Week 6 · Renal Disorders — Interactive Reading Report

Orientation

How to read this week

Week 6 is two subjects wearing one name. The first is the kidney as a filter — infection, injury, and failure across Chapters 42 and 43. The second is the body's chemistry — sodium, potassium, calcium, magnesium, phosphorus, acid–base balance, and the fluids you hang to fix them, all in Chapter 78.

Half one

The kidney as a filter

Urinary tract infection and CAUTI
Pyelonephritis and urosepsis
Glomerulonephritis and nephrotic syndrome
Acute kidney injury — prerenal, intrarenal, postrenal
Acute tubular necrosis
Chronic kidney disease
Renal replacement therapy
Drug dosing when the filter is failing

Diagnostic currency: urine studies, creatinine and GFR, and imaging.

Half two

The body's chemistry

Sodium — hyponatremia, hypernatremia
Potassium — hypokalemia, hyperkalemia
Calcium — hypocalcemia, hypercalcemia
Magnesium — hypomagnesemia, hypermagnesemia
Phosphorus — hypophosphatemia, hyperphosphatemia
Acid–base — metabolic and respiratory, both directions
Intravenous fluid management

Diagnostic currency: the serum level, the ECG, and the ABG.

The thread that ties the two halves together

Every electrolyte disorder is either a gain, a loss, or a shift. Losses come from the gut, the kidney, or the skin; shifts move potassium in and out of cells without changing total body stores. Ask which of the three you are looking at and the treatment follows — and almost every one of them gets an ECG, because the heart is what kills first.

Your reading map

The three chapters behind this week
Ch.	Title	What it actually contains
42	Urinary Tract Infections	UTI definition and colony thresholds · asymptomatic vs symptomatic · lower vs upper tract · uncomplicated vs complicated · CAUTI · recurrence, relapse, reinfection · urethritis · pyelonephritis · urosepsis · glomerulonephritis · nephrotic syndrome · management by antibiogram Talley & Langley
43	Acute Kidney Injury & Chronic Kidney Disease	The kidney's five jobs · AKI definition and the KDIGO/RIFLE/prerenal–intrarenal–postrenal classification methods · acute tubular necrosis · CKD definition and GFR staging · management of common problems in CKD · anemia of erythropoietin deficiency · renal replacement therapy · modifying drug dosages in renal impairment Branham & Hilliard
78	Fluid, Electrolyte, and Acid–Base Imbalances	Hyponatremia and hypernatremia · hypokalemia and hyperkalemia · hypocalcemia and hypercalcemia · hypomagnesemia and hypermagnesemia · hypophosphatemia and hyperphosphatemia · metabolic and respiratory acidosis and alkalosis · intravenous fluid management Culpepper

The numbers worth carrying in

135–145

Normal serum sodium

mEq/L. Hyponatremia is below 135; hypernatremia above 145.

3.5–5.5

Normal serum potassium

mEq/L. The narrowest window in the panel — and the one that stops the heart.

60%

of AKI is prerenal

Diminished renal perfusion with no nephron damage — and the most reversible kind.

69%

of CAUTIs are avoidable

Avoid the catheter, and remove it as soon as it is no longer needed.

Chapter 43 · Primary Kidney Regulation of Physiologic Functions

The Kidney's Job

Chapter 43 opens by naming the five primary physiologic functions the kidney regulates — and one framing caution that shapes the entire week: various regulatory functions are lost at different states of disease progression, and in early disease the onset is often insidious.

Five functions

What the kidney regulates

Acid–base status
Maintain water balance
Electrolyte balance
Hormone production and metabolism
Gluconeogenesis in fasting states

The catch

Loss is uneven and quiet

Various regulatory functions are lost at different states of disease progression. In early disease, the onset is often insidious — the kidney hides its decline until late.

AKI and CKD in perspective

AKI

Abrupt loss

An abrupt loss of kidney function
Recovery is often attained with medical management
Carries a lifelong risk of developing CKD — even after recovery

CKD

Slow progression

Can develop over months to years
Progression is delayed — not reversed — by medical management
AKI in the presence of CKD requires aggressive management to prevent permanent progression

What the two share

In both states, the degree of dysfunction is related to cause and comorbid factors.
Both conditions may require dialysis based on the degree of dysfunction if conservative measures fail.

AKI leaves a scar

Although recovery typically occurs in AKI, the condition is associated with a lifelong risk of developing CKD. AKI patients requiring dialysis are at 10% greater risk for developing end-stage renal disease (ESRD) requiring dialysis — and even with recovered renal function, patients with AKI are more likely to die prematurely after hospital discharge.

Chapter 42 · Urinary Tract Infections

Urinary Tract Infections

A UTI is the presence of a significant number of pathogenic organisms in the urine with the potential to invade tissues of the urinary tract and adjacent structures — the bladder, urethra, prostate, renal parenchyma (kidneys), and collecting system. It causes inflammation in the urinary epithelium and is associated with a positive urine culture.

Uncomplicated

Normal working tract

Occurs in a normal working urinary tract.

Complicated

Defects or comorbidities

Occurs with defects in the urinary tract or in individuals with other health problems — e.g., diabetes, immunosuppression, multi-drug resistant organisms.

Location

Lower vs. upper

Lower — bladder and urethra.
Upper — kidney and ureters.

Colony counts that define infection

How many bacteria make a UTI

The count that "counts" depends on symptoms and how the specimen was obtained. Hover a bar for the full rule.

Symptomatic / low-count rules May indicate infection Bacteriuria / active infection Asymptomatic threshold

Asymptomatic

No symptoms, high count

More than 100,000 colonies of one or more bacterial species in two consecutive urine samples for women and one single sample for men
No clinical urinary tract symptoms
Common in men and women who have genitourinary abnormalities

Symptomatic

Low counts still count

Relatively low colony counts can reflect bacteriuria in the presence of symptoms
Between 10 and 10,000 colonies

Who gets screened

Routine screening for asymptomatic bacteriuria is not indicated except in women who are pregnant, those undergoing invasive genitourinary procedures, or renal transplant recipients.

Catheter-associated UTIs (CAUTIs)

Definition

Catheterized within 48 hr

A CAUTI is a UTI in a patient who has been catheterized within the past 48 hours.

It is caused by a biofilm — a layer of uropathogens living along the catheter.

Prevention

Avoid the catheter

The best strategy to prevent these infections is to avoid catheterization when possible and remove urinary catheters as soon as possible once they are no longer medically necessary.

The number to remember

CAUTI is one of the most common healthcare-associated infections in the world — and 69% of CAUTIs are considered to be avoidable.

Recurrence, relapse, reinfection

Recurrence

Two in 6 months, or three in a year

Two urinary tract infections in the last 6 months or three in the last year.

Relapse

Same organism

Caused from the same uropathogen.

Re-infection

Different organism

Caused by a different uropathogen.

Etiology and the usual organisms

Organism context

Most common

Escherichia coli

The most common causative organism of uncomplicated UTI.

Staphylococcus saprophyticus

Uncomplicated UTI pathogen. (Also does not produce nitrate reductase, so the nitrite dipstick may be falsely negative.)

Enterococcus spp.

Listed under uncomplicated, complicated, and recurrent UTI.

Klebsiella spp. / K. pneumoniae

Uncomplicated UTI and short-term CAUTI (and ESBL Klebsiella in complicated UTI).

Proteus mirabilis

Uncomplicated UTI; long-term CAUTI; recurrent UTI. Most common in elderly men.

Resistant (ESBL) E. coli & Pseudomonas aeruginosa

Complicated-UTI pathogens, joined by Acinetobacter baumannii, Staphylococcus spp., and ESBL Klebsiella.

Short-term CAUTI group

E. coli, Klebsiella spp., Serratia spp., Citrobacter spp., Enterobacter spp.

Long-term CAUTI group

Typically polymicrobial: P. mirabilis, Morganella morganii, Providencia stuartii, Candida spp. — plus the short-term species.

Recurrent group

P. mirabilis, K. pneumoniae, Enterobacter spp., resistant E. coli, Enterococcus spp., Staphylococcus spp.

Both genders

Diabetes mellitus
Urinary instrumentation and catheterization
Obstruction of normal urine flow — calculi, tumors, urethral strictures
Neurogenic bladder disease — stroke, multiple sclerosis, spinal cord injury
Vesicoureteral reflux

Women

Short urethra
Sexual intercourse; new sexual partner (within the past year)
Spermicide or diaphragm (with or without spermicide)
Pregnancy
History of UTI — personal childhood history in premenopausal women < 15 years; first-degree female relative
Urinary incontinence

Men

Prostatic enlargement, resulting in urine residual
Prostatitis
Lack of circumcision
Homosexuality
Sexual partner with vaginal colonization by uropathogens
HIV infection

UTIs are more common in women than in men, but more severe in men. Incidence: 12.6% in women > 18 years; 0.9–2.4 cases per 1,000 in men > 55 years. After a single UTI, 30–44% have recurrent UTI; 50% will have a third episode if there were two previous UTIs in the last 6 months.

Signs and symptoms

Lower tract

Cystitis / urethritis / prostatitis

Dysuria
Urinary frequency
Urgency
Suprapubic pain
Hematuria with bacteriuria
Malodorous urine
Incontinence
Fever and chills are uncommon but may be present
No flank or costovertebral pain

Upper tract

Pyelonephritis / renal abscess

Flank pain or costovertebral-angle tenderness
Fever (temperature > 38 °C)
Hematuria
Nausea and vomiting
Malaise
Shaking chills (rigors)
Tachypnea (related to fever)
Tachycardia (related to fever)
If symptoms last longer than 3 days, abscess formation should be considered

Recurrent UTIs may require a pelvic exam; the probability of a UTI is reduced when vaginal discharge or irritation is present.

Laboratory and diagnostics

Urine culture and sensitivity testing — detection of bacteria in culture is the diagnostic gold standard. Results are not available until 24 hr after collection; point-of-care testing aids early detection.
Clean-catch midstream urinalysis — diagnose UTI with a positive nitrite or leukocyte esterase test; may also diagnose UTI with blood in urine.
Urine microscopy — pyuria: more than 10 leukocytes/ml; bacteriuria: more than 100,000 bacteria/ml (indicates active infection). Occasional erythrocytes, white cell casts, and mild proteinuria may be present in acute pyelonephritis; elevated ESR in pyelonephritis.
Leukocyte esterase dipstick — positive (purple in 60 s); signifies pyuria/WBCs. False positives: kidney stones, tumors, urethritis, poor collection technique. False negatives: uncomplicated or early UTIs.
Nitrate dipstick — positive for protein, blood, nitrates (pink in 30 s); may be false negative in uncomplicated UTI, with diuretics early in the course, with inadequate dietary nitrates, or with bacteria that do not produce nitrate reductase (S. saprophyticus, Enterococcus, Pseudomonas).
CBC — leukocytosis with a left shift in acute pyelonephritis.
Blood culture — may be indicated for suspected pyelonephritis or sepsis.

To rule out urinary retention, obstruction, calculi, and papillary necrosis in men with UTIs and in women with recurrent UTIs, consider:

Post-void residuals
X-ray voiding cystourethrography
CT scan of the abdomen and pelvis — with and without contrast
Ultrasound (US) — pelvis (urethra)
Magnetic resonance imaging of the pelvis — with and/or without contrast

Red flag

Persistent fever or positive blood cultures after the first 3–4 days suggests the need to investigate for obstruction and/or abscess. Abdominal imaging (CT, US, MRI) and urologic consult may be necessary.

Management — per hospital and community antibiograms

For uncomplicated cystitis in women, symptom relief and behavioral measures should be trialed before immediate Rx of antimicrobial agents.

Uncomplicated cystitis — oral regimens
Agent	Dose	Notes
Fosfomycin	3 g PO single dose	Expensive; evidence remains unclear due to increased incidence of resistance
Nitrofurantoin monohydrate/macrocrystal (Macrobid)	100 mg PO BID for 5 days	First-line
TMP-SMX (Bactrim DS)	160 mg/800 mg BID PO for 3 days	3-day regimen preferred over single-dose (high relapse with single-dose), to 7-day; can be ineffective with resistant organisms
Trimethoprim	100 mg BID PO for 3 days	Inform by local antimicrobial resistance patterns
β-lactams (2nd-line)amoxicillin-clavulanate · cefdinir · cefaclor · cefpodoxime	amox-clav 500 mg/125 mg PO q12h or 875 mg/125 mg q12h (severe); cefdinir 300 mg q12h; cefaclor 250–500 mg q8h; cefpodoxime 100 mg q12h — for 3–7 days	Used when other agents cannot be used (inferior efficacy, more adverse effects)

Fluoroquinolones should only be used when no other alternative is available.

Outpatient pyelonephritis regimens
Agent	Dose	Notes
Ciprofloxacin	500 mg BID PO for 7 days; OR 1 g (extended release) daily PO for 7 days	May give an initial IV 400 mg dose before the oral dose
Levofloxacin	750 mg daily PO for 5 days	If fluoroquinolone resistance exceeds 10%, give initial 1 g ceftriaxone IV or a consolidated 24-hr aminoglycoside dose
TMP-SMX	160/800 mg BID PO for 14 days	If susceptibility unknown, consider initial IV 1 g ceftriaxone or a consolidated 24-hr aminoglycoside; empiric use not recommended (resistance). Use cautiously in impaired renal function; encourage PO fluids
Oral β-lactamsamox-clav · cefdinir · cefaclor · cefpodoxime	amox-clav 500 mg/125 mg q12h or 875 mg/125 mg q12h (severe); cefdinir 300 mg q12h; cefaclor 250–500 mg q8h; cefpodoxime 100 mg q12h — for 10–14 days	May not be as effective as other agents including fluoroquinolones

Complicated lower UTI (cystitis), inpatient — based on hospital and community antibiograms:

Levofloxacin 750 mg IV q24h for 5 days or 250 mg IV q24h for 10 days; or ciprofloxacin 200–400 mg IV q12h for 7–14 days (black box: tendinitis, tendon rupture, peripheral neuropathy, exacerbation of myasthenia gravis, CNS effects). Add an aminoglycoside (gentamycin or tobramycin 2 mg/kg IV q8h pending culture; consider renal doses; monitor peak and trough). May complete with PO when afebrile 48 hr (levo 750 mg PO daily or cipro 500 mg PO BID). High C. difficile risk with fluoroquinolones.
Ceftriaxone 1–2 g/day IV or IM q12–24h for 10–14 days; or cefepime 0.5–1 g IV/IM q12h for 7–10 days (mild-to-moderate) and 2 g IV q12h for 10 days (severe).
Piperacillin/tazobactam 3.375 g (3 g piperacillin + 0.375 g tazobactam) IV q6h for 7–10 days.
Aminoglycoside (gentamycin 1 mg/kg IV q8h) with ampicillin (1 g IV q6h for 14 days).

Complicated upper UTI (pyelonephritis), inpatient — treat the same as uncomplicated if not severely ill. For the severely ill:

Treat for 14 days based on susceptibility.
Ceftriaxone 1 g IV q24h; ceftazidime 1–2 g IV q8h.
Piperacillin/tazobactam 3.375–4.5 g IV q6h.
Aminoglycosides gentamicin or tobramycin — consult a pharmacist for pharmacokinetics; may be added initially but not used as monotherapy for pyelonephritis.
Sulfonamides: TMP-SMX (trimethoprim component) 8–10 mg/kg/day IV in 2–4 divided doses q6/8/12h for up to 14 days.
Penicillin-allergic: aztreonam 1–2 g q8h IV, ciprofloxacin 200–400 mg q12h IV, or levofloxacin 500 mg QD IV.
Surgery may be necessary when a structural abnormality or a large stone is blocking the urinary tract.

CAUTI

Consider removing or replacing catheters that have been in place longer than 7 days prior to initiation of treatment.
Bacterial: treat with antibiotic for 3–7 days. Delayed clinical response, bacteremia, hypotension, or severe sepsis may require 10–14 days.
Candiduria with symptoms: fluconazole 200–400 mg/day for 14 days.

Pregnant women

Nitrofurantoin 100 mg PO BID for 5–7 days — except in the first trimester or near term (then use amoxicillin 500 mg PO TID for 3–7 days or amoxicillin/clavulanate 500 mg PO TID for 3–7 days).
Fosfomycin 3 g PO single dose.
Cephalexin 500 mg PO QID for 3–7 days.
Fluoroquinolones cannot be given during pregnancy; sulfonamides cannot be given near the time of delivery.
TMP-SMX, nitrofurantoin, and most β-lactams are safe during lactation and breastfeeding.

Symptom relief

Phenazopyridine (Pyridium) 200 mg PO TID for 2 days — may cause red-orange discoloration of body fluids including urine.
Ibuprofen 400 mg PO TID for 3 days.

Prevention & behavioral measures

Abstinence or reduction in sexual activity; consider contraception other than spermicides (they alter vaginal flora).
PO cranberry products for asymptomatic bacteriuria (especially pregnant women) — less effective than low-dose antimicrobial prophylaxis.
Postmenopausal women: topical estrogen to normalize vaginal flora; probiotics: oral lactobacillus.
Increase water intake, decrease carbonated drinks, do not delay urination, early post-coital voiding, wipe front to back.
Aseptic technique for indwelling catheters; silver-impregnated catheters reduce catheter-related infections.

Prophylaxis for recurrent lower UTI

Postcoital single dose after intercourse: nitrofurantoin 50–100 mg PO; TMP-SMX 40 mg/200 mg or 80 mg/400 mg PO; TMP 100 mg PO; ciprofloxacin 250 mg PO.
Continuous at bedtime: nitrofurantoin 50–100 mg; TMP-SMX 40 mg/200 mg; TMP 100 mg; cephalexin 125–250 mg.
6 months of treatment, followed by observation for reinfection after discontinuing, has been recommended.
May reduce risk in female patients with two episodes within 6 months or at least three within a year.

No need to repeat urinalysis with culture and sensitivity after therapy in uncomplicated cystitis and pyelonephritis — but it must be repeated in pregnant women.

The five entities the syllabus flags

Pyelonephritis, urosepsis, urethritis, glomerulonephritis, and nephrotic syndrome each appear in the reading. Use the filters to separate upper-tract infection, the systemic response, lower-tract infection, and the glomerular syndromes.

Filter by site

Upper tract · infection

Pyelonephritis

Infection of the upper urinary tract (kidney). Signs: flank pain / costovertebral-angle tenderness, fever, hematuria, nausea & vomiting, malaise, rigors, tachypnea, tachycardia; > 3 days suggests abscess.

Labs: leukocytosis with left shift, elevated ESR, white cell casts and mild proteinuria; blood culture if suspected.

Treatment: outpatient FQ (cipro 500 mg BID ×7 d; levo 750 mg daily ×5 d), TMP-SMX 160/800 mg BID ×14 d, or β-lactams ×10–14 d. Severely ill inpatients: 14 days — ceftriaxone 1 g IV q24h, ceftazidime 1–2 g IV q8h, pip/tazo 3.375–4.5 g IV q6h.

Systemic · goal = prevent

Urosepsis

A severe systemic response to infection from UTI, associated with signs/symptoms of systemic inflammation, organ dysfunction, and persistent hypotension.

The stated goal of UTI management is to prevent urosepsis.

Lower tract · infection

Urethritis

Lower urinary tract infection (urethra). Determine gonorrheal versus nongonococcal urethritis and treat according to the pathogen.

Note: urethritis is a listed false positive for the leukocyte esterase dipstick.

Glomerular · AKI

Glomerulonephritis

Glomerular cause of intrinsic AKI; often immunologic — associated with SLE, Sjögren's syndrome, sarcoidosis, cryoglobulinemia, and idiopathic conditions.

Autoimmune diseases may require a renal biopsy; some cases need immunosuppressive agents or plasma exchange to prevent irreversible damage.

Urinalysis: proteinuria at least 1+ or nephrotic-range proteinuria of 3 g/day; hematuria — red cell casts are a classic finding. Workup: ESR, ANA, C3, C4.

Glomerular · proteinuria

Nephrotic syndrome / nephrotic-range proteinuria

The reading frames this as nephrotic-range proteinuria of 3 g per day — common with acute glomerulopathies (acute glomerulonephritis), alongside red blood cell casts and oval fat bodies ("nephrosis").

In chronic intrinsic disease, proteinuria ranges from 1–2 g/day to 2+ g/day in the nephrotic range.

Geriatric considerations

Presentation

Symptoms differ

Mental status changes — lethargy and delirium — are common
May present with falls, incontinence, or increased incontinence
Fecal incontinence is a contributing factor in older adults

Organisms

Different bugs

Elderly women most often have E. coli
Elderly men likely have P. mirabilis, Enterococcus spp., or coagulase-negative staphylococci
Also common: K. pneumoniae, Serratia, Citrobacter, Enterobacter, M. morganii, P. aeruginosa; Providencia spp. in institutionalized patients; group B streptococcal UTI in elderly with diabetes

Fluoroquinolones are the exception

All previously discussed treatments apply to the geriatric population except fluoroquinolones — they are contraindicated or used as a last resort due to tendon and aortic rupture, and they contribute to mental status changes.

69%

of CAUTIs are avoidable

CAUTI is one of the most common healthcare-associated infections in the world.

12.6%

UTI incidence in women > 18

More common in women — but more severe in men.

7.7/1,000

incidence in men > 85 years

UTI is the most common bacterial infection in the elderly, and the most common cause of bacteremia in older men.

30–44%

recurrent UTI after one episode

50% will have a third episode if there were two previous UTIs in the last 6 months.

Chapter 43 · Acute Kidney Injury

Acute Kidney Injury

An acute loss of renal function typically occurring within 24–48 hours. AKI progresses from the inability to excrete metabolic waste products — such as urea nitrogen and creatinine — and the inability to maintain proper fluid and electrolyte balance.

60%

prerenal

Diminished renal perfusion — no nephron damage present.

35%

intrinsic (intrarenal)

Glomerular or tubular defects.

postrenal

Greatest incidence of recovery; least likely to progress to ESRD.

85–90%

of hospital intrinsic AKI is ATN

Acute tubular necrosis accounts for most hospital-associated intrinsic AKI.

Definitions

The creatinine and UO landmarks

Acute increases in serum creatinine from baseline — an increase of at least 0.5 mg/dl
Progresses to complete renal failure when serum creatinine increases by at least 0.5 mg/dl/day and urine output is < 400 ml/day (oliguria)
Generally resolves within 3 months of onset

Epidemiology

Common and costly

Complicates 5–7% of hospital admissions and 30% of ICU admissions — associated with higher mortality
Increased cost, increased length of stay, and increased in- and out-of-hospital mortality
Common causes of intrinsic AKI: sepsis, ischemia, and endogenous and exogenous nephrotoxins

Three major methods used to identify AKI

KDIGO

Preferred

The current preferred three-stage system, based on serum creatinine or baseline change, urine output volume, and GFR decreases in those < 18 years of age.

RIFLE

Risk–Injury–Failure–Loss–ESRD

From the Acute Dialysis Quality Initiative; based on abrupt onset, loss, and the need for RRT coupled with duration. No longer preferred over KDIGO but still used clinically.

Anatomic

Prerenal / intrarenal / postrenal

The third most widely accepted classification — by etiology (the 60/35/5 split above).

KDIGO AKI staging — serum creatinine thresholds

Stage is set by the worse of serum creatinine (× baseline, or absolute) and urine output. Hover each bar for both criteria.

Stage 1 Stage 2 Stage 3

RIFLE method for acute kidney injury
Class	GFR rate reduction	Urine output reduction
Risk	Increase serum creatinine × 1.5, or decrease of GFR > 25% from baseline	UO < 0.5 ml/kg/hr for 6 hr
Injury	Increase serum creatinine × 2, or decrease of GFR > 50% from baseline	UO < 0.5 ml/kg/hr for 12 hr
Failure	Increase serum creatinine × 3 from baseline, or decrease of GFR > 75% from baseline, or serum creatinine ≥ 4, or acute rise of ≥ 0.5 mg/dl	UO < 0.3 ml/kg/hr for 24 hr, or anuria for 12 hr
Loss	Complete loss of renal function for > 4 weeks
ESRD	Need for RRT for > 3 months

This method is no longer preferred by most experts over KDIGO but is still used clinically.

Prerenal vs. intrinsic vs. postrenal

Prerenal (60%)

Diminished perfusion, no nephron damage

Intravascular volume depletion (hemorrhage; GI losses; urinary losses; skin losses)
Vasodilatory states (sepsis, anaphylaxis, drugs)
Decreased cardiac output (severe systolic HF, MI, cardiogenic shock)
Arterial occlusion / vasoconstrictive states (catecholamines)
Liver disease (cirrhosis → hepatorenal syndrome)

Urine: oliguria · urine Na < 20 mEq/L · osmolality > 500 mOsm/L · specific gravity > 1.020 · FENa < 1% · BUN:Cr ≥ 20:1 · sediment none or hyaline casts.

Intrinsic (35%)

Glomerular or tubular defects

ATN — most hospital-associated intrinsic AKI (85–90%)
Acute tubulointerstitial nephritis (10–15% of intrinsic)
Glomerulonephritis (immunologic)
Nephrotoxins — endogenous and exogenous

Urine: urine Na > 20 mEq/L · FENa > 1% · BUN:Cr < 20:1 · osmolality ≤ 350 mOsm (isotonic) · specific gravity fixed (1.0008–1.012) · sediment granular casts / tubular cells.

Postrenal (5%)

Obstruction → decreased GFR

Mechanical — calculi, tumors (prostate, cervical), urethral strictures, BPH, blood clots, occluded catheter
Functional — neurogenic bladder, diabetic neuropathy, spinal cord disease

Urine: volume fluctuates anuria/polyuria · urine Na > 40 mEq/L · FENa variable · BUN:Cr > 20:1 · sediment normal or red/white cells, crystals.

Diminished renal perfusion from a decrease in blood supply to the kidneys; no nephron damage is present.
Drug causes: ACEIs (vasodilate the efferent arteriole, inhibiting intrinsic renal autoregulation), NSAIDs (decrease renal blood flow by constricting the afferent arteriole), diuretics.
Results in increased tubular sodium and water reabsorption (to re-expand circulating volume): oliguria, decreased urine sodium (< 20 mEq/L), high urine osmolality (> 500 mOsm/L), increased specific gravity (> 1.020).
Decreased distal tubular flow → increased urea absorption and decreased potassium secretion, with marginal effect on creatinine → increased BUN-to-creatinine ratio (≥ 20:1).
FENa is a very sensitive test: < 1% prerenal; > 1% (ATN > 2%) intrinsic; varied postrenal.
Increased bicarbonate generation → contraction alkalosis; increased uric acid reabsorption → hyperuricemia; increased ADH → urine osmolality > serum osmolality; hyponatremia with free water loading until volume is restored.
Sediment: none, or hyaline casts.

An abrupt decrease in GFR due to tubular cell damage from renal ischemia or nephrotoxic injury. ATN accounts for most hospital-associated cases of intrinsic AKI (around 85–90%) — usually caused by prolonged periods of renal azotemia leading to tubular injury.

Urine sediment often contains granular casts and renal tubular epithelial cells.
Endogenous nephrotoxins: hemoglobinuria (hemolysis), myoglobinuria (rhabdomyolysis), hyperuricemia, multiple myeloma.
Exogenous nephrotoxins: aminoglycosides, contrast media, ethylene glycol, amphotericin B, cyclosporine, antineoplastics (cisplatin), heavy metals.
Drug-induced principle: the ideal method is to stop the offending agent; if discontinuation is not an option, the drug must be renally dosed based on creatinine clearance.

Source

Hemoglobinuria

Endogenous nephrotoxin from hemolysis.

Myoglobinuria

Endogenous nephrotoxin from rhabdomyolysis.

Hyperuricemia

Endogenous nephrotoxin.

Multiple myeloma

Endogenous nephrotoxin.

Aminoglycosides

Exogenous nephrotoxin.

Contrast media

Exogenous nephrotoxin — see contrast-induced nephropathy below.

Ethylene glycol

Exogenous nephrotoxin — also a dialysis indication as a specific toxin.

Amphotericin B · cyclosporine · cisplatin · heavy metals

Exogenous nephrotoxins (antineoplastics such as cisplatin).

Defined as a rise in serum creatinine between 25–50% within 48 hr of IV contrast.

GFR > 60 is typically considered normal for contrast dosing; current U.S. and international data suggest a GFR of 45 ml/min be used. Low doses of contrast may be used if image quality is not compromised.
Fluid administration (high-level evidence): isotonic IV fluid is beneficial. Normal saline or sodium bicarbonate have proven beneficial over 0.45 normal saline. Normal saline: 1 ml/kg/hr for 6–12 hr before and after. Sodium bicarbonate: 3 ampules of 50 mEq in D5W to 1 liter; 3 ml/kg over 1 hr prior, then 1 ml/kg/hr for 6 hr after.
N-acetylcysteine 600 mg q12h for 48–72 hr (before and after) — not shown superior to fluid alone.
Metformin (or combinations) withheld for 48 hr prior to dye load.
Diuretics (mannitol, furosemide) have not shown benefit and may be harmful; discontinuing ACEIs has not been found to prevent contrast-related injury.

Acute tubulointerstitial nephritis accounts for 10–15% of cases of intrinsic renal failure:

Bacterial pyelonephritis — streptococcal infection, leptospirosis, cytomegalovirus, histoplasmosis, Rocky Mountain spotted fever.
More than 70% of cases are drug-induced hypersensitivity: penicillins, cephalosporins, sulfonamides and sulfonamide-containing diuretics, NSAIDs, rifampin, phenytoin, allopurinol.
Urine sediment: eosinophilia, renal tubular epithelial cast, FENa > 1%; proteinuria may be seen (NSAID-induced, usually modest).

Glomerulonephritis — often immunologic (SLE, Sjögren's, sarcoidosis, cryoglobulinemia, idiopathic):

Serum protein levels often reduced from renal loss of albumin; workup includes ESR, ANA, C3 and C4.
Urinalysis: proteinuria at least 1+ or nephrotic-range proteinuria of 3 g/day; hematuria (red cell casts classic).
Clinical findings may include fever (> 80%), rash (25–50%), arthralgias, peripheral blood eosinophilia.

Management of AKI

Four aims of therapy

Treat the underlying cause.
Correct fluid, electrolyte, and uremic abnormalities.
Prevent complications, including nutritional deficiencies.
Discontinue nephrotoxic agents.

Fluids & diuretics

Volume and loop diuretics

Adjust intake to output; the volume-depleted patient is usually resuscitated with saline.
Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) improve UO but no improvement in survival or need for dialysis — reserve for volume overload.
Furosemide IV q6h initial 20–100 mg; if inadequate within 1 hr, double the dose; repeat until adequate UO (caution: tinnitus, temporary deafness).
Maximize cardiac function and maintain optimal BP for renal perfusion; in suspected BPH avoid sympathomimetics (OTC decongestants).

Nutrition

AKI is catabolic

Total caloric intake 30–45 kcal/kg/day, mostly carbohydrate and lipids.
Not on dialysis: protein restricted to 0.6 g/kg/day.
On dialysis: protein 1–1.5 g/kg/day.

Consider treatment if serum potassium is above 5.5 or with potassium-related EKG changes: peaked T-waves, loss of P-waves, PR or QRS widening, or bradycardia.

Discontinue potassium supplements, potassium-sparing medications, and potassium-rich salt substitutes.
Antagonize proarrhythmic effects: IV calcium (10 ml of a 10% solution of calcium gluconate) — cardioprotective, fastest onset; avoid if digoxin toxicity suspected.
Drive potassium intracellularly: inhaled beta-2 agonist (onset ~30 min); IV regular insulin 10 units (add glucose if blood glucose < 250 mg/dl — typically 25 g dextrose IV, effective ~1 hr, not sustained).
Remove potassium: IV furosemide (peak 30 min, if diuretic responsive); IV sodium bicarbonate (if metabolic acidosis; not first-line unless acidosis).
GI binding agents: sodium polystyrene sulfonate (Kayexalate) 15–30 g PO (adds 1 mEq Na per 1 mEq K removed; expands with water; high doses → bowel obstruction); Patiromer (Veltassa, FDA 2015) and Zirconium cyclosilicate (Lokelma, FDA 2018) — neither swells in the GI tract.
Dialysis is definitive for significantly elevated potassium with renal failure not responding to medical management.

For metabolic acidosis, IV sodium bicarbonate goals are to increase, not normalize, pH (to approximately 7.20 or greater) and plasma bicarbonate (8–10 mEq/L).

Between 20% and 60% of patients need short-term dialysis, particularly when BUN exceeds 100 mg/dl and serum creatinine exceeds 5–10 mg/dl.

Intravascular volume overload — pulmonary edema
Hyperkalemia
Acidosis/alkalosis
Uremia — symptomatic syndrome from increased nitrogenous wastes (azotemia): CNS disturbances, GI symptoms (nausea, vomiting, anorexia), BUN 100–200 mg/dl
Specific drug/toxin — e.g., ethylene glycol or aspirin overdose

Also: renally adjust all medications (assume GFR < 10 ml/min; normal GFR is 80–120 ml/min) and adjust diet — low protein (controversial)/sodium/potassium/phosphorus. Monitor for complications: electrolyte imbalances, volume overload (pulmonary edema), uremia (pericarditis), infection, GI bleeding.

RRT options in AKI

When conventional management fails

In AKI, continuous renal replacement therapy should be used based on the need for fluid removal and correction of electrolyte imbalance when conventional medical management fails. Some form of dialysis is indicated if uremic symptoms develop, such as encephalopathy or pericarditis. Full modality comparison lives in the Renal Replacement Therapy section.

Chapter 43 · Chronic Kidney Disease

Chronic Kidney Disease

Progressive azotemia over weeks, months, or years. CKD is defined by a GFR ≤ 60 ml/min for longer than 3 months, with or without kidney damage — or kidney dysfunction with more than one marker of damage.

Definition

The two ways CKD is diagnosed

GFR ≤ 60 ml/min for longer than 3 months, with or without kidney damage
Kidney dysfunction with more than one of: albuminuria; urine sediment abnormalities; electrolyte abnormalities related to tubular disorders; abnormal histology; abnormal kidney structures on repeat imaging; history of renal transplant

Etiology

Causes

Glomerular disease
Polycystic kidney disease
Hypertensive nephropathy
Diabetic nephropathy
Tubulointerstitial nephritis or necrosis
Obstructive nephropathies
Renal artery stenosis

Associated findings: isosthenuria is common; hypertension is common in most patients; ultrasound shows small kidneys bilaterally; X-rays show renal osteodystrophy.

Staging — five stages of increasing nephron loss

CKD stages by GFR

Each stage reflects an increasing loss of nephrons. The GFR axis runs left (kidney failure) to right (normal). Hover a band for its definition.

Stage 1 (> 90) Stage 2 (60–89) Stage 3a (45–59) Stage 3b (30–44) Stage 4 (15–29) Stage 5 / ESKD (< 15)

Normal GFR is 80–120 ml/min.
MDRD formula: GFR (ml/min/1.73 m²) = 175 × (Scr)^-1.154 × (Age)^-0.203 × (0.742, if female) × (1.212, if African American).
Renal replacement is instituted when GFR falls to 5–10 ml/min.
Many practitioners refer to creatinine clearance as a more accurate estimate of GFR — age and gender dependent. Normal: males 97–137 ml/min/1.73 m²; females 88–128 ml/min/1.73 m².
Cystatin C — a proteinase inhibitor not freely filtered by the glomerulus; a potentially better marker of renal function than creatinine, but not widely available.

Signs and symptoms — by system

Often asymptomatic or vague in the early stages. Filter by system.

System

General

Fatigue, weakness.

Skin

Pruritus; easy bruising; pallor, ecchymosis; excoriations; edema; xerosis; sallow complexion; pale conjunctiva; reversible hair loss and nail changes.

Ear, nose & throat

Metallic taste in the mouth; epistaxis; urinous breath.

Pulmonary

Shortness of breath; rales; pleural effusion.

Cardiovascular

Dyspnea on exertion; retrosternal pain on inspiration and pericardial friction rub (pericarditis from uremia); HTN from volume overload; cardiomegaly.

GI

Anorexia; nausea and vomiting; hiccups.

Genitourinary

Impotence; nocturia; iso-osmolar urine (osmolarity similar to plasma despite fluid intake — marked impairment of concentrating ability).

Neurologic

Irritability; inability to concentrate; decreased libido; stupor; asterixis; myoclonus/hyperreflexia; peripheral neuropathy (with diabetes); restless leg syndrome / loss of vibratory sense; seizures (rare).

Anemia due to erythropoietin deficiency

A defining sign of CKD — see the anemia management accordion below.

Management of common problems in CKD

Monitor weight, standing BP, urine sodium excretion, creatinine clearance, and serum creatinine. Decrease sodium and fluid intake.
Furosemide (Lasix): initially 20–80 mg/day, up to 600 mg/day (confusion, dehydration, muscle cramps; high doses → tinnitus/deafness). Doses up to 1 g/day in CHF/renal failure; continuous infusions 100 mg/hr (no superiority). Remains effective when GFR < 25 ml/min.
Others (not proven more effective than furosemide): metolazone 2.5–20 mg PO daily (with loop only); chlorothiazide 500 mg IV daily (with loop only); bumetanide 0.5–2 mg once daily (repeat q4–5h, max 10 mg/day); torsemide 10–20 mg once daily (up to 200 mg/day).

HTN

Antihypertensives that maintain renal blood flow and reduce glomerular pressure and proteinuria are preferred.
ACEIs and ARBs reduce proteinuria up to 35–40% greater than other antihypertensives — the agents of choice for all CKD patients with an albumin excretion rate (AER) of 30 mg/day or more, unless contraindicated.
Goal BP: < 140/80 mmHg; for proteinuria > 1–2 g: < 125/75 mmHg.

Protein catabolism

Limit protein to 1.3 g/kg/day if at risk of progression; increase restriction to 0.8 g/kg/day if diabetic or GFR < 30. Controversial; reserve restriction for late stage III, IV, and ESRD.
Avoid thyroid hormone, steroids, and tetracycline (increase catabolism). Anabolic agents may help: fluoxymesterone (Halotestin), nandrolone decanoate (Deca-Durabolin).

Acidosis: alkalizing agents when plasma HCO3 < 20 mEq/L — NaHCO3 1 g + 13 mEq sodium (emergencies; may cause volume overload); sodium citrate (Shohl's/Bicitra) 1 mEq/ml; Polycitra (monitor K, avoid in hyperkalemia).
Hyperkalemia: avoid high-potassium foods/meds and hypercatabolic states; medical emergency if K > 7 mEq/L; monitor ECG for flat P waves, peaked T waves, PR > 0.20 s, QRS > 0.10 s, bradycardia.
Hyperphosphatemia: goal 2.5–4.6 mg/dl. Restrict phosphorus (colas, eggs, dairy, meat); GFR < 20–30 ml/min usually requires treatment. Binders: sevelamer (Renvela) 800–3,200 mg TID with meals; lanthanum (Fosrenol) 1,500–3,000 mg/day divided with meals; aluminum hydroxide 300–600 mg TID between meals (acute use, phosphorus > 7 mg/dl; limit 3 days — osteomalacia, neurologic complications; only if hemodialysis unavailable).
Hypocalcemia: treat significant/symptomatic. Nondialysis: no routine calcium unless symptomatic or severe hyperphosphatemia; avoid calcitriol/vitamin D analogs. Dialysis: calcitriol + vitamin D analogs; dialysate calcium 1.25–1.50 mmol/L.
Hypermagnesemia: avoid magnesium-containing laxatives, antacids, and supplements.

CKD causes anemia due to erythropoietin deficiency. First, identify and treat all correctable causes.

Iron PO or IV, based on iron studies; vitamin supplements as needed (caution with multivitamins).
Erythropoiesis stimulating agents (ESAs): IV or subQ up to 3 times a week. Black box: increased risk of stroke, severe HTN, and loss of vascular access — all can lead to death.
Dialysis patients: recommended. Nondialysis: see the hemoglobin thresholds below.

ESA therapy — hemoglobin thresholds (nondialysis)

The reading sets three decision points: 9, 10, and 11 g/dl. Hover a zone for its rule.

Definite use Tailored Do not initiate Hold

Hyperparathyroidism: serial PTH with calcium and phosphate; optimal PTH levels undetermined. CKD 3a–5 (not on dialysis): evaluate hyperphosphatemia, hypocalcemia, vitamin D deficiency; reserve calcitriol/vitamin D analogs for CKD 4–5 with severe hyperparathyroidism; failure to respond → parathyroidectomy. CKD 5 (dialysis): PTH 2–9 × upper normal; calcimimetics — cinacalcet (Sensipar) 30 mg PO daily, etelcalcetide (Parsabiv) 5 mg IV bolus 3× weekly after hemodialysis; calcitriol oral 0.25 mcg daily (titrate to 1 mcg) or IV 1–2 mcg 3× weekly (maintenance 0.5–4 mcg 3× weekly).
Renal osteodystrophy: prevent acidosis, hypocalcemia, hyperphosphatemia. Post-transplant: measure calcium and phosphate weekly; treat with vitamin D, calcitriol, antiresorptives as needed. Monitoring: class 1–3b calcium/phosphate q6–12 mo (PTH once); class 4 calcium/phosphate q3–6 mo, PTH q6–12 mo; class 5 calcium/phosphate q1–3 mo, PTH q3–6 mo; class 3a–5 alkaline phosphatase annually.

≤ 60 ml/min

GFR for > 3 months = CKD

With or without kidney damage.

5–10 ml/min

start renal replacement

Renal replacement is instituted when GFR falls to this range.

35–40%

greater proteinuria reduction

ACEIs and ARBs vs. other antihypertensives — the agents of choice for CKD with AER ≥ 30 mg/day.

Chapter 43 · Renal Replacement Therapy

Renal Replacement Therapy

When conservative measures fail — in AKI or CKD — renal replacement therapy takes over. The reading covers hemodialysis, peritoneal dialysis, and renal transplantation.

Hemodialysis

Intermittent & continuous

Intermittent — most common for chronic management; specialized staff (hospital or clinic); resource and time intensive; useful removing selected drugs in acute toxic states; requires adequate mean arterial pressure (normal ≥ 60 mmHg).
Continuous — similar creatinine clearance to intermittent dialysis: CAVH (arterial access, MAP preferably ≥ 60 mmHg) and CVVHD (external pump, lower BP requirement). Both by trained ICU nurses.
Benefits of continuous over intermittent have not been proven to reduce course, duration, outcome, or mortality in AKI — even with early start.

Peritoneal dialysis

Autonomy, but less clearance

Beneficial for long-term use; improved quality of life (autonomy, independence with schedule); decreased cost for supplies vs. hemodialysis.
Does not provide creatinine clearance rates at the level of other RRT methods — may limit usefulness.
High risk for catheter site and intra-abdominal (peritoneal) infections.
Contraindicated in pregnancy, active inflammatory bowel disease, and placement of abdominal ostomies.

Dialysis modality comparison — relative, per the reading

Qualitative ranking mapped from the reading's descriptions (not measured data): 3 = highest/strongest, 1 = lowest/weakest. Hover a bar for the source wording.

Hemodialysis Peritoneal dialysis Transplant

Most cost-effective — benefit realized at about 1–2 years posttransplant.
Improved quality of life and functionality over chronic dialysis use.
Limited by organ availability; may use a living donor or cadaver within a certain timeframe to increase the potential organ match.
Lifetime burden of immunosuppression and its associated consequences.

In AKI, continuous RRT should be used based on the need for fluid removal and correction of electrolyte imbalance when conventional medical management fails.
The choice of method should be made on patient need, availability of services, and the physiologic stability required by other replacement methods.
Some form of dialysis is indicated if uremic symptoms develop — such as encephalopathy or pericarditis.
Peritoneal dialysis does not provide adequate clearance in catabolic states (major surgery, burns, sepsis) — may require conversion to an alternate method until baseline physiology is restored.

≥ 60 mmHg

MAP for hemodialysis flow

Intermittent HD normally requires adequate mean arterial pressure to attain flow rates for clearance.

1–2 yr

transplant cost-benefit

Transplant is most cost-effective, with the benefit realized at about 1–2 years posttransplant.

3 options

RRT modalities

Hemodialysis · peritoneal dialysis · renal transplantation — in AKI and CKD.

Chapter 43 · Modification of Drug Dosages

Drug Dosing in Renal Impairment

Decreased renal function changes how drugs behave. The reading sorts drugs into three types by how they are eliminated, then lists three consequences of decreased renal function — and four questions to ask before giving any drug to a patient in renal failure.

Type A

Eliminated entirely by the kidney

Renal clearance is everything — these drugs accumulate when the kidney fails.

Type B

Eliminated entirely by extrarenal mechanism

Renal function matters least for these.

Type C

Renal + extrarenal

Eliminated by both renal and extrarenal mechanisms.

Decreased renal function results in

Abnormal excretion rates
Abnormal metabolism rates of certain drugs
Abnormal sensitivity to certain drugs

Four questions before you give the drug

Check first

Ask

Does this drug depend on the kidney for excretion?
Does an excess blood level affect the kidney or cause nephrotoxicity?
Does the effect of the drug alter electrolyte imbalance?
Is the patient susceptible to the drug because of kidney disease?

Clinical anchor

Renally adjust everything

In AKI, renally adjust the dose of all medications: assume GFR is < 10 ml/min (normal GFR is 80–120 ml/min).

If a nephrotoxic drug cannot be stopped, it must be renally dosed based on creatinine clearance — guided by specific drug recommendations and renal clearance rates.

GFR & creatinine clearance — the reference numbers

The ranges that drive dosing decisions. Hover a bar for its definition.

Dialysis / renal-adjust thresholds CKD threshold (≤ 60) Normal GFR Female CrCl Male CrCl

Type A — eliminated entirely by the kidney.
Type B — eliminated entirely by extrarenal mechanism.
Type C — eliminated by renal and extrarenal mechanisms.
Decreased renal function → abnormal excretion rates, abnormal metabolism rates of certain drugs, abnormal sensitivity to certain drugs.
Before administering any drug in renal failure, ask the four questions above.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Sodium — Hyponatremia & Hypernatremia

Serum sodium tracks body water balance: normal 135–145 mEq/L. Hyponatremia is a serum [Na⁺] < 135 mEq/L; hypernatremia is > 145 mEq/L — and hypernatremia always indicates hyperosmolality with a total-body-water (TBW) deficit.

135–145 mEq/L

Normal serum sodium

Hyponatremia < 135; hypernatremia > 145.

5–15%

Hyponatremia in hospitalized patients

Renal water excretion falls below water intake.

3–9%

Hypernatremia in elderly / critically ill

0.3–1% of all hospitalized patients.

Direction

Hypo

Three flavors of hyponatremia

Hypotonic (low serum osmolality, SOsm) — true body-water excess with intra- and extracellular dilution.
Isotonic (normal SOsm) — laboratory artifact: extreme hyperlipidemia or hyperproteinemia displaces water in the sample; body water is normal.
Hypertonic (high SOsm) — ECF sodium diluted by water moving from cells toward nonsodium solute (glucose, mannitol).

Hypo

Etiology by volume status

Hypervolemic — congestive heart failure, hepatic cirrhosis, nephrotic syndrome.
Hypovolemic — blood loss; GI loss (gastric suction, emesis, diarrhea); renal loss (diuresis, aldosterone deficiency); skin loss (sweating, burns).
Euvolemic — SIADH, thiazides (elderly females), renal failure, cortisol deficiency, hypothyroidism, primary polydipsia / forced water intake (marathoners), beer potomania.

Hypo

Laboratory findings

Hypotonic: Na < 135 and SOsm < 270 mOsm/kg (normal 280–295; SOsm ≈ 2 × [Na⁺]).
UOsm < 100 mOsm/L — water intake exceeds renal excretion; UOsm > 100 mOsm/L — ADH effect.
UNa < 20 mEq/L — decreased renal blood flow (hyper- or hypovolemic).
UNa > 40 mEq/L — SIADH, diuretics, renal failure, hypothyroidism, adrenal insufficiency.

Hypo

Management — only hypotonic needs treating

Symptomatic (seizures/coma, Na < 120): 3% hypertonic saline bolus 100 mL over 10 min, repeat ×2 as needed for a 4–6 mEq/L rise.
Then 0.5–2 mL/kg/hr to rise 1–2 mEq/L/hr, max 12 mEq/L in first 24 hr; maximum correction 8–12 mEq/L/24 hr (or 20 mEq/L/48 hr).
Mild: hypovolemic → 0.9% NS; hypervolemic → restrict to 1,000 mL/24 hr + furosemide 40–80 mg IV or PO.

Hyper

Definition

Serum [Na⁺] > 145 mEq/L.
Always indicates hyperosmolality and a deficit of total body water.

Hyper

Etiology

Central (pituitary) diabetes insipidus — lack of ADH secretion.
Nephrogenic diabetes insipidus — failed renal response to ADH.
Water loss > sodium loss — renal osmotic diuresis (glucosuria, mannitol, urea), GI loss, cutaneous loss (burns, sweating).
Excess hypertonic saline — NaHCO₃ for CPR/lactic acidosis, NaCl 3% saline.

Hyper

Laboratory findings

Na > 146 mEq/L with SOsm > 300 mOsm/L.
UOsm < 300 mOsm/L — central or nephrogenic DI.
UOsm 300–400 mOsm/L — osmotic diuresis.
UOsm > 400 mOsm/L — GI, cutaneous, or insensible water loss.

Hyper

Management

Discontinue/reduce excess saline administration.
Replace water: oral water preferred when conscious; IV — mild depletion D5W, moderate 0.45% NS, severe 0.9% NS then 0.45% NS or D5W once stable.
Acute: correct no faster than 1–2 mEq/L/hr; chronic: max 0.5 mEq/L/hr.

Serum sodium scale — symptoms track the number

Zones drawn to scale across 100–180 mEq/L. Hover a zone or marker for its threshold.

Hyponatremia (< 135) Normal (135–145) Hypernatremia (> 145)

Hyponatremia

Symptoms & exam

Neurologic from brain swelling; severity parallels the fall in [Na⁺] — worse with acute (hours to 1–2 days) than chronic (days to weeks) development.
Na 120–125: nausea, malaise, gait instability. Na 110–120: headache, confusion, lethargy, nausea. Na < 110: seizures, coma.
Exam: general neurologic depression, rarely focal findings; hypervolemia → edema/ascites/crackles/gallop/JVD; hypovolemia → postural BP fall and pulse rise, jugular venous collapse.

Hypernatremia

Symptoms & exam

Neurologic from brain-cell shrinkage. Na 146–150 often asymptomatic; 151–160 nausea/weakness/lethargy/confusion/irritability; > 160 stupor/coma.
Thirst/polydipsia in alert patients; polyuria/nocturia suggests a renal basis (DI or osmotic diuresis).
Exam: CNS depression; hypotension, tachycardia, oliguria in volume-depleted states.

The overcorrection trap

Overcorrection or too-rapid a rise in serum sodium can inflict further CNS injury — osmotic demyelination syndrome (ODS), formerly pontine myelinolysis. Correct no faster than the maximums below.

Seizures or coma with Na < 120 mEq/L (acute or chronic)

Restrict water/total fluid to 1,000 mL/24 hr or less.
Bolus 3% hypertonic saline 100 mL over 10 min; remeasure Na; repeat ×2 as needed to achieve a 4–6 mEq/L rise or until symptoms improve.
Then infuse 3% saline at 0.5–2 mL/kg/hr to raise Na by 1–2 mEq/L/hr until a maximum 12 mEq/L rise in the first 24 hr.
Maximum correction: 8–12 mEq/L/24 hr, or 20 mEq/L/48 hr.
Example: Na required = 0.5 × weight (kg) × (120 − Na). An 80 kg patient with Na 107 → (0.5 × 80) × 13 = 520 mEq; infuse 1 L 3% saline ([Na⁺] = 513 mEq/L) over 12–24 hr to reach ≈ 120.

Moderate symptoms or Na < 115 (especially acute)

3% saline 0.5–2 mL/kg/hr with a limit of 10 mEq/L rise in the first 24 hr, then 8 mEq/L/day — or treat by volume status.

Mild or no symptoms

Hypovolemic — address volume loss; infuse 0.9% NS to correct the deficit (ADH secretion stops, kidneys excrete excess water).
Hypervolemic — restrict to 1,000 mL/24 hr; furosemide (Lasix) 40–80 mg IV or PO to restore euvolemia.

SIADH-directed therapy

Conivaptan — hospitalized hypervolemic/euvolemic patients only; 20 mg IV loading dose and continuous IV infusion 40 mg over 24 hr, then 20 mg/24 hr for 1–3 days (max 4 days); must discontinue hypertonic saline and fluid restriction; monitor for hypotension and hypokalemia.
Tolvaptan — Na < 125 or symptomatic resistant to fluid restriction; 15 mg PO starting dose titrated to max 60 mg/day; max use 30 days; monitor ALT/AST.
Demeclocycline — 300 mg PO BID long-term; photosensitizing.
Urea — 0.25–0.5 g/kg or 15–30 g BID PO as 15 g powder (food supplement, not FDA-approved).

Monitor serum Na every 2–4 hr in all symptomatic patients.

Correction rates

Acute (symptomatic): correct no faster than 1–2 mEq/L/hr to avoid cerebral edema.
Chronic: correct at a maximum of 0.5 mEq/L/hr; reduce the excess above 140 by about half over 24 hr.
Estimate water deficit = 0.4 × weight (kg) × [(Na/140) − 1].

Replacement route

Enteral — oral water is preferred in conscious patients.
IV — mild depletion: D5W (avoid hyperglycemia/glucosuria); moderate: 0.45% NS; severe: 0.9% NS, then 0.45% NS or D5W once stabilized.

Water-deprivation test (requires constant monitoring)

Withhold all fluid intake; monitor BP, serum sodium, and UOsm.
When UOsm is nearly constant (< 30 mOsm/L change for 2–3 hr): inject aqueous vasopressin 5 units subQ or desmopressin (DDAVP) 4 mcg subQ; measure urine volume and UOsm after 1–2 hr.
Central DI — UOsm rises to 400–600 mOsm/L.
Nephrogenic DI — little or no rise in UOsm.

Monitor Na every 2–4 hr in acute, every 4–6 hr in chronic hypernatremia.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Potassium — Hypokalemia & Hyperkalemia

The highest-yield electrolyte: normal serum potassium is 3.5–5.5 mEq/L. Hypokalemia is < 3.5 mEq/L; hyperkalemia is > 5.5 mEq/L — and its ECG progression, not the number alone, drives the urgency of treatment.

3.5–5.5 mEq/L

Normal serum potassium

Hypokalemia < 3.5; hyperkalemia > 5.5.

~20%

Hypokalemia in hospitalized patients

And 10–40% of outpatients taking diuretics (correlates with dose).

100 mEq

Body deficit per 0.3 mEq/L fall

Estimated K loss for each 0.3 mEq/L decrease below 4.0 mEq/L.

Hypokalemia

Etiology & findings

Renal loss — diuretics (acetazolamide, loop, thiazides), mineralocorticoid excess, renin-secreting tumor, Cushing, exogenous mineralocorticoid, renal tubular acidosis I/II, Bartter/Gitelman/Liddle, hypomagnesemia.
Nonrenal — emesis/gastric suction, diarrhea (laxative abuse, secretory diarrheas); cell uptake — insulin (DKA), catecholamines, periodic paralyses.
Symptoms: muscle cramps/weakness (may ascend to diaphragmatic paralysis), ileus, palpitations (worse on digoxin), polyuria/polydipsia.
ECG: T-wave flattening, U wave. Urinary K > 25 mEq/L/24 hr = renal wasting; < 25 = nonrenal.

Hyperkalemia

Etiology & findings

Decreased renal excretion — renal failure, adrenal insufficiency, heparin, K-sparing diuretics.
RAAS disruption — ACE inhibitors, ARBs, direct renin inhibitors (especially diabetic kidney disease), NSAIDs, cyclosporine.
Shift/release — insulin deficiency, hemolysis, rhabdomyolysis, tumor lysis, burns, metabolic (hyperchloremic) acidosis, digitalis toxicity, succinylcholine.
Pseudohyperkalemia — in the tube only: hemolysis, platelets > 500,000/mm³, WBC > 100,000/mm³.
ECG: peaked T waves → widened QRS → loss of P wave → sine wave; ECG correlates poorly with fatal-arrhythmia risk.

Hyperkalemia — the ECG progression

The sequence the reading gives. Hover each stage. Hypokalemia, by contrast, shows T-wave flattening and a U wave.

Hyperkalemia — emergency treatment by mechanism

Mechanism

MembraneEKG abnormal

Calcium gluconate 10% — 1 g IV over 1–2 min

Antagonizes the hyperkalemic membrane effect; immediate onset, repeat in 3–5 min if needed.
Does not lower serum K; effect lasts minutes only.
Calcium chloride may be given centrally but has ~3× the calcium per 10 mL — adjust dose to avoid toxicity; monitor serum Ca with each K recheck.

Shift

Regular insulin 10 units IV over 2–5 min

Add glucose D50 25 g in 50 mL D5W IV over 5 min if euglycemic.
Effect in 15–30 min; lasts 30–60 min. Lowers serum K by moving it into cells, not total body K.

Shift

Albuterol 10–20 mg nebulized over 10 min

Effect in 15–30 min; lasts 60–120 min.
Lowers serum K by shifting into cells, not total body K.

Shift

Sodium bicarbonate 50 mEq IV over 2–5 min

Variable efficacy, in acidosis only; may cause dangerous hypernatremia with repeat doses.
Shifts K into cells (not total body K); effect lasts 2–6 hr.

RemoveEKG normal

Furosemide (Lasix) 40–80 mg IV

Increases renal potassium excretion — first-line when the ECG is normal.

Remove

GI potassium binders

Kayexalate 15–45 g with osmotic cathartic — not recommended (GI complications, slow onset).
Patiromer (Veltassa) 8.4 g/day titrated to 25.2 g/day — not for acute hyperkalemia; useful with RAAS inhibitors.
Sodium zirconium cyclosilicate (Lokelma) 10 g PO TID ×48 hr acute, or 10 g/day chronic.

Remove

Hemodialysis / peritoneal dialysis

Removes potassium in renal failure.

Discontinue drugs that enhance potassium excretion.
Estimate 100 mEq K loss for each 0.3 mEq/L decrease below 4.0 mEq/L.
IV KCl (arrhythmias — especially on digitalis — hepatic encephalopathy, or cannot take PO): peripheral max 40 mEq/L; central max 60 mEq/L. Rate max 20 mEq/hr peripheral or 40 mEq/hr central; monitor ECG continuously.
Oral KCl (K-Lor) — acute: max single dose 40 mEq or 20 mEq every 30 min (total 60 mEq), recheck K in 4 hr; chronic: 10–40 mEq/day in 1–2 doses. Extended-release (K-Dur, Micro-K): same dosing.
Potassium-sparing diuretics — spironolactone (Aldactone) 25 mg PO daily; amiloride (Midamor) 5 mg PO daily; eplerenone (Inspra) 25 mg PO daily.
Correct coexisting hypomagnesemia (present in up to 40%) — required to replete body potassium effectively.
High-potassium diet: nuts, dried fruits, tomatoes, potatoes, oranges.

All cases: repeat serum (or plasma) potassium; seek and limit potassium intake; discontinue drugs that limit excretion; obtain an ECG.

ECG normal

Increase renal excretion — furosemide 40–80 mg IV.
Increase GI excretion — binders as above (Kayexalate not recommended); patiromer; Lokelma.
Hemodialysis/peritoneal dialysis in renal failure.

ECG abnormal — monitor until normal

Absent P wave, QRS widening, or sine wave:
- Calcium gluconate 10% 1 g IV over 1–2 min (repeat in 3–5 min; does not lower K; lasts minutes).
- Calcium chloride — central IV only, dose-adjusted (≈3× calcium).
- Regular insulin 10 units IV over 2–5 min + D50 25 g in 50 mL D5W if euglycemic.
- Albuterol 10–20 mg nebulized over 10 min.
- Sodium bicarbonate 50 mEq IV over 2–5 min (acidosis only).
- Then diuretic, GI binder, or dialysis to remove potassium.
Peaked T waves alone: insulin/glucose or albuterol to shift, plus diuretic/binder/dialysis to remove.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Calcium — Hypocalcemia & Hypercalcemia

Total serum calcium is normally 8.6–10.2 mg/dL; ionized calcium (iCa, the physiologically active fraction) is normally 4.6–5.3 mg/dL (1.12–1.30 mmol/L). Correct total calcium upward by 0.8 mg/dL for each 1 g/dL decrease in albumin.

8.6–10.2 mg/dL

Normal total calcium

Hypocalcemia < 8.6; hypercalcemia > 10.2 (corrected).

1.12–1.30 mmol/L

Normal ionized calcium

4.6–5.3 mg/dL. Hypo < 4.5 mg/dL (1.1 mmol/L); hyper > 5.3 mg/dL (> 1.30 mmol/L).

40–70%

Hypocalcemia in acute pancreatitis

A key etiology to remember.

Direction

Hypo

Definition & correction

Total Ca < 8.6 mg/dL, or iCa < 4.5 mg/dL (1.1 mmol/L). Correct Ca upward by 0.8 mg/dL per 1 g/dL albumin decrease.

Hypo

Etiology

Hypoparathyroidism (usually surgical — post-thyroidectomy/parathyroidectomy).
Hypomagnesemia (especially Mg < 1 mEq/L).
Pancreatitis (40–70% in acute pancreatitis).
Vitamin D deficiency; chronic alcoholism; acute tumor lysis, rhabdomyolysis, massive transfusion.
Drugs: phenytoin, cisplatin, estrogen therapy.

Hypo

Findings

Mental changes (depression, anxiety, confusion); tremors, ataxia, dystonia; tetany, seizures, weakness.
Chvostek sign — facial twitch on tapping the ipsilateral facial nerve; Trousseau sign — carpal spasm inflating BP cuff to occlude the brachial artery for 3 min.
Proximal weakness, hyperactive DTRs; dry skin, brittle hair/nails.
ECG: prolonged QTc, nonspecific T-wave changes.

Hypo

Management

Symptomatic/acute/NPO: calcium chloride 1 g (10%) IV central over 3–5 min, or calcium gluconate 1 g (10%) IV peripheral over 3–5 min for 2 doses; then 1 g/hr calcium gluconate in 500 mL D5W/NS over 3 hr.
Chronic: calcium carbonate 2–3 g elemental/day; ergocalciferol (Drisdol) 50,000 IU; calcitriol (Rocaltrol) 0.5–2 mcg/day.

Hyper

Definition

Total Ca corrected for albumin > 10.2 mg/dL, or iCa > 5.3 mg/dL (> 1.30 mmol/L).

Hyper

Etiology

Hyperparathyroidism — most common cause; 10–20% of hypercalcemia.
Malignancy — most common in hospitalized patients (lung, renal, breast); PTHrP; local bone resorption.
Vitamin D excess (sarcoidosis 15–20%); vitamin A intoxication; hyperthyroidism (10–20%); immobilization; thiazides.

Hyper

Findings

Neuro: lethargy → coma, depression/memory impairment, personality changes.
GI: nausea/vomiting, constipation. Musculoskeletal: proximal weakness, bone pain. Renal: polyuria/nocturia (nephrogenic DI), renal colic.
Exam: global CNS dysfunction; depressed/absent DTRs; hypertension (moderate/chronic) or hypotension (severe).
ECG: shortened QTc. Labs: PTH, TSH/free T4, vitamin D (25(OH)D3, 1,25(OH)2D3), PTHrP, bone survey.

Hyper

Management

Severe (malignancy): 0.9% NS to induce diuresis > 200 mL/hr; calcitonin 4–8 IU/kg q12h subQ/IM (few days only); bisphosphonates; furosemide 40–80 mg IV q6–8h; hemodialysis with low-calcium bath.
Chronic: prednisone 40–80 mg/day; furosemide 40–80 mg PO BID + 6–8 g sodium diet; calcium diet 750–1,000 mg/day.

Total serum calcium scale

Drawn to scale across 7–12 mg/dL. Ionized calcium (iCa) is the physiologically active fraction — normal 4.6–5.3 mg/dL (1.12–1.30 mmol/L).

Hypocalcemia (< 8.6) Normal (8.6–10.2) Hypercalcemia (> 10.2)

Symptomatic, acute (tetany/seizures), or NPO: calcium chloride 1 g (10% solution) IV into a central vein over 3–5 min; or calcium gluconate 1 g (10%) in a peripheral IV over 3–5 min for 2 doses. Then 1 g/hr calcium gluconate in 500 mL D5W or NS over 3 hr.
Asymptomatic, chronic: calcium carbonate (or other salt) 2–3 g elemental calcium/day in divided doses — start CaCO₃ 500 mg PO 3–4× daily (1.5–2 g/day).
Vitamin D: ergocalciferol (Drisdol) 50,000 IU PO once daily or weekly per deficiency severity (monitor Ca); calcitriol (Rocaltrol) 0.5–2 mcg/day.

Severe hypercalcemia (typically malignancy)

IV 0.9% NS to restore volume and induce diuresis > 200 mL/hr.
Calcitonin (Calcimar, Miacalcin) 4–8 IU/kg every 12 hr subQ/IM — effective only a few days.
Bisphosphonates (caution in renal insufficiency): pamidronate (Aredia) 60–90 mg IV over 4 hr, repeat after 7 days; etidronate (Didronel) 7.5 mg/kg in 250 mL NS over 2–3 hr ×3 days; zoledronic acid (Zometa) 4 mg IV over 15 min, may repeat after 7 days.
Furosemide (Lasix) 40–80 mg IV every 6–8 hr to maintain urine output 150–200 mL/hr (with NS or 0.45% NS).
Hemodialysis with low-calcium bath.

Chronic hypercalcemia

Prednisone 40–80 mg/day PO initial dose, reduced as allowed (best for sarcoidosis, hypervitaminosis D, lymphoma).
Furosemide 40–80 mg PO BID, plus 6–8 g sodium diet.
Reduced-calcium diet: 750–1,000 mg/day.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Magnesium — Hypomagnesemia & Hypermagnesemia

Normal serum magnesium is 1.5–2.5 mg/dL. Hypomagnesemia is < 1.5 mg/dL; hypermagnesemia is > 2.5 mg/dL — with clinical consequences that track the number all the way to coma and death.

1.5–2.5 mg/dL

Normal serum magnesium

Hypomagnesemia < 1.5; hypermagnesemia > 2.5.

80–85%

Hypomagnesemia in alcohol withdrawal

From cellular uptake of magnesium.

20–45%

Hypomagnesemia with loop/thiazide diuretics

30% incidence with chronic alcohol use.

Direction

Hypo

Etiology

Renal loss — loop/thiazide diuretics (20–45%), chronic alcohol (30%), aminoglycosides, amphotericin B, cisplatin.
GI loss/malabsorption — persistent diarrhea, laxative abuse, prolonged PPI use, malabsorption/IBD.
Deficient intake — alcohol, protein-calorie malnutrition; cellular uptake — alcohol withdrawal (80–85%), IV insulin (DKA).

Hypo

Findings

Muscle weakness; neurologic symptoms from tremors to seizures.
Trousseau and Chvostek signs; muscle fasciculations/tremors.
Severe hypomagnesemia: serum Ca and K also decrease; urinary Mg < 3 mEq/24 hr denotes body deficiency.
ECG: prolonged QTc, ventricular arrhythmias.

Hypo

Management

Parenteral if symptomatic or hypocalcemic: mild — 4 g MgSO₄ IV in 1 L D5W over 3–6 hr, then 2–4 g over 12–24 hr (goal Mg > 1.5; > 2.0 if arrhythmia risk); severe — 2 g IV in 30–50 mL D5W over 5–10 min (IV push for arrhythmias).
Oral: Slow-Mag 143 mg BID; Mag-Ox 400 400 mg BID; Magtab SR 84 mg BID.

Hyper

Definition & etiology

Serum Mg > 2.5 mg/dL; clinical consequences unusual below 4.0 mEq/L.
Decreased renal function (almost always present); ongoing intake (antacids — Maalox; cathartics — Epsom salt, Milk of Magnesia, magnesium citrate); massive intake (IV MgSO₄ in eclampsia); hypothyroidism, adrenal insufficiency, lithium.

Hyper

Findings

Weakness → paralysis with early difficulty swallowing; lethargy; nausea/emesis.
Hypotension; diminished/absent DTRs (Mg 3.5–7 mg/dL); flaccid paralysis incl. respiratory (8–11 mg/dL); coma/death (> 12 mg/dL).
ECG: lengthening PR, widening QRS, complete heart block.

Hyper

Management

Stop magnesium intake.
ECG changes: calcium gluconate 1 g (10%) peripheral IV over 3–5 min up to 3 doses; calcium chloride 1 g (10%) central IV; furosemide 40 mg IV plus 0.45% NS 50–100 mL/hr.
Hemodialysis — for ECG changes, or consider for any serum Mg > 4 mg/dL.

Serum magnesium scale — where symptoms begin

Drawn to scale across 0–13 mg/dL. Hover a zone or marker for its clinical threshold.

Hypomagnesemia (< 1.5) Normal (1.5–2.5) Hypermagnesemia (> 2.5)

Stop magnesium intake (all cases).
Diminished/absent deep tendon reflexes — serum Mg 3.5–7 mg/dL.
Weakness to flaccid paralysis including respiratory muscle paralysis — 8–11 mg/dL (hypoventilation or respiratory distress).
Coma or death — > 12 mg/dL.
ECG changes → calcium gluconate 1 g (10%) peripheral IV over 3–5 min (up to 3 doses) or calcium chloride 1 g (10%) central IV over 3–5 min; furosemide 40 mg IV plus 0.45% NS 50–100 mL/hr.
Hemodialysis for ECG changes, or consider for any serum Mg > 4 mg/dL.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Phosphorus — Hypophosphatemia & Hyperphosphatemia

Normal serum phosphorus is 2.5–4.5 mg/dL (adults). Hypophosphatemia is < 2.5 mg/dL (severe < 1.5); hyperphosphatemia is > 5 mg/dL in adults (> 6 mg/dL in children).

2.5–4.5 mg/dL

Normal serum phosphorus

Hypo < 2.5 (severe < 1.5); hyper > 5 adults (> 6 children).

> 55

Danger: P × Ca product

Ectopic calcification risk when phosphorus × calcium exceeds 55.

800–1,000 mg/day

Phosphorus dietary restriction

For hyperphosphatemia.

Direction

Hypo

Definition & etiology

< 2.5 mg/dL; severe < 1.5.
Urinary loss — diuretics, DKA, hyperparathyroidism, Fanconi syndrome, amphotericin B.
Cellular uptake — increased glucose utilization (DKA/alcohol withdrawal, TPN), acute respiratory alkalosis, burns.
GI — chronic alcohol, phosphate binders (PhosLo/Os-Cal, Renagel, Fosrenol), malabsorption.

Hypo

Findings

Irritability, confusion, paresthesias; weakness.
Muscle weakness including diaphragmatic weakness — makes weaning from mechanical ventilation difficult.
Severe: hemolysis (↑ free hemoglobin, ↓ haptoglobin), rhabdomyolysis (↑ CK, positive urinary myoglobin), metabolic acidosis.

Hypo

Management

Oral: sodium/potassium neutral phosphorus (Neutra-Phos, K-Phos Neutral) 1–2 g PO daily in divided doses.
IV: P 2.3–2.7 → 15 mMol; 1.5–2.2 → 30 mMol; < 1.5 → 45 mMol (Na or K phosphate in 250 mL D5W).

Hyper

Definition & etiology

> 5 mg/dL adults (> 6 children).
Deficient renal excretion — renal failure (usually GFR < 25 mL/min; most common cause), hypoparathyroidism/pseudohypoparathyroidism.
Redistribution — tumor lysis, rhabdomyolysis/crush, acute respiratory acidosis.
Increased absorption — phosphate salts/cathartics, vitamin D therapy.

Hyper

Findings

None, or related to secondary hypocalcemia.
Ectopic calcification when P × Ca > 55: cornea/acute conjunctivitis; skin (grainy feel, pruritus); vascular calcification on plain film/CT; cardiac (valvular/arterial calcification, conduction defects, increased cardiac mortality).

Hyper

Management

Peritoneal or hemodialysis in acute/chronic renal failure; dietary restriction 800–1,000 mg/day.
Phosphate binders with meals: calcium acetate 667–1,334 mg TID; sevelamer 800–3,200 mg TID; lanthanum 500–1,000 mg TID.

Serum phosphorus scale

Drawn to scale across 1–6.5 mg/dL. Markers show severe hypophosphatemia (< 1.5) and hyperphosphatemia (> 5 adults, > 6 children).

Hypophosphatemia (< 2.5) Normal (2.5–4.5) Hyperphosphatemia (> 5)

Oral: sodium or potassium neutral phosphorus (Neutra-Phos, K-Phos Neutral) 1–2 g PO daily in divided doses.
IV (sodium or potassium phosphate):
- Serum P 2.3–2.7 mg/dL — 15 mMol in 250 mL D5W IV over 4–5 hr.
- Serum P 1.5–2.2 mg/dL — 30 mMol in 250 mL D5W over 8–10 hr.
- Serum P < 1.5 mg/dL — 45 mMol in 250 mL D5W over 12–15 hr.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Acid–Base Disorders

Four primary disorders, two axes. The arterial pH points to the primary disorder (acid pH = primary acidosis). Normal: pH 7.35–7.45, pCO₂ 35–45 mmHg, HCO₃⁻ 22–26 mEq/L, anion gap 8–10 mEq/L.

7.35–7.45

Normal arterial pH

Acidemia < 7.35; alkalemia > 7.45.

35–45 mmHg

Normal pCO₂

Respiratory component of the ABG.

22–26 mEq/L

Normal bicarbonate

Metabolic component.

8–10 mEq/L

Normal anion gap

AG = Na − (Cl + HCO₃).

Compensation — how fast it happens

Respiratory disorders are compensated metabolically via renal HCO₃⁻ regulation — 3–5 days to begin, up to a week for full compensation. Metabolic disorders are compensated by pulmonary pCO₂ regulation — minutes to begin, hours for full compensation. A mixed disorder is more than one primary disorder at once.

Type

MetabolicAcidosis

Metabolic acidosis

pH < 7.35; HCO₃⁻ < 22 mEq/L; respiratory alkalosis (↓ pCO₂) compensates.

Normal AG (< 12) — HCO₃⁻ loss or H⁺ + Cl⁻ gain: diarrhea, pancreatic drainage, RTA I/II/IV, stage 3 CKD (GFR > 30 but < 60), HCl/ammonium chloride.
High AG (> 15) — nonchloride acid anion: lactic acidosis, DKA, alcoholic ketoacidosis, CKD stage 4–5/acute kidney injury, salicylate, methanol, ethylene glycol.
Kussmaul breathing; hypotension; sweet breath in ketoacidosis.

MetabolicAlkalosis

Metabolic alkalosis

pH > 7.45; HCO₃⁻ > 28 mEq/L; respiratory acidosis (↑ pCO₂) compensates.

GI H loss — vomiting, gastric aspiration. Renal H loss — secondary hyperaldosteronism (diuretics, vomiting, K depletion ± Mg deficiency), primary aldosteronism, Cushing, renal artery stenosis.
Bicarbonate gains (only in renal insufficiency) — NaHCO₃, citrate (transfusion), acetate (TPN/dialysis).
Headache, lethargy → coma; tetany/seizure (↓ iCa); arrhythmias; postural hypotension.

RespiratoryAcidosis

Respiratory acidosis

pH < 7.35; pCO₂ > 45 mmHg; metabolic alkalosis (↑ HCO₃⁻) compensates.

Acute hypoventilation — opiates (major cause), CNS injury, neuromuscular disease (myasthenia, Guillain-Barré, polio), airway obstruction (status asthmaticus, bronchitis, emphysema), chest disorders (flail chest, pneumothorax, kyphoscoliosis).
Chronic — COPD, obesity hypoventilation, diaphragmatic weakness (ALS).
Drowsiness → coma, headache, anxiety, confusion, hallucinations, dyspnea.

RespiratoryAlkalosis

Respiratory alkalosis

pH > 7.45; pCO₂ < 35 mmHg; metabolic acidosis (↓ HCO₃⁻) compensates.

Acute hyperventilation — anxiety/pain, fever, head trauma, salicylate toxicity; pulmonary (edema/CHF, pneumonia, PE, asthma, sepsis).
Chronic — high altitude, pregnancy, hepatic insufficiency/cirrhosis.
Light-headedness, confusion, perioral/digital paresthesias, chest tightness, muscle cramps; carpopedal spasm.

The four disorders on one map

Rows are pH direction, columns are the primary organ. Hover a quadrant for its full ABG pattern.

Acidosis (pH < 7.35) Alkalosis (pH > 7.45)

NaHCO₃ therapy is controversial; rarely indicated when pH is 7.10 or greater. DKA: not required/recommended. Lactic acidosis: NaHCO₃ may increase lactate.
NaHCO₃ injection — very hypertonic unless diluted; limit to 50–100 mEq (1–2 ampules).
Isotonic infusion: HCO₃ required = 0.5 × weight (kg) × (20 − serum HCO₃); add 3 ampules (150 mEq) to 1 L D5W over 6–12 hr.
Shohl solution (Bicitra) — 1 mL (1 mEq)/kg daily; start 30 mL PO BID. NaHCO₃ tablets — 650 mg ≈ 8 mEq; start 650 mg PO TID.
Treat the cause — stop GI HCO₃ losses; methanol/ethylene glycol/salicylate/alcoholic ketosis (see poisoning chapter); DKA (0.9% NS + insulin); lactic acidosis (maintain perfusion; 0.9% NS more effective than NaHCO₃).
Osmolar gap = SOsm(measured) − SOsm(calculated). The reading states that a value < 10 in high-AG acidosis suggests exogenous acid (toxic alcohol) intoxication — but that threshold appears reversed in the source. See the flag below. For elevated AG, measure serum lactate or methanol/ethylene glycol levels.

Volume-depleted states: discontinue diuretics/volume-depleting agents; infuse 0.9% NS IV at 100–150 mL/hr.
KCl replacement for all potassium-depleted or potassium-losing states.
Acetazolamide (Diamox) 250–500 mg IV or PO BID — especially useful in volume-expanded states, or after mechanical ventilation in chronic hypercapnic pulmonary disease.
Excess-aldosterone states may require spironolactone or eplerenone.
Hemodialysis against a low-HCO₃⁻ bath.

Acute

Assist ventilation — CPAP mask or intubation with mechanical ventilation.
Reverse CNS depression — naloxone (Narcan) 0.4–2 mg IV for opioid overdose; flumazenil (Romazicon) 0.2 mg (2 mL) IV over 30 s for benzodiazepine overdose (watch for withdrawal seizures).
Reverse obstruction — albuterol 180 mcg inhaled aerosol every 6 hr; ipratropium (Atrovent) 36 mcg nebulized every 6 hr; mechanical extraction of secretions/foreign bodies.

Chronic

Avoid respiratory depression (sedatives, excess O₂); nocturnal CPAP; vigorous treatment of the underlying disorder.

Treat the underlying cause.
Anxiety/hyperventilation — reassurance; rebreathing into a paper bag or a disconnected oxygen mask.
Chronic respiratory alkalosis — generally none required.

Source error — the osmolar gap threshold is reversed

The reading states that an osmolar gap below 10 in a high-anion-gap acidosis suggests exogenous acid (toxic alcohol) intoxication. Standard teaching is the opposite: a gap greater than 10 is what raises suspicion of methanol or ethylene glycol.

Treat this as a typo in your assigned reading, and know both. It appears alongside a garbled formula in the same line (Glucose/1 = BUN/2.8, which should be Glucose/18 + BUN/2.8). If an exam question turns on the osmolar gap, the > 10 rule is the clinically correct one.

Chapter 78 · Fluid, Electrolyte & Acid–Base Imbalances

Intravenous Fluid Management

Total body water (TBW) is 50–60% of body weight (lower in women and the obese, higher in men and the lean). Its solute composition differs by compartment, but total solute concentration — osmolality — is equal (isotonic) across compartments.

50–60%

TBW as share of body weight

Lower in women/obese; higher in men/lean.

60% / 40%

ICF / ECF of TBW

ICF ≈ 60% of TBW; ECF ≈ 40% of TBW.

80% / 20%

Interstitial / intravascular of ECF

Interstitial is protein-poor; intravascular is protein-enriched.

Body fluid compartments, partitioned

Top bar: total body water. Bottom bar: the extracellular fluid split. Hover a segment.

Intracellular Extracellular Interstitial Intravascular

Purposes of IV fluid administration

Volume

ECF repletion & maintenance

Depletion: hypotension, decreased pulses/delayed capillary refill, tachycardia, postural BP fall/HR rise, decreased IJV filling, IVC collapse (sonography); decreased CVP/PCWP.
Excess: hypertension, IJV distention, edema, increased CVP/PCWP.

Osmolality

Body-water adjustment

Water deficit → hypernatremia / serum hyperosmolality.
Water excess → hyponatremia / serum hypoosmolality.

Delivery

Therapeutic agents

Electrolytes (K, Mg, Ca, bicarbonate, phosphate); nutrition (glucose/lipids, amino acids, water-soluble vitamins, trace elements Zn/Mn); drugs.

Composition of common IV fluids

Tonicity / class

Isotonic

Normal saline (0.9% NaCl)

Approximately isotonic to plasma; distributes to the ECF.
≈ one-third of infused volume remains in the vascular space at full distribution.
Volume resuscitation (shock, sepsis, hemorrhage, burn), fluid challenges, drug delivery for saline-stable drugs.

IsotonicDextrose

D5W (5% dextrose in water)

Approximately isotonic to plasma; distributes to intracellular and extracellular spaces.
Equivalent to giving pure water once the dextrose has been metabolized; < 10% remains in the vascular space.
Repletion/maintenance of body water, treatment of severe hypernatremia, drug delivery when ECF expansion is undesirable.

Isotonic

Lactated Ringer's (LR)

Contains NaCl, KCl, CaCl₂, Na lactate; approximately isotonic to plasma though slightly hypotonic.
Distributes to the ECF (similar to NS); the lactate is metabolized in the liver to generate bicarbonate buffer.
Repletion/resuscitation with blood loss; trauma/surgical maintenance; gaining favor for septic or burn patients. Monitor for iatrogenic metabolic alkalosis (prolonged use) or metabolic acidosis in liver disease.

Isotonic

Plasma-Lyte

Buffered saline solution similar to LR: sodium, potassium, and magnesium cations with chloride, gluconate, and acetate anions; acetate is metabolized to generate buffer.

Hypotonic

½ NS (0.45% NaCl)

Hypotonic to plasma. Half the volume (pure-water equivalent) distributes to total body water; half (NS equivalent) to the ECF; about one-sixth stays in the vascular space.
Maintenance fluid (most common use): saline component replaces NaCl losses, free-water component replaces insensible losses.
Replacement: restores ECF volume deficit plus the water deficit in hyperosmolar (hypernatremic) states.

Dextrose

Dextrose in saline (D5NS, D5½NS, D5¼NS)

Equivalent to the corresponding saline solution, plus supplies 200 kcal energy per liter.

Hypertonic

Hypertonic saline / bicarbonate

Hypertonic NaCl (3% saline) — used in hyponatremia correction; hypertonic NaHCO₃ — for CPR or lactic acidosis (see sodium and acid–base sections).

Colloid

Colloid solutions

Large-molecular-weight particles retained in the vascular space for selective vascular expansion — little advantage over crystalloids in most patients.
25% albumin — bolus in hypoalbuminemic patients after high-volume paracentesis (> 4 L), hypotension in hemodialysis, or hypotensive hypoalbuminemia requiring diuresis.
5% albumin — comparable to NS; use in plasmapheresis/apheresis. Fresh frozen plasma — only for replacing depleted clotting factors, not fluid therapy.

Electrolyte solutions are for specific replacement therapy: sodium bicarbonate (see Acid–Base above); KCl added to any dextrose or saline solution at a final concentration of 10–60 mEq/L.
25% human albumin — expensive; best given in bolus in hypoalbuminemic patients who have had high-volume paracentesis (> 4 L), hypotension in hemodialysis, or hypotensive hypoalbuminemic patients requiring diuresis.
5% albumin in saline — expensive; comparable to NS alone; not of value in raising oncotic pressure; may replace fluid in plasmapheresis/apheresis.
Fresh frozen plasma — expensive; should not be used for fluid therapy, only when depleted clotting factors must be replaced.

For Study

What to lock in

This week is mostly numbers. Anchor each one to the value that changes management, and to the organ that fails first when it is wrong.

Normal ranges

The panel in one glance

Sodium 135–145 mEq/L
Potassium 3.5–5.5 mEq/L
Calcium 8.6–10.2 mg/dL
Magnesium 1.5–2.5 mg/dL
Phosphorus 2.5–4.5 mg/dL

Correct it

Albumin-corrected calcium

Serum calcium travels bound to albumin. Correct the measured calcium upward by 0.8 mg/dL for each 1 g/dL decrease in serum albumin — otherwise you will under-call hypercalcemia in a hypoalbuminemic patient.

Stage it

KDIGO AKI, stage 1

Creatinine 1.5–1.9× baseline or a rise of ≥ 0.3 mg/dL, or urine output < 0.5 mL/kg/hr for 6–12 hours. Stage 3 includes starting renal replacement therapy at all.

Define it

CKD by GFR

GFR ≤ 60 mL/min for longer than 3 months, with or without kidney damage — plus one or more of albuminuria, urine sediment abnormalities, tubular electrolyte abnormalities, or abnormal histology.

Compare

How fast compensation happens

Respiratory problem → the kidney compensates, taking 3–5 days to begin and up to a week for full correction. Metabolic problem → the lung compensates in minutes, complete in hours. A metabolic problem with a normal pCO₂ is therefore not compensated — it is too early.

Reverse it

Why prerenal AKI matters

Prerenal injury is 60% of AKI: diminished perfusion with no nephron damage. It is the kind you can still fix by restoring volume and perfusion — which is why the history and volume assessment come before anything else.

Find it

Persistent hyperphosphatemia

Almost always deficient renal phosphate excretion, and usually at a GFR below 25 mL/min. If phosphorus is stuck high, think kidney before diet.

Look for it

Magnesium hides with potassium

Loop diuretics and thiazides waste magnesium. Refractory hypokalemia is often hypomagnesemia in disguise — you cannot fix the potassium until you replace the magnesium.

Prevent it

CAUTI

69% of catheter-associated UTIs are avoidable. The best strategy is to avoid catheterization when possible and remove the catheter as soon as it is no longer medically necessary.

Sequence it

Every electrolyte gets an ECG

Potassium, calcium, and magnesium all change the ECG, and the rhythm is what kills. Treat the ECG and the patient before you chase the number — especially in hyperkalemia.

Dose it

Renal dosing is not optional

Decreased renal function changes both what drug you choose and how much you give. Check the renal dosing column before the first dose, not after the level comes back.

Filter it

UTI: uncomplicated vs complicated

Uncomplicated = normal, working urinary tract. Complicated = a defect in the tract or a host problem — diabetes, immunosuppression, multidrug-resistant organisms. The distinction drives duration and drug choice.

Self-Check

Rapid-fire review

14 questions covering all three chapters. Answer out loud first, then reveal.

State the normal serum sodium range, and the values that define hyponatremia and hypernatremia.

Normal is 135–145 mEq/L. Hyponatremia is < 135 mEq/L; hypernatremia is > 145 mEq/L. Hypernatremia always indicates hyperosmolality — a deficit of total body water.

State the normal serum potassium range, and the thresholds for hypokalemia and hyperkalemia.

Normal is 3.5–5.5 mEq/L. Hypokalemia is < 3.5 mEq/L; hyperkalemia is > 5.5 mEq/L.

A patient's measured serum calcium is 9.0 mg/dL and their albumin is 2 g/dL. What is the corrected calcium, and why does it matter?

Correct upward by 0.8 mg/dL for each 1 g/dL decrease in albumin. Two grams below normal adds roughly 1.6 mg/dL, giving about 10.6 mg/dL — which is hypercalcemia, not a normal value. Without the correction you would miss it.

Give the normal ranges for magnesium and phosphorus. What level of phosphorus is considered severe hypophosphatemia?

Magnesium normal is 1.5–2.5 mg/dL (hypomagnesemia below 1.5, hypermagnesemia above 2.5). Phosphorus normal is 2.5–4.5 mg/dL; hypophosphatemia is below 2.5, and it is severe below 1.5 mg/dL.

List the KDIGO stage 1 criteria for acute kidney injury.

Serum creatinine 1.5–1.9 times baseline, or an increase of ≥ 0.3 mg/dL; or urine output < 0.5 mL/kg/hr for 6–12 hours. Stage 3 is 3.0 times baseline, creatinine ≥ 4.0 mg/dL, or the initiation of renal replacement therapy.

Name the three major methods used to classify acute kidney injury.

1. KDIGO — the current preferred three-stage system based on creatinine, urine output, and GFR. 2. RIFLE — risk, injury, failure, loss, ESRD; no longer preferred by most experts but still used clinically. 3. Prerenal, intrarenal, and postrenal etiology.

Which AKI category is the most common, what percentage of cases does it account for, and what is its defining feature?

Prerenal — about 60% of cases. It is diminished renal perfusion from decreased blood supply to the kidneys, and critically, no nephron damage is present, which makes it the most reversible.

State the GFR criterion in the definition of chronic kidney disease, and list the additional findings that also satisfy it.

GFR ≤ 60 mL/min for longer than 3 months, with or without kidney damage. CKD is also defined by kidney dysfunction with more than one of: albuminuria, urine sediment abnormalities, electrolyte abnormalities related to tubular disorders, or abnormal histology.

A patient has a primary metabolic acidosis. How quickly does the body compensate, and by what mechanism?

By pulmonary regulation of pCO₂ — it begins within minutes and reaches full compensation in hours. This is why a metabolic acidosis with a normal pCO₂ is uncompensated: it simply has not had time yet.

A patient has a primary respiratory acidosis. How long does compensation take?

The kidney compensates by retaining bicarbonate, which takes 3–5 days to begin and up to a week for full compensation. A chronic respiratory acidosis therefore shows an elevated HCO₃⁻; an acute one does not.

What percentage of catheter-associated urinary tract infections is considered avoidable, and what is the best prevention strategy?

69%. The best strategy is to avoid catheterization when possible and remove the catheter as soon as it is no longer medically necessary. CAUTIs are caused by a biofilm along the catheter.

Which diuretics most commonly cause hypomagnesemia, and why does it matter when you are also treating hypokalemia?

Loop diuretics and thiazides cause renal magnesium loss. It matters because hypomagnesemia causes refractory hypokalemia — you cannot correct the potassium until the magnesium is replaced.

A patient has persistently elevated serum phosphorus. What is the most common cause, and at roughly what GFR does it appear?

Deficient renal phosphate excretion from acute or chronic renal failure — usually once the GFR falls below 25 mL/min. It is the most common cause of persistent hyperphosphatemia.

Distinguish uncomplicated from complicated urinary tract infection, and say why the distinction matters.

Uncomplicated occurs in a normal, working urinary tract. Complicated occurs with a defect in the urinary tract, or in patients with other health problems such as diabetes, immunosuppression, or multidrug-resistant organisms. The distinction drives drug choice and duration of therapy.

References

Sources

Every statement above comes from the assigned Week 6 reading.

Chapters

Talley, M. H., & Langley, K. J. (2021). Urinary tract infections. In Practice considerations for adult-gerontology acute care nurse practitioners (3rd ed., Chapter 42). Los Angeles, CA: Barkley & Associates.

Branham, S. W., & Hilliard, T. (2021). Acute kidney injury and chronic kidney disease. In Practice considerations for adult-gerontology acute care nurse practitioners (3rd ed., Chapter 43). Los Angeles, CA: Barkley & Associates.

Culpepper, R. M. (2021). Fluid, electrolyte, and acid–base imbalances. In Practice considerations for adult-gerontology acute care nurse practitioners (3rd ed., Chapter 78). Los Angeles, CA: Barkley & Associates.

Selected sources cited in the reading

Barasch, J., Zager, R., & Bonventre, J. V. (2017). Acute kidney injury: A problem of definition. The Lancet, 389(10071), 779–781.

Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L., Palevsky, P., & The ADQI Workgroup (2004). Acute renal failure — definition, outcome measures, animal models, fluid therapy and information technology needs: The Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical Care, 8, R204–R212.

Brown, J. R., Rezaee, M. E., Marshall, E. J., & Matheny, M. E. (2016). Hospital mortality in the United States following acute kidney injury. BioMed Research International, 2016, 1–6.

Delos Santos, R., Rossi, A., Coyne, D., & Maw, T. T. (2019). Management of post-transplant hyperparathyroidism and bone disease. Drugs, 79(5), 501–513.

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