Rhabdomyolysis is the destruction or breakdown of skeletal muscle fibers that results in the release of intracellular contents into the bloodstream. The document discusses various causes of rhabdomyolysis including physical trauma, excessive exertion, infections, drugs, toxins, and metabolic disorders. It also describes the pathophysiology involving decreased ATP production and increased intracellular calcium levels leading to muscle cell damage. Diagnosis involves elevated creatine kinase and presence of myoglobin in urine or blood. Treatment focuses on aggressive fluid resuscitation to prevent acute kidney injury from myoglobin toxicity, along with urine alkalinization and potentially mannitol diuresis.

1. Rhabdomyolysis
Dr. Osama El-Shahat
Head of Nephrology Department
New Mansoura General Hospital (international)
ISN Educational Ambassador

2. WEEKLY SCIENTIFIC
MEETING
Nephrology Department
New Mansoura General Hospital
(international)

3. Definition
 Destruction or disintegration of striated
muscle resulting in the leakage of the
intracellular muscle constituents into the
circulation and extracellular fluid

4. Cause
s
Exertional &
Traumatic
Inherited metabolic
Miscellaneous Acquired metabolic
Hypoxia / Ischemia
Drugs

5. Etiology of
rhabdomyolysis
Physical
Causes
 Trauma & Compression
• Traffic or working accidents
• Disasters
• Torture
• Abuse
• Long term confinement to the same
position
 Occlusion or hypo perfusion of muscular
Vs
• Thrombosis
• Embolism
• Vs clamping
• Shock
 Electric current
• High voltage electric injury
• Lightening
• Cadioversion
 Straining muscular exercise
• Exercise
• Epilepsy
• Psychiatric agitation
• Delirium tremens
• Tetanus
• Amphetamine overdose
• Ecstasy
• Status asthmatics
 Temperature related
• Exercise
• High ambient temperature
• Sepsis
• Narcoleptic malignant syndrome
• Malignant hyperthermia
Critical care 2005 – 9,158-169

6. Non physical
causes
 Metabolic myopathies
• McArdle disease
• Mitochondrial respiratory chain
enzyme deficiencies
• Carnitine palmitoyl transferas
deficiency
• Myoadenlyate deaminase
deficiency
• Phosphofructokinase deficiency
•
 Drug & toxins
• Regular & illegal drugs
• Toxins
• Snake & insect venom
 Polymyositis/dermatomyositis
 Infections
• Local and metastatic infections
 Endocrinolgic cause
• Hyper/hypothyrodism
 Systemic effect
• Toxic shock syndrome
• Influenza
• HIV
• Herpes viruses
• Coxsackie virus
 Electrolyte abnormalities
• Hypokalemia
• Hypocalcaemia
• Hyponatremia & hypernatremia
• Hypophosphatemia
• Hyper osmotic conditions
Critical care 2005 – 9,158-169

7. Drugs that may
induce
rhabdomyolysis

8. Statin related
rhabdomyolysis
 Directly or indirectly impairs the production or use
of ATP by skeletal muscle
 Increases energy requirements that exceed the rate of
ATP production
 Interfere with ATP production by reducing levels of
coenzyme Q, chronic myositis syndrome
 Risk factors: high dosages, increasing age, female,
renal and hepatic insufficiency, DM and concomitant
therapy with drugs such as fibrates

9. Exertional Rhabdomyolysis
 Exercise beyond physical capabilities
 ATP demand outweighs supply resulting in
cellular membrane breakdown
 Intense exercise in normal individuals
 Grand mal seizure
 Delirium tremens
 Physical abuse
 Contact sports
 Crush injury
 Compression

10. Factors in the development of
Exertional Rhabdomyolysis
 Fitness level
 Experience with the type of exercise being
Performed
 Intensity of exercise
 Type of exercise (eccentric vs concentric)
 Ambient temperature
 Hydration level
 Fasting
 Associated illness

11. Causes of Cellular Destruction in
Rhabdomyolysis
 Direct injury to cell membrane (ex. crushing,
tearing, burning..)
 Severe electrolyte disturbance disrupting
sodium-potassium pump
 Muscle cell hypoxia leading to
depletion of ATP

13. Physical injury
Compression
Ischemia
Excessive contractions
Electric injury
Hyperthermia
Non physical injury
•Metabolic myopathies
•Drug & toxins
•Infection
•Electrolyte
•Endocrine disorder
Decrease
intracellular ATP
Sarcoplasmic
Ca++ influx
Reperfusion
injury
Compartment
syndrome
•Increase phospholipase A2
•Increase Ca++ dependent
phosphorylases
•Increase nucleases
•Increase proteases
•Increase free radicals
•Increase local BMN cells
R
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Primary cellular injury inrcease intracellular Ca++ secondary injury Activation
Goldman: Cecil Medicine 23rd ed
Patho-physiology

15. Etiology of acute renal injury
with rhabdomyolysis
Acute
kidney
injury
Direct toxicity of
myoglobin in tubular
cells
Hypovolemia and
decrease renal
perfusion
Cast formation
decreasing tubular
flow

16. Cellular Patho-
physiology
 Influx of extra cellular contents
 (sodium, water, chloride, calcium)
 Efflux from damaged muscle cells
 (potassium, phosphates, lactic acid and other
organic acids, purines,
myoglobin,thromboplatin, creatinine,
creatine kinase)

17. Influx and Efflux of Extra and Intra Cellular
Fluids During Cellular Destruction
Chemical composition
Extracellular
(mEq/L)
Intracellular
( mEq/L)
Sodium 142 10
Potassium 4 140
Calcium 2.4 0.0001
Magnesium 1.2 58
Chloride 103 4
Bicarbonate 28 10
Protein ( myoglobin,
CKetc)
5 40

18. Myocyte Injury
Hours of
ischemia
0 2 4 6
Tolerable-no
permanent
histological
changes
Irreversible
anatomic and
functional
changes
Muscle
necrosis

19. When to Suspect Rhabdo
 Occurs in up to 85% of patients with traumatic injuries.
 Those with severe injury who develop rhabdomyolysis-
induced renal failure have a 20% mortality rate
 Multiple orthopedic injuries
 Crush injury to any part of the body (eg: hand)
 Laying on limb for long period of time –patient “found
down”
 Long surgery
 Brown urine

20. AXIOM
Sudden collapse during physical exertion carried
out under warm climatic conditions should be
primarily diagnosed as
rhabdomyolysis
(unless and until proven otherwise)

21. What to Watch for if you suspect Rhabdo:
 Clinical: Ms pain, weakness, dark urine
 Hypovolemia, shock
 Electrolyte abnormalities : ↑K+, ↓ Ca++
(sequestered in injured tissues)

22. Early Signs and
Symptoms
 weakness
 fatigue
 headache
 slowed
mentation
 thirst
 muscle cramps
 nausea,
vomiting
 diarrhea

23. Causes of reddish-brown
discoloration of the urine

24. Characteristics of urine and plasma in the different
conditions that may cause red discoloration of the
urine
Characteristic Rhabdomyolysi
s
Haemolysis Hematuria
Red discoloration
plasma
Positive
benzidine dipstick
Presence of
erythrocyte by
urine microscopy
Elevated CK
concentration in
the blood

25. Approach to the patient with red
or brown urine

26. Diagnosis
 Serum CKMM
 Correlates w/severity of rhabdo
 Normally 145-260 U/L
 100,000’s not uncommon
 high t(1/2): 1.5 days
 Rises within 12 hours of the onset
 Peaks in 1–3 days, and declines
3–5 days
 5000 U/l or greater is related to
renal failure
 Serum myoglobin
t(1/2) 2-3 h
Excreted in bile
sample UA
uric acid
crystals

27. Creatine kinase(CK);CPK ( 38-174U/L for M
26-140 U/L for F )
 CPK can be divided to 3 isoenzymes:
1-MM or CK3 96-100%(Skletal muscle and
cardiac) is the isoenzyme that constitutes almost
all the circulatory enz. In the healthy person
2-BB or CK1 0%(brain,GIT,Genitourinary)
3MB or CK2 0-6%

28. Creatine kinase(CK);CPK
 CK levels rise within 12 hours of muscle
injury, peak in 24-36 hours, and decrease at a
rate of 30-40% per day.The serum half-life is
36 hours. CK levels decline 3-5 days after
resolution of muscle injury ; failure of CK
levels to decrease suggests ongoing muscle
injury or development of a compartment
syndrome. The peak CK level, especially
when it is higher than 15,000 U/L, may be
predictive of renal failure.

29. Myoglobin(5-70ng/ml)
 Plasma myoglobin measurements are not
reliable, because myoglobin has a half-
life of 1-3 hours and is cleared from
plasma in the urine within 6 hours. Urine
myoglobin measurements are therefore
preferable.

30.  UA-myoglobinuria
 dipstick will be (+) for
hemoglobin, RBC’s and
myoglobin
 Microscopy: no RBC’s, brown
casts, uric acid crystals
 Other measures: carbonic
anhydrase III, aldolase
 Serum creatinine :
disproportionate to BUN
 Uric acid
 Leucocytosis
 Hypoalbuminemia
 Haematocrite
 Urine Na +
 K +
 Ca + +
 Po4
 Gluc.in urine
 Pigment casts
(+) for blood

31. Clinical Manifestations &
Complications
 Early signs:
ɚ Hyperkalemia, ɚ Hypocalcemia,
ɚ Hyperphosphatemia, ɚ Hyperuricemia,
ɚ Acidosis
Early complications:
ɚ Cardiac arrhythmia
up to cardiac arrest & death
ɚ Hypovolemia
 Late complications:
ɚ Acute renal failure ɚ DIC
ɚ Compartment syndrome ɚ Hypercalcemia
ɚ Infection ɚ MOSF ɚ ARDS
ɚ Fascial compartment compression syndrome
American Family Physician (2002) 65:907-912

32. TREATMENT
 Fluid Resuscitation
Is the cornerstone of treatment and must
be initiated as soon as possible. No
randomized trials of fluid repletion
regimens in any age group have been
done.

33. Patients with a CK elevation in excess of 2-3
times the reference range, appropriate clinical
history, and risk factors should be suspected of
having rhabdomyolysis. For adults, administer
isotonic fluids at a rate of approximately 400
mL/h (may be up to 1000 mL/h based on type
of condition and severity) and then titrate to
maintain a urine output of at least 200 mL/h
or 3 ml per kilogram

34.  Because injured myocytes can
sequester large volumes of ECF,
crystalloid requirements may be
surprisingly large. Consider central
venous pressure measurement or Swan-
Ganz catheterization in patients with
cardiac or renal disease. Repeat the CK
assay every 6-12 hours to determine the
peak CK level.

35.  The composition of repletion fluid is
controversial and may also include
sodium bicarbonate, esp. in NS is used.

36.  To prevent renal failure, many
authorities advocate urinary alkalization,
mannitol, and loop diuretics. Check
urine pH. If it is less than 6.5, alternate
each liter of normal saline with 1 liter of
5% dextrose plus 100 mmol of
bicarbonate.

37.  Alkalinization of urine benefits:-
1-Decrease precipitationof the Tamm–Horsfall
protein–myoglobin complex
2- Inhibits reduction–oxidation (redox)cycling
of myoglobin and lipid peroxidation , thus
ameliorating tubule injury.
3- Counteract VC

38. Dirutics
 Remains controversial, but it is clear that it should
be restricted to patients in whom the fluid repletion
has been achieved.Mannitol may have several
benefits: as an osmotic diuretic, it increases urinary
flow and the flushing of nephrotoxic agents through
the renal tubules; as an osmotic agent, it creates a
gradient that extracts fluid that has accumulated in
injured muscles and thus improves hypovolemia;
finally,it is a free-radical scavenger

39.  During the time mannitol is being
administered, plasma osmolality and the
osmolal gap (i.e., the difference between
the measured and calculated serum
osmolality) should be monitored
frequently and therapy discontinued if
adequate diuresis is not achieved or if
the osmolal gap rises above 55 mOsm
per kilogram

40. Late Treatment
 Dialysis –
◦ intermitted preferred to
continuous
 Reduce use of anticoagulants
in trauma patients
◦ Peritoneal dialysis is
inadequate
◦ The removal of myoglobin
by plasma exchange has
not demonstrated any
benefit

41. Take Home Message
 Impairment of the production or use of ATP is the basic
cause.
 Most useful laboratory findings are elevated CK(>
5000U/L related to ARF), initial detection of myglobolin.
 Management: Aggressive hydration, diuresis, urine
alkalinzation, free-radical scavengers, dialysis.
 Do not treat hypocalcemia unless symptom developed.
 Conditioning by regular exercise to prevent ″white-collar
rhabdomyolysis ″ .

42. ‫الرحيم‬‫الرحمن‬‫هللا‬ ‫بسم‬

43. *‹‫حى‬ ‫شئ‬ ‫كل‬ ‫الماء‬ ‫من‬ ‫وجعلنا‬›*
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