3. Definition
Destruction or disintegration of striated
muscle resulting in the leakage of the
intracellular muscle constituents into the
circulation and extracellular fluid
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
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
12.
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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a
b
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Primary cellular injury inrcease intracellular Ca++ secondary injury Activation
Goldman: Cecil Medicine 23rd ed
Patho-physiology
14.
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
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)
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
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 ″ .