1) A 32-year-old man presented with weakness, myalgias, and muscle tenderness. Laboratory tests found elevated creatine kinase consistent with rhabdomyolysis. He admitted to using crack cocaine for 2 days.
2) Rhabdomyolysis occurs when skeletal muscle is damaged, allowing intracellular contents to leak into circulation. This can cause kidney damage, electrolyte abnormalities, and other complications.
3) The most common causes of rhabdomyolysis are overexertion, compression injuries, and illicit drug use like cocaine. Prompt diagnosis and aggressive treatment of complications can decrease morbidity and mortality.
Management of interstitial fibrosis and tubular atrophy in renal transplantation
[1] Interstitial fibrosis and tubular atrophy (IFTA) is a major cause of chronic allograft nephropathy and long-term renal allograft loss. [2] IFTA can be caused by both immunological factors like acute rejection and chronic antibody-mediated rejection as well as non-immunological factors like CNI toxicity, viral infections, ischemia-reperfusion injury and hypertension. [3] Clinical management of IFTA focuses on assessing and addressing the underlying causes, tight blood pressure and glucose control, lipid management, and modulating immunosuppression when appropriate.
This document discusses cell adaptation, injury, and death. It describes how cells can adapt to stress through hypertrophy, hyperplasia, metaplasia, or atrophy. Prolonged or excessive stress can lead to cell injury, which is initially reversible but becomes irreversible over time due to membrane damage. The two main forms of cell death are necrosis, which is unprogrammed and inflammatory, and apoptosis, which is genetically programmed and does not induce inflammation. Necrosis can be coagulative, liquefactive, caseous, gangrenous, or fibrinoid depending on its characteristics.
This document discusses chronic allograft nephropathy (CAN), a leading cause of late kidney transplant failure. CAN is characterized by slow progressive graft dysfunction, proteinuria, hypertension, and histological findings of interstitial fibrosis and tubular atrophy. Risk factors include acute rejection episodes, donor age, HLA mismatch, and calcineurin inhibitor toxicity. The pathophysiology involves both immune and non-immune mechanisms of cumulative injury over time. Diagnosis relies on biopsy findings and treatment focuses on modifying risk factors.
This patient is a 25-year-old male who received a living related kidney transplant in 2008. In September 2011, he developed worsening renal function that stabilized with treatment. However, he lost follow up until presenting in September 2013 with diarrhea, nausea, and renal dysfunction. A kidney biopsy showed chronic humoral rejection and transplant glomerulopathy. He was treated with plasma exchanges and has since stabilized with a creatinine of 3.2 mg%.
1. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an overproduction of red blood cells without an identifiable stimulus. It commonly presents with erythrocytosis, splenomegaly, thrombosis, and pruritus.
2. The main cause of PV is a mutation in the JAK2 gene, but some patients have mutations in exon 12. Diagnosis requires tests to distinguish absolute from relative erythrocytosis. Treatment focuses on phlebotomy and medications to control symptoms and prevent complications.
3. Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm involving clonal proliferation and
Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the proliferation of granulocytic cells due to a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome. This translocation results in an abnormal tyrosine kinase that dysregulates cell proliferation, survival, and differentiation. CML progresses through chronic, accelerated, and blast crisis phases defined by increasing blast cell counts in the blood and bone marrow. Diagnosis is confirmed by blood smear, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome or BCR-ABL1 fusion gene. Prognosis depends on response to tyrosine kinase inhibitor treatment, which aims to induce a complete
This document discusses chronic leukemias and myeloproliferative disorders including chronic myeloid leukemia (CML) and myelofibrosis. CML is distinguished from other myeloproliferative disorders by the presence of the Philadelphia chromosome and BCR-ABL fusion gene. CML is characterized by leukocytosis, thrombocytosis, and anemia. It progresses through chronic, accelerated, and blast phases defined by increasing blast counts and symptoms. The massive spleen seen in CML is indicative of the underlying myeloproliferative process.
The document discusses several pre-leukemic disorders and congenital defects that can progress to acute myeloid leukemia (AML) if not treated. These include myelodysplastic syndrome (MDS), marrow failure syndromes like aplastic anemia, and genetic conditions like Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome. MDS is characterized by dysplastic and ineffective hematopoiesis leading to cytopenias. Fanconi anemia results from a DNA repair defect and patients have a high risk of developing AML. Dyskeratosis congenita causes bone marrow failure below age 20 due to telomere dysfunction. Treatment options discussed include hematopoietic
Management of interstitial fibrosis and tubular atrophy in renal transplantation
[1] Interstitial fibrosis and tubular atrophy (IFTA) is a major cause of chronic allograft nephropathy and long-term renal allograft loss. [2] IFTA can be caused by both immunological factors like acute rejection and chronic antibody-mediated rejection as well as non-immunological factors like CNI toxicity, viral infections, ischemia-reperfusion injury and hypertension. [3] Clinical management of IFTA focuses on assessing and addressing the underlying causes, tight blood pressure and glucose control, lipid management, and modulating immunosuppression when appropriate.
This document discusses cell adaptation, injury, and death. It describes how cells can adapt to stress through hypertrophy, hyperplasia, metaplasia, or atrophy. Prolonged or excessive stress can lead to cell injury, which is initially reversible but becomes irreversible over time due to membrane damage. The two main forms of cell death are necrosis, which is unprogrammed and inflammatory, and apoptosis, which is genetically programmed and does not induce inflammation. Necrosis can be coagulative, liquefactive, caseous, gangrenous, or fibrinoid depending on its characteristics.
This document discusses chronic allograft nephropathy (CAN), a leading cause of late kidney transplant failure. CAN is characterized by slow progressive graft dysfunction, proteinuria, hypertension, and histological findings of interstitial fibrosis and tubular atrophy. Risk factors include acute rejection episodes, donor age, HLA mismatch, and calcineurin inhibitor toxicity. The pathophysiology involves both immune and non-immune mechanisms of cumulative injury over time. Diagnosis relies on biopsy findings and treatment focuses on modifying risk factors.
This patient is a 25-year-old male who received a living related kidney transplant in 2008. In September 2011, he developed worsening renal function that stabilized with treatment. However, he lost follow up until presenting in September 2013 with diarrhea, nausea, and renal dysfunction. A kidney biopsy showed chronic humoral rejection and transplant glomerulopathy. He was treated with plasma exchanges and has since stabilized with a creatinine of 3.2 mg%.
1. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an overproduction of red blood cells without an identifiable stimulus. It commonly presents with erythrocytosis, splenomegaly, thrombosis, and pruritus.
2. The main cause of PV is a mutation in the JAK2 gene, but some patients have mutations in exon 12. Diagnosis requires tests to distinguish absolute from relative erythrocytosis. Treatment focuses on phlebotomy and medications to control symptoms and prevent complications.
3. Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm involving clonal proliferation and
Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the proliferation of granulocytic cells due to a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome. This translocation results in an abnormal tyrosine kinase that dysregulates cell proliferation, survival, and differentiation. CML progresses through chronic, accelerated, and blast crisis phases defined by increasing blast cell counts in the blood and bone marrow. Diagnosis is confirmed by blood smear, bone marrow biopsy, and genetic testing to detect the Philadelphia chromosome or BCR-ABL1 fusion gene. Prognosis depends on response to tyrosine kinase inhibitor treatment, which aims to induce a complete
This document discusses chronic leukemias and myeloproliferative disorders including chronic myeloid leukemia (CML) and myelofibrosis. CML is distinguished from other myeloproliferative disorders by the presence of the Philadelphia chromosome and BCR-ABL fusion gene. CML is characterized by leukocytosis, thrombocytosis, and anemia. It progresses through chronic, accelerated, and blast phases defined by increasing blast counts and symptoms. The massive spleen seen in CML is indicative of the underlying myeloproliferative process.
The document discusses several pre-leukemic disorders and congenital defects that can progress to acute myeloid leukemia (AML) if not treated. These include myelodysplastic syndrome (MDS), marrow failure syndromes like aplastic anemia, and genetic conditions like Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome. MDS is characterized by dysplastic and ineffective hematopoiesis leading to cytopenias. Fanconi anemia results from a DNA repair defect and patients have a high risk of developing AML. Dyskeratosis congenita causes bone marrow failure below age 20 due to telomere dysfunction. Treatment options discussed include hematopoietic
This document summarizes recent changes in the classification of myeloproliferative neoplasms according to the 2016 World Health Organization classification. It discusses the reclassification of chronic myeloid leukemia as chronic myeloid leukemia and updates to the diagnostic criteria for conditions such as polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic neutrophilic leukemia. New genetic markers and provisions for incorporating treatment response are included. Representative images of peripheral blood smears and bone marrow biopsies are also presented.
Drug induced bone marrow suppression can occur through direct toxicity or idiosyncratic reactions. The timing and severity of myelosuppression from chemotherapy depends on the drug characteristics, patient factors, and blood cell life cycles. Common mechanisms include damaging proliferating progenitor cells or stem cells in the bone marrow. Diagnosis involves monitoring blood counts, and treatment focuses on managing complications and supporting blood cell production.
This document discusses white blood cell disorders and hematological neoplasms, specifically myeloid neoplasms which include myeloproliferative diseases, myelodysplastic/myeloproliferative diseases, and myelodysplastic diseases. It also mentions acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, and some genetic abnormalities associated with acute myeloid leukemia like t(8:21), t(15:17), and Inv 16.
AML is characterized by accumulation of abnormal blast cells in the bone marrow and impaired production of normal blood cells. It results from clonal expansion of myeloid precursor cells with reduced ability to differentiate. Treatment involves induction chemotherapy with anthracyclines and cytarabine to achieve complete remission, defined as less than 5% blasts in the bone marrow. Risk is then assessed based on genetics to determine if additional chemotherapy or stem cell transplant is needed.
The document discusses various myeloproliferative neoplasms (MPNs) including classic MPNs such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis as well as atypical MPNs. It provides details on the diagnostic criteria, signs and symptoms, genetic mutations involved, and treatment approaches for these different MPNs. Chronic myelogenous leukemia is also examined as it represents a distinct MPN characterized by the Philadelphia chromosome genetic abnormality.
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
Hairy cell leukemia is a chronic B-cell lymphoproliferative disorder characterized by "hairy" appearing cells. It was first described in the 1950s and primarily affects middle-aged white men. Diagnosis involves identification of characteristic cells in blood and bone marrow samples. Treatment options have evolved over time from splenectomy to purine analogs like cladribine and pentostatin, which achieve high response rates. Rituximab is also effective, especially for relapsed/refractory cases. The goal of treatment is long-term remission and management of symptoms.
This document discusses acute lymphoblastic leukemia (ALL). It defines ALL as a malignant disorder of hematopoietic stem cells characterized by an increased number of white blood cells in the bone marrow or peripheral blood. ALL is classified based on the type of cell affected (lymphoblastic or myeloid) and whether the disease is acute or chronic. The document describes the epidemiology, risk factors, clinical presentation, investigations including blood tests and bone marrow biopsy, classification systems, treatment involving induction, consolidation and maintenance phases, supportive care, medications used, and prognosis for ALL patients.
This document provides an overview of acute myeloid leukemia (AML). It discusses the historical background, classification, clinical features, risk stratification, diagnostic evaluation, and treatment regimens for AML. Key points include that AML is characterized by infiltration of blood and bone marrow by proliferative myeloid cells, the WHO classification system is based on clinical features, morphology, cytogenetics and molecular abnormalities, risk is stratified by cytogenetics and molecular markers, and treatment involves supportive care, induction chemotherapy, and consideration of novel targeted therapies or stem cell transplant depending on risk factors.
Part i neoplastic proliferation of wbcspecialclass
1. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are considered the same disease that differs only in the degree of lymphocytosis in the peripheral blood.
2. CLL is characterized by an absolute lymphocyte count greater than 4,000 per mm3 in the peripheral blood, while SLL typically presents as lymph node enlargement.
3. Both CLL and SLL are incurable but typically indolent cancers of mature B cells that most often affects adults over age 50 and has a median survival of 4-6 years.
1. Acute myelogenous leukemia (AML) is a clonal, malignant disease characterized by accumulation of abnormal blast cells in the bone marrow and impaired production of normal blood cells.
2. AML results from a series of somatic mutations in a primitive hematopoietic progenitor cell. Additional mutations are required for progression to AML.
3. Standard induction treatment involves "7+3" chemotherapy with cytarabine and an anthracycline, achieving remission in 55-90% of patients. Post-remission therapy aims to prolong remission.
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
This document provides information on chronic myelogenous leukemia (CML), including its definition, history, epidemiology, etiology, pathogenesis, clinical features, diagnosis, disease course, treatment, and more. Some key points:
- CML is a stem cell disease characterized by increased white blood cells, anemia, splenomegaly, and the Philadelphia chromosome.
- It has three phases: chronic, accelerated, and blast crisis. Treatment depends on the phase and may include tyrosine kinase inhibitors like imatinib, interferon, chemotherapy, and stem cell transplantation.
- The disease is caused by the BCR-ABL fusion gene which results in uncontrolled tyrosine kinase activity and increased proliferation of
This document discusses organ transplantation and rejection. It describes the major histocompatibility complex and human leukocyte antigen system which regulate acceptance or rejection of transplants. It outlines the different types of graft rejection including acute cellular rejection, chronic rejection, and antibody-mediated rejection. Risk factors, limited treatment options, and the organs commonly transplanted - kidney, heart, liver, and lung - are also summarized. Diagnostic criteria and grading of rejection in transplant biopsies of these organs are provided.
This document discusses various causes of cell injury and death, including oxygen deprivation, physical agents, chemicals, infectious agents, immune reactions, genetic defects, and nutritional imbalances. It describes the morphological changes that occur in reversible cell injury, including swelling and fatty change, as well as irreversible cell injury known as necrosis. Necrosis results in loss of cell integrity and contents. The document outlines different patterns of tissue necrosis, such as coagulative, liquefactive, gangrenous, caseous, and fibrinoid necrosis.
Multiple myeloma is a cancer of plasma cells that results in overproduction of abnormal antibodies in the bone marrow. It commonly causes bone pain, fractures, anemia, and kidney problems. Risk factors include age over 60 and exposure to chemicals like pesticides, radiation, or certain industrial chemicals. Treatment may include chemotherapy, steroids, stem cell transplantation, radiation, surgery, and newer drugs like thalidomide, lenalidomide, and bortezomib to improve outcomes. Despite recent advances, multiple myeloma remains incurable and patients often relapse, highlighting the need for additional therapeutic options.
This document discusses myeloproliferative neoplasms (MPNs), which are clonal stem cell disorders characterized by excessive proliferation of one or more myeloid cell lines in the bone marrow and peripheral blood. MPNs include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is driven by the Philadelphia chromosome and BCR-ABL fusion gene. PV, ET and PMF are typically caused by a mutation in the JAK2 gene known as JAK2 V617F. The clinical features, diagnostic criteria, complications and treatment approaches for each MPN subtype are described.
he term myeloproliferative neoplasms (MPN) describes a
group of conditions arising from marrow stem cells and characterized by clonal proliferation of one or more haemopoietic
components in the bone marrow and, in many cases, the liver
and spleen. They are often called the myeloproliferative diseases. The three major non‐leukaemic disorders included in
this classification are:
1 Polycythaemia vera (PV);
2 Essential thrombocythaemia (ET); and
3 Primary myelofibrosis.
This document provides an overview of calciphylaxis, a calcification syndrome associated with cutaneous necrosis. It is most commonly seen in patients with end-stage renal disease and secondary hyperparathyroidism. The document discusses the pathophysiology, risk factors, clinical features, diagnosis, and management of calciphylaxis. Calciphylaxis results from calcification of small and medium blood vessels and has a reported mortality of 60-80% mainly due to infection and organ failure. It typically presents as painful, violaceous skin lesions and ulceration on the limbs. Diagnosis involves clinical assessment along with lab tests showing abnormalities in calcium, phosphorus, and parathyroid hormone levels.
This document summarizes recent changes in the classification of myeloproliferative neoplasms according to the 2016 World Health Organization classification. It discusses the reclassification of chronic myeloid leukemia as chronic myeloid leukemia and updates to the diagnostic criteria for conditions such as polycythemia vera, essential thrombocythemia, primary myelofibrosis, and chronic neutrophilic leukemia. New genetic markers and provisions for incorporating treatment response are included. Representative images of peripheral blood smears and bone marrow biopsies are also presented.
Drug induced bone marrow suppression can occur through direct toxicity or idiosyncratic reactions. The timing and severity of myelosuppression from chemotherapy depends on the drug characteristics, patient factors, and blood cell life cycles. Common mechanisms include damaging proliferating progenitor cells or stem cells in the bone marrow. Diagnosis involves monitoring blood counts, and treatment focuses on managing complications and supporting blood cell production.
This document discusses white blood cell disorders and hematological neoplasms, specifically myeloid neoplasms which include myeloproliferative diseases, myelodysplastic/myeloproliferative diseases, and myelodysplastic diseases. It also mentions acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, and some genetic abnormalities associated with acute myeloid leukemia like t(8:21), t(15:17), and Inv 16.
AML is characterized by accumulation of abnormal blast cells in the bone marrow and impaired production of normal blood cells. It results from clonal expansion of myeloid precursor cells with reduced ability to differentiate. Treatment involves induction chemotherapy with anthracyclines and cytarabine to achieve complete remission, defined as less than 5% blasts in the bone marrow. Risk is then assessed based on genetics to determine if additional chemotherapy or stem cell transplant is needed.
The document discusses various myeloproliferative neoplasms (MPNs) including classic MPNs such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis as well as atypical MPNs. It provides details on the diagnostic criteria, signs and symptoms, genetic mutations involved, and treatment approaches for these different MPNs. Chronic myelogenous leukemia is also examined as it represents a distinct MPN characterized by the Philadelphia chromosome genetic abnormality.
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
Hairy cell leukemia is a chronic B-cell lymphoproliferative disorder characterized by "hairy" appearing cells. It was first described in the 1950s and primarily affects middle-aged white men. Diagnosis involves identification of characteristic cells in blood and bone marrow samples. Treatment options have evolved over time from splenectomy to purine analogs like cladribine and pentostatin, which achieve high response rates. Rituximab is also effective, especially for relapsed/refractory cases. The goal of treatment is long-term remission and management of symptoms.
This document discusses acute lymphoblastic leukemia (ALL). It defines ALL as a malignant disorder of hematopoietic stem cells characterized by an increased number of white blood cells in the bone marrow or peripheral blood. ALL is classified based on the type of cell affected (lymphoblastic or myeloid) and whether the disease is acute or chronic. The document describes the epidemiology, risk factors, clinical presentation, investigations including blood tests and bone marrow biopsy, classification systems, treatment involving induction, consolidation and maintenance phases, supportive care, medications used, and prognosis for ALL patients.
This document provides an overview of acute myeloid leukemia (AML). It discusses the historical background, classification, clinical features, risk stratification, diagnostic evaluation, and treatment regimens for AML. Key points include that AML is characterized by infiltration of blood and bone marrow by proliferative myeloid cells, the WHO classification system is based on clinical features, morphology, cytogenetics and molecular abnormalities, risk is stratified by cytogenetics and molecular markers, and treatment involves supportive care, induction chemotherapy, and consideration of novel targeted therapies or stem cell transplant depending on risk factors.
Part i neoplastic proliferation of wbcspecialclass
1. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are considered the same disease that differs only in the degree of lymphocytosis in the peripheral blood.
2. CLL is characterized by an absolute lymphocyte count greater than 4,000 per mm3 in the peripheral blood, while SLL typically presents as lymph node enlargement.
3. Both CLL and SLL are incurable but typically indolent cancers of mature B cells that most often affects adults over age 50 and has a median survival of 4-6 years.
1. Acute myelogenous leukemia (AML) is a clonal, malignant disease characterized by accumulation of abnormal blast cells in the bone marrow and impaired production of normal blood cells.
2. AML results from a series of somatic mutations in a primitive hematopoietic progenitor cell. Additional mutations are required for progression to AML.
3. Standard induction treatment involves "7+3" chemotherapy with cytarabine and an anthracycline, achieving remission in 55-90% of patients. Post-remission therapy aims to prolong remission.
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
This document provides information on chronic myelogenous leukemia (CML), including its definition, history, epidemiology, etiology, pathogenesis, clinical features, diagnosis, disease course, treatment, and more. Some key points:
- CML is a stem cell disease characterized by increased white blood cells, anemia, splenomegaly, and the Philadelphia chromosome.
- It has three phases: chronic, accelerated, and blast crisis. Treatment depends on the phase and may include tyrosine kinase inhibitors like imatinib, interferon, chemotherapy, and stem cell transplantation.
- The disease is caused by the BCR-ABL fusion gene which results in uncontrolled tyrosine kinase activity and increased proliferation of
This document discusses organ transplantation and rejection. It describes the major histocompatibility complex and human leukocyte antigen system which regulate acceptance or rejection of transplants. It outlines the different types of graft rejection including acute cellular rejection, chronic rejection, and antibody-mediated rejection. Risk factors, limited treatment options, and the organs commonly transplanted - kidney, heart, liver, and lung - are also summarized. Diagnostic criteria and grading of rejection in transplant biopsies of these organs are provided.
This document discusses various causes of cell injury and death, including oxygen deprivation, physical agents, chemicals, infectious agents, immune reactions, genetic defects, and nutritional imbalances. It describes the morphological changes that occur in reversible cell injury, including swelling and fatty change, as well as irreversible cell injury known as necrosis. Necrosis results in loss of cell integrity and contents. The document outlines different patterns of tissue necrosis, such as coagulative, liquefactive, gangrenous, caseous, and fibrinoid necrosis.
Multiple myeloma is a cancer of plasma cells that results in overproduction of abnormal antibodies in the bone marrow. It commonly causes bone pain, fractures, anemia, and kidney problems. Risk factors include age over 60 and exposure to chemicals like pesticides, radiation, or certain industrial chemicals. Treatment may include chemotherapy, steroids, stem cell transplantation, radiation, surgery, and newer drugs like thalidomide, lenalidomide, and bortezomib to improve outcomes. Despite recent advances, multiple myeloma remains incurable and patients often relapse, highlighting the need for additional therapeutic options.
This document discusses myeloproliferative neoplasms (MPNs), which are clonal stem cell disorders characterized by excessive proliferation of one or more myeloid cell lines in the bone marrow and peripheral blood. MPNs include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is driven by the Philadelphia chromosome and BCR-ABL fusion gene. PV, ET and PMF are typically caused by a mutation in the JAK2 gene known as JAK2 V617F. The clinical features, diagnostic criteria, complications and treatment approaches for each MPN subtype are described.
he term myeloproliferative neoplasms (MPN) describes a
group of conditions arising from marrow stem cells and characterized by clonal proliferation of one or more haemopoietic
components in the bone marrow and, in many cases, the liver
and spleen. They are often called the myeloproliferative diseases. The three major non‐leukaemic disorders included in
this classification are:
1 Polycythaemia vera (PV);
2 Essential thrombocythaemia (ET); and
3 Primary myelofibrosis.
This document provides an overview of calciphylaxis, a calcification syndrome associated with cutaneous necrosis. It is most commonly seen in patients with end-stage renal disease and secondary hyperparathyroidism. The document discusses the pathophysiology, risk factors, clinical features, diagnosis, and management of calciphylaxis. Calciphylaxis results from calcification of small and medium blood vessels and has a reported mortality of 60-80% mainly due to infection and organ failure. It typically presents as painful, violaceous skin lesions and ulceration on the limbs. Diagnosis involves clinical assessment along with lab tests showing abnormalities in calcium, phosphorus, and parathyroid hormone levels.
Brief Review Of Chemotherapeutic Agents And Renal Failureguest6940925
The document provides an overview of chemotherapeutic agents that can cause renal failure. Several classes of chemotherapy drugs like cisplatin, carboplatin, cyclophosphamide, ifosfamide, and nitrosoureas are discussed in terms of their mechanisms of nephrotoxicity and clinical manifestations. Strategies for prevention and management of renal toxicity from chemotherapy are also briefly reviewed.
Epidemiology of Acute Kidney Injury (AKI)
By Dr. Usama Ragab
Lecturer of Internal Medicine
I have discussed the epidemiology, etiology of acute kidney injury
Acute kidney injury (AKI) is a major public health problem associated with high mortality and morbidity. It can occur in 1-2% of hospitalized patients and up to 50-65% of patients in the ICU. AKI is defined based on changes in serum creatinine and urine output using the RIFLE, AKIN, and KDIGO criteria. The causes of AKI include sepsis, surgery, cardiogenic shock, nephrotoxins, obstruction and hepatorenal syndrome. The pathology involves tubular injury, endothelial dysfunction, inflammation and vasoconstriction. Evaluation of AKI includes assessing volume status, potential causes, urine analysis and imaging. Management involves treating the underlying cause, fluid
An overview of the management of Rhabdomyolysis, put together for the weekly Emergency Medicine registrar teaching session at Wollongong Hospital ED. Information in the presentation is from both the journals and medicine 2.0 (and in particular "FOAMed" -the free open access medical education network that aims to improve sharing of medical education resources through the web). Enjoy. @trainthetrainer
This document summarizes an article about calciphylaxis, a calcification syndrome associated with cutaneous necrosis. It is most commonly seen in patients with renal disease and secondary hyperparathyroidism. The summary is:
1) Calciphylaxis is a life-threatening vasculopathy usually seen in patients with renal disease that can cause cutaneous necrosis.
2) It has a high mortality rate of 60-80% due to wound infection, sepsis, and organ failure.
3) Risk factors include elevated calcium, phosphorus, and parathyroid hormone levels. Diagnosis involves clinical findings as well as evidence of vessel calcification on imaging and histology.
This document summarizes an article about calciphylaxis, a calcification syndrome associated with cutaneous necrosis. It is most commonly seen in patients with renal disease and secondary hyperparathyroidism. The summary is as follows:
1) Calciphylaxis is a life-threatening vasculopathy that usually affects patients with renal disease. It causes ischemic cutaneous necrosis and has a high mortality rate.
2) Clinically, it presents with violaceous, reticulate skin lesions and areas of cutaneous necrosis. Risk factors include elevated calcium, phosphorus, and parathyroid hormone levels.
3) Diagnosis involves clinical findings as well as evidence of vessel calcification on imaging and hist
Slides includes the introduction to drug induced renal disease, pathogenic mechanism by which drug acts on kidney, list of drugs and risk factors.
pathogenic mechanism like altered Interglomerular, Rhabdomyolysis, tubular toxicity, etc.
Acute tubular necrosis is a common cause of acute kidney injury where the renal tubular epithelial cells become damaged. It typically occurs in hospitalized patients following ischemia, exposure to toxins, or sepsis. Acute tubular necrosis progresses through clinical phases of initiation, extension, maintenance, and recovery. Treatment focuses on identifying at-risk patients and preventing hypotension and nephrotoxic exposures to avoid injury in the first place. An interprofessional team approach is important for managing the complex patients who develop this condition.
Rhabdomyolysis is a clinical syndrome resulting from skeletal muscle necrosis and the release of intracellular contents into circulation. Common causes in adults include trauma, excessive muscular activity, genetic disorders, infections, drugs/medications, and ischemic injury. Alcohol and drugs are associated with up to 80% of cases in adults. Clinical presentation includes muscle pain and weakness. Diagnosis is based on a significant elevation of creatine kinase levels in blood. Left untreated, rhabdomyolysis can lead to kidney injury or failure.
AKI is characterized by a sudden impairment of kidney function resulting in the retention of waste products normally cleared by the kidneys. It is diagnosed by an increase in BUN/creatinine and/or decrease in urine output. AKI can range from asymptomatic lab abnormalities to life-threatening complications. Common causes include ischemia, nephrotoxins, sepsis, surgery, and obstruction of urine flow. A careful history, physical exam, urine analysis, and consideration of potential causes are used to diagnose the type and severity of AKI.
The document discusses nephrotic syndrome, which is defined as heavy proteinuria, low serum protein and albumin levels, and edema. The most common type in children is minimal change nephrotic syndrome, which accounts for 83% of primary nephrotic syndrome cases. Treatment involves hospitalization, bed rest, dietary modifications like salt restriction, and steroid therapy like prednisone over 8-12 weeks. Complications can arise from the disease itself or side effects of treatment.
Acute Kidney Injury (AKI), also known as Acute Renal Failure, can be defined as an abrupt loss of kidney function over hours to days resulting in retention of waste products and electrolyte dysregulation. The document discusses the definition, epidemiology, classification, evaluation, and management of AKI. It provides details on the RIFLE and AKI Network classification systems. Common causes of AKI include acute tubular necrosis (ATN) due to ischemia, nephrotoxins, or endogenous factors. ATN is characterized by patchy necrosis of tubular epithelial cells and higher mortality is associated with more severe AKI and underlying comorbidities.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise stimulates the production of endorphins in the brain which elevate mood and reduce stress levels.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
ISO/IEC 27001, ISO/IEC 42001, and GDPR: Best Practices for Implementation and...PECB
Denis is a dynamic and results-driven Chief Information Officer (CIO) with a distinguished career spanning information systems analysis and technical project management. With a proven track record of spearheading the design and delivery of cutting-edge Information Management solutions, he has consistently elevated business operations, streamlined reporting functions, and maximized process efficiency.
Certified as an ISO/IEC 27001: Information Security Management Systems (ISMS) Lead Implementer, Data Protection Officer, and Cyber Risks Analyst, Denis brings a heightened focus on data security, privacy, and cyber resilience to every endeavor.
His expertise extends across a diverse spectrum of reporting, database, and web development applications, underpinned by an exceptional grasp of data storage and virtualization technologies. His proficiency in application testing, database administration, and data cleansing ensures seamless execution of complex projects.
What sets Denis apart is his comprehensive understanding of Business and Systems Analysis technologies, honed through involvement in all phases of the Software Development Lifecycle (SDLC). From meticulous requirements gathering to precise analysis, innovative design, rigorous development, thorough testing, and successful implementation, he has consistently delivered exceptional results.
Throughout his career, he has taken on multifaceted roles, from leading technical project management teams to owning solutions that drive operational excellence. His conscientious and proactive approach is unwavering, whether he is working independently or collaboratively within a team. His ability to connect with colleagues on a personal level underscores his commitment to fostering a harmonious and productive workplace environment.
Date: May 29, 2024
Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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Training: ISO/IEC 27001 Information Security Management System - EN | PECB
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How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
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1. Resident Grand Rounds
Series Editor: Mark A. Perazella, MD
Rhabdomyolysis
Lauren A. Walter, MD
Michael H. Catenacci, MD
A 32-year-old man with no significant past medical history presented to the emergency department with complaints of weak-
ness, myalgias, and muscle stiffness. Physical examination was notable for a low-grade fever at 100.8°F, mild tachycardia at 110 bpm,
and moderate tenderness on palpation of the muscle groups of the calves, thighs, biceps, triceps, and shoulder girdle. Cardiac aus-
cultation revealed no murmurs, neurologic examination showed no focal deficits, and skin examination was normal. On further
questioning, the patient admitted to using crack cocaine for 2 days. Notable laboratory values were as follows: a white blood cell
count of 15,000 cells/µL (normal, 4500–11,000 cells/µL), creatine kinase level of 16,500 IU/L (normal, 40–150 IU/L), blood urea
nitrogen level of 29 mg/dL (normal, 8–23 mg/dL), creatinine level of 1.1 mg/dL (normal, 0.6–1.2 mg/dL), and potassium level of
4.0 mEq/L (normal, 40–150 mEq/L). Urine myoglobin was not detected, urinalysis was normal, and urine toxicologic screen
was positive for cocaine. Rapid influenza testing was negative. The patient was admitted to the medical floor with a diagnosis of
cocaine-induced rhabdomyolysis.
R
habdomyolysis is an uncommon disease cium levels are also maintained by active sequestration
process with profound sequelae if it is not into the sarcoplasmic reticulum and mitochondria.
identified and treated expediently. Approxi- Damage to the myocyte cell membrane may be
mately 26,000 cases of rhabdomyolysis are re- caused directly through trauma (eg, crush injury) or
ported annually in the United States.1 Rhabdomyolysis indirectly through lack of adequate energy in the form
accounts for an estimated 8% to 15% of cases of acute of ATP (eg, vigorous sustained exercise). Regardless of
renal failure and is associated with a mortality rate of the cause, damage to the sarcolemma leads to a loss of
5%.2,3 Morbidity and mortality are usually the result of ionic gradients, thus increasing intracellular calcium.4
hyperkalemia, metabolic acidosis, and acute renal fail- This influx of calcium increases the activity of intracel-
ure. Clinical presentation varies, ranging from a nearly lular proteolytic enzymes that degrade the muscle cell.
asymptomatic illness to a fulminant and life-threatening As the myocyte degenerates, intracellular compounds
disease process with multiorgan system failure. This are extruded into the extracellular fluid and plasma.
article reviews the pathophysiology, etiology, clinical fea- These compounds may include myoglobin, aldolase,
tures, and management of rhabdomyolysis. potassium, uric acid, lactate dehydrogenase, aspartate
transaminase, creatine kinase (CK), and phosphate.5,6
PATHOPHYSIOLOGY In excess, these substances may have toxic effects on
Rhabdomyolysis is a clinical syndrome caused by distant organ systems.
injury to striated muscle. Despite the numerous condi- During myocyte destruction, the level of free myo-
tions that can cause rhabdomyolysis, there is a single globin in the plasma increases, resulting in higher
common pathway involving injury to skeletal muscle, quantities of myoglobin that are filtered by the kid-
breakdown of the myocyte cell membrane, and release neys.7 Myoglobinemia and myoglobinuria have long
of intracellular contents into the extracellular fluid been associated with the development of acute kidney
and circulation. The normal cellular function of the injury in rhabdomyolysis.8 Myoglobin is directly toxic to
myocyte is maintained by ionic gradients generated by renal tubular cells, a process that is likely mediated by
adenosine triphosphate (ATP)–dependent pumps em-
bedded within the cell membrane. Sodium-potassium
pumps maintain a low intracellular sodium level, which Dr. Walter is a resident and Dr. Catenacci is an assistant professor and as-
favors efflux of calcium in exchange for sodium by a sistant residency program director; both are at the Department of Emergency
separate ion exchange channel. Low intracellular cal- Medicine, University of Alabama at Birmingham, Birmingham, AL.
www.turner-white.com Hospital Physician January 2008 25
2. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
TAKE HOME POINTS
Direct toxicity
of myoglobin on
• The single common pathophysiologic pathway in renal tubular cells
rhabdomyolysis involves damage to the myocyte
cell membrane, extrusion of intracellular muscle
contents into the circulation, and toxic effects on
distant organ systems.
• The diagnosis of rhabdomyolysis is best achieved
through careful clinical suspicion in combination
with an elevated serum creatine kinase level. Acute
kidney injury
• Renal injury may be averted through aggressive
intravascular volume replacement, maintenance of
high urinary flows, urinary alkalinization, and man-
nitol therapy.
• Indications for dialysis include refractory hyperka-
Cast formation, Hypovolemia
lemia, refractory acidosis, and volume overload.
decreasing and decreased
• Early diagnosis, combined with aggressive treat- tubular flow renal perfusion
ment of complications, may decrease morbidity
and mortality.
Figure. Etiology of acute kidney injury in patients with rhabdo-
myolysis.
free radicals.9,10 In the presence of acidosis and hypo-
volemia, myoglobin reacts with Tamm-Horsfall protein as DIC, is paramount to ensure their early detection
and precipitates into casts, which may then obstruct (Table 1).
tubular flow. Hypovolemia and overall decreased renal
perfusion also can compound renal injury. The Figure ETIOLOGY
depicts the multifactorial nature of acute kidney injury In the United States, the most common causes
in rhabdomyolysis patients. Rhabdomyolysis-induced of rhabdomyolysis are muscle overexertion, muscle
acute kidney injury is principally caused by damage to compression, and the use of illicit drugs (eg, cocaine,
the renal parenchyma and is thus classified as acute amphetamines) or alcohol.12 However, a myriad of eti-
intrinsic renal failure (AIRF). This syndrome is associ- ologies has been reported as inciting factors. Traumatic
ated with a low specific gravity of urine, pigmented causes of rhabdomyolysis include blunt trauma, crush
casts, and a high fractional excretion of sodium. injury, and strenuous exercise. Nontraumatic etiologies
The release of intracellular electrolytes from dying can be broadly divided into toxicologic, infectious, and
myocytes may be life-threatening. Rapid release of metabolic causes. The classic case of crush injury lead-
intracellular potassium, especially in the setting of ing to skeletal muscle destruction and rhabdomyolysis
acute kidney injury and metabolic acidosis, may pre- is a familiar textbook presentation. However, recogni-
cipitate malignant cardiac dysrhythmias. Heart blocks, tion of rhabdomyolysis caused by toxins, infections (eg,
ventricular tachycardia, ventricular fibrillation, pulse- influenza, HIV), or hereditary metabolic myopathies
less electrical activity, and asystole may occur with little requires a higher degree of clinical suspicion.
warning. Intracellular phosphorus may rapidly precipi-
tate in muscle tissues with calcium, which is reflected Toxins
by the early development of hyperphosphatemia and As illustrated by the case presentation, cocaine is a
hypocalcemia. common cause of rhabdomyolysis, particularly in urban
The hematologic system and clotting cascade also patient populations. Cocaine-induced muscle injury
may be affected by rhabdomyolysis. Necrosis of muscle, may occur through multiple mechanisms: vasospasm
in combination with release of tissue thromboplastin, with muscular ischemia, seizures, hyperpyrexia, coma
may lead to disseminated intravascular coagulation with muscle compression, and direct myofibrillar dam-
(DIC) and hemorrhagic complications.11 Aggressively age.13 In a series of patients with cocaine-induced rhab-
monitoring for complications of rhabdomyolysis, such domyolysis, 13 of 39 patients developed acute kidney
26 Hospital Physician January 2008 www.turner-white.com
3. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
injury, the patients’ mean CK level was 12,187 IU/L Table 1. Complications Associated with Rhabdomyolysis
(range, 1756–85,000 IU/L), and 6 patients died.14 Acute renal failure
Numerous medications have been implicated in
Disseminated intravascular coagulation
cases of rhabdomyolysis, including zidovudine, colchi-
Electrolyte and metabolic derangements
cine, isoniazid, opiates, benzodiazepines, corticosteroids,
Hypoalbuminemia
statins, and fibric acid derivatives. Statin drugs inhibit the
3-hydroxy-3-methylglutaryl coenzyme A reductase and Hypocalcemia (early)
are potent reducers of low-density lipoprotein cholester- Hypercalcemia (late)
ol. As these drugs are commonly prescribed, they merit Hyperkalemia
particular attention. In rare cases, statin drugs may cause Hypernatremia
myopathy and life-threatening rhabdomyolysis. The inci- Hyperphosphatemia
dence of life-threatening rhabdomyolysis appears to be Hyperuricemia
quite low with statin monotherapy (0.44 per 10,000 years Cardiac dysrhythmias
of patient use), with the exception of cerivastatin, which Compartment syndromes
was withdrawn from the market voluntarily by its manu- Shock
facturer in 2001. Increased risk of developing rhabdo-
Death
myolysis occurs in elderly persons, in diabetic patients,
and when a statin is combined with a fibric acid deriva-
tive (5.98 per 10,000 years of patient use).15 Statins block
production of farnesyl pyrophosphate, an intermediate CLINICAL FEATURES
in the synthesis of coenzyme Q10 (Co Q10). Co Q10 is The clinical presentation of rhabdomyolysis is di-
important in mitochondrial energy production. It has verse. Some patients present with an acute medical
been hypothesized that statin-induced Co Q10 defi- or traumatic condition with rhabdomyolysis as a clear
ciency is involved in the pathogenesis of statin myopa- complication. In other patients, rhabdomyolysis may
thy, and that supplemental Co Q10 may reduce risk in be found by laboratory testing alone, prompting a
certain patient populations.16 search for an inciting condition. Classically, patients
with rhabdomyolysis report myalgias, muscle weakness
Infections and swelling, and dark-colored urine. Nonspecific
The pathogenesis of rhabdomyolysis associated systemic symptoms, such as malaise, fever, abdominal
with infections (whether bacterial, viral, or fungal) pain, and nausea and vomiting, may also be seen.
is thought to be the result of direct cell invasion and Initial assessment of symptoms may prove difficult in
cellular degeneration by the pathogen.17 In adult patients with altered mental status, intoxication, elec-
patients, Legionella species are classically associated trolyte imbalance, or uremic encephalopathy.
with rhabdomyolysis. Other bacteria linked to rhab- Physical examination may show signs of dehydra-
domyolysis include Salmonella species, group A β- tion, such as dry mucous membranes, decreased skin
hemolytic streptococci, Francisella tularensis, and Esche- turgor, and delayed capillary refill. The overlying skin
richia coli. Influenza A and B are the most common may be bruised or discolored if trauma has occurred.
viruses associated with rhabdomyolysis, while HIV re- With the development of a compartment syndrome,
mains an important consideration. Studies estimate that the affected area may demonstrate pain on passive
up to 25% of AIDS patients suffer from a myopathic range of motion, sensory deficits, motor deficits, or
disease that may be complicated by rhabdomyolysis.18 signs of vascular insufficiency (a late finding).
Genetic Disorders DIAGNOSIS
In cases where the etiology remains elusive, a genetic By definition, rhabdomyolysis is the breakdown of
disorder should be considered. Genetic disorders should skeletal muscle cells with the subsequent release of
be suspected particularly in pediatric patients with recur- intracellular contents. Assaying for elevated levels of
rent rhabdomyolysis after minimal to moderate exertion these intracellular contents establishes the diagnosis.
or following a viral infection. Any genetic disorder associ-
ated with decreased energy production may cause rhab- Serum Creatine Kinase
domyolysis, which can include disorders of carbohydrate Serum CK level is the most sensitive laboratory test
metabolism, fatty acid oxidation, nucleoside metabolism, for detecting rhabdomyolysis.19 As muscle cells degrade
myopathies, and mitochondrial defects. and release CK into the plasma, the degree of CK
www.turner-white.com Hospital Physician January 2008 27
4. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
elevation correlates directly with the degree of muscle idly cleared via plasma metabolism and urinary excre-
necrosis. Serum CK levels begin to rise 2 to 12 hours tion. This rapid clearance results in normal levels of
after muscle injury, peak at 1 to 3 days, and usually de- myoglobin within 1 to 6 hours following onset of mus-
cline within 3 to 5 days after muscle injury ceases.20 CK cle injury. As such, serum and urine myoglobin levels
levels that remain persistently elevated are indicative of may be only transiently abnormal in some cases of
continued muscle injury, a compartment syndrome, or rhabdomyolysis and therefore should not be relied
decreased renal clearance due to acute kidney injury.2 upon for a definitive diagnosis.
Rhabdomyolysis cannot be defined by a specific
CK level. Most authorities would agree that a 5-fold or Other Diagnostic Studies
greater increase in serum CK is consistent with the di- Other useful laboratory tests include measurement
agnosis, although levels 40 times greater than normal of serum electrolytes. Early in the course of illness,
may often be seen.21 Early rhabdomyolysis should be hyperkalemia, hyperphosphatemia, and hypocalcemia
suspected in at-risk patients with only a 2- to 3-fold in- are seen frequently. Assessment of serum potassium
crease in serum CK. Serial CK levels should be trended levels is essential for averting malignant cardiac dys-
for progression in these patients. rhythmias in rhabdomyolysis-induced acute kidney
Clinical context is also important to consider when injury. Measurement of urine electrolytes and creati-
evaluating CK levels, as higher levels do not always in- nine allows for computation of fractional excretion of
dicate a higher risk for complications. Young healthy sodium, which may help differentiate AIRF caused
athletes may have elevated CK levels as a normal con- by rhabdomyolysis (> 1%) from prerenal azotemia
sequence of muscle damage during vigorous physical (< 1%). If concomitant DIC is present, thrombocyto-
exertion. These patients would not be expected to ex- penia, hypofibrinogenemia, prolonged bleeding times,
perience complications or progress to acute renal fail- and an elevated d-dimer level may be seen.
ure. However, elderly debilitated patients with lower Finally, directed laboratory testing aimed at un-
elevations in total CK levels could progress to renal covering the precipitating cause of rhabdomyolysis is
failure and therefore would represent a greater clinical important. Diagnostic evaluations may include toxi-
concern. Such distinctions are important to make in cologic testing, bacteriologic cultures, viral assays, and
terms of treatment decisions, expected complications, radiographic imaging. Genetic analysis, nerve testing,
and prognosis. Contrast the case of an elderly woman muscle biopsy, and the forearm ischemic test may be
with chronic kidney disease and a total CK level of indicated in patients who are suspected of having an
5000 IU/L with that of a young healthy marathon run- underlying genetic abnormality. The forearm ischemic
ner with a total CK level of 7000 IU/L after a race. This test is performed as follows. Baseline urine myoglobin,
elderly patient requires aggressive management, includ- venous lactate, CK, and ammonia levels are obtained at
ing rehydration, bicarbonate infusion, and admission, rest prior to testing. A sphygmomanometer cuff is then
whereas the marathon runner may only require oral placed on the arm and inflated to 200 mm Hg to in-
rehydration in the emergency department followed by a duce ischemia. The patient is instructed to repetitively
repeat CK level several hours later. grasp an object firmly in the hand for 2 to 3 minutes.
The blood pressure cuff is then released and removed
Serum and Urine Myoglobin from the arm, and laboratory testing is repeated at 0, 5,
Serum and urine myoglobin levels appear to be less 10, and 20 minutes. Elevation of lactate and ammonia
sensitive tests for establishing the diagnosis of rhabdo- to levels below what is normally expected during anaer-
myolysis. Myoglobin is a skeletal muscle protein involved obic metabolism is evidence of a pathway disturbance,
in oxidative metabolism. Necrotic muscle cells release and an enzyme deficiency is suggested.23
myoglobin, which is then excreted in the urine when
the plasma concentration exceeds 1.5 mg/dL. Myoglo- MANAGEMENT
binuria causes the typical reddish-brown urine discolor- Prevention of Complications
ation seen with rhabdomyolysis, clinically appreciable If patients present in extremis, attention should be
when urine myoglobin exceeds 100 mg/dL.22 As myo- given to basic airway, breathing, and circulatory mea-
globin is a heme-containing compound, myoglobinuria sures (Table 2). On stabilization, prevention of the early
will result in a positive urine dipstick for blood despite and late complications of rhabdomyolysis becomes para-
the absence of red blood cells on microscopic analysis. mount in all patients. Management strategies should
Following muscle necrosis, myoglobinemia occurs be tailored to clinical context, which considers risk of
before CK elevation does and subsequently is rap- progression and complications. Variables such as the
28 Hospital Physician January 2008 www.turner-white.com
5. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
inciting factor, patient age, patient comorbidities, and the Table 2. Managing Rhabdomyolysis
presence of preexisting renal disease should be assessed Prehospital care
when deciding upon the aggressiveness of therapy.
If rhabdomyolysis is suspected, establish peripheral access and begin
Volume resuscitation with isotonic crystalloid is the IV rehydration with normal saline
primary therapy for preventing rhabdomyolysis-induced
Initial hospital stabilization/treatment
renal injury. Increasing intravascular volume increases
glomerular filtration rate (GFR), dilutes myoglobin and Supportive care: ABC measures; treat associated life-threatening
injuries
other nephrotoxins extruded during muscle injury, and
Confirm/establish diagnosis with history, physical examination, labora-
improves overall oxygen delivery to ischemic tissue. In-
tory studies (eg, creatine kinase, creatinine, electrolytes, etc)
fusions of 10 to 15 mL/kg/hr of normal saline should
Rehydrate aggressively with normal saline at 10–15 mL/kg/hr to
be used initially, followed by hypotonic saline after achieve urinary output of 2 mL/kg/hr; switch to hypotonic saline
initial resuscitation is completed.24 Fluids should be after resuscitation is complete
titrated to an ideal urinary output of 2 mL/kg/hr.25,26 Continue rehydration for first 24–72 hr in moderate to severe cases
Infusion should continue until adequate resuscitation or until patient is hemodynamically stable
has occurred and clinical and chemical evidence of In moderate to severe cases with risk of progression to acute renal
myoglobinuria has disappeared (usually by the third failure, preexisting renal disease, or evidence of metabolic acidosis
day of hospitalization). Patients may require impressive and dehydration, consider urinary alkalinization. The goal urine pH
amounts of fluid resuscitation to maintain adequate uri- of ≥ 6.5 is achieved by adding 3 ampules of sodium bicarbonate to
1 L of 5% dextrose in water; the solution is infused at an initial rate
nary output, as considerable fluid may be sequestered of 100 mL/hr
in injured muscles. For optimal outcomes, vigorous
In the nonoliguric patient, consider mannitol 1g/kg IV over 30 min,
intravenous fluid rehydration should be started in the followed by 5 g/hr IV, for a total of 120 g/day; use mannitol to
prehospital setting in crush injury patients at risk for de- assist diuresis only in patients who have received adequate volume
veloping rhabdomyolysis.27 In patients with significant replacement
comorbidities such as heart failure, central venous pres- Monitor for and treat hyperkalemia aggressively
sure monitoring may be required to optimally assess the Monitor urinary output and renal function closely
patient’s volume status. Monitor for coagulopathy, compartment syndromes, and sepsis in
Additional measures are indicated to prevent acute severe cases
kidney injury in patients at moderate to high risk of Consider hemodialysis in conjunction with a nephrologist for:
renal injury. Predictors for the development of acute Fulminant renal failure with uremic encephalopathy
kidney injury include preexisting renal disease, a peak Uremic pericardial effusion with tamponade physiology
CK level in excess of 6000 IU/L, dehydration (hema- Refractory hyperkalemia, volume overload, or metabolic acidosis
tocrit > 50%, serum sodium level >150 mEq/L, ortho-
Attempt to identify the inciting factor and stop further muscle
stasis, pulmonary wedge pressure < 5 mm Hg, urinary damage and disease progression
fractional excretion of sodium < 1%), sepsis, hyperka-
Disposition
lemia or hyperphosphatemia on admission, and the
presence of hypoalbuminemia.2 Two such preventive In mild to moderate cases with stable electrolytes that are respond-
ing to rehydration, admit to a general medicine ward
measures are urinary alkalinization with sodium bicar-
In patients with electrolyte abnormalities or underlying cardiac or
bonate and the use of the osmotic diuretic mannitol.
renal disease, admit to a monitored bed
Dehydration and metabolic acidosis favor precipi-
In severe cases, including those with fulminant renal failure with
tation of myoglobin in renal tubules, enhancing and sequelae (pulmonary edema, symptomatic hyperkalemia, oliguria/
exacerbating its nephrotoxic effects. Urinary alkaliniza- anuria), persistent hypotension, or DIC, admit to intensive care unit
tion is thought to enhance renal myoglobin clearance
by increasing its solubility. Although large randomized ABC = airway, breathing, circulation; DIC = disseminated intravascular
coagulation; IV = intravenous.
trials are lacking, urinary alkalinization is recommend-
ed in patients with moderate to high risk of renal fail-
ure, preexisting renal disease, evidence of metabolic cause hypocalcemia and hypokalemia. Therefore, se-
acidosis, or significant dehydration. The goal urine pH rial measurements of both serum electrolytes and uri-
of 6.5 or higher can be obtained by adding 1 ampule nary pH should be performed.
of sodium bicarbonate (44 mEq) to 1 L of 50% normal Mannitol is an osmotic diuretic commonly used to
saline or 2 to 3 ampules (88–132 mEq) to 1 L of 5% expand intravascular volume, promote renal vasodila-
dextrose in water. This solution is then administered tion, and increase GFR in rhabdomyolysis patients.
at a rate of 100 mL/hour. Of note, alkalinization can Mannitol increases urine flow, which may help prevent
www.turner-white.com Hospital Physician January 2008 29
6. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
obstruction from myoglobin-containing casts.28 Man- ney injury may develop in 30% to 40% of patients with
nitol also may draw fluid from the interstitial space, rhabdomyolysis. Indications for emergent hemodialysis
thus decreasing muscle edema in a concomitant com- include hyperkalemia with evidence of cardiac instabil-
partment syndrome.29 Mannitol is administered intra- ity, refractory metabolic acidosis, volume overload with
venously either as 1 g/kg over 30 minutes or as 25 g pulmonary edema, uremic pericardial effusion with
initially followed by 5 g/hr for a total of 120 g/day.30 tamponade, and progressive renal failure with uremic
Mannitol should be given only after adequate volume encephalopathy. Early consultation with a nephrologist
resuscitation has occurred and should be avoided in is recommended.
cases of oliguria. Loop diuretics (eg, furosemide) have Early in rhabdomyolysis, hyperphosphatemia and
been used to enhance urinary output in some oliguric hypocalcemia are seen as myocyte-released phosphate
rhabdomyolysis patients.31 However, they may acidi- precipitates with calcium in injured muscle. Early
fy the urine and worsen myoglobin-induced toxicity. treatment should be limited, as late hypercalcemia
Therefore, loop diuretics should be avoided in patients and hypophosphatemia will develop in most patients.
who have not been adequately hydrated. Late hypercalcemia, more common with concomitant
As mentioned previously, monitoring and treat- renal failure in advanced disease, may require volume
ment of electrolyte derangements in rhabdomyolysis expansion and diuretic therapy.
patients is critical. Hyperkalemia is a life-threatening A compartment syndrome may cause or complicate
complication of rhabdomyolysis, causing cardiac insta- rhabdomyolysis. Compartment syndrome occurs when
bility and dysrhythmias. Conventional treatment for the circulation to tissues within a closed space is com-
hyperkalemia (eg, calcium salts, sodium bicarbonate, promised by increased pressure within that space.33
glucose, insulin, albuterol, sodium polystyrene) should This syndrome may develop either early or late in the
be employed. In the presence of profound hyper- clinical course of rhabdomyolysis, particularly in a
phosphatemia caused by muscle necrosis, calcium salts traumatized limb due to crush injury. If compartment
may be less effective, as the administered calcium may syndrome is suspected clinically and intracompartmen-
combine with the extracellular phosphate rapidly.32 tal pressures exceed 35 mm Hg, emergent fasciotomy
should be considered.34
Admission As mentioned previously, DIC may be a life-
All patients with rhabdomyolysis should be admitted threatening complication seen in rhabdomyolysis pa-
for intravenous hydration, serial laboratory evaluation, tients. DIC in this setting is usually worse during the
and management of potential complications. Clinical third through fifth days after admission.11 Serial labo-
context should determine level of admission. An un- ratory measurements of coagulation times, platelet
monitored bed may be appropriate for healthy patients counts, and fibrinogen levels may be necessary. Life-
who respond to rehydration and have stable electrolyte threatening hemorrhage can occur, and it should be
levels. A monitored bed may be most appropriate for treated with fresh frozen plasma.
the first 24 to 48 hours, particularly in elderly patients,
severely injured patients, and patients who have car- SUMMARY
diac or renal comorbidities, as these patients tend to The various etiologies and clinical presentations of
develop hyperkalemia and cardiac dysrhythmias. Place- rhabdomyolysis are diverse. With nontraumatic causes
ment in the intensive care unit is appropriate for pa- of rhabdomyolysis, the physician must maintain a high
tients who develop severe complications, such as acute clinical suspicion in patients with predisposing factors.
kidney injury requiring dialysis, cardiac instability due History and physical examination may be suggestive,
to hyperkalemia, shock, and DIC. but laboratory confirmation of elevated CK levels is
In the appropriate setting, an otherwise healthy young essential in making the diagnosis. Management rests
patient, typically an athlete with a minimally elevated CK on the prevention and early identification of compli-
level, may be considered for outpatient management. cations. Acute kidney injury may be averted through
These patients should be able to orally rehydrate, dem- early and aggressive rehydration, alkalinization of the
onstrate a falling CK level on serial testing, and have urine with sodium bicarbonate, and judicious use of
stable electrolyte levels. Close primary care follow-up and mannitol. Life-threatening hyperkalemia, compart-
detailed discharge instructions are important. ment syndromes, and DIC should be anticipated and
treated immediately. With prompt recognition and
Management of Complications aggressive treatment, the morbidity and mortality of
Despite instituting preventive measures, acute kid- rhabdomyolysis may be diminished. HP
30 Hospital Physician January 2008 www.turner-white.com
7. Walter & Catenacci : Rhabdomyolysis : pp. 25–31
16. Marcoff L, Thompson PD. The role of coenzyme Q10 in stain-associated my-
Corresponding author: Michael H. Catenacci, MD, Department of opathy: a systematic review. J Am Coll Cardiol 2007;49:2231–7.
Emergency Medicine, JTN 266, University of Alabama at Birmingham, 17. Huerta-Aldin AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis
—an overview for clinicians. Crit Care 2005;9:158–69.
619 19th Street South, Birmingham, AL 35249; mcaten@uab.edu. 18. Authier FJ, Chariot P, Gherardi RK. Skeletal muscle involvement in human
immunodeficiency virus (HIV)-infected patients in the era of highly active
antiretroviral therapy (HAART). Muscle Nerve 2005;32: 247–60.
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