removed from the tubular lumen for every 1 that was passed into the plasma it is still considered to be bicarbonate reabsorption
=> Particularly useful for reducing pH
55
Type B intercalated cells: slide 21
Bicarbonate chloride anti-porter expressed on apical side of intercalated cell in the membrane so that HCO3- ions are moved into tubular lumen whilst Cl- ions are passed into intercalated cells while the ATPases: the H+K+ ATPase and the H+ ATPase are expressed on basolaminar side of the cell.
Similar ish reaction to type A
There is enzyme Ca which catalyses reaction between CO2+H20 to make HCO3- and H+ but the direction they are transferred is the opposite compared to type A
=> Thus Type B are HCO3- and K+ secreting cells and H+ reabsorbing cells therefore they can bring down pH by bringing the plasma more acidic
56
Kidneys secrete ammonia
2 buffer systems in tubular lumen where urine is made - Why
As urine can only hold so many free H+ ions otherwise the pH would drop so slow that it would be unsustainable so tubules cannot maintain a urinary pH below ~ 5.5
=>Thus there are 2 systems to buffer this
57
During acidosis: low pH to buffer secreted H+ what are the 2 systems?
1. Filtered phosphate as a urinary buffer
2. Secreted NH3 as a urinary buffer
58
Filters phosphate as a urinary buffer - how does this work?
Monohydrogen phosphate HPO42- combines with
secreted hydrogen ions to form dihydrogen phosphate H2PO4 - which is then excreted in the urine.
59
Secreted NH3 as a urinary buffer - how does it work?
When acidosis exists, the tubular cells secrete
ammonia (NH3) into the tubular fluid once the normal
urinary phosphate buffers are saturated
60
What is respiratory acidosis? See slide 24
Acidosis that occurs when the lungs fail to remove excess carbon dioxide from our bloodstream during the process of respiration is respiratory acidosis.
61
What is metabolic acidosis? See slide 24
Acidosis that occurs when the digestive and urinary systems fail to breakdown and maintain the proper level of acids in the blood is known as metabolic
acidosis.
62
Ammonia genesis results in?
SEE SLIDE 23
Ammonia made by breaking down amino acids combination such as glutamine
Ammonia genesis results in lipid soluble ammonia which can react with H+ in the cell and then be pumped into the tubular fluid via anti-porter which also transports Na or the ammonia unbound by H+ ion can pass across the membrane as its lipophilic and combine with free protons in the tubular fluid to buffer those ions and this ammonium can be excreted in the urine
63
Is the excretion by kidneys a fast/slow process?
May take too long to prevent what?
Excretion by the kidneys is a relatively slow process,
and may take too long to prevent acute acidosis
resulting from a sudden decrease in pH (e.g., during
exercise).
64
Increased-breathing response to exercise helps to do what with pH and how?
The increased-breathing response to exercise helps
to counteract the pH-lowering effects of exercise by
removing CO2, a component of the principal pH
buffer in the blood.
65
Acid-base imbalances - Respiratory acidosis?
1. Plasma pH?
2. Primary disturbance?
3. Compensation mechanism?
1. Low
2. Increased pCO2
3. Increased renal net acid excretion with resulting increase in serum bicarbonate
66
Acid-base imbalances - Respiratory alkalosis?
1. Plasma pH?
2. Primary disturbance?
3. Compensation mechanism?
1. High
2. Decreased pCO2
3. Decreased renal net acid excretion with resulting decrease in serum bicarbonate
67
Acid-base imbalances - Metabolic1 acidosis?
1. Plasma pH?
2. Primary disturbance?
3. Compensation mechanism?
1. Low
2. Decreased HCO3^-
3. Hyperventilation with resulting low pCO2
68
Acid-base imbalances - Metabolic alkalosis?
1. Plasma pH?
2. Primary disturbance?
3. Compensation mechanism?
1. High
2. Increased HCO3^-
3. Hypoventilation with resulting increase in pCO2
69
Metabolic acidosis includes all types of acidosis other than those caused by what?
Caused by excess CO2 in body fluids
70
Metabolic acidosis causes? 5
– Severe diarrhea
– Diabetes mellitus
– Strenuous exercise
– Renal failure
– Side effect of potassium-sparing diuretics
(spironolactone, eplerenone, amiloride)
71
Metabolic acidosis compensations: 3
– Buffers take up extra H+
– Lungs blow off additional H+ generating CO2
– Kidneys excrete more H+ and conserve more HCO3
72
What can metabolic acidosis cause in relation to the heart?
Tachyarrhythmias
73
Hyperventilation can happen in response to?
Metabolic acidosis
74
What is Kussmaul respiration?
Is deep, sighing breaths in severe metabolic acidosis (it helps to blow off CO2), eg diabetic or alcoholic ketoacidosis, renal impairment.
75
During respiratory acidosis - what happens to CO2?
↑ CO2
Result of abnormal CO2 retention arising from hypoventilation
76
Possible causes of respiratory acidosis? 5
Lung disease - most commonly chronic obstructive pulmonary disease
Depression of respiratory center by drugs or disease
Nerve or muscle disorders that reduce respiratory muscle activity
Holding breath
Airway obstruction
77
2 compensations for respiratory acidosis include?
– Chemical buffers immediately take up additional H+
– Kidneys are most important in compensating for respiratory acidosis
78
Symptoms of respiratory acidosis?
Dyspnea, disorientation or coma, headache and drowsiness, hyperkalemia or hypoxemia
79
Treatment of respiratory acidosis? 5
Treat underlying cause, monitor ABGs, support ventilation, correct electrolyte balance and iV sodium bicarbonate
80
Causes of metabolic alkalosis? 4
– Vomiting
– Burns
– Ingestion of alkaline drugs
– Thiazide diuretics, K+ sparing diuretics
81
What is metabolic alkalosis?
Reduction in plasma [H+], pH caused by relative deficiency of non-carbonic acids
82
Compensations for metabolic alkalosis?
Chemical buffer systems immediately liberate H+
Ventilation is reduced
If condition persists for several days, kidneys conserve H+ and excrete excess HCO3- in the urine
83
Symptoms of metabolic alkalosis?
Confusion due to decreased LOC, dizzy, irritable, nausea, vomiting, diarrhea, restlessness followed by lethargy, hypokalemia, tremors, muscle cramps, tingling of fingers and toes, compensatory hypoventilation , dysrhythmias: tachycardia
84
Possible causes of respiratory alkalosis?
Physiologic mechanisms at high altitude
CNS causes: Stroke; subarachnoid bleed; meningitis.
Others: Mild/moderate asthma, anxiety; altitude; high temperature; pregnancy; pulmonary emboli (reflex hyperventilation); drugs, e.g. salicylates (Aspirin).
85
Compensations 2 of respiratory alkalosis?
– Chemical buffer systems liberate H+
– If situation continues a few days, kidneys compensate by conserving H+ and excreting more HCO3 -
86
What is respiratory alkalosis?
Primarily due to excessive loss of CO2
from body as result of hyperventilation
87
Vitamin D what happens in kidney?
Conversion of Vit D to calcitriol
Enhances Ca2+ absorption
Increases Ca2+ in plasma
88
What is Rickets?
SEE SLIDE 35
Softening and weakening of bones in children, usually because of an extreme and prolonged vitamin D deficiency
89
Active and transcellular Ca2+ transport is
carried out as a three-step process:
1. Entry of Ca2+ through the (hetero)tetrameric epithelial Ca2+ channels, TRPV5 and TRPV6
2. Ca2+ bound to calbindin diffuses to the basolateral membrane.
3. At the basolateral membrane, Ca2+ is
extruded via a ATP-dependent Ca2+ -
ATPase (PMCA1b) and a Na+ /Ca2+ exchanger (NCX1).
90
The active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3 ], stimulates?
The individual steps of transcellular Ca2+ transport by increasing the expression levels of the luminal Ca2+ channels, calbindins, and the extrusion systems.
91
[Ca^2+] plasma value?
~2 mmol/L
92
What is the mechanism of epithelial Ca^2+ transport?
Epithelia can absorb Ca2+ by paracellular
and transcellular transport.
Passive, paracellular Ca2+ transport takes
place across the tight junctions driven by
the electrochemical gradient for Ca2+ (blue
arrow).
93
Respiratory alkalosis? What happens to body - symptoms:
Seziures
Increased anxiety
Increased irritability
Hyper reflexes and muscle cramping
Decreased or normal BP
Tachycardia
Numbness and tingling of extremities
Hyperventilation: increased rate and depth
