Nephrology JC070: Electrolyte And Acid-base Disorders Flashcards
Physiology of Kidney
Proximal tubule:
- Reabsorb ***NaCl, Glucose, a.a., fluids, HCO3
- Secrete drugs, poisons, H
LoH:
- Concentration gradient created for subsequent H2O reabsorption
- Thin Descending limb permeable to H2O only —> **H2O leave into interstitium by osmosis
- Thick Ascending limb permeable to NaCl only —> actively **pump Na out —> create salty interstitium —> draw H2O from Descending limb + Collecting duct
Distal tubule:
- Fine tuning of electrolyte + acid-base
- some NaCl reabsorption
- ***K, H excretion
Collecting duct:
- **NaCl, **Urea, H2O reabsorption by concentration gradient created by LoH
Common acid-base + electrolyte problems
記: pH, Na, K
- Acidosis
- Metabolic
- Respiratory - Alkalosis
- Metabolic
- Respiratory - Na
- Hypo
- Hyper - K
- Hypo
- Hyper
Definition of Acid-base disorders
Acidaemia: [H] > normal
Alkalaemia: [H] < normal
Acidosis: a process leading to ↑ in plasma [H]
Alkalosis: a process leading to ↓ in plasma [H]
Normal pH: **7.4 (7.35-7.45) ([H]: **40 nmol/L)
- lethal: pH <7.1 / >7.7
Compensation mechanisms:
- Lungs: **immediate
- Kidneys: take **several days
When well compensated:
- no acidaemia / alkalaemia despite an underlying acidosis / alkalosis process
Compensatory mechanisms
Primary metabolic acidosis (↓ HCO3):
- stimulate respiratory centre —> ↓ pCO2 —> compensatory respiratory alkalosis
Primary metabolic alkalosis (↑ HCO3):
- suppress respiratory centre —> ↑ pCO2 —> compensatory respiratory acidosis
Primary respiratory acidosis (↑ pCO2):
- kidney compensate by conserving HCO3 —> ↑ HCO3 —> compensatory metabolic alkalosis
Primary respiratory alkalosis (↓ pCO2):
- kidney compensate by excreting HCO3 —> ↓ HCO3 —> compensatory metabolic acidosis
Metabolic acidosis
↓ HCO3 (***<22)
- normal [HCO3]: 22-28 mmol/L
- compensated with hyperventilation —> ↓ pCO2
Diagnosis:
1. Ensure this is Metabolic acidosis
- Determine Serum **Anion Gap (AG): high / normal
- Anion gap = **Na - Cl - HCO3 - Normal Serum AG acidosis
- determine Urine AG: [Urine Na + Urine K - Urine Cl] (advanced)
- NaHCO3 infusion / Acid loading test: Proximal / Distal RTA (advanced) - Look for any **Osmolar Gap (OG): Measured osmol - Calculated osmol
- detect **unmeasured osmotically active substances (e.g. toxic alcohols) - Any mixed acid/base disorder (ΔAG vs ΔHCO3)?
- too advanced for MBBS
Osmolar gap
Osmol gap = Measured osmol - Calculated osmol
***Calculated osmol: 2xNa + Urea + Glucose (cation = anion, other cations ~ bounded Na)
↑ Osmol gap: presence of unmeasured ***osmotically active substances (e.g. alcohol-related compounds ingestion)
Anion Gap
Universal law: Charges must be balanced
- Total plasma cations = anions
Plasma cations: Na, K, Ca, Mg
- only Na is present in significant + may have great variations
Measured anions: Cl, HCO3
Measured cations - Measured anion = **Unmeasured anion (i.e. AG)
- Anion gap = **Na - Cl - HCO3
- Normal anion gap: ~8-14
High AG acidosis vs Normal AG acidosis:
- similar Na levels
- both have ↓ HCO3
- **↑ Cl in normal AG acidosis
- **↑ unmeasured anions in high AG acidosis
***High AG acidosis
↑ AG: ↑ unmeasured anion in blood
Causes:
1. **Ketoacidosis: DKA, Alcoholic ketoacidosis
2. **Lactic acidosis
3. ***Renal failure (SO4, PO4, hippurate, others)
4. Ingestion of salicylate, formic acid (methanol), glycosylate (ethylene glycol)
5. Rhabdomyolysis (release of organic acids)
6. Altered AG in paraproteinaemia (e.g. ↓ in IgG gammopathy, ↑ in IgA gammopathy)
***Normal AG acidosis
↑ [Cl]
Causes:
1. Loss of HCO3, with **compensatory ↑ Cl (via **Anion exchanger Cl/HCO3)
- GI loss: **Diarrhoea
- Renal loss: **Proximal RTA (Type 2: Fail to reabsorb HCO3), ***Carbonic anhydrase inhibitor
- Failure to excrete H
- **Distal RTA (Type 1: Fail to excrete H, reabsorb K —> hypoK acidosis)
- **Type 4 RTA - Ingestion of excessive Cl
- ***NH4Cl - Increased reabsorption of Cl
- Ureterosigmoidostomy
***L-Lactic acidosis
Overproduction of L-lactate —> ∵ **O2 deficiency (type A)
1. **Circulatory problems (e.g. hypotension, shock)
2. **Respiratory problem —> hypoxia
3. **Hb problem (e.g. CO poisoning)
4. ↑ Metabolic demand (e.g. grand mal seizure, severe exercise)
—> Rate of production can be up to 72 mmol/min with total hypoxia in type A (hypoxia)
Reduced metabolism of L-lactate **without hypoxaemia (type B)
1. **Liver problem
2. **Alcoholism
3. Thiamine deficiency
4. **Phenformin, Metformin
Diagnosis:
1. ***High AG metabolic acidosis
2. High plasma lactate level (normal <2)
Treatment:
1. Improve O2 delivery to tissue (most effective)
- correct hypotension, hypoxaemia
- NaHCO3 therapy ineffective unless lactate production controlled
- buy time for life saving
- Na load limits its massive use - Haemodialysis with ***HCO3 dialysis
***General management of Metabolic acidosis
- Determine cause of acidosis + treat underlying cause:
- some causes have independent threat to life e.g. methanol poisoning
- there maybe specific treatment for certain causes e.g. methanol poisoning - Correction of HCO3 by NaHCO3
Risk of NaHCO3 therapy
1. ***HypoK induction
—> shifting K into cells, esp. in patients with existing HypoK / loss of K with contracted ECF resulting normokalaemia (e.g. DKA)
-
**Hypocalcaemia
- esp. in CRF patients —> **tetany, seizure - Volume expansion form ***Na load
- 200 mmol NaHCO3 given —> 200 mmol Na given —> >1L of normal saline (156) - ***Paradoxical cerebral acidosis
- Too rapid correction —> too much HCO3 —> push equilibrium to make more CO2 —> diffuse into CSF from plasma (while HCO3 cannot diffuse through BBB) —> accumulation of CO2 in CSF —> ↑ H —> cerebral acidosis
How to use Urgent IV NaHCO3 replacement appropriately
- Estimation of HCO3 needed
- HCO3 deficit = HCO3 deficit in litre x HCO3 space (= BW x 0.6)
- usually only ***half the amount is given (BW x 0.3) - Give half of dose initially, recheck afterwards
- Only replace [HCO3] to safe level acutely (pH ~7.1), then followed by slower correction / correction by other means
- Beware of ***fluid overload esp. in oliguric patients
Renal Tubular Acidosis
Normal AG acidosis with:
1. Hypo K
- Proximal RTA (type 2: ∵ loss of HCO3 (∵ ineffective reabsorption in proximal tubule))
- Distal RTA (type 1: ∵ failure of H excretion)
- Mixed (type 3)
- Hyper K
- Type 4 RTA (aldosterone deficiency)
Proximal RTA (Type 2)
Normally HCO3 ***totally reabsorbed in proximal tubule if concentration below reabsorption threshold (~25 mmol/L)
Pathogenesis:
↓ HCO3 reabsorption threshold in proximal tubules
—> loss of HCO3 in urine —> low plasma HCO3
—> **normal AG metabolic acidosis with **compensatory HyperCl
- **alkaline urine despite acidosis, **urine pH usually >6
Effect:
1. **Loss of Na coupling with loss of HCO3
—> Hypovolaemia
—> **Hyperaldosteronism
—> ***HypoK
- Associated with Hyperphosphaturia, Hypercitraturia (preventing nephrocalcinosis / stones), Hyperuricuria
- Hyperphosphaturia
—> Rickets, Osteomalacia - Fanconi syndrome
- a pan-dysfunction of proximal tubules with **amino-aciduria, **glycosuria on top of RTA, hyperphosphataemia
Summary (↓ HCO3 reabsorption):
- Alkaline urine
- Na: ↓
- K: ↓ (hyperaldosteronism)
- HCO3: ↓
- Hyperphosphaturia —> Rickets, Osteomalacia
- Hypercitraturia
- Hyperuricuria
- Amino-aciduria, Glycosuria (Fanconi syndrome)
Distal RTA (Type 1)
Pathogenesis:
***Due to inability to excrete H:
1. Failure of pumping H against concentration gradient
- H/ATPase pump defect
- H back leak
- ↑ H permeability
Effect:
1. ***Urine pH always >6 ∵ failure to maintain a steep plasma-urine H gradient
- ↓ H excretion
—> ↑ K excretion for exchange of Na reabsorption in distal tubule
—> ***HypoK - Acidosis
—> ↑ Ca reabsorption from bone + ↓ Tubular Ca, PO4 reabsorption
—> Hypercalciuria, Nephrocalcinosis / stones
Summary (Inability to excrete H):
- Alkaline urine
- K: ↓ (↑ K excretion for exchange of Na reabsorption)
- Hypercalciuria, Nephrocalcinosis / stones
***Causes of Proximal + Distal RTA
Proximal RTA (type 2: HCO3 loss)
Hereditary
1. Cystinosis
2. Galactossaemia
3. ***Wilson’s disease
4. Lowe’s syndrome
Acquired
1. Dysparaproteinaemia
2. Toxins: Heavy metal poisoning
3. Drugs: **Carbonic anhydrase inhibitors
4. Renal disease: **Amyloidosis, renal transplant rejection, Sjögren’s syndrome
5. HyperPTH, HyperCa
Distal RTA (type 1: Inability to excrete H)
Hereditary
1. **Primary hypercalciuria
2. Marfan syndrome
3. **Ehlers-Danlos syndrome
Acquired
1. Autoimmune disease: **Sjogren’s, RA, SLE, PBC
2. Drugs: Amphotericin B, Lithium, Analgesic nephropathy
3. Renal disease: **CRF, urinary tract obstruction, interstitial nephritis, medullary sponge disease
4. **Paraproteinaemia, hypergammaglobulinaemia
5. **HyperPTH, hyperVit D
Diagnosis of RTA
Clinical suspicion when:
1. Normal AG acidosis with **HypoK
- hint: ↑ Cl with normal Na
2. Urine pH >5.5 (*Alkaline urine) in presence of acidaemia
Confirmatory tests:
1. **Fractional excretion of HCO3 (FE HCO3): Proximal RTA
2. **Acid loading test (NH4Cl): Distal RTA
Fractional excretion of HCO3
Test whether there is excessive HCO3 loss in urine
FE HCO3 = (Urine [HCO3] / Plasma [HCO3]) ÷ (Urine [Cr] / Plasma [Cr])
Proximal RTA: **>15% (i.e. HCO3 loss)
- sensitivity ↑ after **NaHCO3 infusion at 0.5-1.0 mmol/kg/hour to bring up plasma HCO3 level, urine pH >7.5
Distal RTA: normal (i.e. <5%)
Acid loading test (NH4Cl)
Test whether urine can be acidified: i.e. whether a steep H gradient across plasma and urine can be maintained
***Oral NH4Cl 0.1g/kg to bring acidosis
Normal: urine pH <5.5
***Distal RTA: urine pH remains >6.0 (i.e. Inability to excrete H)
Proximal RTA: variable
Type 4 RTA
Characterised by:
- Normal AG metabolic acidosis + ***HyperK (vs other RTA: HypoK)
Pathogenesis:
- ***Aldosterone deficiency / resistance
Aldosterone promotes distal K + H secretion, Na reabsorption
- Retention of K —> HyperK
- ↓ H excretion —> Acidosis (usually mild)
- Urine pH variable
Causes:
1. Drugs
- **ACEI, ARB
- **K sparing diuretics (spironolactone, amiloride, triamterene)
- Cyclosporin A, Tacrolimus
- ***Hyporeninism
- DM nephropathy - ***Renal failure
- ***Mineralocorticoid deficiency
- Kidney transplant rejection - tubulitis
Management of RTA
Type 1 and 2 RTA:
1. **Oral NaHCO3 to correct acidosis
- **very high dose is required in proximal RTA ∵ loss of HCO3 in urine
- **K citrate is a better alternative for Distal RTA (citrate —> HCO3 by liver)
2. **K supplement for HypoK
3. ***Steroid for Distal RTA due to Sjogren
Type 4 RTA:
1. Stop / ↓ inciting drugs
2. ***Loop diuretics + Low K diet for HyperK
Metabolic alkalosis
Causes:
1. Loss of H
- GI loss: **vomiting, nasogastric drainage
- Renal loss
—> **Diuretics (Loop, Thiazide), **HypoK
—> **Mineralocorticoid excess: primary / secondary
—> Bartter’s / Gitelman’s syndrome
- Retention of HCO3
- Intake of NaHCO3
- Milk-alkali syndrome
Treatment:
1. If ECF contracted, **expand with saline —> HCO3 will ↓ with expansion
2. Correct HypoK
3. If ECF expanded, correct alkalosis with **IV HCl / ***oral NH4Cl
Na homeostasis
[Na] does **NOT reflect absolute content of Na in body but **amount of solvent: H2O
- primarily an ***extra-cellular cation
In the absence of Na loss / retention:
- HypoNa —> H2O retention
- HyperNa —> H2O depletion
Situation will be complicated when concomitant Na loss / retention
Na in kidney:
- ***67% reabsorbed in PCT
- 25% reabsorbed in Ascending LoH
- 5% reabsorbed in DCT
- 3% reabsorbed in Collecting duct
Pseudohyponatraemia
↓ Serum [Na] but normal osmolality
- ∵ occupation of large amount of non-water (e.g. Fat, Paraprotein) in plasma
—> ↑ plasma volume while actual plasma water Na is normal
—> [Na] appears to be low
Causes:
1. **Hyperglycaemia
2. **↑↑ TG
3. ***Paraproteinaemia
4. ↑↑ WCC
Clue:
- Check serum osmolality —> normal
Confirmation:
- Check plasma water [Na]
***Approach to HypoNa
睇3樣野: Serum osmolarity (判定係咪True HypoNa)
—> Volume status + Urine Na (3x2表)
- ***Serum Osmolarity
- low —> true HypoNa - ***Volume status
- Urine osmolarity (>100 = ADH is working, appropriate?)
- ***Urine Na level (>20 = inappropriate i.e. SIADH)
HypoNa
—> Serum osmolarity (+ RFT, TFT, cortisol, Urine osmolarity, Urine Na)
—> ↓ Serum osmolarity —> True hyponatraemia
—> Volume status
- Hypovolaemia (***Na depletion)
—> ↓ Na intake
—> Renal (Urine Na ↑)
—> Extra-renal loss (Urine Na ↓) - Hypervolaemia (Dilutional)
—> Urine Na ↓ + Urine osmolarity ↑ —> CHF, cirrhosis, nephrotic syndrome
—> Urine osmolarity ↓ —> Primary polydipsia - Euvolaemia
—> SIADH
Causes of SIADH
CL Lai: 記any CNS + respiratory diseases
- CNS
- **Meningitis, Encephalitis, Brain abscess
- **Head trauma, SAH, CVA, ↑ ICP - Respiratory
- **CA lung
- **Chest infection
- Positive pressure breathing - Drugs
- ***SSRI
- Ecstasy - ***Hypothyroidism
SIADH vs Addison’s disease
SIADH:
- Everything is low
- Low K
Addison’s disease:
- Normal / High K
- High eosinophil count (∵ cortisol promote eosinophil migration into BM)
Treatment of SIADH (CL Lai)
- Fluid restriction
- Furosemide 20mg
- Vaptan
- IV Na (beware of central pontine myelinolysis)
HypoNa
S/S:
- **Non-specific (e.g. malaise, lethargy, headache)
- **Confusion, convulsion, coma
- More serious with acute hypoNa
Acute:
- <48 hours
- more serious symptoms, severe symptoms at [Na] <120
- less complications if corrected rapidly
Chronic:
- >72 hours
- symptoms may not develop even [Na] <110
- ***more prone to CNS complications with rapid correction
Management:
- Rate of correction should be **slow for chronic hypoNa (>2 days) —> <0.5 mmol/L/hr or <12 mmol/L/day
- Too rapid correction —> **Central pontine myelinolysis
- Treat according to ECF volume status —> estimate amount of H2O + Na needed
- **Hypertonic saline should only be used in very experienced hands!
- **Demeclocycline / ***V2 antagonist can be considered in SIADH
Clinical features of Central pontine myelinolysis (CL Lai):
- Cranial nerve deficits
- Quadriparesis
H2O + Na replacement in contracted ECF
- Assess degree of volume depletion / excess
- mildly dehydrated: loss of skin turgor: 5% BW loss
- moderate: postural hypotension: 10% BW loss
- severe: shock: 15% loss
- mild edema: 5% in excess - ***Replace volume depletion with normal saline cautiously
- initial 1/3 can be given in first 8 hours, reduce speed afterwards
- monitor [Na] regularly
Approach to HyperNa
睇3樣野: Volume status
—> Serum osmolarity, Urine osmolarity (Ratio)
Serum osmolarity, Urine osmolarity, RFT, CaPO4, Plasma renin + aldosterone, 9am cortisol
- Hypervolaemia (Salt gain)
—> **Primary hyperaldosteronism / **Cushing’s syndrome / ***Acute salt loading - Isovolaemia / Hypovolaemia
- Urine osmolarity»_space; Serum osmolarity (Serum osmolarity太低有問題)
—> ***Extrarenal fluid loss (most common)
- Urine osmolarity < Serum osmolarity (Urine osmolarity太低)
—> Water deprivation test / DDAVP test
—> No change in urine osmo —> **Nephrogenic DI
—> ↑ urine osmo —> **Cranial DI
Management of HyperNa
In pure H2O loss —> calculate H2O deficit
- Water deficit = TBW x ([Na]/140 - 1)
Rate of volume replacement
- 1/3 rule:
—> 1/3 in first 8 hours
—> 1/3 in second 16 hours
—> 1/3 in third 24 hours
- Rmb to replace any ongoing H2O loss
Rate of [Na] correction
- too rapid will lead to ***cerebral edema ∵ rapidly reduced plasma osmolality —> influx of H2O into cells
- maximal ↓ of 12 mmol / 24 hours unless seriously symptomatic
K homeostasis
**Intracellular cation (diffuse slowly outwards, Na-K ATPase pumps K into cells)
- Normal serum K 3.5-5 (intracellular: 150)
- Highly influenced by **acid-base status (acidosis —> K moves ***out of cells, vice versa)
- Severe HypoK + HyperK are life-threatening electrolyte disturbances —> Cardiac arrhythmia
Approach to HypoK
Rule out intracellular K shift:
- **Insulin
- **Catecholamine
- **β2 agonist
- **Metabolic alkalosis
- ***Hypokalaemic periodic paralysis
HCO3 ↑ (**Metabolic alkalosis)
- TTKG <3 (trans-tubular potassium gradient) (i.e. Extra-renal loss)
—> **Vomiting
- TTKG >=3 (i.e. Renal loss)
—> Normal BP
—> **Diuretics, **Bartter’s syndrome, ***Gitelman’s syndrome - TTKG >=3 (i.e. Renal loss)
—> ↑ BP
—> **Renal artery stenosis, **Primary aldosteronism, ***Cushing’s syndrome, Liddle’s syndrome
HCO3 ↓ (**Metabolic acidosis)
—> Normal AG
—> Urine AG -ve —> **Diarrhoea, **Proximal RTA
—> Urine AG +ve —> **Distal RTA
TTKG
Transtubular K gradient:
- Attempt to over-ride interference from urinary concentration to determine urinary K loss
TTKG:
- Tubular [K] / Serum [K]
or
- (Urine [K] / Serum [K]) ÷ (Urine osmo / Serum osmo)
(∵ Tubular [K] = Urine [K] x Serum osmo / Urine osmo)
In presence of HypoK, TTKG >4:
- high [K] in terminal cortical collecting duct (i.e. ***renal loss)
HypoK
Risk / Complications / Symptoms
1. **Muscle weakness, paralysis (proximal muscle myopathy)
2. **Cardiac arrhythmia, particularly when [K] <2.0
3. ECG changes (記)
- Large U wave
- **Loss of T wave
- **Prolonged QT interval
4. ***Ileus, constipation
5. Rhabdomyolysis
6. Polyuria
Management:
1. Oral replacement when mild
-
**IV KCl
- oral not possible e.g. vomiting
- moderate to severe hypoK (e.g. <=2.5)
- **always rmb to dilute IV KCl in NS - Exact amount of K needed cannot be calculated ∵
- largely intracellular
- discrepancy between ICF and ECF [K]
- initial distribution in ECF only - 40 mmol K will ↑ [K] 1.5 mmol/L
Approach to HyperK
Exclude **PseudohyperK (e.g. **haemolysis) + **Drugs (e.g. K supplement, NSAID, **ACEI, ARB, **K-sparing diuretics, salt substitute)
1. **Renal failure
2. ***Hypoaldosteronism
3. Shift from cells
HyperK
S/S
1. **Muscle weakness (usually when >8)
2. **Cardiac arrhythmia
- may occur when >6
- rate of ↑ of K important —> more tolerable with chronic HyperK
- ECG changes (記)
—> **Peak T
—> **Widening of QRS
—> ***Loss of P
(—> prolonged PR intervals, sinusoidal)
Diagnosis of HyperK
- History
- Diet
- ***Drug history - Repeat [K] if no apparent cause found (pseudohyperK? ***Haemolysis)
- P/E: volume depleted?
- ***Renal function test
- TTKG <6 indicates inappropriate renal response to hyperK
Management of HyperK
Emergency? (Arrhythmia, ECG changes)
記: Resonium, IV insulin, NaHCO3, Loop diuretic
- ***IV Calcium
- effect within several mins
- stabilise cardiac membrane —> protects heart (↑ threshold potential) but not ↓ [K]
- may repeat injection 5 mins later if effect not seen - ***NaHCO3 infusion
- shift K into cells
- effect within 30 mins, last for several hours - ***IV insulin / dextrose
- 10 units to 30g glucose (60ml D50) —> shift K into cells (self notes: Insulin stimulate Na/K-ATPase)
- effect within 1 hour, but effect may last for only 5-6 hours - Urgent haemodialysis
- most effective in removing K
- but takes time to to set up
Non-emergency:
1. **Cation-exchange resin - Na/Ca resin
- oral / enema
- e.g. **Resonium
2. **Loop diuretics if not oliguric
3. Remove underlying cause
- remove drugs
- volume expansion for depletion
4. **Correct metabolic acidosis (by NaHCO3)
5. Dialysis (for end stage renal disease / chronic renal failure, HD / PD)
6. Low K diet
(Resonium (web):
- Insoluble polymer cation-exchange resin
- Exchange with H in stomach —> H exchange with K from intestinal cells
1. Resonium A (Na)
- exchange H with Na
2. Resonium C (Ca)
- exchange K with Ca)
Bartter syndrome, Gitelman’s syndrome (Self notes)
Bartter syndrome: Defective NKCC (~Loop diuretic)
Gitelman’s syndrome: Defective NCCT (~Thiazide)
