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Rhabdomyolysis - Form Pathogenesis to Bedside - Dr. Gawad
1. Rhabdomyolysis
Form Pathogenesis to Bedside
Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC)
Alexandria - EGY
drgawad@gmail.com
AKI Workshop – Ras El Bar – Feb 2015
2. To download the lecture with full
animation please contact me on
drgawad@gmail.com
3. Bywaters EG, Beall D. Br Med J. 1941;1:427-432.
During bombing of London in World War II
19. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
20. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Na-K ATPase
Pump
Ca ATPase
Pump
Ca
ATPase
Pump
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
21. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Na-K ATPase
Pump
Ca ATPase
Pump
Ca
ATPase
Pump
Depletion of ATP
Disturbance of
ATPase function
↑ Intracellular &
Mitochondrial Ca
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
22. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Ca
ATPase
Pump
Depletion of ATP
Disturbance of
ATPase function
↑ Intracellular &
Mitochondrial Ca
↑ Intracellular Ca
→ increased skeletal muscle
cell contractility and the
production of ROS → skeletal
muscle cell death
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
23. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Ca
ATPase
Pump
Depletion of ATP
Disturbance of
ATPase function
↑ Intracellular &
Mitochondrial Ca
↑ Intracellular Ca
→ increased skeletal muscle
cell contractility and the
production of ROS → skeletal
muscle cell death
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
24. Non Traumatic - Rhabdomyolysis
MyocyteCellSerum
Sarcoplasmic
Reticulum (Ca
Store)
Ca
ATPase
Pump
Depletion of ATP
Disturbance of
ATPase function
↑ Intracellular &
Mitochondrial Ca
↑ Intracellular Ca
→ increased skeletal muscle
cell contractility and the
production of ROS → skeletal
muscle cell death
Intracellular Contents
Na
Ca
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
27. ATN
When to Suspect?
Clinical Presentation & Lab Ix
• The reported frequency of AKI ranges from 15 to over
50 percent
• CK < 20,000 U/l → lower risk of AKI
• CK levels 5000 U/l + coexisting conditions (sepsis,
intravascular volume contraction, acidosis) → AKI risk
increases.
Melli G. Medicine (Baltimore). 2005 Nov;84(6):377-85.
Bosch X. N Engl J Med. 2009 Jul 2;361(1):62-72.
Bosch X, Poch E, Grau JM. N Engl J Med. 2009;361:62-72.
29. ATN
When to Suspect?
Clinical Presentation & Lab Ix
Myoglobin excreted in urine
Dark, reddish-brown urine
(+ve dipstick)
-ve microscopic evaluation of
the urine for RBCs
(less than five per high-powered field) - Sanders PW, Agarwal A. In: Nabel EG, ed. ACP Medicine, A Textbook
of Medicine. Hamilton, Canada: Decker Intellectual Properties; 2010.
- Huerta-Alardín AL. Crit Care. 2005 Apr;9(2):158-69. Epub 2004 Oct 20
- Giannoglou GD. Eur J Intern Med. 2007 Mar;18(2):90-100.
30. ATN
When to Suspect?
Clinical Presentation & Lab Ix
Myoglobin excreted in urine
Dark, reddish-brown urine
(+ve dipstick)
-ve microscopic evaluation of
the urine for RBCs
(less than five per high-powered field)
Routine urine testing
for myoglobin by urine
dipstick evaluation
may be negative in up
to 50% of patients
with rhabdomyolysis
• Myoglobin appears in the urine
when the plasma concentration
exceeds 1.5 mg/dL
• Myoglobin has a short half-life of
only 2-3 hours
• A suggested role for extrarenal
metabolism and clearance of
myoglobin
Giannoglou GD. Eur J Intern Med. 2007 Mar;18(2):90-100.
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
Wakabayashi Y. Intensive Care Med. 1994;20(2):109-12.
32. ATN
When to Suspect?
Clinical Presentation & Lab Ix
Giannoglou GD. Eur J Intern Med. 2007 Mar;18(2):90-100.
Gabow PA. Medicine (Baltimore). 1982 May;61(3):141-52.
However, more than half of patients may
not report muscular symptoms
Muscle pain, Weakness
35. ATN
When to Suspect?
Clinical Presentation & Lab Ix
Serum Level:
1500 to over 100,000 IU/L
Type:
Mainly
CK-MM,
Small
amount
CK-MB 2 -12
hours
after
injury
24 -72
hours
after
injury
3-5 days
after
injury
cessation
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
36. ATN
When to Suspect?
Clinical Presentation & Lab Ix
Serum Level:
1500 to over 100,000 IU/L
Type:
Mainly
CK-MM,
Small
amount
CK-MB 2 -12
hours
after
injury
24 -72
hours
after
injury
3-5 days
after
injury
cessation
CK serum half-life
= 1.5 days
declines 40 to 50 % of
the previous day’s value
If CK does not decline
as expected
= continued muscle
injury or the
development of a
compartment
syndrome
Khan FY. Neth J Med. 2009 Oct;67(9):272-83
37. MyocyteCell
CK, LDH
Purines
Electrolytes (esp. K + and PO4)
Aminotransferase enzymes
Lactate
Myoglobin
Serum When to Suspect?
Clinical Presentation & Lab Ix
Thromboplastin +
other prothrombotic
substances
Chatzizisis YS. Eur J Intern Med. 2008 Dec;19(8):568-74
38. MyocyteCell
CK, LDH
Purines
Electrolytes (esp. K + and PO4)
Aminotransferase enzymes
Lactate
Myoglobin
Serum When to Suspect?
Clinical Presentation & Lab Ix
Thromboplastin +
other prothrombotic
substances
DIC
(infrequent complication)
Chatzizisis YS. Eur J Intern Med. 2008 Dec;19(8):568-74
41. Volume Replacement (Hydration)
• What? Isotonic saline
• Target? UOP should be maintained around
200-300 ml/h
• Continued until
–plasma CK levels decrease to <5000 unit/L
–urine is dipstick negative for hematuria
1
Hatamizadeh P. Am J Kidney Dis. 2006 Mar;47(3):428-38.
Sever MS, Vanholder R. Clin J Am Soc Nephrol.2013;8:328-335.
42. Volume Replacement (Hydration)1
Paletta CE. Ann Plast Surg. 1993 Mar;30(3):272-3.
Carefully assess:
Volume status, UOP
(Take care of HYPERVOLEMIA)
Compartment syndrome may develop after
fluid resuscitation, with worsening edema of
the limb and muscle
43. Bicarbonate Infusion2
To Whom?
CK > 5000 / Sever injury, providing the following conditions are met:
●Severe hypocalcemia is not present
●Arterial pH is <7.5 ●Serum HCO3 < 30 mEq/L
How?
- Infuse 150 mL of 8.4 % NaHCO3
mixed with 1 L of 5 % dextrose
(alternating with isotonic saline)
- The initial rate of infusion is
200 mL/hour
- the rate is adjusted to achieve
a urine pH of >6.5.
When to stop?
1- symptomatic hypocalcemia
2-arterial pH > 7.5
3-serum bicarbonate >
30 mEq/L.
4-urine pH does not rise
above 6.5 after 3-4 hrs
Monitor
art pH &
Ca / 2hrs
Melli G. Medicine (Baltimore). 2005 Nov;84(6):377-85.
44. Mannitol Infusion3
To Whom?
Urinary flow is adequate (defined as >20 mL/hour)
Patients with extremely high serum CK levels (greater than
30,000 unit/L) Brown CV. J Trauma. 2004 Jun;56(6):1191-6.
How?
given at a rate of 5 g/h
added to each liter of
infusate and not exceeding
1 to 2 g/kg/day.
When to stop?
1- osmolal gap rises above
55 mosmol/kg
2- diuresis of 200 to
300 mL/hour cannot be
achieved
(increased risk of
hyperosmolality, volume
overload, and hyperkalemia )
Sever MS, Vanholder R, Lameire N. N Engl J Med. 2006;354:1052-1063.
46. Hypocalcemia4
Give Ca supplement ONLY IF:
1- Symptomatic hypocalcemia
2- Management of hyperkalemia
Why?
During the recovery phase:
Release of calcium from injured muscle → serum Ca levels
return to normal and may rebound to significantly elevated
levels
Akmal M. J Clin Endocrinol Metab. 1986 Jul;63(1):137-42.
47. Treat the cause
• The specific cause is frequently evident from
the history or from the immediate
circumstances preceding the disorder.
• Consider toxicology screen for drugs, viral
screen, TSH if cause not apparent.
48. PROGNOSIS
The overall prognosis for patients with heme-
induced AKI is favorable as most survivors recover
sufficient kidney function to be dialysis
independent, and many will recover to normal or
near-normal kidney function
Woodrow G. Ren Fail. 1995 Jul;17(4):467-74.
49. • Rhabdomyolysis may be traumatic or non traumatic
• Final common pathway of pathogenesis is the leak of
intramuscular contents into circulation
• Final common pathway is sequestration of Ca & H2O
into muscles
• Hallmark of AKI is ATN
50. • Dipstick may be –ve for myglobinuria
• Muscle pain may be absent
• Re-rise of CK = Compartment syndrome or metabolic
disorder
• Corner stone of management is hydration
51. • NaHCO3 = Precautions = Weak evidence
• Mannitol = Precautions = Weak evidence
• Ca supplement = Precautions
• Prognosis is good