acid base homeostasis Flashcards
(117 cards)
1
Q
what is the total CO2 produced per day?
A
25mol
2
Q
what is the total of unmetabolised acid produced per day?
A
50mmol/day and plasma [H+] is 40nmol/L
3
Q
what does the maintenance of plasma H+ depends on when there is enormous turnover?
A
buffers, nitrogenous waste and carbon dioxide excretion
4
Q
what is the cycle of metabolism in H+ maintenance?
A
metabolism feeds in as an input to the maintenance of normal H+ which then has buffers controlling it. The output then goes to the kidney as H+ and the lungs as CO2
5
Q
where does H+ production come from?
A
incomplete metabolism of glucose - intermediary anaerobic process where glucose - 2 lactate + 2H+
incomplete triglyceride metabolism resulting in ketogenesis where triglycerides make free fatty acids and H+ and then free fatty acids make ketones and H+
amino acid metabolism (ureagenesis) where the metabolism of neutral amino acids generated H+
6
Q
where does glucose metabolism occur?
A
mainly in the skeletal muscles and RBCs
7
Q
where does triglyceride metabolism and ketogenesis occur?
A
triglyceride metabolism in the adipose tissue to make FFAs and to make ketones is in the liver
8
Q
what is the H+ concentration like and why is it so tightly controlled?
A
it is low in relation to other concentrations of major ions and cannot be allowed to rise or fall by a lot because H+ will avidly bind to proteins changing their conformation and structure
9
Q
what are the other major ions in the plasma and what are their concentrations?
A
Na+ = 140mmol/L K+ = 4.5mmol/L Cl- = 100mmol/L HCO3 = 25mmol/L
10
Q
what is the role of buffers?
A
they buffer H+ in mmol quantity but must keep it in nmol quantity
11
Q
what are buffering systems?
A
they are solutions which resists change to pH when an acid or base is added and ensure that H+ can be transported and excreted without causing damage to physiological processes
12
Q
what are the main buffering systems?
A
bicarbonate, ammonia, phosphate, haemoglobin and proteins
13
Q
what are acids and bases and give example equations?
A
acids are proton donors - Hcl - H+ + Cl-
bases are proton acceptors - OH + H+ - H2O
14
Q
what is pH?
A
it is the negative logarithm of the hydrogen ion concentration - pH = -log10[H+]
ph + log10(1/[H+])
15
Q
why are logarithims used?
A
to make the wide range of H+ concentrations seen - more manageable
16
Q
what is the normal range for pH and H+ in a patient?
A
pH from 7.35-7.45 and H+ from 35-45nmol/L
17
Q
what is acidosis?
A
it is the abnormal processes or conditions that lower the arterial pH
18
Q
what does a ph<7.35 mean?
A
the hydrogen concentration is >45nmol/L and the patient is acidaemic and vice versa for alkaemic
19
Q
what is Ka and pKA?
A
in chemistry p means the negative logarithm of and therefore as the Ka is the acid dissociation constant the pKa is the negative logarithm of this
20
Q
what are the values for pKa and Ka if the acid is strong?
A
the pKa is low and the Ka is high
21
Q
if HA - A- +H+ then what does Ka equal?
A
Ka = ([A-][H+])/[HA]
A- is the conjugate base
22
Q
in physiology why is CO2 an acid and HCO3 a base?
A
H2O + CO2 - H2CO3 - HCO3- + H+
23
Q
what is the henderson hasslebalch equation?
A
it explains how acids and bases contribute to pH
pH = pKa + log10([base]/[acid])
24
Q
how is CO2 an acid?
A
when dissolved in plasma it makes H2Co3 which is carbonic acid and then readily dissociates to H+
25
what is the pathway of HCO3-
it acts as a base - it accepts H+ to form carbonic acid and then is converted to CO2 for excretion from the lungs
26
what does blood pH depend on?
not the amounts of CO2 or HCO3 but the ratio between them
27
what is the concentration of CO2?
it is pCO2 (partial pressur of CO2) x solubility constant (a = 0.225 for CO2)
28
what will the pH of the blood be in a bicarbonate buffering is pKA is 6.1?
pH = 6.1 + log10([HCO3-]/(pCO2xa)) - Ph will be proportional to [HCO3-]/pCO2
29
why can HCO3- not buffer CO2?
because of the equation so would just result in more CO2 being produced - equilibrium of CO2 therefore relies on non bicarbonate buffers
30
what are phosphate buffers important in?
concentrations of them are too low to make an appreciable difference in plasma but form an important buffer in urine
31
what in the phosphate buffering system makes a buffer pair?
monohydrogen phosphate and dihydrogen phosphate - HPO42- + H+ - H2PO4-
32
what else forms a buffer pair?
ammonia and ammonium ions - NH3 + H+ - NH4+
33
what is NH3 used for?
important buffer in urine
34
how is most ammonia in body stored?
in ammonium ion form
35
what is Hb with regards to buffering?
it is a non bicarbonate buffer and therefore is important for buffering CO2 - it reduced CO2, produced HCO3 and forms HHB from Hb
36
what is the cycle of buffering in RBCs
CO2 in plasma diffuses in and reacts with water using carbonic anhydrase to make H2CO3. This then makes HCO3- which diffuses out into the plasma and H+ which reacts with HBO8 to make HHb and 4O2 which then diffuses out into the plasma. Cl- from plasma also diffused in due to chloride shift
37
how do proteins buffer?
they have weakly acidic and basic groups due to their amino acid composition and therefore can donate and accept protons to some extent
38
what is the main plasma protein?
albumin - it is a net negatively charged protein that can mop up H+
39
what other proteins also play a role in buffering?
bone proteins
40
what does the liver do?
it is a site of acid base metabolism and is the dominant site of lactate metabolism in the Cori Cycle. It is the only site of urea synthesis which is a waste product of ammonia metabolism
41
how can lactic acidosis result?
from increased production such as in anaerobic glycolysis or from decreased consumption such as in liver disease - metabolic acidosis
42
what does hyperammonaemia result from and what does it result in?
it is when the liver is unable to perform urea cycle which usually converts toxic ammonia to urea for excretion. It can occur in liver failure and the ammonia will then stimulate the respiratory centre resulting in hyperventilation which causes the patient to blow off CO2 and results in respiratory alkalosis
43
what is glycolysis?
occurs in the muscle and is glucose conversion to lactacte with production of ATP
44
how can decreased consumption in the Cori cycle result in lactic acidosis ?
a decrease of fatty acids mean that less ATP is produced so lactate in the liver cannot be converted to glucose through gluconeogenesis
45
what are the functions of the lungs?
excretion of CO2 - respiratory control mechanisms are extremely sensitive to pCO2 and in a healthy person the rate of elimination will be equal to the rate of production meaning that the pCO2 will be constant
46
what is the oxyhaemoglobin curve?
describes the relationship between pO2 and % saturation
47
what will happen when pO2 increases or decreases?
increase - O2 will bind to Hb - high affinity therefore the curve shifts left and decrease is opposite
48
what is needed when the curve shifts to the right?
it means that Hb has reduced its affinity for O2 because the pO2 has decreased so it is being released so a higher pO2 is needed to maintain the saturation
49
when will affinity reduce and curve shift right?
increase in body temperature, increase in carbon dioxide or acid, increased 2-3DPG and hypoxia or anaemia
50
why does increased H+ result in shift to right?
increases the Bohr effect - higher H+ will alter the amino acid residues on the Hb molecules meaning that the deoxyhaemoglobin is stabilised so has a lower affinity for O2 in this state
51
when will the curve shift left?
reduced temp, reduced 2-3 DPG, decreased H+ and CO
52
what are the kidneys for?
the excretion of H+ ions and regeneration of HCO3- in the distal tubules and the reabsorption of HCO3- in the proximal tubule resulting in acidic urine with almost no bicarbonate
53
what happens in the distal tubules?
HCO3- is generated from CO2 and H2O under the action of carbonic anhydrase which then dissociates into H+ and HCO3-
H+ actively secreted as H2PO4 dihydrogen phosphate ions into glomerular filtrate in exchange for Na+
Na+ and HCO3- are then pumped into the plasma
continued formation of H+ in renal tubular cells that is accompanied by generation of HCO3- through the excretion of H+ which will maintain the buffering capacity
54
why is bicarbonate reabsorbed?
some of the CO2 that is formed from the excreted H+ and HCO3- is already present in the glomerular filtrate and will diffuse into the tubular cells to provide substrate for continued formation of H2CO3
55
why can bicarbonate not be reabsorbed directly and has to be broken down to CO2?
lumeal membranes are impermeable to it
56
how does glutamine make urine?
glutamine is converted to glutamate and gives of NH4+. Glutamate is then converted to a-ketoglutarate giving of NH4+. These are then converted to NH3 which with H+ and a base makes urine
57
what is the role of aldoesterone?
mineralocorticoid action in the kidney - excretion of potassium and hydrogen ions are excreted into the distal tubule with the reabsorption into the tubular cells of Na+. An increase of aldosterone will lead to an incrase in sodium reabsorption and therefore increase in excretion of Na+ and K+
58
how does the GIT buffer?
H+ secreted into stomach bu Hcl and HCO3- into duodenum from pancreas to neutralise the stomach acid
59
what can some chemicals and the G6PD mutation result in?
MetHb - the Hb is in the Fe3+ state rather than 2+ - doesn't have the same affinity for O2
60
what must blood gas analysis samples be?
well mixed, heparinised whole blood and no air bubbles. They must be analyses immediately and not sent via pneumatic tubes
61
what is the standard sample of blood gas and what is it particularly good for?
the arterial and if paricularly interested in pO2
62
what is the result of air bubbles?
they can affect PO2, which can cause often clinically insignificant increase in pH and decrease in pCO2
63
why must samples on blood gas be done immediately?
there is a time dependent increase in pCO2 due to ongoing in vitro glycolysis and decrease in pO2
64
what is the result of doing a blood gas sample in pneumatic tube?
will cause any air present in the sample to mix rapidly which changes the partial pressure of gases within it
65
what is looked for on a blood gas machine?
gases - pO2 and pCO2
pH
metabolites - glucose and lactate
electrolytes - sodium potassium chloride and calcium
co-oximetry - total Hb, oxygen sats, oxyHb, COHb and MetHb
derived parameters - base excess and standard bicarbonate, total CO2 and anion gap
66
what is metabolic acidosis/alkalosis?
it is a primary disorders of acid base pathology that is caused by no respiratory elements - acidosis is a reduction in HCO3- and vice versa
67
what is respiratory acidosis/alkalosis?
it is a primary disorder that is caused by altered respiration - acidosis is caused by increased pCO2 and vice versa
68
what are compensatory mechanisms?
changes in bicarbonate concentration from renal regeneration that can occur to compensate for respiratory disorders - slow
changes in pCO2 and RR to occur to compensate for metabolic disorders - fast
69
what is the point of compensatory mechisms?
aim to restore a neutral pH - full compensation will rarely occur
70
which is the only compensatory mechanisms that fully compensates?
chronic respiratory alkalosis
71
when do you expect mixed disorders?
when the pH is within the reference range but bicarb and CO2 are not - compensation will fall outside of the expected limits
72
what are the reference ranges?
they are different in every hospital so check each time
73
what is the reference range for main lab bicarbonate?
it is an approximation of bicarbonate that is calculated in part from CO" - it is sometimes called total CO2 with a range of 22-29mmol/L
74
what is the standard bicarbonate?
it is a calculated parameter that removes all of the respiratory contribution. Therefore any abnormalities that are within the reference range will be respiratory but if the range is abnormal then will be metabolic. Standard is not often used and therefore assume main lab. The range is 22-26mmol/L
75
what are two other methods of estimating buffers?
the anion gap and the base excess
76
what is the base excess?
it is the amount of acid or alkali needed to titrate the blood pH to 7.4 - takes into account all buffers not just bicarbonate. It tells us if there is a metabolic component to the disorder. it goes from -2.3 - 2.3 mmol.L - negative will be metabolic acidosis below -2.3 - base decifict,and above 2.3 will be metabolic alkalosis - base excess
77
what is the anion gap?
it is the difference between the sum of measured anions and cations and therefore will not be zero in healthy patients because not all anions are taken into account. The equation is ([Na+]+[K+]) - ([Cl-] = [HCO3-]) and an increased anion gap shows that there are significant amount of unmeasured anions present which could be lactate, ketones, salicylate, proteins
78
what are the signs of metabolic acidosis?
subjective dysponea (respiratory stimulation), nausea, vomiting, anorexia, deep laboured breathing pattern known as Kussmaul breathing and other symptoms from the underlying disorder
79
what is the underlying biochemistry of metabolic acidosis?
it is pCO2, HCO3- and pH decrease, and H+ and pO2 increase
80
what are the causes of metabolic acidosis?
increased acid formation, acid ingestion, loss of bicarbonate or decreased acid excretion
81
how does increased acid formation occur?
there is an increased anion gap plus uraemia - this can be from ketoacidosis in starvation, alcoholics or diabetics. lactic acidosis type A - tissue hypoxia or B - metabolic or toxic causes, poisoning from salicylate or toxic alcohols or inherited organ acidosis
82
how can loss of bicarbonate occur?
GI - diarrhoea or fistula
| renal - RTA type 2 (proximal) or carbonic anhydrase inhibitors such as acetazolamide
83
how can decreased acid secretion occur?
from uraemia which can be from renal failure or from RTA type 1 which is distal
84
what is RTA?
renal tubular acidosis
85
what are the physiological responses to metabolic acidosis?
there is buffering or compensation
86
what comprises buffering in MAcid?
the acute H+ increase is resisted by bicarbonate meaning this will decrease, and proteins are important in chronic acidosis
87
what comprises compensation in MAcid?
there is respiratory - this is self limiting as it overall generates CO2 but the respiratory centre is stimulated and the patient will hyperventilate so blows off CO2
there is also renal where the turnover of HCO3- is increased and the urine H+ excretion is maximised
88
what is the management of MAcid?
identify and treat the cause - carefully give IV sodium bicarbonate if the pH is less than 7 and oral bicarbonate in CKD and RTA types 1 and 2
89
what are the risks of bicarbonate treatment in MAcid?
there is rebound alkalosis possible and rapid correction will impair the oxygen delivery
90
what is the typical biochemistry of Malk?
the pH, HCO3- and pCO2 increases and the pO2 and H+ decreases
91
what are the signs of Malk?
usually relate to the underlying disorder - more severe alkalosis will increase the protein binding of Ca2+ meaning that there is hypocalcaemia - this means there can be headaches, lethargy and neuromuscular excitability which is sometimes with delerium tetany and seizures. There will also be a lowered threshold for arrhythmias
92
what are the causes of Malk?
there is loss of H+ from vomiting, bicarbonate administration or potassium depletion in the cells or kidneys
93
why does H+ decrease in cells and in the kidneys?
in the cells K+ is transported out of RBCs to increase the plasma concentration however this results in H+ ions moving into the cells to maintain electroneutrality leading to plasma decrease in plasma H+
in the kidneys H+ is excreted favourable over K+ to maintain the K+ for the aldosterone controlled renal transporter
94
what is the physiological response to Malk?
there is buffering resulting in the release of H+ from buffers and compensation which is in the kidneys or respiratory?
95
what comprises respiratory?
reduced respiration rate to retain CO2 - self limiting as an increase in pCO2 will stimulate the respiratory centre
96
what comprises renal compensation?
it is difficult to identify but a decreased GFR will lead to inappropriate bicarbonate reabsorption and potassium deficiency will lead to persistence of alkalosis
97
what is the treatment of Malk?
treat the underlying cause and treat factors that allow the persistence of alkalosis such as replacing the potassium
98
what is the typical biochemistry of Racid?
the pH, pO2 decrease and the H+, CO2 and HCO3- increase
99
what are the signs of Racid?
they are relating to the underlying disorder but may complain of dyspnoea
100
what are the causes of Racid?
defective control of respiration (CNS depression or disease or neurological disease) or defective respiratory function (pulmonary disease or mechanical)
101
what comprises CNS disease or depression?
CNS depression - anaesthetics, sedatives, opiates or narcotics
disease - trauma, haemorrhage, infarction, tumour or infection
102
what comprises neurological disease?
spinal cord lesions, Guillain-Barre syndrome or MND
103
what comprises mechanical defective function?
pneumothorax, myopathies, pleural effusions or inadequate mechanical ventilation
104
what comprises pulmonary disease?
COPD, severe asthma, impaired perfusion (massive pumonary embolism)
105
what is the physiological response to Pcid?
buffering - limited by haemolglobin
compensation: renal - maximal bicarbonate reabsorption, all phosphate excreted as H2PO4 not HPO42- and increase in urinary NH4+
respiratory - increase in pCO2 stimulating the respiratory centre
106
what is the management of Racid?
treat underlying cause, maintain adequate pO2 and avoid hypoxia to respiratory centre, avoid rapid pCO2 correction for risk of alkalosis
107
what is the typical biochemistry of Ralk?
ph, pO2 will increase and HCO3-, pCO2 and H+ decrease
108
what are the signs and symptoms of Ralk?
related to underlying cause but increased protein Ca2+ binding, hypoglycaemia, lethargy, headaches, neuromuscular excitability, tetany, delerium and seizures
109
What are the causes of Ralk?
central (head injury, trauma, cytokine sepsis, salicylate drugs, hyperventilation and liver disease toxins)
iatrogenic (excessivle mechanical ventilation)
pulmonary (embolism, oedema, pneumonia or asthma)
110
what is the physiological response to Ralk?
there is buffering (release of H+ from non bicarbonate buffers) or compensation (inhibitory effect of decreased CO2 is overwhelmed by primary cause) and renal (reduced HCO3- regeneration through the preservation of the CO2 substrate)
111
what is the management of Ralk?
treat the underlying cause, rapid symptomatic release by rebreathing and sedation or prevention of hyperventilation
112
what are the different types of compensation?
full - returns pH to normal
partial - not returned to normal
over does not occur in any acid-base disorder
113
what will a pCO2 decrease and a a pH increase be?
respiratory alkalosis
114
what will a HCO3- increases and a pH increase be?
metabolic alkalosis
115
what are mixed disorders?
they are two or more primary acid base disorders presenting in the same patient that can be additive or counter balancing
116
what are the results of additive mixed disorder?
vomiting and CCF - metabolic alkalosis presents with loss of H+ and respiratory alkalosis increased respiratory rate
respiratory failure
respiratory acidosis - increased pCO2 and metabolic acidosis will be increased lactic acid
117
what is the result of a counter balancing disorder?
salicylate poisoning resulting in metabolic acidosis and respiratory alkalosis and vomiting and renal failure results in metabolic alkalosis and acidosis (decreased renal H+ excretion)
