✅ Lytes, Acid-Base, Injury, Vasculitis Flashcards
Acute urinary retention (AUR)
The major risk factors for development of AUR include:
- Male sex (AUR rarely occurs in women)
- Advanced age (~33% of men age >80 will develop AUR)
- History of benign prostatic hyperplasia
- History of neurologic disease (eg, mild cognitive impairment)
- Surgery (especially abdominal surgery, pelvic surgery, and joint arthroplasty)
- Medications (eg, anesthetics, opioids, anticholinergics) that are common precipitants.
In a patient with suspected AUR who is unable to void, the diagnosis is confirmed by bladder ultrasound demonstrating >300 mL of urine. Treatment is with insertion of a Foley catheter, and urinalysis should be collected to rule out urinary tract infection (a potential cause of AUR). Obesity, abdominal ascites, or tissue edema may render bladder ultrasound inaccurate; in such cases, Foley catheter insertion can be both diagnostic and therapeutic.
Postoperative oliguria (< 0.5 mL/kg/hr) requires immediate assessment with initial portable bladder scan (if available) to assess bladder volume. Patients with significant urinary retention and likely distal obstruction require Foley catheterization to restore normal urine output and resolve or prevent hydronephrosis, tubular atrophy, and renal injury. If catheterization does not relieve the patient’s oliguria or if there is no significant urinary retention, the patient’s AKI may be due to other etiologies (ie, intrinsic, pre-renal).
Low Serum (plasma) Osmolality: 2 [Na+] + [BUN] / 2.8 + [glucose] /18
One approach to determining the etiology of hyponatremia is an assessment of the patient’s volume status. Evidence of volume overload (eg, peripheral edema, jugular venous distension) is consistent with hypervolemic hyponatremia, which occurs in heart failure, renal failure, and liver cirrhosis. Evidence of volume depletion (eg, dry mucous membranes) suggests hypovolemic hyponatremia, which occurs in patients with dehydration. Euvolemic (eg, moist mucous membranes, absence of peripheral ADH (SIADH).
Hx: Symptoms occur at a serum sodium level of 110 meq/L and include obtundation, coma, seizures, and death (if untreated). In general, symptoms tend to be worse when the hyponatremia develops quickly.
Tx:
🧂🧂🧂 3% NaCL?: Serum sodium level should be corrected to 120 meq/L at a rate of 1 to 2 meq/L/h; when this level is achieved, the rate of correction is slowed to 0.3 to 0.5 meq/L/h.
The quantity of sodium chloride required to increase the serum sodium concentration is calculated as:
TBW (L) × (Desired serum [sodium] − Actual serum [sodium]), where the desired [sodium] is 120 meq/L
Seizure and respiratory arrest, the main cause of permanent CNS damage in hyponatremia. ICU care, with frequent monitoring of the serum sodium level and CNS status, is critical. Once the Na has risen 4 to 8 mEq/L and the symptoms have improved, the rate of hypertonic saline infusion can be decreased.
🧂🧂🧂 Hypertonic saline is reserved for ❗ acute symptomatic hyponatremia.
Correcting hyponatremia TOO rapidly can lead to osmotic demyelination syndrome (previously known as 🧠central pontine myelinolysis), which is characterized by flaccid paralysis, dysarthria, and dysphagia. The rate of sodium correction must be 0.3 to 0.5 meq/L/h or less. 10-12 in a 24 hour period for normal risk patients
“HYPERVOLEMIC” (High ECF volume) w/ low EABV (“HYPOTONIC”)
<strong>E </strong>= Extracellular
<strong>A </strong>= Arterial
Heart Failure, Liver Failure, Nephrotic syndrome, Renal Insufficency
The kidney is conserving both sodium and water because renal perfusion is compromised by poor cardiac output.
Dx:
Liver Disease or HF ?
Renal conservation of sodium and water is documented by a low 🚽 urine sodium concentration (<10 [20] meq/L) and highly concentrated urine (frequently >450 mOsm/kg )
Tx:
- Treatment of the underlying cause
- Dietary sodium restriction to 2 to 3 g/day
- 🚱water restriction to 1 to 1.5 L/day
- 🎡Diuretics
- Desire: Urine Na+ 60-80 w/ home dose (4 hours after)
- Desire: Urine Na+ 80-120 w/ IV dose
HYPOVOLEMIC (Low ECF volume) w/ low EABV
<strong>E </strong>= Extracellular
<strong>A </strong>= Arterial
GI Loss, Vomiting, Diarrhea
In hypovolemic states, ADH release is stimulated by the decreased ECF volume status and leads to free-water retention.
Remember that, even when ECF volume is decreased, hyponatremia almost always indicates free-water excess (hypotonicity).
GI Losses
🤮 Vomiting
Dx: If volume loss is due to vomiting, a low urine chloride concentration is corroborative.
💩Diarrhea
Px: Dry mucous membranes, hypotension, and tachycardia.
Dx:
GI Loss
The urine indices reflect renal sodium conservation (🚽 urine sodium concentration <10 [20] meq/L) and water conservation (urine osmolality greater than the serum osmolality and frequently >450 mOsm/kg).
Tx:
🧂 Intravenous (IV) normal saline as well as managing the condition that precipitated the volume loss.
🎡Diuretics, Renal Loss
Elevated 🚽 urine sodium (> 20 mEq/L) suggests salt wasting (early diuretic use)
Surreptitious diuretic use is sometimes employed as a means to lose weight.
EUVOLEMIC (normal EABV) w/ low ECF
<strong>A </strong>= Arterial
<strong>E </strong>= Extracellular
SIADH
Adrenal Insufficiency
Hypothyroidism
Drugs
Reset Osmostat
Inadequate Osmols
PP
SIADH
Renal defect in excreting free water.
An increase in water intake does not produce an increase in water excretion because ADH release is relatively fixed.
Type A: Grossly elevated levels of ADH unresponsive to osmotic deviations
Type B: An abnormally low osmotic threshold for ADH release
Type C: ADH levels that are persistently in the physiologic range and are neither suppressed by a low plasma osmolality nor stimulated by a rising plasma osmolality.
Type D: Normal osmoregulation (ie, ADH secretion varies appropriately with the plasma osmolality), but the urine is concentrated even if ADH release is suppressed.
Type E: Decline in plasma ADH as the serum sodium concentration increases during infusion of hypertonic saline.
Etiologies
- CNS disturbance (eg, stroke, hemorrhage, trauma)
- Medications (eg, carbamazepine, SSRIs, NSAIDs)
- Lung disease (eg, pneumonia)
- Ectopic ADH secretion (eg, small cell lung cancer)
- Pain &/or nausea
Clinical features
- Euvolemia (eg, moist mucous membranes, no edema, no JVD)
- Mild/moderate hyponatremia - nausea, forgetfulnessm [Serum sodium 130-135 mEq/L][Serum sodium 120-130 mEq/L may display mild symptoms (lethargy, forgetfulness)].
- Severe hyponatremia - seizures, comaSerum sodium <120 mEq/L may have severe symptoms (eg, profound confusion, seizures, coma). Cx: Cerebral edema and brainstem herniation.
Laboratory findings
- Hyponatremia
- Serum osmolality <275 mOsm/kg H2O (hypotonic)
- Urine osmolality >100 mOsm/kg H2O (and usually greater than 300 mOsm/kg H2O) WITHOUT evidence of hypovolemia [ADH prevents the kidneys from excreting dilute urine]
- High Urine sodium >40 mEq/L [due to euvolemia]
- Low serum uric acid 🧶
- Low blood urea nitrogen (BUN) levels🍔
Management
💀 Chest CRX and Head CT
🚱 Free water restriction for asymptomatic patients. [Insensible and urinary water loss results in a rise in serum Na+ and serum osmolality and symptom improvement.]
🧂🧂🧂 Hypertonic saline (3% saline) is used to treat patients who are symptomatic [CNS symptoms such as confusion, obtundation, or seizures] Administered to raise the serum sodium out of the danger zone. [Increase in the serum sodium level by approximately 4 to 6 mEq/L over the first 24 hours is sufficient.]
Salt Tablets
❌ Normal Saline: Normal saline (0.9%) and half normal saline (0.45%) have electrolyte concentrations of approximately 300 and 150 mOsm/kg H2O, respectively. Intravenous infusion of either of these fluids would cause a net increase in total body free water and worsen the hyponatremia.
🏃🏽♀️Exercise-associated hyponatremia (EAH) is a recognized phenomenon that may occur in individuals participating in prolonged exercise (eg, marathons, triathlons). Depending on the degree of hyponatremia, patients may be asymptomatic or mildly symptomatic (eg, lethargy, nausea) or may demonstrate severe symptoms (eg, seizures, profound confusion) that, when present, are indicative of life-threatening hyponatremia.
The largest contributing factor to EAH is the ingestion of large amounts of hypotonic fluid (eg, water, some sports drinks) during and immediately following prolonged exercise. In addition, many individuals with EAH demonstrate temporary inability to excrete appropriately dilute urine (urine osmolality inappropriately remains >100 mOsm/kg H2O), which is consistent with syndrome of inappropriate antidiuretic hormone (SIADH). In these individuals, excessive ADH secretion is triggered by nonosmotic stimuli (eg, exertion, pain, hypoglycemia, nausea) that occur during intense exercise.
PP
Primary polydipsia is more common in patients with psychiatric conditions (eg, schizophrenia), possibly due to a central defect in thirst regulation. These patients continue to drink water despite a decreased serum osmolality that should normally inhibit the thirst reflex.
The kidney increases water excretion, which dilutes the urine maximally to an osmolality <100 mOsm/kg. However, hyponatremia can develop if the water intake is higher than the kidney’s ability to excrete water. Patients with significant hyponatremia can develop confusion, lethargy, psychosis, and seizures.
The normal renal capacity for water excretion is approximately 15 L/day. A massive increase in water intake occurs in psychogenic polydipsia or, rarely, in hypothalamic diseases.
- Urine sodium concentration >20 meq/L)
- ADH levels are normal
- Urine osmolality appropriately low (<100 mOsm/kg H2O)
- Very dilute urine (ie, urine specific gravity of 1.001 or 1.002)
Tx: 🚱 Water restriction
Inadequate Osmoles
Severely decreased solute intake (in the setting of ongoing free water intake) and polydipsia.
At least 50 mOsm needed to excrete 1 L of water via the urinary tract; malnourished patients may not have adequate osmoles to excrete excess free water.
- ADH levels are normal
- Urine osmolality appropriately low (<100 mOsm/kg H2O)
Tx: Water restriction until nutrition can be corrected
“Tea and toast?” “Beer potomania?”
Glucocorticoid Deficiency
Renal defect in excreting free water. increased ADH release
Mineralocorticoid deficiency typically presents with hyperkalemia and metabolic acidosis
Hypothyroidism
Renal defect in excreting free water. increased ADH release
Reset osmostat
Pregnancy
HYPERTONIC (hyperosmolal) Hyponatremia
Hyperglycemia
Measured sodium concentration can be corrected by the following calculation:
Corrected [Na+] = Measured [Na+] + 0.016 × ([Glucose] − 100)
! Other solutes capable of this effect include mannitol, radiographic contrast media, sorbitol, and glycine (sorbitol and glycine are used as irrigants during bladder or uterine surgical procedures)
ISOTONIC (pseudohyponatremia)
Measurement in a falsely large volume; an interfering substance displaces water in the sample.
The most common space-occupying substances are:
Lipids (eg, severe hyperlipidemia)
Paraproteins (eg, multiple myeloma).
Hyperglycemia Patients with DKA can have pseudohyponatremia due to hyperglycemia;
Serum sodium concentration >145 meq/L
Central Diabetes Insipidus 🗿
Nephrogenic Diabetes Insipidus 🗿
Mineralcorticoid Excess
🧂🧂🧂 Hypertonic Saline (Iatrogenic)
🍭Hyperglycemia
Diuretics
💩GI losses
😰Skin losses
💨 Respiratory Tract losses
GI losses
Most commonly, hypernatremia is due to loss of hypotonic fluids with inadequate water replacement.
Associated with ICF contraction; Defective thirst mechanism, inadequate access to water, or a renal concentrating defect. Patients with an intact thirst mechanism do not develop significant hypernatremia unless their access to water is restricted by unconsciousness, immobility, or an altered mental status.
Hx: GI, renal, cutaneous, or pulmonary losses.
Weakness, lethargy, seizures, and coma.
Dx: Both thirst and ADH levels should be elevated
Tx: 0.9% NS replacement, 💧 free water replacement, and correction of the underlying problem leading to hypotonic fluid loss; ADH (desmopressin, vasopressin) administration.
The water deficit is estimated by the formula:
Water deficit = TBW – (Desired [sodium]/Current [sodium]) × TBW
Because of the presence of idiogenic osmoles created by the brain to protect ICF volume, correcting hypernatremia too quickly can lead to cerebral edema. Extreme care must be taken to correct serum sodium concentration at a rate ≤1 meq/L/h, with a goal of 50% correction at 24 to 36 hours and complete correction in 3 to 7 days.
Cx:
Half normal saline and 5% dextrose are hypotonic solutions. As such, they should NEVER be used for initial resuscitation because they quickly exit the intravascular system and lower the sodium too rapidly. Precipitous drops in sodium levels can cause cerebral edema.
🗿 Nephrogenic Diabetes Insipidus
To distinguish between central (ADH deficiency) and nephrogenic (peripheral resistance to ADH action) diabetes insipidus, vasopressin (ADH by another name) is administered. If the urine osmolality rises and the urine output falls, the diagnosis is central DI. There will be little response to vasopressin in nephrogenic DI.
💊Lithium induces ADH resistance by impairing water reabsorption in the collecting duct. Patients typically develop acute-onset nocturia, polyuria and polydipsia. If water intake is inadequate, significant hypernatremia and central nervous system symptoms can develop. Discontinuing lithium is recommended, with salt restriction and selected diuretics (eg, amiloride) as an alternative for patients who cannot stop lithium.
Hx: Drugs (eg, lithium, foscarnet), hypokalemia, hypercalcemia, sickle cell disease and trait, and amyloidosis.
Tx: The first step is to restore volume with isotonic fluids (0.9% saline). Isotonic fluid is not usually used in hypernatremia, but it is recommended in patients with marked volume depletion and hemodynamic instability. Once the patient is euvolemic, the fluid can be switched to a hypotonic fluid (5% dextrose preferred over 0.45% saline) for free water supplementation. The serum sodium should be corrected by 0.5 mEq/dL/hr without exceeding 12 mEq/dL/24 hr.
Cx: Cerebral edema can occur if the sodium is corrected too quickly.
Hypercalcemia
Severe hypercalcemia (ie, serum calcium >14 mg/dL) can cause weakness, gastrointestinal distress, and neuropsychiatric symptoms (eg, confusion, stupor, coma), especially with a rapid rise in serum calcium. Patients are typically volume-depleted due to polyuria and decreased oral intake.
Management of hypercalcemia
Severe (calcium >14 mg/dL) or symptomatic
- Short-term (immediate) treatment
- Normal saline hydration plus calcitonin 🤵🏼
- Avoid loop diuretics unless volume overload (heart failure) exists
- Long-term treatment
- Bisphosphonate (zoledronic acid)
Moderate (calcium 12-14 mg/dL)
- Usually no immediate treatment required unless symptomatic
- Treatment is similar to that for severe hypercalcemia
Asymptomatic or mild (calcium <12 mg/dL)
- No immediate treatment required
- Avoid thiazide diuretics, lithium, volume depletion & prolonged bed rest
Patients with severe hypercalcemia require aggressive saline hydration to restore intravascular volume and promote urinary calcium excretion. Calcitonin, by inhibiting osteoclast-mediated bone resorption, quickly reduces serum calcium concentrations and can be administered concurrently with saline. Bisphosphonates (eg, pamidronate, zoledronic acid) also inhibit bone resorption and provide a sustained reduction in calcium levels. However, the calcium-lowering effect of bisphosphonates is delayed, usually occurring over 2-4 days, and they are typically given after initial administration of saline and calcitonin).
Primary hyperparathyroidism
PTH [normally 10-65 pg/mL]
The most common cause of hypercalcemia diagnosed in the outpatient setting.
Hx: This disorder also may be found during the evaluation of osteoporosis or nephrolithiasis.
Increased 👨🏽🔬PTH:
Increased 1,25-dihydroxy (vitamin 🔋D3) levels
Increased osteoclast-mediated bone resorption 🦴
Enhanced distal tubular reabsorption of calcium 🦴
Decreased proximal tubular reabsorption of phosphorus
Increased 🚽 urine phosphate and calcium levels.
Increased 1α-hydroxylase 🤖 expression in the kidney, leading to increased production of 🤖 1,25-dihydroxy vitamin D, which further increases GI calcium absorption.
Dx: Associated with elevated serum calcium, low phosphate, PTH in the normal range (20%) or elevated (80%), normal or elevated alkaline phosphatase, and normal or elevated urine calcium.
Hypercalcemia of malignancy
Hypercalcemia of malignancy may be due to local osteolytic hypercalcemia or to humoral hypercalcemia of malignancy, in which a tumor that does not involve the skeleton secretes a circulating factor that activates bone resorption.
Dx: Associated with elevated calcium, normal or low phosphate (elevated if GFR <35 mL/min/1.73 m2), normal or elevated PTHrP (not needed for diagnosis), normal or elevated alkaline phosphatase, and elevated urine calcium. Low PTH?
Tx:
Asymptomatic or mild hypercalcemia (calcium <12 mg/dL) does not require urgent therapy, but hypercalcemia of malignancy may worsen over time.
Control of the tumor with chemotherapy.
💦Saline diuresis (infusion): Normalization of intravascular volume with saline will improve delivery of calcium to the renal tubule and aid in excretion of calcium. As the kidneys excrete excess sodium from the saline, excretion of calcium will follow
Bisphosphonates (eg, zoledronic acid) inhibit the osteoclastic activity of bone, stabilizing destructive bony tumors and reducing the risk of skeletal-related events such as pathologic fracture and malignant hypercalcemia.
Metastatic bone disease
High calcium levels impair the ability of the nephron to concentrate urine, which results in inappropriate water loss from the kidney. Hypercalciuria without hypercalcemia is most common.
Dx: Associated with elevated calcium, normal or elevated phosphate, elevated alkaline phosphatase (most cases), and variable PTHrP. Low PTH?
Multiple myeloma
Common cause of hypercalcemia in patients with decreased GFR and anemia.
Dx: Associated with elevated calcium, elevated phosphate, normal alkaline phosphatase, normal or low PTHrP, and abnormal serum protein immunoelectrophoresis. Low PTH?
Granulomatous disease (eg, sarcoidosis, tuberculosis)
Hypercalcemia can result from excessive ingestion or production of either 25-hydroxy vitamin D (calcidiol) or 1,25-dihydroxy vitamin D (calcitriol). The mechanism of hypercalcemia is the result of increasing GI calcium absorption and bone resorption.
Dx: Associated with elevated calcium, elevated phosphate, elevated alkaline phosphatase (but may not be of skeletal origin), elevated urine calcium, and elevated vitamin D. Low PTH?
Milk-alkali syndrome
MAS is caused by excessive intake of calcium and absorbable alkali (eg, calcium carbonate preparations used in patients with osteoporosis). The resulting hypercalcemia causes renal vasoconstriction and decreased glomerular blood flow. In addition, inhibition of the Na-K-2Cl cotransporter (due to activation of calcium-sensing receptors in the thick ascending loop) and impaired antidiuretic hormone activity lead to loss of sodium and free water. This results in hypovolemia and increased reabsorption of bicarbonate (augmented by the increased intake of alkali).
Consider in healthy persons in whom primary hyperparathyroidism has been excluded. Excessive ingestion of calcium carbonate to treat osteoporosis or dyspepsia can result in hypercalcemia, metabolic alkalosis, and kidney insufficiency. Metabolic alkalosis stimulates the distal tubule to reabsorb calcium, contributing to hypercalcemia.
Hx: Medications that raise the risk of MAS include thiazide diuretics, ACE inhibitors/angiotensin II receptor blockers, and nonsteroidal anti-inflammatory drugs. In addition to hypercalcemia, metabolic findings in MAS include hypophosphatemia, hypomagnesemia, metabolic alkalosis, and acute kidney injury. Parathyroid hormone levels are suppressed.
Dx: Associated with elevated calcium, elevated phosphate, elevated creatinine, normal alkaline phosphatase, elevated bicarbonate, and variable urine calcium. Low PTH?
Immobilization
Hypercalcemia of immobilization is likely due to increased osteoclastic bone resorption. The risk is increased in patients with a pre-existing high rate of bone turnover (eg, younger individuals, Paget disease).
Occurs in persons with high bone turnover before an immobilizing event (eg, untreated primary hyperparathyroidism, hyperthyroidism, Paget disease of bone).
Dx: Associated with elevated calcium, elevated phosphate, elevated alkaline phosphatase, and elevated urine calcium. Low PTH?
The onset of hypercalcemia is usually around 4 weeks after immobilization, although patients with chronic renal insufficiency may develop hypercalcemia in as little as 3 days.
The onset of hypercalcemia due to immobilization is often insidious, and the presenting symptoms can be nonspecific. Bisphosphonates inhibit osteoclastic bone resorption and are effective in treating hypercalcemia of immobilization and reducing the associated bone loss.
Hyperthyroidism
Hypercalcemia is a frequent incidental finding in hyperthyroidism, which results from direct stimulation of osteoclasts by thyroxine or triiodothyronine. Low PTH?
Benign familial hypocalciuric hypercalcemia
Constitutive overexpression of the calcium-sensing receptor gene.
Dx: Elevated calcium, low phosphate, and a calcium-creatinine clearance ratio <0.01 [calculated as (Urine calcium ÷ Serum calcium) × (Serum creatinine ÷ Urine creatinine)]. Normal PTH?
HYPOCALCEMIA
Calcium normally 9-10.5 mg/dL
Causes
- Neck surgery (parathyroidectomy)
- Pancreatitis
- Sepsis
- Tumor lysis syndrome
- Acute alkalosis
- Chelation: blood (citrate) transfusion, EDTA (ethylenediaminetetraacetic acid), foscarnet
Clinical features
- Muscle cramps
- Chvostek & Trousseau signs
- Paresthesias
- Hyperreflexia/tetany
- Seizures
Treatment
- IV calcium gluconate/chloride
Decreased 👨🏽🔬PTH production
ⓂHypomagnesemia causes decreased production of 👨🏽🔬PTH as well as decreased end-organ response to the hormone. 🍻 Alcohol causes increased urinary losses of magnesium which then leads to the mentioned effects on PTH and ultimately to hypocalcemia. Hypomagnesemia alone would 🅿increase phosphorus by decreasing parathormone effect.
⚪Hypoalbuminemia
Approximately 40% of circulating calcium is bound to proteins (predominantly albumin). Hypoalbuminemia will lower the total serum calcium level; therefore, measured calcium levels are corrected upward based on the extent of hypoalbuminemia. Conversely, hyperalbuminemia is associated with an increase in total calcium.
The serum calcium concentration INCREASES by 0.8 mg/dL for every 1 g/dL decrease in serum albumin; the corrected calcium level can be calculated using the following formula:
Corrected calcium = (measured total calcium) + 0.8 × (4.0 g/dL − serum albumin in g/dL)
“Add 0.8 mg/dL to the observed calcium level for every 1 g reduction in the albumin level (from 4 used as normal)”
An ionized calcium level is consistent and accurate regardless of the albumin level of a patient. Direct measurement of ionized calcium is performed in many clinical laboratories, but it requires special handling and may not be readily available.
Plasma calcium exists in 3 forms: ionized calcium (45%), albumin-bound calcium (40%), and calcium bound to inorganic and organic anions (15%). Homeostasis of these forms is significantly influenced by the extracellular pH level. An increased extracellular pH (due to respiratory alkalosis ) causes hydrogen ions to dissociate from albumin molecules, thereby freeing up the albumin to bind with calcium. This increase in the affinity of albumin for calcium leads to decreased levels of ionized calcium.
Ionized calcium is the only physiologically active form, which means that a decrease in ionized calcium can result in the clinical manifestations of hypocalcemia (eg, crampy pain, paresthesias, carpopedal spasm) even though total calcium is unchanged.
- Chvostek sign
- Trousseau sign
🍊 Citrate in transfused blood binds ionized calcium, which is the biologically active fraction (total calcium levels will not be significantly affected). Hypocalcemia is uncommon following blood transfusion in patients with normal liver function as citrate is rapidly metabolized by the liver; however, 🐄 hepatic dysfunction can. Other infused substances that can chelate calcium in the blood include lactate, foscarnet, and sodium ethylenediaminetetraacetic acid (EDTA).
Tx:
Oral calcium (carbonate or citrate) supplementation.
Intravenous calcium guconate/chloride more rapidly increases the serum calcium level and may be indicated in patients with very low (< 7.5 mg/dL) calcium levels or more significant clinical findings associated with the hypocalcemia, such as severe musculoskeletal weakness, tetany, or electrocardiographic conduction abnormalities.
Recombinant form of parathyroid hormone (teriparatide) is available, although its primary use is in the treatment of advanced osteoporosis in selected patients. Although teriparatide holds promise as a potential therapy for chronic hypoparathyroidism, its safety and long-term effectiveness for this indication have not been established, and it does not have Food and Drug Administration approval for treatment of acute hypoparathyroidism.
🅿 HYPOPHOSPHATEMIA
Hypophosphatemia is defined as a serum phosphorus concentration less than 2.5 mg/dL and is most common in patients with a history of chronic 🍻 alcohol use, critical illness, or malnutrition.
Respiratory alkalosis is one of the commonest causes of hypophosphatemia; it results from shift of phosphate from the extracellular to the intracellular space.
Dx: Most patients with hypophosphatemia are asymptomatic, but symptoms of weakness may manifest at serum phosphorus levels < 2.0 mg/dL. Levels less than 1.0 mg/dL may result in respiratory muscle weakness, hemolysis, rhabdomyolysis or tumor lysis. Serum uric acid >15 mg/dL suggests rhabdomyolysis or TLS.
🍗Refeeding syndrome is caused by an intracellular shift of 🅿phosphorus; calories provided to a patient after a prolonged period of starvation serve as a stimulus for cellular growth, which consumes phosphorus in the form of phosphorylated intermediates such as adenosine triphosphate.
Hx: Persons who chronically 🍻abuse alcohol frequently may develop refeeding syndrome, largely because of underlying poor nutrition. The syndrome may also be the result of intravenous infusion IV of glucose in malnourished patients. Such patients have clear clinical evidence of malnutrition. In addition, malnutrition almost always causes hypoalbuminemia.
Tx: If the refeeding syndrome occurs, the level of nutritional support should be reduced, and the hypophosphatemia, hypokalemia, and hypomagnesemia should be corrected. Moderately to severely ill patients with marked edema or a serum phosphorus level less than 2.0 mg/dL should be hospitalized for intravenous therapy to correct electrolyte deficiencies. Continuous telemetry may also be needed to monitor cardiopulmonary physiology.
HYPERKALEMIA
Tx: Restrict dietary potassium, ensure adequate hydration, and use loop diuretics as necessary.
Severe hyperkalemia (>6.0 meq/L [6.0 mmol/L]) is associated with life-threatening cardiac dysrhythmias; patients with severe hyperkalemia require emergent hospitalization for medical management.
Stabilize (Cacl) Temporize (Insulin, NaHCO3, beta-agonist); decrease total body K+ (loop Diuretics, kayexylate, dialysis)
Calcium gluconate
Raises threshold for depolarization (myocardial membrane stabilization)
Sodium bicarbonate
Shifts potassium intracellularly. Patients with severe kidney disease or hypervolemic states, such as CHF, may not tolerate alkalinization or the associated sodium load. Ideally, the serum bicarbonate and creatinine should be checked before intravenous sodium bicarbonate is administered.
Insulin/glucose
Shifts potassium intracellularly. In euglycemic patients, a combination of insulin (10U) and glucose (25g) is typically administered concomitantly to decrease the risk of hypoglycemia (can lower the serum potassium level by 0.5 to 1.0). In hyperglycemic patients insulin alone should be given.
β-Agonists (eg, inhaled albuterol)
Shifts potassium intracellularly. Probably more effective than IV sodium bicarbonate. It
Measures to promote potassium loss from the body (Kayexalate, furosemide, or dialysis) take time to work.
Loop diuretics
Increases renal excretion of potassium. Depending on the patient’s kidney function and volume status, may be considered, but they take hours to work and should not take the place of immediate therapy.
Sodium polystyrene sulfonate (kayexelate)
Ion exchange resin binding potassium in the gut; may be no more effective than laxatives and has been associated with intestinal necrosis; ; need good bowel function. The delayed onset of action of this drug prevents this from being the best initial intervention.
Dialysis
Extracorporeal removal of potassium
.1 for every 10 mEq
HYPOKALEMIA
-
Surreptitious vomiting
- Physical findings that are characteristic of surreptitious vomiting are scars/calluses on the dorsum of the hands, and dental erosions. The dorsal scars result from repeated chemical/mechanical injury as the patient uses his/her hands to induce vomiting. Dental erosions result due to increased exposure to gastric acid. Surreptitious vomiting may also result in hypovolemia and hypochloremia, which in turn lead to a low urine chloride concentration.
- Diuretic abuse (Potassium-wasting diuretics)
- Bartter syndrome
- Gitelman’s syndrome
- Hypokalemia, alkalosis and normotension, but their urine chloride concentrations are high.
- Diarrhea
Hx: In some patients, clinically significant hypokalemia can result, causing muscle weakness, arrhythmias, and EKG changes. Other common side effects of beta-2 agonists include tremor, headache and palpitations.
Symptoms of hypokalemia depend on the severity of the imbalance, but can include weakness, fatigue, and muscle cramps. Flaccid paralysis, hyporeflexia, tetany, rhabdomyolysis, and arrhythmias may occur with severe hypokalemia (serum concentration <2.5 mEq/L). An ECG will show broad flat T waves, U waves, ST depression, and premature ventricular beats. Atrial fibrillation, torsades de pointes, and ventricular fibrillation can occur.
Beta-2 agonists like albuterol reduce serum potassium levels by driving potassium into cells.
Ddx: Metabollic Acidosis
([serum bicarbonate] <22 meq/L ; pH <7.35)
Serum Anion Gap: [Na+] – ([Cl-] + [HCO3 -]). The normal anion gap is 12 ± 2.
Osmolal gap is present when the measured plasma osmolality exceeds the calculated plasma osmolality by >10 mOsm/kg H2O (10 mmol/kg H2O).
🚽 Urine anion gap = (Urine [Sodium] + Urine [🍌Potassium]) – [Urine Chloride]
Urine anion gap normally 30 to 50 mEq/L
Urine ammonium may be estimated by calculating the urine anion gap
➗ Compensations:
Acute Metabolic Acidosis:
❄Winter’s formula: Pco2 = (1.5 × [Bicarbonate]) + 8 (+/- 2)
If matched, this indicates a compensated primary metabolic acidosis with respiratory compensation.
The normal compensatory response in metabolic acidosis is for the PCO2 to decrease
by 1 to 1.5 mm Hg for each 1-mEq decrease in HCO3.
Chronic Metabolic Acidosis: Pco2 = [Bicarbonate] + 15
Quick check: Pco2 value should approximate last two digits of pH
Failure of Pco2 to decrease to the expected value indicates complicating respiratory acidosis
Excessive decrease of Pco2 indicates complicating respiratory alkalosis.
Corrected serum bicarbonate: Calculated to determine if a complicating metabolic disturbance is present:
Corrected [HCO3] = measured [HCO3] + (measured anion gap – 12)
Increased serum anion gap:
- Ketoacidosis (DKA, Alcohol Abuse, starvation)
- Lactic acidosis (ischemia, sepsis, shock, drugs)
- Exogenous substances (Methanol, Ethylene glycol, Salicylates, toluene)
Salicilates: Aspirin stimulates central respiratory drive (medullary respiratory center) to cause tachypnea and respiratory alkalosis. In addition, aspirin causes an anion gap metabolic acidosis due to increased production and decreased renal elimination of organic acids (eg, lactic acid, ketoacids)[suppression of oxidative phosphorylation].
• Chronic kidney disease (Uremia)
Isoniazid/Iron (poisoning) classically presents in children age <6 due to unintentional ingestion of prenatal vitamins or concentrated ferrous sulfate tablets. Iron causes direct mucosal damage to the intestinal tract, leading to abdominal pain, vomiting, diarrhea, and bleeding (hematemesis, melena).
Normal serum anion gap (hyperchloremic): Common causes include renal tubular acidosis, bicarbonate loss owing to diarrhea. HARDASS (Hyperalimnetation,Addisons (mineralocorticoid [Adrenal] deficiency),RTA, 💩Diarrhea,Acetazolamide,Spronolactone,Saline Infusion). Toluene inhalation (glue sniffing)?
• ➕ Positive 🚽 urine anion gap: Metabolic acidosis of kidney origin related to the inability to excrete acid and the resulting a positive UAG related to minimal urine ammonium excretion.
○ Type I RTA (normo- or hypokalemic), caused by impaired distal tubule acidification, (The kidney’s ability to excrete hydrogen ions in response to acidemia is impaired) should be considered in patients with a normal anion gap acidosis, hypokalemia, a positive urine anion gap, and a urine pH >5.5 🔵 alkali) in the setting of systemic acidosis; serum bicarbonate concentration may be as low as ≅10 mEq/L (10 mmol/L).
Hx: Autoimmune disorders such as Sjögren syndrome, systemic lupus erythematosus, or rheumatoid arthritis; drugs such as lithium or amphotericin B; hypercalciuria; and hyperglobulinemia; The persistently increased pH encourages the development of kidney stones (nephrolithiasis and nephrocalcinosis).
○ Type IV RTA (hyperkalemic), should be suspected in patients with a normal anion gap metabolic acidosis associated with 🍌 hyperkalemia and a slightly positive urine anion gap. Type 4 RTA occurs most often in patients with 🍭diabetes who have mild to moderate kidney insufficiency. The disorder is caused by hyporeninemic hypoaldosteronism, which is characterized by deficient angiotensin II production caused by both decreased renin production and an intraadrenal defect leading to aldosterone deficiency. urine pH <5.5
Normal 🚽 urine anion gap
○ Type II RTA (normo- or hypokalemic), caused by reduced proximal tubule bicarbonate reabsorption 🏎 (defect in regenerating bicarbonate in the proximal tubule) and should be suspected in patients with a normal anion gap metabolic acidosis, a normal urine anion gap, hypokalemia, and an intact ability to acidify the urine to a pH of <5.5 while in a steady state. serum [HCO3] ≅ 16–18 mEq/L (16-18 mmol/L)
Glycosuria, phosphaturia, uricosuria, aminoaciduria, and tubular proteinuria (Fanconi syndrome). Proximal RTA is associated with glycosuria, phosphaturia, and aminoaciduria (Fanconi syndrome).
• ➖ Negative 🚽 urine anion gap: Metabolic acidosis of extrarenal origin (usually gastrointestinal) caused by significantly increased urine ammonium excretion, which is used as a measure of the kidney’s ability to excrete acid.
○ Patients with increased gastrointestinal (GI) losses of bicarbonate and potassium have intact renal tubular function that results in a compensatory increase in urine ammonium production, indicating increased acid secretion by the kidney; ureterosigmoidostomy.
○ Ingestion of acid
Respiratory Acidosis
(arterial PCO 2 > 45 mm Hg; pH < 7.35)
Compensations:
Acute Respiratory Acidosis: 1 meq/L increase in bicarbonate for each 10 mm Hg (1.33 kPa) increase in Pco2
Chronic Respiratory Acidosis: 3.5 meq/L increase in bicarbonate for each 10 mm Hg (1.33 kPa) increase in Pco2
Failure of the bicarbonate concentration to increase to the expected value indicates complicating metabolic acidosis
Excessive increase in the bicarbonate concentration indicates complicating metabolic alkalosis.
- Respiratory center depression (stroke, infection, tumor, opiates, COPD, OHS, post-ictal, drug overdose causing hypoventilation)
- Neuromuscular failure (muscular dystrophy, ALS, Guillain-Barré syndrome, myasthenia gravis)
- Decreased respiratory system compliance (kyphoscoliosis, interstitial lung disease ((ILD/DPLD))
- Increased airway resistance or obstruction (asthma, COPD, OHS)
- Increased dead space or ventilation–perfusion mismatch (pulmonary embolism, COPD, OHS)
COPD
Chronic retention of carbon dioxide. Renal compensation for persistent hypercapnia results from stimulation of secretion of protons at the level of the distal nephron.
Dx: The urine pH decreases, and excretion of urine ammonium, titratable acid, and chloride is enhanced. Consequently, the reabsorption of bicarbonate throughout the nephron is enhanced.
OHS
Patients with OHS “can’t breathe” (due to excess weight and altered lung mechanics) and “won’t breathe” (due to decreased chemosensitivity to hypercapnia from persistent nocturnal hypoventilation).
Hx: Daytime hypercapnia (PaCO2 >45 mm Hg) in an obese patient (BMI >30 kg/m2, often >40 kg/m2) without another explanation for the hypercapnia. Most patients have coexisting obstructive sleep apnea with frequent apneic events and daytime hypersomnolence. Other features of OHS include dyspnea, polycythemia, respiratory acidosis with compensatory metabolic alkalosis, pulmonary hypertension, and cor pulmonale.
Obesity reduces chest wall and lung compliance, leading to a decrease in tidal volumes and total lung capacity and an increase in airway resistance. As a result, higher levels of ventilatory drive are required to maintain normocapnia, but there is an inability to exhale excess CO2 during the day (due to persistent restriction). This leads to CO2 accumulation overnight, with subsequent chronic respiratory acidosis. Renal bicarbonate excretion is decreased as a compensatory mechanism; this blunts the ventilatory response to the increased CO2 and contributes to hypoventilation.
([serum bicarbonate] >28 meq/L; pH >7.45)
Compensations: For each 1 meq/L increase in bicarbonate, Pco2 should increase 0.7 mm Hg
Decrease in CO2 = presence of a concurrent respiratory alkalosis.
- 🤮Vomiting/Nasogastric suctioning
- Thiazide and loop diuretic therapy
- Contraction alkalosis
- Exogenous bicarbonate in the setting of kidney dysfunction
- Low cardiac output (low effective arterial blood volume)
Saline-responsive metabolic alkalosis
Hx: Patients typically develop volume depletion (eg, hypotension, orthostasis) and low serum Cl- due to chloride loss in the gastric secretions.
The ECF loss leads to increased renal mineralocorticoid levels, increased renal sodium and chloride reabsorption, and increased urinary H+ and K+ excretion. The end result is decreased urine chloride, 🍌hypokalemia, and metabolic alkalosis.
Tx: Usually corrects with isotonic saline infusion alone and restores both ECF volume and low serum Cl-.
Chloride unresponsive (urine [chloride] >15 meq/L
- Elevated mineralocorticoid activity (primary hyperaldosteronism, Cushing syndrome)
- Exogenous mineralocorticoid
- Bartter, Gitelman, Liddle syndromes (genetically based tubular disorder)
- Some forms of congenital adrenal hyperplasia
- Severe hypokalemia
- Chronic licorice ingestion
Hx: Patients can have expanded extracellular fluid (ECF) with hypervolemia (eg, primary hyperaldosteronism, Cushing syndrome, excessive black licorice ingestion) or appear hypo/euvolemic (eg, Bartter syndrome, Gitelman syndrome).
Tx:
Saline-unresponsive typically presents with a higher level of urinary chloride (>20 mEq/L).
These conditions require treatment of the underlying disorder; the metabolic alkalosis is not corrected by saline infusion alone.
(arterial PCO 2 <35 mm Hg ; pH >7.45)
Compensations: If there is complete, appropriate compensation for the primary process, it is often described as being a “pure” acid-base disorder. Compensation would not return the pH all the way back to 7.4.
Acute Respiratory Alkalosis: 2 meq/L decrease in bicarbonate for each 10 mm Hg (1.33 kPa) decrease in Pco2
Chronic Respiratory Alkalosis: 4 to 5 meq/L decrease in bicarbonate for each 10 mm Hg decrease in Pco2
Failure of the bicarbonate concentration to decrease to the expected value indicates complicating metabolic alkalosis.
Excessive decrease in the bicarbonate concentration indicates complicating metabolic acidosis.
- CNS stimulation (stroke, infection, tumor, fever, pain)
- Drugs (aspirin, progesterone, theophylline, caffeine)
- Hyperventilation 💨 (😰Anxiety, psychosis, Pregnancy)
- Pulmonary Hypertension, Pulmonary Embolism 🔴
- Pulmonary parenchymal Disease (Pneumonia, pulmonary fibrosis)
- Hypoxemia (🗻low atmospheric oxygen, severe anemia, lung disease, right-to-left shunt, heart failure, sepsis)
REBREATHING AIR
Plasma calcium exists in 3 forms: ionized calcium (45%), albumin-bound calcium (40%), and calcium bound to inorganic and organic anions (15%). Homeostasis of these forms is significantly influenced by the extracellular pH level. An increased extracellular pH (due to respiratory alkalosis) causes hydrogen ions to dissociate from albumin molecules, thereby freeing up the albumin to bind with calcium. This increase in the affinity of albumin for calcium leads to decreased levels of ionized calcium.
Ionized calcium is the only physiologically active form, which means that a decrease in ionized calcium can result in the clinical manifestations of hypocalcemia (eg, crampy pain, paresthesias, carpopedal spasm) even though total calcium is unchanged. Thus, patients can experience signs and symptoms of hypocalcemia due to respiratory alkalosis likely caused by hyperventilation, as may be seen in pulmonary embolism.
Acute Kidney Injury 🤕(AKI)
Acute kidney injury (AKI) develops over hours to days and is usually diagnosed in hospitalized patients or following a procedure.
- Stage 1 (risk) Creatinine Increase of ≥150%–200% Urine output <0.5 mL/kg/h for >6 h
- Stage 2 (injury) Creatinine Increase of ≥200%–300% Urine output <0.5 mL/kg/h for >12 h
- Stage 3 (failure) Creatinine Increase of >300% or >4 mg/dL (353.6 µmol/L) with acute increase ≥0.5 mg/dL (44 µmol/L) Urine output <0.3 mL/kg/h for >24 h or anuria for 12 h
Intrinsic AKI is divided into oliguric (≤400 mL/24 h) and nonoliguric (>400 mL/24 h) forms.
Prerenal
- BUN/creatinine ratio
- Typically >20
- Urine sodium
- <20 mEq/L
- Fractional excretion of sodium
- <1%
- Urine osmolality
- >500 mOsm/kg
- Urine specific gravity
- >1.020
- Microscopy
- Bland
AKI can be categorized as prerenal (eg, low urine sodium [eg, <20 mEq/L], elevated blood urea nitrogen (BUN)/creatinine ratio [eg, >20]), postrenal (eg, hydronephrosis on ultrasound), or intrinsic.
Urinalysis with microscopic examination
Significant proteinuria suggests glomerular disease.
Hematuria:
No erythrocytes suggests rhabdomyolysis.
Isomorphic, normal-appearing erythrocytesand the absence of proteinuria = nonglomerular bleeding. In a patient age younger than age 40 years, greater than3 erythrocytes/high-power field on two or more occasions constitutes hematuria and is a common finding on urinalysis. A single episode in older patients or in those at risk ( smoking history, occupational exposure to chemicals or dyes, age older than 40 years, a history of gross hematuria, a urologic disorder, irritative voiding symptoms, urinary tract infection, analgesic abuse, or pelvic irradiation) should initiate a full evaluation of the upper and lower urinary tract.
Dysmorphic erythrocytes suggest acute glomerulonephritis. Glomerular hematuria also is characterized by the presence of dysmorphic erythrocytes or acanthocytes, which are erythrocytes that retain a ring shape but have “blebs” protruding from their membrane, giving them a characteristic shape (compared with acanthocytes in the blood, in which the membrane protrusions appear to have a “spiked” shape).
Urine pH may range between 4.5 and 8.0.
Specific gravity ranges between 1.003 and 1.035, with the specific gravity of normal serum being approximately 1.010. Excretion of urine with a persistently low specific gravity (<1.007) is called hyposthenuria and may indicate a loss of concentrating ability (eg, diabetes insipidus). High urine specific gravity may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention (eg, heart failure).
The detection of proteinuria implies an albumin excretion rate (AER) of ≥300 mg/24 h. However, the detection of lesser but still abnormal degrees of albuminuria (albumin excretion rates of 30–300 mg/24 h) requires other quantitative methods.
The dipstick protein indicator is insensitive to tubular proteins and immunoglobulins; identification of the latter (eg, Bence-Jones proteins secondary to multiple myeloma) is best accomplished by a 24-hour urine collection for total protein with protein electrophoresis and immunofixation. Lysed neutrophils and macrophages release indoxyl esterase, which can be detected by multireagent dipstick technology (leukocyte esterase positive).
A positive reaction for urine nitrite may indicate the presence of bacteria that reduce nitrate, most commonly gram-negative pathogens. Whereas a positive result for both urine leukocyte esterase and urine nitrites is 68% to 88% sensitive for urinary tract infection,
Eosinophils may be seen in the urine of patients with AKI caused by drug-induced interstitial nephritis and in a variety of other conditions, including rapidly progressive glomerulonephritis, prostatitis, renal atheroemboli, and small-vessel vasculitis.
Renal tubular epithelial cell casts may be produced by desquamation of epithelial cells associated with acute tubular necrosis, proliferative glomerulonephritis, or interstitial nephritis. Hyaline casts are composed of Tamm-Horsfall glycoprotein and normally may be seen in increased numbers in concentrated urine specimens. Granular casts are hyaline casts containing aggregated filtered proteins and may be seen in patients with albuminuria and proteinuria. Degenerated cellular casts may appear granular and upon further degeneration are described as waxy casts.
Prerenal
Decrease in ECF volume:
Decrease in RBF
Altered intrarenal hemodynamics
BUN/creatinine ratio: Typically >20
Urine sodium: <20 mEq/L
Fractional excretion of sodium: <1%
Urine osmolality: >500 mOsm/kg
Urine specific gravity: >1.020
Microscopy: Bland
Decrease in ECF volume
GI losses; Hemorrage
Hx: volume loss (eg, vomiting, diarrhea), the presence of orthostatic symptoms, decreased urine volume, or urine that appears more concentrated.
Px: Signs of hypovolemia, such as tachycardia, a postural pulse rate increase of >30/min, dry axillae, flat neck veins, and dry oral mucosa. Elevated jugular venous pressure, an S3 gallop, and pulmonary crackles on lung examination.
Dx:
Low urine flow is associated with reabsorption of urea along the nephron, and patients with prerenal failure frequently have a BUN–creatinine ratio >20:1, urine sodium <10 mEq/L (10 mmol/L) or FENa > 1% suggests ATN. FENa ≤ 1% suggests prerenal azotemia (when oliguria is present) and AGN; bland urine sediment, and urine specific gravity >1.018 (high urine specific gravity) may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention. Prerenal disease is associated with a normal urinalysis.
Spot urine sodium: Volume depletion leads to activation of hormonal systems aimed at conserving salt and water and is characterized by high urine osmolality and low urine sodium concentration (<10 meq/L), with a fractional excretion of sodium of <1%.
Tx: Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients.
Decrease in RBF
Heart Failure, Renal artery stenosis
Hx: Heart failure, liver disease, and the nephrotic syndrome, which are other conditions associated with decreased effective circulating volume.
Px: Spider telangiectasia, jaundice, and ascites support a diagnosis of liver disease.
Dx: CT angiography (renal artery stenosis, or renal vascular lesion). High urine specific gravity may reflect an appropriate response to water loss or dehydration or may indicate a pathologic state of fluid retention (eg, heart failure).
Tx: Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients.
Altered intrarenal hemodynamics
NSAIDS, Calcineurin Inhibitors, ACE, ARBs, Sepsis, Hypercalcemia, Cirrhosis/hepatorenal syndrome, abdominal compartment syndrome
Hx: Medications that can alter effective circulating volume, such as NSAIDs, ACE inhibitors, ARBs, diuretics, and vasodilators.
Px: Increases in intraabdominal pressure from massive ascites or edematous bowel can lead to abdominal compartment syndrome, which limits both renal arterial perfusion and renal venous outflow. A distended, tense abdomen supports a diagnosis of abdominal compartment syndrome, which can be confirmed by placing a pressure transducer into the bladder.
Tx: Treat volume depletion with normal saline; if severe anemia is present, transfuse packed red blood cells. If the serum albumin level is extremely low or if a patient has portal hypertension and ascites, albumin may be beneficial as a volume expander in select patients
▪ INTRA-RENAL
Atheroembolic and thromboembolic disease
Intrarenal vascular disease
Acute glomerulonephritis
Acute tubular necrosis
Acute interstitial nephritis
Intrarenal tubular obstruction
Renal vein obstruction
Hepatorenal Syndrome
vasculature (vasculitis, microangiopathic hemolytic anemia).
Atheroembolic and thromboembolic disease
Hx: Recent invasive vascular procedures that may result in atheroembolic kidney disease (eg, angiography, aortic stenting, aneurysm repair). Fever, joint pain, fatigue, rashes, and jaundice. Atrial fibrillation or recent myocardial infarction may be associated with thromboembolic disease.
Px: Clues to vasculitis include palpable purpura, petechiae, joint swelling, and skin rashes. The presence of a fine, reticular (netlike) red to purple rash (livedo reticularis) or blue toes (“blue toe syndrome”) suggests atheroembolic disease.
Dx: Atheroembolic disease characterized by urinary eosinophils.
Renal infarction
Renal infarctions occur from a variety of etiologies (eg, atrial fibrillation, renal artery trauma, hypercoagulability).
Renal infarctions typically manifest with acute flank pain, nausea, and vomiting; fever may also occur. Urinalysis classically demonstrates hematuria and proteinuria without casts. A rise in serum creatinine may occur but is more common with bilateral or very large, unilateral infarction. Other characteristic laboratory abnormalities include an elevated lactate dehydrogenase level, leukocytosis, and elevation in C-reactive protein. A contrast-enhanced CT scan or MRI demonstrating a wedge-shaped cortical infarction is diagnostic.
Intrarenal vascular disease
Hx: Vasculitis (i.e., PAN), malignant hypertension, or TTP-HUS.
Dx: Characterized by hematuria with erythrocyte or granular casts, mild proteinuria, and leukocytes. Look for schistocytes and decreased platelets on peripheral smear, which imply a thrombotic microangiopathy, such as hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. If present, confirm hemolysis with serum lactate dehydrogenase and haptoglobin concentrations.
Tx: Begin renal replacement therapy (dialysis) in all patients with uremic signs or symptoms (nausea, vomiting, altered mental status, seizures, pericarditis) as well as patients who have hyperkalemia, metabolic acidosis, or volume overload that cannot be easily managed with medication.
Acute glomerulonephritis
Primary glomerular damage leads to decreased glomerular filtration rate with eventual development of significant volume overload (eg, pulmonary edema, distended neck veins, anasarca). Abnormal urinary sediment (red blood cells, red blood cell casts) and variable degrees of proteinuria are present on urinalysis. Serum creatinine can also be elevated. The increased volume also leads to hypertension. Significant proteinuria (3+) eventually leads to hypoalbuminemia, which further contributes to the edema.
Glomerular diseases present with proteinuria and sometimes an active urinary sediment (dysmorphic red cells, white blood cells, and red cell casts).
⚪ Nephrotic syndrome is characterized by heavy proteinuria (>2+ protein by dipstick, urine P:C >3.5 g/d)[3+ (300 mg/dL) or 4+ (1000 mg/dL)] and a relatively bland urine sediment, which may contain hyaline or hyaline-granular casts, lipids, and none to moderate numbers of erythrocytes. Other proteins (eg, Bence-Jones proteins, myoglobin) can cause severe proteinuria, but, since they do not cause albumin loss in the urine, they do not cause the nephrotic syndrome.
Characterized by high-grade proteinuria ( >3.5 g/24 h), hypoalbuminemia, hyperlipidemia, and edema. Usually “Bland” urine sediment; Hyaline casts; Lipiduria; oval fat bodies; Hypercoagulability.
Hypoalbuminemia can cause significant peripheral edema but usually does not cause pulmonary edema. Alveolar capillaries have a higher permeability to albumin at baseline (reducing oncotic pressure difference) and greater lymphatic flow than skeletal muscle, protecting the lungs from edema.
Membranous Nephropathy (common) cause of idiopathic nephrotic syndrome in adults.
🍭 Diabetic nephropathy (common in adults) Dx: Biopsy
Noninflammatory
📏 Minimal change disease (common in kids) While it often presents as primary renal disease, it is also seen in association with other conditions like NSAID use with concomitant interstitial nephritis and Hodgkin disease. Clinically, patients present as described with sudden onset of edema, nephrotic syndrome, and amorphous urinary sediment on the urinalysis. Tx: Trial of 🌑 corticosteroids precedes renal biopsy. [cyclophosphamide, chlorambucil, or mycophenolate mofetil.]
Focal segmental glomerulosclerosis (FSGS): Hx: More common in intravenous drug users with HIV. Tx: Fairly responsive to corticosteroid and cytotoxic therapy.
Amyloid
🔴 Nephritic syndrome is characterized by varying degrees of proteinuria and an active urine sediment, which may contain granular casts, moderate to large numbers of dysmorphic erythrocytes, and erythrocyte casts.
Characterized by hematuria, variable proteinuria, and hypertension, often with other systemic manifestations. Common causes include postinfectious glomerulonephritis, IgA nephropathy, and membranoproliferative glomerulonephritis.
Proteinuria (UPCR): Variable; may be <3.5 g/g
Urine sediment: Dysmorphic RBCs, RBC casts, Granular casts
🥧 Postinfectious glomerulonephritis: Acute glomerulonephritis usually occurs a week or two after the sore throat (ie, to give enough time for vigorous antibody production against the streptococcal antigens). Poststreptococcal GN is now a rare condition in the adult population of developed nations.
Inflammatory
Diffuse proliferative glomerulonephritis
Membranoproliferative glomerulonephritis (MPGN): Depressed C3 is caused by an autoantibody that directly activates the third component of complement. A progressive clinical course and erratic response to therapy are typical.
IgA nephropathy (common) (Berger): Berger disease is associated with IgA deposits in the mesangium. Patients with IgA nephropathy often have an exacerbation of their hematuria with intercurrent respiratory illnesses.
Anti-glomerular basement membrane (anti-GBM) disease causes a nephritic picture with hematuria and rapidly progressive renal insufficiency. Light microscopy often reveals crescent formation, and immunofluorescence shows linear IgG staining of the GBM.
❗ Rapidly progressive glomerulonephritis (RPGN) is a clinical syndrome characterized by a swift loss of kidney function, hematuria, proteinuria, and glomerular crescent formation. The syndrome may be caused by many primary or secondary glomerular diseases, including those previously listed.
Px: Some patients with the nephritic syndrome have dermal inflammation that manifests as palpable purpura, necrosis, ulcers, or nodules. Renal–dermal syndromes (SLE, Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis, and cryoglobulinemia).
Dx: Dysmorphic erythrocytes suggest acute glomerulonephritis. Glomerular hematuria also is characterized by the presence of dysmorphic erythrocytes (especially erythrocytes with blebs, termed acanthocytes).
Assays for anti–glomerular basement membrane antibody, ANCA, and markers for immune complex diseases (eg, antinuclear antibodies (ANA), anti–double-stranded DNA antibodies, cryoglobulins, antibodies to hepatitis B or C virus, complement concentrations [MPGN]) may further refine the diagnosis; low complement concentrations suggest lupus nephritis, postinfectious and membranoproliferative glomerulonephritis, and mixed cryoglobulinemia (Hep C).
Tx: Begin renal replacement therapy (dialysis) in all patients with uremic signs or symptoms (nausea, vomiting, altered mental status, seizures, pericarditis) as well as patients who have hyperkalemia, metabolic acidosis, or volume overload that cannot be easily managed with medication.
Cx:
SLE commonly affects the kidneys and may cause nephritic or nephrotic syndrome. A kidney biopsy often is needed to make a specific diagnosis and to guide therapy. To prevent irreversible kidney damage, early treatment with a high-dose glucocorticoid is indicated for patients whose condition raises strong suspicion for lupus nephritis
Poststreptococcal glomerulonephritis (PSGN)
Clinical features
- Can be asymptomatic
- If symptomatic:
- Gross hematuria (tea- or cola-colored urine)
- Edema (periorbital, generalized)
- Hypertension
Laboratory findings
- Urinalysis: + protein, + blood, ± red blood cell casts
- Serum:
- ↓ C3 & possible ↓ C4
- ↑ Serum creatinine
- ↑ Anti-DNase B & ↑ AHase (antihyaluronidase)
- ↑ ASO & ↑ anti-NAD (from preceding pharyngitis)
Acute poststreptococcal glomerulonephritis (APSGN) is an immune-mediated disease that occurs approximately 1-4 weeks after group A streptococcal (GAS) pharyngitis OR impetigo. Pathogenesis involves the postinfectious formation of nephritogenic-specific streptococcal antigens and antibody complexes. These immune complexes are then deposited within the glomerular basement membraneand mesangium, causing activation of the complement system and accumulation of complement component C3 in the glomerular deposits. Therefore, laboratory findings include decreased C3 levels with possible elevation in serum creatinine.
Symptomatic patients with APSGN may develop hematuria, edema, and hypertension several weeks after GAS skin or throat infection. Urinalysis typically reveals red blood cells with or without protein and red blood cell casts. Most patients recover with supportive care (eg, blood pressure management).
Goodpasture syndrome
Goodpasture syndrome is a progressive glomerulonephritis accompanied by pulmonary disease (ie, alveolar hemorrhage); biopsy reveals linear IgG deposition in the GBM.
- Pulmonary symptoms
👾Acute tubular necrosis (ATN)
Acute tubular necrosis
- BUN/creatinine ratio: Typically normal (~10-15)
- Urine sodium: >40 mEq/L
- Fractional excretion of sodium: >2%
- Urine osmolality: ~300 mOsm/kg
- Urine specific gravity: <1.020
- Microscopy: Muddy brown casts
Common causes include ischemia (eg, shock), drugs (eg, radiocontrast), and other nephrotoxins. Tubular damage limits reabsorptive capacity, resulting in a high urine sodium (typically >40 mEq/L) and fractional excretion of sodium (>2%). Creatinine, which varies inversely with glomerular filtration, is elevated, but the BUN/creatinine ratio is normal at ~10-15:1, in contrast to prerenal AKI (where passive urea reabsorption leads to an elevated BUN/creatinine ratio).
Renal injury usually causes hypocalcemia due to reduced phosphorus clearance leading to calcium phosphate salt formation.
Hx: Radiocontrast agents [contrast-induced nephropathy (CIN)], drugs (aminoglycosides, amphotericin B, cisplatin), and episodes of hypotension. Patients who are using cocaine or who are found comatose from drug ingestion may develop rhabdomyolysis. Patients with lymphoma or leukemia who develop tumor lysis after chemotherapy
Initiation phase of ATN corresponds with the original ischemic or toxic insult and lasts about 36 hours. During this phase, there is only a slight decrease in urine output as renal tubular cell damage begins.
Maintenance phase, tubular damage is fully established and patients commonly have oliguria, fluid overload, and electrolyte abnormalities (🍌hyperkalemia, metabolic acidosis). This second phase of ATN usually lasts 1-2 weeks, during which the glomerular filtration rate (GFR) stabilizes at a level well below normal with a rise in serum creatinine.
Recovery phase of ATN is characterized by re-epithelization of tubules. It manifests with vigorous diuresis (sometimes > 3 L/day), but because the renal tubules cannot yet function fully, electrolyte balance is still altered. A high volume, hypotonic urine may lead to decreased serum concentrations of K, Mg, PO4, and Ca. Hypokalemia is one of the most serious complications of the recovery phase of ATN. The majority of patients eventually experience complete restoration of renal function.
Dx: Muddy brown casts, tubular epithelial cell casts, high urine sodium concentration (>20 mEq/L), and FENa >1%. Increased CPK, myoglobin, a renal tubular toxin. Severe hyperphosphatemia suggests acute rhabdomyolysis or TLS. Serum uric acid >15 mg/dL suggests rhabdomyolysis or TLS. In patients with multiple myeloma, immunoglobulin light chains can precipitate within the renal tubules.
Tx: In patients who require contrast studies, use of low osmolar contrast agents and hydration (intravenous 0.9% saline)[with bicarbonate]s to promote urine flow and avoid volume contraction has been shown to decrease the risk for CIN.
Cx: MM-induced 🥛hypercalcemia is due to osteoclast activating factors and can cause AKI (vasoconstriction, tubular calcium deposition). Light chains reabsorbed by the proximal tubules are directly toxic. Intratubular light chain casts form if the resorptive capacity is overwhelmed, worsening tubular damage. Glassy light chain casts are often present; however, the urinalysis may be bland if cast formation has not yet occurred. Urine dipstick typically demonstrates mild proteinuria (only detects albumin); however, a quantitative 24-hour protein assay will demonstrate elevated protein excretion (Bence-Jones proteinuria)
Ddx: Immune-complex mediated vasculitis
Development of antibody-antigen (immune) complexes (IC) is called the Arthus reaction; deposition of these complexes in blood vessel walls initiates complement activation, an influx of inflammatory cells, thrombus formation, and hemorrhagic infarction. In the skin, palpable purpura, the most common cutaneous finding in IC-mediated vasculitis, results from extravasation of erythrocytes through damaged vessel walls. These nonblanching lesions are distributed symmetrically in dependent areas of the body, where tissue hydrostatic pressure is increased (eg, lower extremities, buttocks). On light microscopy, cellular infiltrates consisting predominantly of neutrophils within and around vessel walls are seen, along with endothelial swelling and proliferation and neutrophil degranulation; hence, the term leukocytoclastic vasculitis.
Anti-glomerular basement membrane (Goodpasture) disease
IgA vasculitis (Henoch-Schönlein purpura)
Cryoglobulinemic vasculitis
Cutaneous leukocytoclastic angiitis (hypersensitivity vasculitis)
Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis)
