2. Nephrology Case Presentation Douglas Stahura DO 17 September 2002

3. “Set the appropriate learning environment”

4. Learning Objectives Rhabdomyolysis – Definition – Acute renal failure – Pathophysiology – Clinical presentation – Treatment – Case studies

5. Case 1 56 y/o CF presented with Acute MI, developed pulseless right lower extremity. Normal renal function.

6. Case 2 48 y/o CM found “down” after 3 days in his kitchen. Unresponsive, hypotensive, anuric. Na 185, Glucose 2500, CPK 18,000

7. Case 3 62 y/o “gentleman” found by police in park unresponsive and smelling of alcohol. Thin, cachetic, hypotensive. Bun 22, Creatinine = 7.6, CPK=22,000

8. Case 4 19 y/o AAF presents with weakness and falls. 3 rd ED visit in 7 weeks. K=2.8, CPK=19,000, BUN=55, Creatinine=6.2

9. Case 5 18 y/o CM presents by squad from local arena where “The Who” reunion tour kicked off. “Festival seating” caused a rush at the gate. Pt has extensive bruising and crush injuries.

10. Case 6 Earthquake levels 4 story apartment building trapping 18 people. The injured present to trauma stations from 1 to 30 hours after the collapse.

11. Case 7 76 y/o AAM presents with nausea and anorexia x2 weeks. Now feels week. Dark urine. PMH: CAD, DM2, HTN BUN=110, creatinine=8.2, CPK 42,000

12. Case 8 27 y/o Air Force Captain presents on Monday with red discolored urine that started Sunday.

13. Case 9 17 y/o AAF presents from home by EMS in seizure. Further efforts require 90 minutes to gain control of her convulsions.

14. Case Studies All the above cases were complicated by acute renal failure induced by endogenous toxicity to myoglobin released by damage to muscle cells – rhabdomyolysis

15. Definition Rhabdomyolysis – Muscle necrosis – Release of intracellular constituents of muscle cells Severity – Asymptomatic enzyme elevation – Life threatening enzyme elevation, electrolyte disturbances, acute renal failure

16. Myoglobinuric Acute Renal Failure Classic description from 1941 when Bywaters described “crush syndrome” in which victims of the London Blitz trapped and crushed in bombed buildings would, despite rescue, die of uremia soon afterwards

17. Myoglobinuric Acute Renal Failure Myoglobin – heme containing protein – Freely filtered at the glomerulus Proximal endocytic reabsorption is overwhelmed Delivery to distal tubule is increased

18. Myoglobinuric Acute Renal Failure Acute Tubular Necrosis (ATN) is provoked – Intrarenal vasoconstriction by scavenging NO – Third spacing of fluids leads to hypovolemia – Obstructing tubular casts, especially in acidic urine – Iron may be directly toxic

19. TraumaCrush, Burn, Electric shock IschemiaVascular occlusion, compression,substance abuse (EtOH, heroin) ExerciseMarathon, convulsions MetabolicHypokalemia, Hypophosphatemia InfectionHyperthermia, virus, bacterial DrugsFibrates, HMG CoA reductase inhibitors InflammatoryPolymyositis GeneticMcArdle’s, PFK-1 deficiency, carnitine palmityl transferase deficiency

20. Clinical Findings Muscle pain is variable Urinalysis – Dipstick strongly positive for blood – Few if any RBC’s on microscopic – Color may be red-brown-black CPK elevated – General correlation of CPK with ARF (>16,000)

21. Clinical Findings Creatinine – Serum levels high out of proportion to BUN Electrolytes – Potassium, Uric acid, Lactic acid, phosphorous released by necrotic myocytes – Hypocalcemia due to calcium-phosphate precipitation

22. Treatment Fluid replacement – Saline infusion @ 1.5 L/hr Forced diuresis +/- urinary alkalinization – Goal is suggested as 300 cc/hr –.45 NS + 10 gm Mannitol + 40 Meq NaHCO 3

23. Treatment Mannitol – Diuresis maintains high flow rate through tubules – Possible free radical scavenging effect Alkalinization – May provide theoretical advantage in preventing conversion of myoglobin to methemoglobin – May cause precipitation of calcium phosphate in urinary system

24. Treatment Role of acute dialysis – Does not remove myoglobin – May be needed to control the severity of hyperkalemia – CVVHDF may not be able to manage

25. Case 1 56 y/o CF presented with Acute MI, developed pulseless right lower extremity. Normal renal function. Pt has occluded aorto-bifem bypass, pulseless, cold, pale-to-blue, painful leg.

26. Case 2 48 y/o CM found “down” after 3 days in his kitchen. Unresponsive, hypotensive, anuric. Na 185, Glucose 2500, CPK 18,000 Pt lay on the floor in his kitchen >72 hours in one position. Has muscle breakdown on right side of head, shoulder, arm, hip leg.

27. Case 3 62 y/o “gentleman” found by police in park unresponsive and smelling of alcohol. Thin, cachetic, hypotensive. Bun 22, Creatinine = 7.6, CPK=22,000 Chronic alcoholics have pre-existing hypophosphatemia – Increased renal losses, damage to proximal epi – Decreased GI intake/absorption – Muscle depletion of phosphorous

28. Case 3 Superimposed second metabolic insult result in hypophosphatemic rhabdo (ATP theory) Respiratory alkalosis – prolonged intense hyperventilation as seen with EtOH withdrawal – Increase in pH activates glycolysis increasing phosphorylated compounds within the cell. Serum phosphorous falls precipitously

29. Case 4 19 y/o AAF presents with weakness and falls. 3 rd ED visit in 7 weeks. K=2.8, CPK=19,000, BUN=55, Creatinine=6.2 Hypokalemic periodic paralysis can be associated with hypophosphatemia.

30. Case 5 18 y/o CM presents by squad from local arena where “The Who” reunion tour kicked off. “Festival seating” caused a rush at the gate. Pt has extensive bruising and crush injuries. Classic crush syndrome, can be associated with compartment syndrome

31. Case 6 Earthquake levels 4 story apartment building trapping 18 people. The injured present to trauma stations from 1 to 30 hours after the collapse. Classic crush syndrome Fluids initiated in the field to replete volume and force diuresis may be of significant benefit even before a pt is freed, or crushed limb is reperfused.

32. Case 7 76 y/o AAM presents with nausea and anorexia x2 weeks. Now feels week. Dark urine. PMH: CAD, DM2, HTN BUN=110, creatinine=8.2, CPK 42,000 Pt has dysmetabolic syndrome Hyperlipidemia treated with statin and fibrate

33. Case 8 27 y/o Air Force Captain presents on Monday with red discolored urine that started Sunday. Previously healthy, no meds, no previous urinary complaints (hematuria/proteinuria) You happen to remember that WPAFB held annual Air Force marathon on Saturday.

34. Case 9 17 y/o AAF presents from home by EMS in seizure. Further efforts require 90 minutes to gain control of her convulsions. Intense electrical stimulation of muscles can cause rhabdo

35. References Comprehesive Clinical Nephrology, Johnson, Feehally, London, UK,2000 Harrison’s Principles of Internal Medicine 14th, Fauci, New York, NY 1998 The Kidney 6th, Brenner and Rector,Philadelphia, PA 2000