Pathophysiology: Electrolyte Disorders Flashcards
Hypokalemia [K+] Frequency of occurrence
- ~3% of ambulatory patients
- ~20% of hospitalized patients
- ~40% of pts prescribed with thiazide diuretics
Hypokalemia [K+] increases mortality risk in patients with:
- Heart failure (HF)
- Chronic Kidney Disease (CKD)
Decreased serum [K+] of?
- less than 3.5 mEq/L
- Severe: ~2-2.5 mEq/L
Causes of Hypokalemia
- Losses
- transcellular shift
- inadequate intake
- pseudohypokalemia
Hypokalemia evaluation Laboratory
- [K+] < 3.5 mEq/L –check magnesium
May also need to evaluate:
• Urine electrolytes
• Acid-Base status
History for Hypokalemia Evaluation: PMH, Medications
- past medical history: cardiac, renal, thyroid
- medications: insulin, beta-agonists
- volume loss
Hypokalemia evaluation of physical exam
- EKG: cardiac assessment
- weakness, paralysis: neurologic assessment
Hypokalemia symptoms
DA SIC WALT
- decreased intestinal motility: nausea, vomiting, ileus
- alkalosis
- shallow respirations
- irritability
- confusion, drowsiness
- weakness, fatigue
- Arrythmias
- Lethargy
- Thready pulse
Pseudohypokalemia
- delayed sampling process
- leukocytosis
Hypokalemia: Pathophysiology MOA: Inadequate Intake
- normal renal physiology continues to excrete K+ even with no K+ intake
- extreme decreased K+ intake coupled with hypomagnesemia results in significantly worse hypokalemia:
-> Anorexia nervosa
-> crash diets
-> alcoholism (delirium tremens)
-> intestinal malabsorption
Why does hypomagnesium exacerbate hypokalemia
- Magnesium inhibits K+ secretion in the distal nephron
- correct magnesium first, then potassium will correct
Hypokalemia: MOA Losses
- GI Losses: vomiting, diarrhea
Hypokalemia: Renal Losses
Mi TyPO
- osmotic diuresis
- polydipsia
- mineralocorticoid excess (see meds)
- Type I and Type II Renal Tubular acidosis
Medications that causes Hypokalemia
- Laxatives/Enemas (OTC)
- Diuretics: (loop, thiazide)
- Corticosteroids: (dexamethasone, fludrocortisone)
- Amphotericin B
- Cisplatin
- Penicillin antibiotics (high dose): (ticarcillin, carbenicillin, piperacillin)
Medications for Hypokalemia (meds that cause Hypokalemia)
BADFIT
B- Beta 2 antagonists
A- Amphotericin B
D- Digoxin
F- Furosemide, foscarnet
I- insulin
T- Thiazides
High dose penicillin examples
- penicillin, piperacillin, ticarcillin
Hypokalemia MOA: High dose penicillin
- increased Na+ delivery to distal tubule
- results in excretion of K+
Amphotericin B MOA:
- inhibits secretion of H+ in collecting duct causing Mag++ depletion
- Mag++ depletion causes K+ sweating
Hypokalemia: Aminoglycosides MOA:
- gentamicin, tobramycin, Cisplatin, Foscarnet
- deplete Mag++ resulting in K+ wasting
Fludrocortisone MOA
- significant retention of Na
- increase of Na+ leads to decrease of K+
Example of Loop Diuretics
- Furosemide (Lasix) -> “Water Pill”
Loop diuretic inhibits what? and where? and results in what?
- Na, K, Cl in the thick ascending limb
- resulting in significant Na+ concentration gradient
Loop diuretic delivers Na+ where? Results in what?
- Thick ascending limb
- reabsorption of Na and increased excretion of K+
Where else does Loop diuretics occur and what happens?
- in the collecting duct
- enhanced Na+ delivery results in K+ loss in the collecting duct
25% of filtered Na is normally reabsorbed in?
- in the loop of Henle
Loop diuretics and Thiazide diuretics
- loss of Na+ & water
- hypokalemic metabolic alkalosis
- increased Ca2+ loss
Thiazide Diuretics MOA:
- hydrochlorothiazide
- Inhibits Na, Cl, in the distal convoluted tubule
- The lower [Na] results in more calcium reabsorption.
- increased delivery of Na+ to the collecting duct
How does Thiazide affect calcium reabsorption?
- it inhibits Na in the convoluted tubule
- the lower the [Na], the more calcium reabsorption
How does Thiazide influence K+?
- increased delivery of Na to the collecting duct
- results in reabsorption of Na and increased excretion of K
10% of filtered Na is absorbed where?
- distal convoluted tubule
Renal Tubular Acidosis (RTA)
- pH issue in blood caused from either K+ or HCO3
- results in hyperchloremic metabolic acidosis with a normal serum anion gap
- location: Bownman’s capsule
Type 1 Renal Tubular Acidosis (RTA)
- location: Distal Tubule
- impaired hydrogen ion secretion = increase hydrogen ions in blood
- pH urine >5.5
- hypokalemia
- renal stones (+ or -)
Type 2 Renal Tubular Acidosis (RTA)
- location: proximal tubule
- problem with reabsorption of HCO3
- high urine pH initially; later < 5.5
- hypokalemia
- bone demineralization (+ or -)
Type 4 Renal Tubular Acidosis (RTA)
- problem with aldosteronism
- location: distal tubule
- decreased aldosterone
- secretion or aldosterone
- resistance
- urine pH <5.5
- HYPERkalemia
Type 1 RTA characteristics
CHHAS
- hereditary
- Cirrhosis
- Autoimmune diseases: Sjoren, Systemic Lupus Erythematosis (SLE)
- Hypercalciuria
- Sickle cell
Type 1 RTA Drugs
- Lithium
- Amphotericin B
Type 2 RTA Etiology
- hereditary
- Fanconi’s syndrome
- Multiple Myeloma
- Amyloidosis
- Heavy Metal Poisoning
Type 2 RTA Drugs
- carbonic anhydrase inhibitors
- vitamin D deficiency
Type 4 RTA Etiology
- Hypoaldosteronism
- Pseudohypoaldosteronism
- kidney disease
Type 4 RTA drugs
- ACE inhibitors (ACEI)
- NSAIDs
- Amiloride
- Spironolactone
- Heparin
Renal Tubular Acidosis (RTA) symptoms
- headache, weakness, Nausea, Vomiting
- Kussmaul breathing
Transcellular Shifts Hypokalemia MOA
- Alkalosis
- Beta2-adrenergic stimulation
Hypokalemia: Transcellular Shifts associated diseases
- refeeding syndrome
- Thyrotoxicosis
- Delirium tremens
- select drug intoxications
Transcellular shifts Hypokalemia associated Medications
- insulin
- Beta2-sympathomimetics
- decongestants
- Amphotericin B
- increased activity Na/K ATPase pump
Albuterol
Xanthines - theophyllin
- Beta2 agonist medications
Thyrotoxicosis
- increased sensitization of Na/K ATPase pump
Alkalemia
- transcellular shift in hypokalemia
- exchange of H+/K+ in buffering system
- vomiting, diarrhea, metabolic alkalosis
Refeeding syndrome
- shift to carbohydrate metabolism
- ex: insulin release
Frequency of occurrence of Hyperkalemia [K+]
- 1% of healthy ambulatory patients
- 10% of hospitalized patients
- most common in elderly with impaired renal function
- [K+] of >5 mEq/L
- severe: [K+] >7 mEq/L
Causes of Hyperkalemia
- impaired excretion
- transcellular shifts
- pseudohyperkalemia
- increased intake
Characteristics of Hyperkalemia
- often asymptomatic
- repeat serum K+
- BUN/SCr
- ABG
- Serum glucose
- rare [K+] intake
- crush injury
Past Medical History for Hyperkalemia
- Physical Exam (PE): blood pressure (BP), volume status
- heart disease, CKD, diabetes
Obtain an ECG for Hyperkalemia if:
- [K+] >6 mEq/L
- has symptoms
Hyperkalemia PMH:
- heart disease, diabetes, CKD
Hyperkalemia symptoms
- MURDER
- Muscle cramps
- Urine abnormalities
- Respiratory distress
- Decreased cardiac contractility
- EKG changes
- Reflexes
Hyperkalemia Past medical history
- cardiac, renal, diabetes, liver disease
Hyperkalemia Medications
- ACE inhibitors
- ARB
- NSAIDs
- K+ sparing diuretic
- heparin
- trimethoprim
- lithium
- calcineurin inhibitors
- beta-blockers
- digoxin
- somatostatin
Hyperkalemia PE
- EKG: cardiac assessment
- Weakness: paralysis -> neurologic assessment
Hyperkalemia Laboratory
- Repeat [K+] >5 mEq/L
- Chem 7: BUN, CO2, SCr, glucose, Cl, K+, and Na+
- Urine electrolytes
- Acid-Base status
Common progression of ECG changes in Hyperkalemia
- Peaked T-waves
- P-wave flattening
- PR-interval prolongation
- widening QRS complex
- Sine waves
Hyperkalemia: Renal Impairment
- AKI
- CKD
Hyperkalemia: Transcellular shifts
- Rhabdomyolysis
- burns
- necrosis
- transfusion
- acidosis
- low insulin, hyperosmolality
- Drug-induced K+ channel activation
- hyperkalemic period paralysis
- beta-blockers, digitalis
- hemolysis
- exercise
Pseudohyperkalemia
- hemolysis
- IV fluids containing [K+]
- familial hyperkalemia
- cell hyperplasia (erythro-, thrombo-, leukocytosis)
increased [K+] production true Hyperkalemia
- TLS
- Crush injury
- hemolysis
Decreased urinary excretion causes hyperkalemia
- acute or chronic kidney injury
- Hypoaldosternonism
- Pseudohypoaldosteronism
- reduced distal flow/tubular delivery
Hypoaldosternonism
- [K+] sparing diuretics, RAAS blockage, heparin, CNI, NSAIDs
Causes of Pseudohyperkalemia
- Collection Technique: mechanical trauma, fist clenching, prolonged tourniquet use, delayed processing, cold sample storage, WBC K+ release during pneumatic transport (CLL)
- increased Platelets WBC: [K+] release from platelets during clotting process
- [K+] release from WBC with fragile membranes
- Other: Heparin/EDTA tubes
- Post-splenectomy
- Familial pseudohyperkalemia
Increased intake hyperkalemia
- [K+] supplementation
- Foods
- RBC transfusion
- [K+] salt substitutes
- Drug: Penicillin G Potassium
Transcellular Shifts MOA: Hyperkalemia
- Na+/K+ ATPase activity results in decreased intracellular [K+] influx
- increased [K+] release
Transcellular Shifts Hyperkalemia Medications
- Beta blockers
- Somatostatin
- Succinylcholine
- High serum digoxin concentration
How is [K+] increased in hyperkalemia?
- cell breakdown/lysis
- Hypertonicity
- Hyperglycemia
- Mannitol infusions
- ALL these cause H2O efflux
Mannitol
- inhibits Na+ and H2O reabsorption in the proximal tubule, loop of Henle
- expands ECF volume
- dilutes bicarbonate
- creating dilutional acidosis
- resulting in hemolysis of RBC
- results intracellular volume
- hypernatremia risk
- occurs predominately during high doses of this drug
Impaired Excretion: Hyperkalemia
- acute kidney injury (AKI)
- chronic kidney disease
- decreased distal renal flow
- AKI - CKD - CHF -Cirrhosis
Hyperkalemia medications that lower aldosterone
- ACE inhibitors
- ARB
- Heparin
- decreased aldosterone results in increased renin
Hyperkalemia medication(s) that increase aldosterone
- [K+] sparing diuretics
- NSAIDs
Primary renal tubule defects in Hyperkalemia
- sickle cell disease
- lupus (SLE)
- amyloidosis (injury to distal tubule)
Urine [Na+] concentration in Hyperkalemia
- <20 mmol/L
- decreased distal flow of Na+ and H2O
Disease based Hyperkalemia
MACHINE
- Medications: ACEI, ARBs, K+ sparing, NSAIDs
- Acidosis: Metabolic, Respiratory
- Cellular destruction: Burns, Rhabdomyolosis
- Hyperaldosteronism, hemolysis
- Intake: excessive
- Nephrons: renal failure
- Excretion: impaired
Drug causes in Hyperkalemia
THANKSC
- Trimethoprim
- Heparin
- ACEI, ARBs
- NSAIDs
- K+ sparing diuretics
- Succinylcholine
- Cyclosporine
Hypomagnesemia [Mag++] Epidemiology
- serum concentrations are NOT reliable index of total body magnesium concentrations
- 42% hospitalized pts with hypokalemia have hypomagnesemia
- ~65% in intensive care patients
- increases mortality risk in pts in: Critically ill patients
- serum [Mag++] of <1.8 mEq/L
- severe: [Mag++] ~<1.25 mEq/L
Causes of Hypomagnesemia
- decreased intake
- endocrine related
- GI Loss/ Malabsorption
- Increased renal loss
- Endocrine related
- Misc.
- Lab range: 1.7 - 2.3 mg/dL
Summary of Hypomagnesemia: Physiologic mechanism
- Relax smooth muscles: lungs
- Laxative
- relax skeletal muscle: leg muscles
- NMDA-Calcium blocker
- Regulate heart contractility
- vasodilation
- regulate calcium level
Hypomagnesemia clues
- Neuromuscular: Weakness, tremor, muscle fasciculation, positive Chvostek’s sign, positive Trousseau’s sign, Dysphagia
- CNS: depression, agitation, nystagmus, seizures
- Cardiac: Arrythmia, ECG changes
- Metabolic: hypokalemia, hypocalcemia
- must correct Mag++ then K+ will correct
History for Hypomagnesemia
- GI diseases
- chronic diarrhea
- alcohol use/abuse
Hypomagnesemia Laboratory
- serum magnesium
- consider ordering: K+, Ca++
Hypomagnesemia Intake MOA:
- rare except for parenteral nutrition that contains no magnesium
- protein-calorie malnutrition
- PPI
Hypomagnesemia GI Losses MOA:
- severe/ prolonged diarrhea
- Crohn’s disease
- Ulcerative colitis
- short bowel syndrome
- Celiac disease
- Whipple’s disease
Hypomagnesemia Endocrine causes MOA:
- primary and secondary hyperaldosteronism
- SIADH
- “Hungry” bones
- Diabetes mellitus
Hypomagnesemia Misc. MOA:
- Stress
- Chronic alcoholism
- excessive lactation
- heat
- extreme exercise
- CABG
Causes of Hypomagnesemia
- malnutrition
- malabsorption
- metabolic acidosis
- alcoholism
- medications
- proton pump inhibitors
- diuretics (loop, thiazide)
- cisplatin: Starts ~3 weeks in; Persistent: avg 5 months
- aminoglycosides: may necrosis proximal tubule
- amphotericin B
- pentamidine: IV administration only
Where do Mag++ absorption occurs?
- thick ascending limb
- and this is also where medications can impact
Proton pump inhibitors (PPIs)
- do NOT impact in thick ascending limb
- ex: Lansoprazole, pantoprazole
PPIs MOA:
- inhibit Mag++ transporter
Loop diuretics in Hypomagnesemia MOA
- decrease Mag++ when Na+ increase
Loop diuretics in Hypomagnesemia location
- ascending limb
Amphotericin B, Aminoglycosides, Pentamidine
- decrease reabsorption in the distal tubule
- decrease reabsorption in the loop of Henle
Calcineurin inhibitors examples:
- cyclosporine
- tacrolimus
- MOA: downregulation of Mag transport proteins in loop of Henle, Distal tubule
Epidermal growth factor receptor inhibitors
- cetuximab, panitumumab, mattuzumab
- MOA: downregulation of Mag transport proteins in loop of Henle, Distal tubule
Hypermagnesemia epidemiology
- common in Stage 4, Stage 5 CKD
- very rare
- may occur if taking antacids
- serum concentrations are NOT reliable index of total body [Mag++]
- laboratory measures extra-cellular concentration
- caused by renal failure and excessive intake of Mag++ containing antacids
Hypermagnesemia causes
- impaired renal function
- intake: laxatives
- tumor lysis syndrome
- ingestion: antacids, Epsom salt
- over correction: IV administration
Symptoms of Hypermagnesemia
- nausea
- vomiting
- neurologic impairment
- depressed nerve function
- skeletal muscle contraction
- muscle weakness
- bradycardia
- hypotension
- hypotension
- EKG change: prolonged QRS, PR, QT intervals
Hypocalcemia epidemiology
- more common in elderly or malnourished
- 15-50% incidence in intensive care patients
- rarely requires emergent treatment
- 40%: bound to plasma proteins, predominately albumin
- unbound/ionized is the active form
- correct Ca++
- ionized [Ca++] of <4.4mg/dL
- total [Ca++] of <8.6 mg/dL
Hypocalcemia causes
- alteration in PTH effect
- vitamin D deficiency
- Medications/Misc.
Hypocalcemia symptoms
SPASMODIC
- spasm
- parethesia
- seizures
- muscle tone increased (smooth)
- orientation impaired, confused
- dermatitis
- impetigo (rare but serious)
- cardiovascular, Chvostek’s sign
Hypocalcemia past medical history:
- CKD
- Vitamin D deficiency
- hypoparathyroidism
Hypocalcemia medications
- loop diuretics
- anticonvulsants
- bisphosphonates
- calcitonin cinacalcet
- antibiotics (INH, rifampin, foscarnet)
Hypocalcemia laboratory
- repeat calcium
- obtain PTH
- consider other labs: Mag, ABG
Physical exam Hypocalcemia
- Chvostek’s sign: spasm of facial muscle
- Trousseau’s sign: carpopedal spasm
Hypocalcemia MOA
- decreased parathyroid hormone (PTH) dependence
- increased PTH dependence
Decreased PTH dependence Hypocalcemia
- hypoparathyroidism
- hypomagnesemia
Increased PTH dependence Hypocalcemia
- vitamin D deficiency
- CKD
- Sepsis
- Tumor lysis syndrome
- AKI
Hypocalcemia medications MOA
MOA-Chelation: Foscarnet
- increased Enzyme processing of Vitamin D:
- increased excretion (cinacalcet)
- blocked bone resorption
- induction of Hypomagnesemia
Which medications increase enzyme processing of vitamin D
- Phenobarbital
- Phenytoin
- Ketoconazole
Which medications increase excretion (cinacalcet)
- Furosemide
Which medications blocked bone resorption
- Denusomab
- Bisphosphonates
- Fluoride
Induction of Hypomagnesemia
- Aminoglycosides
When there is low serum Mag++ in hypocalcemia
Replete & rule out:
- GI losses
- renal losses
- alcoholism
- malnutrition
- drug-induced
During elevated PTH level in Hypocalcemia
Secondary hyperparathyroidism etiologies:
- CKD/ESRD
- Malabsorption
- Vit D deficiency or resistance
- Pseudohypoparathyroidism (PTH resistance)
Inappropriately Normal/Low PTH level in Hypocalcemia
Evaluate for hypoparathyroidism:
- destruction of parathyroid glands (ex: thyroid surgery, autoimmune)
- irradiation
- infiltrative disease (very rare)
Low serum 25-OH Vit in Hypocalcemia
Replete and Rule out:
- GI losses
- low dietary intake
- low sunlight
Other causes of hypocalcemia
- acute pancreatitis
- sepsis/severe illness
- hyperphosphatemia (Ca++ deposited in bone)
- large volumes of blood (citrate chelates Ca++)
Epidemiology of Hypercalcemia [Ca++]
- Hyperparathyroidism: more common in women, age > 50 years
- Cancer causing: dependent on tumor type, occurs in 15-70%
- ~15-50% incidence in intensive care patients
- total serum [Ca++] of > 10.2 mg/dL
- Severe ≥ 13 mg/dL
- Crisis ≥ 15 mg/dL
Hypercalcemia causes
- increased bone resorption
- increased GI reabsorption
- tubular reabsorption (renal)
Hypercalcemia symptoms
- fatigue/weakness
- Polyuria/polydipsia/nocturia
- anorexia
- depression
- anxiety
Hypercalcemia signs
- Nephrolithiasis
- Acute or chronic kidney disease
- severe: ventricular arrythmias
- calcification in tissues
Hypercalcemia causes (2)
CHIMPANZEE
- Calcium supplements
- Hyperparathyroidism
- Immobilization, iatrogenic
- Multiple myeloma, Milk alkali syndrome (ex: lithium)
- Parathyroid hyperplasia
- Alcohol
- Neoplasm (breast or lung cancer)
- Zollinger Ellison syndrome
- Excessive vitamin D
- Excessive vitamin A
- Sarcoidosis
Hypercalcemia causes (3)
BACKME
- Bone pain
- Arrhythmias
- Cardiac arrest
- Kidney stones
- Muscle weakness
- Excessive urination
Hypercalcemia Endocrine disease MOA
- adrenal insufficiency
- Hyperthyroidism
- Acromegaly
Hypercalcemia Medications
- Thiazide diuretics
- Lithium
- Vit D
- Vit A
- Calcium
- Aluminum/magnesium
- antacids
- Theophylline
- Tamoxifen
- Ganciclovir
Hypercalcemia Neoplasms MOA
- bone metastasis
- breast
- lung
- head/neck/esophagus
- multiple myeloma
- lymphoma
- leukemia
Hypophosphatemia Epidemiology
- rare in ambulatory persons
- 18-28%n incidence in critically ill pts
- Serum [PO4-] of < 2.7 mg/dL
- Severe < 1.5 mg/dL
Hypophosphatemia causes
- decreased GI absorption
- increased Renal excretion
- metabolic causes
- medications
Hypophosphatemia decreased GI Absorption
- alcoholism
- Vit D deficiency
- malabsorption
- excess intake aluminum based antacids
- parenteral nutrition
- fasting/starvation
Hypophosphatemia: Increased Renal excretion
- Hyperparathyroidism
- DKA
- Osteomalacia
- RTA
- ATN
- Hypokalemia, hypomagnesium
- multiple myeloma
- Fanconi syndrome
Hypophosphatemia: Metabolic
- Respiratory alkalosis
- Hungry bone
- DKA
- Refeeding syndrome
Mild hypophosphatemia
- mostly asymptomatic
- MOA: decreased [PO4-] results in increased Hgb for oxygen, creates tighter connection, doesn’t release in muscle
- decrease phosphate results in decrease in ATP that impacts function of leukocytes, platelets, encephalopathy, cardiomyopathy
Hyperphosphatemia causes
- acute phosphate load
- transcellular shit
- decreased renal shift
- pseudohyperphosphatemia
- Serum [PO4-] > 4.5 mg/dL
Hyperphosphatemia symptoms
- Tetany
- seizures
- hypotension
- calcifications in soft tissue
Hyperphosphatemia: decreased renal excretion
- renal failure (acute, chronic)
- Hypoparathyroidism
- Thyrotoxicosis
Hyperphosphatemia: Transcellular shift
- acidosis
- leukemia
- lymphoma
- tissue ischemia
Hyperphosphatemia: Acute phosphate load
- phosphate enemas, laxatives
- tumor lysis syndrome
- Vit D intoxication
- Hemolysis: transfusion, rhabdomyolysis
Pseudohyperphosphatemia
Endogenous:
- hemolysis
- hyperlipidemia
- hyperbilirubinemia
Exogenous:
- Amphotericin B
- Heparin
- Tissue plasminogen activator
Calcitonin release
- decreases serum calcium
PTH release results in?
- works on bone and kidney to increase serum calcium
