Acid Base Flashcards
Delta ratio
Used to determine if there are multiple processes in met acidosis
Change in AG/change in bicarbonate
<0.4 - NAGMA
0.4-0.8 - mixed
1-2 - HAGMA
>2 - HAGMA with pre-existing met alkalosis
Urinary AG
Na + k - cl
Differentiate between renal and GI cause for NAGMA
Renal causes - increased (due to increased urinary bicarb)
GI causes - decreased (due to increased ammonia secretion)
Base excess vs standard base excess
BE - dose of acid or base required to return the pH to 7.4 of a while blood sample, at 37 deg, PaCO2 40 (isolates the metabolic disturbance from the respiratory)
standard base excess -
dose of acid or base required to return the pH of an anaemic blood sample to 7.4, calculated for Hb 50g/l
- assesses the buffering of whole extracellular blood, not just Hb rich intravascular fluid
Normal SBE with abnormal anion gap -
HAGMA with pre-existing met alkalosis
Negative SBE with normal anion gap
anion gap uncorrected for a low albumin
NAGMA
Boston rules - acute resp acidosis
For every 10mmHg rise in PaCO2 the bicarb will increase by 1
Boston rules - chronic resp acidsis
for every 10mmHg rise in PaCO2 the bicarb will rise by 4
Boston rules - Acute resp alkalosis
for every 100mmHg decrease in PaCo2 the bocarb will fall by 2
Boston rules - metabolic acidosis
PacO2 = (1.5x bicarb) + 8
Boston rules - met alkalosis
PaCo2 = (0.7 x bicarb) + 20
Causes of rasied Anion gap
Ketoacidosis - alcohol, starvation, diabetic Metformin uraemia pyroglutamic acidosis iron, isoniazid lactate ethylene glycol salicylates
Osmolal gap
scans for unmeasured osmotically active molecules
difference between measured and calculated osmolality
normal gap is <10mOsmol/kg
Causes of raised gap
- methanol
- etylene glycol
- manninol
- glycine
- acetone
- glycerol
Causes of normal anion gap and high osmolar gap
Any substance administered into bloodstream which does not dissociate into bloodsream to change pH
Mannitol glyceine non-metabolised glycols maltose ethanol
Albumin (falsely normal AG)
Causes of high anion gap and high osmolar gap
Endocrine and metabolic causes -
- lactate
- alcoholic or diabetic ketoacidosis
- acute kidney injury
Toxicological causes -
- methanol intoxication (anion is formic acid)
- ethylene glycol (anions are glycolic and oxalic acid)
- salycilate (anions are salycilate and lactate)
- any toxin causing a massive lactic acidosis 0 eg isoniazid
Causes of high anion anion gap and normal osmolar gap
abnormally large value of albumin
late stage toxic alcohol intoxication (the extra osmoles have been metabolised)
Clinical features of acidosis
Most severe at pH <7.2 (7.15 when try to correct)
Reduced myocardial contractility, arrythmias, systemic arteriolar dilatations, venoconstriction, centralisation of blood volume
Pulmonary vasoconstriction, hyperventilation, respiratory muscle failure
Reduced splanchnic tone and renal blood flow
Increased metabolic rate, catabolism, reduced ATP synthesis
Conusion, drowsiness
Increase iNO expression, pro-inflammatory cytokine release
Hyperglycaemia, hyperkalaemia
Cell membrane pump dysfinction
Bone loss, muslce wasting
specific issues with formate
blindness and cerebral oedema
specific issues with oxalate
crystalluria, renal failure, hypercalcaemia
specific issues with salycilate
tinnitus, hyperventilation and fever due to uncoupling of oxidative phosphorylation
Approach to metabolic acodisis
Anion Gap - ?unmeasured anions, if normal - changes in bicarb or chloride are the cause
Delta ration - quantifies the conribution of anions and chloride/bicarb to the change in pH
- can identify mixed diosrders
Urine anion gap (for NAGMA) -
high - renal cause
low or negative - GI
Caculate osmolar gap (for HAGMA)
Causes of NAGMA
CAGE
CHloride
acetazolamide/addisions
GI loss - diarrhoea, fistulae, ureteroenterostomies, pancreatoenterostomies
Extras - RTA, recovery phase of DKA
RTA types
Type 1 -
- distal - continues to resporb cl despite acidosis
- severe acidosis
- severe hypOK
- urine very alkaline
Causes - autoimmune disease, hyperCa conditions, post renal Tx, wilsons disease, drugs - cyclophosphamide
Type 2 -
- proximal - interefence with bicarb resorption (bicard is excreted when it shouldn’t be)
- moderate acidosis
- moderate hypOK
- caused by fanconi syndrome, amyloid, light chain disease, drugs - lead, acetazolamide
- need huge intake of bicarbinate to correct
Type 4 - hypoaldosteronism/hypoadrenalism cause metabolic acidosis by causing loss of renal sodium and decreasing chloride secretion
- mild acidosis
- hypERK
Causes
- failure of renin secretion
- angiotensin system failure - ACEi, ARBs, heparin
- decreased aldosterone secretion - primary hypoaldosteronism, prin=mary adrenal insufficiency, steroids, NSAIDS, critical illness
- aldosterone receptor malfunction - calcineurin inhibitors (tacro), spinonolactone
- ENaC Na channel blockade (aldosterone responsive epithelial Na channel) - amiloride, trimethoprim
Treated with synthetic mineralicorticoid eg fludrocortisone
Types of lactic acidosis
A - impaired tissue oxygention
- shock, regional ischaemia, severe hypoxia, severe anaemia, carbon monoxide poisoning
B1 - due to disease state
- malignancy, thiamine deficiency, ketoacidosis, HONK, spetic shock, impaired hepatic or renal clearance
B2 - drug induced
- beta2 adrenoceptor agonists
- metformin
- cyanide
- isoniazid
- propofol
- toxic alcohols eg methanole
- salycilates
B3 - inborn errors of metabolism
- pyruvate dehydrogenase deficicney
- electron transport chain defects
- G6PD
Causes of raised lactate in sepsis
endogenous catecholamine release and administration of infusions
circulatory failure due to hypoxia and hypotension
microvascular shunting
inhibition of pyruvate dehydrogenase by endotoxin
coexistant liver disease
slowed hepatic blood flow, impairment clearance
D lactate
produced by bacteria in the colon and usually we can metabolise large amounts
D lactate is not routinely measured, and so may be a cause of a HAGMA with ‘normal’ lactate
Present with neurological symptoms - confusion, slurred speech, obtundation, ataxia
Risk factors -
- short gut
- post-pancreatectyom who dont take enzyme supplements
- patients to take extra lactobacillus
- symptoms are exacerbated by food intake (cardbohydrate is fermented -> D lactate)
Pyroglutamic acidosis
rare, but lots of SAQs
occurs due to glutathione depletion in patients who are already glutathione deplete
Mechanism -
- pyroglutamic acid is produced by an enzyme that is stimulated with low glutathione stores -> accumulation of pyroglutamic acid
May be depleted by
- sepsis
- paracetamol
chronically by - liver disease and malnutrition
Diagnosis depends on detection of 5-oxoproline (urinary or serum level)
Risk factors -
- paracetamol
- sepsis
- chronic alcohol/liver failure of any cause
- old age
- weird diet/malnutriotn
- flucloxacillin, vigabatrin (cause dysfunction of 5-oxoprolinase)
- renal failure
Mx -
- cessation of causative agent (if present)
- NAC
Pathophysiology of ketoacidosis
genertion of ketones is normal response to fasting (following depletion of hepatic glycogen stores)
In glucose-poor environment - too much oxaloacetate is diverted away into gluconeogenesis
-restricts entry of acetyl-coA in to Krebs cycle -> diverted in ketogenesis
Also an increase in beta-oxidation of fatty acids (lipolysis)
Starvation -> decreased insulin and increased lipolysis -> increased delivery of FFAs to liver which exceeds capacity of ACoA to enter krebs cycle -> ketogenesis
Types of ketoacidosis
starvation (after 3 days) - due to decreased intake of carbs, decreased insulin. Ketogensis due to inadequate glycogen stores
- mild acidosis
- low ketones
- BSL low
- concerns about refeeding sydrome
Alcoholic - starvation following a binge
- hepatic metabolism of ethanol depletes NAD and increases NADH -> favours converstion of acetoacetate to beta hydroxybutyrate
- moderate acidosis, low BSL
Diabetic
- absence of insulin and presence of stress hormones/glucagon -> hepatic lipid metabolism switches to ketogenesis
Toxic alcohols
contribute to HAGMA by being metabolised
Alcohol dehydrogenase is the enzyme common to all
- if this is blocked, the alcohols are benign (and are excreted rapidly via kidneys)
Ethanol -> acetate
Methanol -> formate
Ethylene glycol -> glycolic acid
- one mouthful is enough
- stages 1) intoxication (high AG but no acidosis) 2) coma and seizures with metabolic acidosis 3) cardiac toxicity
- key diagnostic feature is calcium oxalate crystals
Management - bicarbonate and alcohol (to overwhelm alcohol dehydrogenase), fomepiozole, dialysis
Ethylene glycol treatment
bicarbonte
Ethanol
fomepizole (competitive anatagonist to alcohol dehydrogenase)
Dialysis - main indication is high osmolar gap
Causes of metabolic alkalosis
Exogenous strong cation excess -
- Na bicarb or citrate
- beta lactam
- hypercalcaemia
Primary derangement of homeostatic mechanisms -
- failure of bicarb in ESRF
- hypoalbuminaemia
Enteric chloride depletion -
- gastric loss or loss due to villious adenoma
Renal chloride depletion -
- diuretic induced
- post hypercapnic state
- Bartters and Gitelmmans, cyctic fibrosis
- hypokalaemia, HypoMg
Mineralocorticoid excess -
- renin secreting adenoma
- RAS
- primary hyperaldosteronism
- steroid administration/cushings
How to determine cause of met alk
History - ?beta lactams, steroids, CF Urinary chloride Blood pressure trends Serum renin levels Serum aldosterone levels
Causes of respiratory acidosis
Increased inspired fraction of CO2
Decreased alveolar ventilation (increases by 3mmHg for each minute of apnoea)
Increased metabolic CO2 production
Calculation of bicarb dose
body weight x 0.3 x SBE
body weight x0.3 x (desired bicarb - measured bicarb)
Adverse effects of Na bicarb
phlebitis hyperNa volume overload HypOK ionised hypOCa left shift of ODC impaired clearance of lactate intracellular acidosis (maybe) hypercapnea
ABG changes in pregnancy
increased pH decreased CO2 increased O2 decreased bicarb 2.3DPG increases p50 remains the same becuase of the alkalosis
