B&B Renal: Electrolytes Flashcards
Potassium
Electrolytes
Myocardial & skeletal muscle action potentials depend on potassium
* Imbalance:
* Heart: EKG changes. arrhythmias
* Muscle: weakness
- EKG changes: peaked T waves; QRS widening
- Arrhythmias: sinus arrest; AV block
- Muscle weakness: paralysis (LE –> trunk –> UE)
Signs & Symptoms
Hyperkalemia
Most common cause of hyperkalemia
Etiology
Reduced K+ excretion in urine
* Acute & chronic kidney disease
Hyperkalemia
Etiology
- Reduced K+ excretion in urine
* Acute & chronic kidney disease
* Type IV RTA - Increased K+ release from cells
- Acidosis: H+/K+ exchange; H+ in, K+ out
- Insulin deficiency: inactive Na+/K+ ATPase
- Beta-Blockers: inactive Na+/K+ ATPase
- Digoxin: inactive Na+/K+ ATPase
- Lysis of cells: K+ released from lytic cells
- Hyperosmolarity: H2O w/ K+ leaves cells
HIgh intracellular concentration of K+
Na+/K+ ATPase
Transporter
Uses ATP to pump 3 Na+ out of cells & 2 K+ into cells
* Activators:
* Insulin
* Epinephrine
* Inhibitors:
* Beta-Blockers
* Digoxin
Hyperkalemia
Treatment
Aldosterone
* Stimulates renal K+ secretion
- EKG changes: flattened T waves; U waves
- Arrhythmias: PACs, PVCs; bradycardia
- Muscle weakness: paralaysis (LE –> trunk –> UE)
Signs & Symptoms
Hypokalemia
Most common causes of hypokalemia
Etiology
- Diuretics: Loop
- Vomiting / Diarrhea
Loop diuretics block NKCC in TAL
Hypokalemia
Etiology
- Increased renal losses
- Diuretics
- Type I & II RTAs
- Increased GI losses
- Vomiting
- Diarrhea
- Increased K+ entry into cells
- Hyperinsulinemia: overactive Na+/K+ ATPase
- Beta-Agonists: overactive Na+/K+ ATPase
- Alkalosis: H+/K+ exchange; K+ in, H+ out
- Hypomagnesemia
- Promotes urinary K+ excretion
- Cannot correct K+ until Mg+ is corrected
Beta-Agonists: albuterol, terbutaline, dobutamine
- Often asymptomatic
- May cause recurrent kidney stones
- Acute: polyuria, polydipsia
Signs & Symptoms
Hypercalcemia
- Acute: nephrogenic diabetes insipidus
- Loss of ability to concentrate urine
- AQP downregulation in CD principal cells
- Excessive free water excretion
- Decreased GFT –> acute renal failure
- Presentation: polyuria & polydipsia
Hypercalcemia
Etiology
- Hyperparathyroidism: Ca2+ resorption from bone
- Malignancy: degradation of bone releases Ca2+
- Hypervitaminosis D: exogenous alcitriol; sarcoid
- Milk-Alkali syndrome: excess calcium carbonate
- Tetany = muscle twitches
- Trousseau’s sign
- Chvostek’s sign
- Seizures
Signs & Symptoms
Hypocalcemia
* Ca2+ blocks Na+ channels in neurons
* Low Ca2+: spontaneous contractions
* High Ca2+: muscle weakness
* Hyperexcitability of neurons & motor endplates
* Trousseau’s sign: hand spasm with BP cuff
* Chvostek’s sign: facial muscle contraction with tapping on nerve
Tetany = classic sign of hypocalcemia
Hypocalcemia
Etiology
- Hypoparathyroidism: no Ca2+ resorption
- Renal failure: low 1,25-Vit D results in low Ca2+
- Pancreatitis: Mg/Ca saponification of necrotic fat
- Drugs: foscarnet
- Magnesium: hypo- / hypermagnesemia
Hyperphosphatemia
Etiology
- Reduced phosphate excretion into urine
* Acute & chronic kidney disease - Hypoparathyroidism: increased PO4- resorption
- Huge phosphate load due to lysis of cells
* Tumor lysis syndrome
* Rhabdomyolysis
Calcium-Phosphate in Renal Failure
- Impaired phosphate excretion
- High serum phosphate levels
- Increased precipitation of serum Ca2+
- Impaired Vitamin D activation
- Low serum 1,25-(OH)2 Vitamin D levels
- Reduced absorption of Ca2+ in GI tract
- Both contribute to hypocalcemia
- Hyperphosphatemia + hypocalcemia = characteristic of renal failure
Hypocalcemia induces PTH secretion; PTH increases Ca2+ & decreases PO4-
Hyperphosphatemia
Symptoms
- Most patients are symptomatic
- Symptomatic patients present with symptoms of hypocalcemia
- Phosphate precipitates serum Ca2+
- Hyperphosphatemia –> hypocalcemia
- Metastatic calcifiations (calciphylaxis)
- Seen in CKD with chronic hyperphosatemia
- Excess phosphate is taken up by VSM
- VSM osteogenesis –> calcification
- Presentation:
- Increased SBP: less vascular compliance
- Small vessel thrombosis: painful nodules, skin necrosis
- Main acute symptom: weakness
- Often presents as respiratory muscle weakness
- Chronic: bone loss, osteomalacia
Signs & Symptoms
Hypophosphatemia
* Due to ATP depletion
Hypophosphatemia
Etiology
- Primary hyperparathyroidism
- High PTH: PO4 excretion
- Diabetic ketoacidosis (DKA): glycosuria
- Osmotic diuresis: PO4 excretion
- Refeeding syndrome in alcholics
- Low phosphate due to malnutrition
- Food intake –> metabolism –> lower PO4
- Antacids: ammonium hydroxide
- Fanconi syndrome: impaired PO4 resorption
- Neuromuscular toxicity:
- Decreased reflexes
- Paralysis
- Bradycardia, hypotension, cardiac arrest
- Hypocalcemia
Signs & Symptoms
Hypermagnesemia
* Mg blocks Ca & K+ channels
* Neuromuscular toxicity
* Cardiac dysfunction
* Mg inhibits PTH secretion
* Hypocalcemia
Cause of hypermagnesemia
Etiology
Renal insufficiency
* Impaired Mg2+ excretion
- Neuromuscular excitability
- Tetany
- Tremor
- Cardiac arrhythmias
- Hypocalcemia
- Hypokalemia
Signs & Symptoms
Hypomagnesemia
Hypomagnesemia & Ca2+
Hypomagnesemia
- Low Mg2+ –> stimulates PTH release like Ca2+
- Increased GI absorption & renal reabsorption of Mg2+ along with Ca2+
- Very low Mg2+ –> inhibits PTH release
- Some Mg2+ is needed for normal Ca2+ receptor function in parathyroid gland
- Dysfunction –> suppressed PTH release
- Hypocalcemia seen in severe hypomagnesemia
Hypomagnesemia & K+
Hypomagnesemia
Mg2+ inhibits K+ excretion
* ROMK: apical membrane of CD cells
* Facilitates K+ secretion into urine
* Channel is inhibited by Mg2+
* Hypomagnesemia –> excess K+ excretion
* Results in hypokalemia
* K cannot be corrected until Mg is corrected
* Need Mg2+ to close ROMK
ROMK: renal outer medullary K channel
Hypomagnesemia
Etiology
- GI losses (secretions contain Mg): diarrhea
- Renal losses: loop & TZ diuretics; alcohol abuse
- Pancreatitis: Mg/Ca saponification of necrotic fat
- Drugs: omeprazole; foscarnet
Omeprazole –> impairs GI absorption of Mg2+
Hypomagnesemia
Etiology
- GI losses (secretions contain Mg): diarrhea
- Renal losses: loop & TZ diuretics; alcohol abuse
- Pancreatitis: Mg/Ca saponification of necrotic fat
- Drugs: omeprazole; foscarnet
Omeprazole –> impairs GI absorption of Mg2+
Foscarnet
Antiviral pyrophosphate analog
* Binds & inhibits viral DNA pol
* Adverse effects –> all electrolyte imbalances:
* Nephrotoxicity (limiting side effect)
* Seizures (due to electrolyte imbalances)
* Hypocalcemia (chelates calcium)
* Hypomagnesemia (increases renal losses)
* Hypokalemia
* Hypophosphatemia
* Hypercalcemia
* Hyperphosphatemia
Major regulators of Na+ & H20 Balance
Na+ / H2O Balance
- ADH
- SNS
- RAAS
Low ECV
Na+ / H2O Balance
- Low ECV can lead to low BP
- Can cause orthostatic hypotension
- Dizziness / fainting when standing up
- Low ECV activates:
- SNS
- RAAS
- Result: Na+ / H2O retention
- Some disease states have chronically low ECV
- Chronic activation of SNS & RAAS
- Chronic Na+/H2O retention by kidneys
Orthostatic hypotension = classic sign of any cause low ECV
Antidiuretic Hormone (ADH)
Na+ / H2O Balance
Promotes retention of free water
* Stimuli for release
* Hyperosmolarity
* Volume loss
* Plasma osmolality: major physiological stimulus
* Hyperosmolarity detected by hypothalamus
* ADH released by posterior pituitary gland
* ADH increases renal H2O resorption
* Responds to H2O intake to maintain [Na]
* Volume loss: 2nd trigger; non-osmotic release
* Activated with very low ECV
Water Balance
Na+ / H2O Balance
- Water balance is maintained by ADH
- ADH –> retention of excess free water
- Levels modified to adjust H2O retention
- Water balance is reflected by serum Na+
- Serum Na+ is maintained at 140 mEq / L
- Normal Na+: H2O in = H2O out (balance)
- Hyponatremia: H2O in > H2O out
- Hypernatremia: H2O in < H2O out
Excess Water
Regulation
H2O retention decreased to maintain normal [Na]
* High ECV = low osmolality
* Inhibits release of ADH
* Decreased H2O reabsorption
* Increased H2O excretion
Restricted Water
Regulation
H2O retention increased to maintain normal [Na]
* Low ECV = high osmolality
* Stimulates release of ADH
* Increased H2O reabsorption
* Decreased H2O excretion
Na+ Balance
Na+ / H2O Balance
- Serum Na+ is maintained at 140 mEq/L
- Excess Na+ –> high osmolality
- High osmolality –> H2O retention –> normal Na+
- H2O retention –> increased ECV
- Sodium intake expands ECV
Excess Na+
Na+ Balance
H2O retention increased to maintain normal [Na]
* Excess Na+ –> high osmolality
* Stimulates release of ADH
* Increased H2O reabsorption
* Decreased H2O excretion
* Increased ECV
Restricted Na+
Na+ Balance
H2O retention decreased to maintain normal [Na]
* Restricted Na+ –> low osmolality
* Inhibits release of ADH
* Decreased H2O reabsorption
* Increased H2O excretion
* Decreased ECV
ECV
Regulation
ECV is controlled by SNS & RAAS
* Low ECV: active SNS & RAAS
* High ECV: inactive SNS & RAAS
* Na+ alters ECV –> alters SNS & RAAS activation
Na+ Balance
Regulation
- Excess intake –> expanded ECV; weight gain
- High ECV: inactive SNS & RAAS
- Result: increased Na+ excretion
- Na+ out = Na+ in
- Balance restored
- Restricted intake –> contracted ECV; weight loss
- Low ECV: active SNS & RAAS
- Result: increased Na+ retention
- Na+ out = Na+ in
- Balance restored
Na+ / H2O Imbalance
Effects
- H2O imbalance
- Alters serum [Na]
- Results in hyponatremia / hypernatremia
- Na+ imbalance
- Alters TBW / ECV
- Results in hypovolemia / hypervolemia
GI Losses
Na+ / H2O Imbalance
Nausea, vomiting, diarrhea
* Results in activation of SNS & RAAS
* Volume loss (low ECV) –> ADH release
* Driven by volume sensors
* No longer controlled by serum [Na]
* Non-osmotic release of ADH
* Water balance control by ADH lost
* Free water always retained by kidneys
* [Na] determined by relative intake / losses
* Often results in hyponatremia
* Drinking free water –> H2O intake
* Not eating –> no Na+ intake
Heart Failure
Na+ Imbalance
Low CO –> chronically low ECV
* Chronic activation of SNS & RAAS
* Na+ balance is disrupted
* Chronic Na+ retention by kidneys
* Na+ excretion is always reduced
* High Na+ intake: Na+ in > Na+ out
* Often results in hypervolemia
* Free H2O is retained to balance [Na]
* ECV does not increase w/ fluid retention
* Failing heart unable to increase CO
* HF pts always have low ECV
* Result: congestion
* Pulmonary edema
* Elevated JVP
* Pitting edema
Heart Failure
H2O Imbalance
Low CO –> chronically low ECV
* Chronic non-osmotic release of ADH
* ADH levels always high
* Release driven by volume sensors
* No longer controlled by serum [Na]
* Water balance control by ADH lost
* Free H2O always retained by kidneys
* [Na] determined by relative intake / losses
* Often results in hyponatremia
SIADH
Syndrome of Inappropriate ADH Secretion
Excess ADH release
* Excess H2O retention –> hyponatremia
* Normal total body water
* H2O retention –> expanded ECV
* Inactive SNS & RAAS
* Na+ excretion –> reduces ECV
* Na+ balance restored
* Key findings:
* Hyponatremia
* Normal volume status
* Concentrated urine
Sodium Disorders
Water Balance
Disorders involving water balance
* Hyponatremia = too much water
* Hypernatremia = too little water
Sodium Symptoms
- Hypo- & hypernatremia affect braim
- Low Na+ = low plasma osmotic pressure
- Fluid into tissues
- Brain swells
- High Na+ = high plasma oncotic pressure
- Fluid out of tissues
- Brain shrinks
- Malaise, stupor, coma
- Nausea
Symptoms
Hyponatremia
Hyponatremia
Diagnostic Tests
- Plasma osmolality
- Urinary Na+
- Urinary osmolality
Plasma Osmolality (pOsm)
Hyponatremia
Amount of osmotically active solutes present in plasma
* Key solute: Na+
* Normal pOsm: 285 mOsm/kg
* Osmolality should be low in hyponatremia
Hyponatremia with High Osmolality
Plasma Osmolality
Hyperglycemia or mannitol
* Glucose / mannitol = osmoles
* Raises plasma osmolality
* Draws water out of cells into plasma
* Increases blood volume & dilutes [Na]
* Results in hyponatremia
Hyponatremia with Normal Osmolality
Plasma Osmolality
Artifact in serum Na+ measurement
* Solutes in plasma interfere with measurement
* Hyperlipidemia
* Hyperproteinemia
Urine Osmolality
Urine Studies
Concentrations of all osmoles in urine
* Osmoles: Na, Cl, K, Urea
* Varies with H2O intake & urinary concentration
* Low uOsm: dilute urine; H2O excretion
* High uOsm: concentrated; H2O retention
Urinary Sodium
Urine Studies
- Normal: >20 mEq/L
- Varies with dietary Na+ & free H2O in urine
- Usually high when urine osmolarity is high
- Exceptions: involve SNS & RAAS activation
- Increased Na+ & H2O resorption
- Low urinary Na+, high uOsm
- Examples: hemorrhage, HF, cirrhosis
Hyponatremia
General Principles
- Urine should be dilute
- Free H2O > solutes
- Low urine osmolality (< 100 uOsm/kg)
- Low urine Na+ (< 30 mEq/L)
- If urine is dilute:
- Kidneys responding appropriately
- ADH is appropriately low
- Problem is outside kidneys
- If urine is not diluted:
- Kidneys are not responding appropriately
- Too much ADH or impaired kidney function
Hyponatremia
Etiology
- Heart failure & cirrhosis
- Impaired renal function
- High ADH
- Psychogenic polydipsia / dietary causes
Heart Failure & Cirrhosis
Etiology
- Perceived hypovolemia
- HF: low CO –> low ECV
- Cirrhosis: vasodilation –> low SVR
- Non-osmotic release of ADH
- Chronic production of ADH
- Chronic H2O retention
- Urine is not diluted (uOsm > 100)
- Clinical signs of hypervolemia
- Excess H2O intake will result in hyponatremia
Advanced Renal Failure
Impaired Renal Dysfunction
Impaired H2O excretion –> increased H2O retention
* Urine cannot be diluted –> min uOsm rises
* Min uOsm is minimum urine osmolarity (i.e., max dilution) that kidneys can achieve in setting of low ADH
* Normally with low ADH: uOsm < 100
* Renal failure: uOsm = 200-250
* Key point: increased uOsm in setting of hyponatremia indicates abnormal response to low serum [Na]
* Urine should be diluted (low uOsm) during hyponatremia to eliminate excess H2O
* May present with euvolemia or hypervolemia
Diuretics
Impaired Renal Function
Promote Na+ & H2O excretion
* Can disrupt Na+ / H2O balance and cause hyponatremia
* Most common with TZ diuretics
Loop Diuretics
Diuretics
Block Na+ reabsorption by NKCC in TAL of Henle
* NKCC creates medullary osmotic gradients
* TAL is impermeable to H2O
* Na+ reabsorption increases interstitial Osm & decreases urinary Osm
* Osmotic gradients are driving force for H2O resorption
* NKCC inhibition diminishes medullary gradients
* Results in inability to resorb free H2O
* Low likelihood of excess H2O resorption resulting in hyponatremia
* Diuretic effects: decrease Na+ reabsorption & decrease ability to reabsorb H2O
NKCC: Na-K-Cl channel
Thiazide (TZ) Diuretics
Diuretics
Block Na+ reabsorption by NCC in distal tubule
* NCC inhibition decreases Na+ reabsorption
* Increases urinary Na+ & uOsm
* Medullary osmotic gradients remain intact
* Ability to resorb free H2O is intact
* Higher likelihood of excess H2O retention resorption resulting in hyponatremia
* Diuretic effect: decrease Na+ reabsorption
NCC: Na+/Cl- cotransporter
High ADH
Hyponatremia
Dehydration results in high ADH
* Any cause of dehydration
* Vomiting, diarrhea
* Diaphoresis
* Serum [Na] depends on H2O intake
* Excess free H2O intake –> hyponatremia
High ADH
Etiology
- Adrenal insufficiency –> increases ADH
- Loss of cortisol: ADH release is uninhibited
- Loss of aldosterone: loss of Na+ / H2O loss
- Hypothyroidism
- SIADH
- Inappropriate ADH release
- Must exclude other causes: HF, cirrhosis, dehydration, thyroid / adrenal disease
SIADH
Etiology
- Drug-induced: carbamazepine, cyclophosphamide
- Paraneoplastic syndrome: SCLC
- CNS diseases
- Pulmonary disease
SIADH
Diagnostic Criteria
- Hypotonic hyponatremia: low pOsm, low serum [Na]
- Normal liver, renal, cardiac function
- Cinical euvolemia
- Nornal thyroid, adrenal function
- Concentrated urine: uOsm >100 mOsm/kg
SIADH
Treatments
- Most common: fluid restriction
- Special treatment: demeclocycline
* Tetracycline antibiotic
* ADH antagonist
Psychogenic Polydipsia
Hyponatremia
- Occurs in psychiatric patients
- Compulsive water drinkers
- Hyponatremia –> need to drink >18 L/day
- Low uOsm (<100)
- Kidneys respond appropriately
- Water intake is just too high
- Water restriction resolves hyponatremia
Volume Status in Hyponatremias
- Hypervolemic
- Cirrhosis
- CHF
- Renal failure
- Euvolemic
* SIADH
* Hypothyroidism
* Secondary adrenal insufficiency
* Renal failure
* Polydipsia
* Dietary - Hypovolemic
* Dehydration
* Diuretics
* Primary adrenal insufficiency
Euvolemic Hyponatremia
Diagnosis
Measure urinary Osm
* uOsm <100: kidneys responding appropriately
* Psychogenic polydipsia
* Diet (tea, beer)
* uOsm >100: kidneys not responding
* SIADH
* Hypothyroidism
* Renal failure
Hypovolemic Hyponatreamia
Diagnosis
Measure urinary [Na]
* u[Na] <30 mEq/L: extra-renal etiology
* Vomiting
* Diarrhea
* Sweating
* u[Na] >30 mEq/L: renal etiology
* Diuretics
* Primary adrenal disease (low aldosterone)
Increased ADH & uOsm
Hyponatremia
- Hypervolemic: low ECV –> H2O retention
- Cirrhosis
- CHF
- Euvolemic
* SIADH
* Hypothyroidism
* Secondary adrenal insufficiency - Hypovolemic: low ECV –> H2O retention
* Dehydration
* Diuretics
* Primary adrenal insufficiency
Decreased ADH & uOsm
Hyponatremia
Euvolemic: polydipisa, dietary
* Kidneys responding appropriately but unable to excrete adequate amount of free H2O
Decreased ADH, Increased uOsm
Renal failure: hypervolemic or euvolemic
* Kidneys unable to dilute urine despite low ADH
Hyponatremia
Treatment
- Fluid restriction
- 3% saline infusion
- Vaptan-drugs: block ADH
* Main use: severe hyponatremia in HF
Central Pontine Myelinolysis
Osmotic Demyelination Syndrome
- Associated w/ overly rapid correction of low [Na]
- > 10 mEq/L increase in [Na] per 24 hours
- Causes demyelination of central pontine axons
- Lesion at base of pons
- Loss of corticospinal & corticobulbar tracts
- Results in quadriplegia
- Irritability
- Stupor
- Coma
Symptoms
Hypernatremia
Hypernatremia
Etiology
- Water loss
- Skin & lungs: loss of H2O»_space; Na+
- Kidneys respond by concentrating urine & retaining free H2O
- High ADH
- High uOsm
- Diabetes insipidus (DI)
- Loss of ADH activity
- Central: loss of ADH release from pituitary
- Nephrogenic: ADH insensitivity
* Congenital (rare
* Acquired: many causes
Acquired DI
Etiology
Acquired ADH insensitivity
1. Hypercalcemia
2. Hypokalemia
3. Drugs: lithium, amphotericin B
Diabetes Insipidus
Diagnosis
- Suspected with polyuria & polydipsia
- Serum [Na]: typically normal
- Water loss stimulates thirst
- Hypernatremia occurs if not enough H2O intake
- Central lesion (DI) can impair thirst
- uOsm: low (50-200 mOsm/kg)
- Fluid restriction
- After 8 hours of no fluid, urine should be concentrated
- If urine is dilute –> absent/ineffective ADH
- Administration of vasopressin / desmopressin
- Should concentrate urine if kidneys are functional
- Concentrated urine = central DI
- Dilute urine = nephrogenic DI
Hypernatremia
Treatment
- Water (ideally PO)
- IV fluids (D5W, isotonic but no Na+)
Central DI
Treatment
Desmopressin
* ADH analog
* No vasopressor effect (unlike vasopressin)
Nephrogenic DI
Treatment
TZ diuretics & NSAIDs
* TZ diuretics
* Mild state of volume depletion causes increased Na+ / H2O resorption in proximal tubule
* Less H2O delivery to collecting ducts
* Paradoxical antidiuretic effects
* NSAIDs
* Inhibit renal synthesis of prostaglandins
* Prostaglandins = ADH antagonists
