Pathophysiology of septic shock

Author(s):  
John M. Litell ◽  
Nathan I. Shapiro

The pathophysiology of sepsis is the result of a dysregulated host response to infection. Interactions between conserved pathogenic signals and host recognition systems initiate a systemic reaction to local infection. Pro- and anti-inflammatory intermediates and associated coagulatory abnormalities lead to altered macrovascular, microvascular, and mitochondrial function. Uncorrected, these processes yield similar patterns of failure in multiple organ systems. Mortality increases with successive organ failures. Although commonly thought to be a manifestation of impaired renal circulation, septic acute kidney injury may be due primarily to non-haemodynamic factors. Pulmonary parenchymal dysfunction in sepsis also contributes to failures in other organ systems. Sepsis involves complex alterations in myocardial function, vascular tone, and capillary integrity, which are mediated by elevated concentrations of inflammatory cytokines, inducible nitric oxide, and reactive oxygen species, among others. Gut hypomotility and translocation of enteric flora likely contribute to a persistent inflammatory response. This perpetuates the pathophysiological pattern of sepsis, and can lead to the delayed onset of these features in patients with other types of critical illness. The neurological manifestations of sepsis include acquired delirium, which is also probably due to circulatory and inflammatory abnormalities, as well as alterations in cerebral amino acid metabolism. Critical illness-related corticosteroid insufficiency and derangements in glucose metabolism are among the endocrine abnormalities commonly seen in septic patients. Restoration of homeostasis requires early haemodynamic resuscitation and aggressive infectious source control.

2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.


2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Sam Kant ◽  
Steven P. Menez ◽  
Mohamed Hanouneh ◽  
Derek M. Fine ◽  
Deidra C. Crews ◽  
...  

Abstract The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.


Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 506
Author(s):  
Diana Dobilienė ◽  
Jūratė Masalskienė ◽  
Šarūnas Rudaitis ◽  
Astra Vitkauskienė ◽  
Jurgita Pečiulytė ◽  
...  

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 h was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39–49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Siqi Xu ◽  
Youguang Gao ◽  
Qin Zhang ◽  
Siwei Wei ◽  
Zhongqing Chen ◽  
...  

Sepsis often results in damage to multiple organ systems, possibly due to severe mitochondrial dysfunction. Two members of the sirtuin family, SIRT1 and SIRT3, have been implicated in the reversal of mitochondrial damage. The aim of this study was to determine the role of SIRT1/3 in acute kidney injury (AKI) following sepsis in a septic rat model. After drug pretreatment and cecal ligation and puncture (CLP) model reproduction in the rats, we performed survival time evaluation and kidney tissue extraction and renal tubular epithelial cell (RTEC) isolation. We observed reduced SIRT1/3 activity, elevated acetylated SOD2 (ac-SOD2) levels and oxidative stress, and damaged mitochondria in RTECs following sepsis. Treatment with resveratrol (RSV), a chemical SIRT1 activator, effectively restored SIRT1/3 activity, reduced acetylated SOD2 levels, ameliorated oxidative stress and mitochondrial function of RTECs, and prolonged survival time. However, the beneficial effects of RSV were greatly abrogated by Ex527, a selective inhibitor of SIRT1. These results suggest a therapeutic role for SIRT1 in the reversal of AKI in septic rat, which may rely on SIRT3-mediated deacetylation of SOD2. SIRT1/3 activation could therefore be a promising therapeutic strategy to treat sepsis-associated AKI.


2021 ◽  
Vol 9 (1) ◽  
pp. 6-6
Author(s):  
Inderbir Padda ◽  
Nimrat Khehra ◽  
Urooj Jaferi ◽  
Dina Mosabbeh ◽  
Harshan Atwal ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its effects on the organ systems have been summarized in recent literature with predominant pulmonary characteristics as a hallmark of the COVID-19 virus. Considering its accelerated appearance from Wuhan, China, in December 2019, extrapulmonary effects have been reported globally of SARS-CoV-2 involving the central nervous system (CNS), cardiovascular, gastrointestinal, renal, and hematologic systems; thus, the potential mechanisms, pathophysiology, clinical characteristics, management, outcome, and case reports per organ system are summarized in depth. The authors interpreted articles composed of case reports, case-series, meta-analysis, cohort studies, retrospective studies, and narrative reviews focusing on COVID-19 confirmed cases and their effects on the organ systems. Prevalent clinical organ system complexities include pneumonia, acute respiratory distress syndrome (ARDS), pulmonary hypertension, pulmonary embolism, hypertension, cardiac arrhythmias, myocarditis progressing to fulminant myocarditis, anorexia, nausea, vomiting, diarrhea, liver dysfunction, encephalopathy, encephalitis, meningitis, intracerebral hemorrhage, acute kidney injury, and hypercoagulability causing stroke and disseminated intravascular coagulation (DIC). This comprehensive literature review article will help clinicians and researchers gain insight about SARS-CoV-2 and its diverse effects on multiple organ systems involved, therefore help implement prospective management and preventative measures.


This textbook encompasses the knowledge, skills, and expertise needed to deliver excellent nursing care to critically ill patients. Emphasis is placed on a holistic and compassionate approach towards humanizing the impact of the environment, organ support, and monitoring, as well as critical illness itself. Chapters cover the general aspects of critical care such as the critical care environment or critical care continuum and specific organ systems and diseases. The structure of the systems chapters reminds the reader of the underlying anatomy and physiology as well as highlighting areas of particular relevance to critical care. The focus on priorities for management builds on the ABCDE assessment and offers insight into key interventions in urgent situations as well as outlining evidence-based practice. The book is ideal for those new to the critical care environment, but will also act as a reminder for more experienced nurses when faced with a new situation or when teaching/mentoring students. The patient and their family remain the centre of all This new edition brings the definitions, pathophysiology, and management of fast-changing and challenging areas such as ARDS, sepsis and multiple organ dysfunction, resuscitation, and acute kidney injury up to date as well as including any evidence-based changes associated with nursing practice in critical care. A new chapter covers major incident planning and management and the role of critical care in pandemic situations.


Author(s):  
Lalatendu Mohanty ◽  
Aditya Dhanawat ◽  
Partisha Gupta ◽  
Guncha Maheshwari

Introduction: Scrub typhus is a re-emerging illness in the South-East Asia and other parts of the world caused by Orientia tsutsugamushi, which is a mite-borne bacterium belonging to the Rickettsiaceae family. It has varied clinical manifestations and affects multiple organ systems. In Asia, about 1 million new cases are identified annually. Aim: The aim was to conduct a retrospective study to observe the clinical profile and complications of scrub typhus in South-Eastern India. Materials and Methods: Clinical data of 240 patients who were 18 years of age or above, admitted in the Department of Internal Medicine and diagnosed with scrub typhus by means of IgM Enzyme-linked Immune Sorbent Assay (ELISA) was collected. Demographic profile, clinical signs and symptoms, laboratory parameters, co-infections and complications were reviewed. Statistical analyses were performed using Chi-square test. Results: Majority of the patients were males, between the age of 18-29 years and lived in rural areas. Forty-three (17.9%) patients were admitted in the ICU and the remaining in wards. Sixty-nine (28.8%) patients had consolidation and 11 (4.6%) had Acute Respiratory Distress Syndrome (ARDS). Twenty-one (8.8%) patients had jaundice and 76 (31.7) had hepatomegaly. Twenty-one (8.8%) patients had meningo-encephalitis and 18 (7.5%) had acute kidney injury. Twelve (5%) patients had co-infection with dengue and 8 (3.3%) had malaria. Conclusion: This study shows wide and varied presentation of scrub typhus infection along with the course of the disease and response to the treatment. The diagnostic clues such as fever, eschar, rashes, lymphadenopathy should be kept in mind by a primary care physician as early recognition and treatment can prevent its dangerous complications and reduce the mortality due to the disease. Occurrence of co-infections should also be kept in mind for better management of the patient.


Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Sigrid Beitland ◽  
Ingrid Os ◽  
Kjetil Sunde

Background. Acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) is a severe complication in trauma patients. The aim of the study was to assess primary traumatic injuries and secondary organ failures in severe posttraumatic AKI.Methods. Retrospective review of adult trauma patients admitted to the trauma centre at Oslo University Hospital Ullevål. Injury severity score (ISS) was used to assess the severity of primary injuries, and sequential organ failure assessment (SOFA) score was utilized to measure secondary organ failures.Results. Forty-two (8%) of 506 trauma patients admitted to intensive care unit developed AKI treated with CRRT, whereof 40 (95%) suffered blunt trauma mechanisms. Patients had extensive primary organ injuries with median (interquartile range) ISS 36 (27–49). The majority of the patients had respiratory (93% intubated) and cardiovascular (67% with inotropic and/or vasoactive medication) failure within 24 hours after admission. AKI was often part of multiple organ failure, most frequently respiratory and cardiovascular failure, affecting 33 (75%) and 30 (71%) of the patients, respectively.Conclusion. Trauma patients with AKI undergoing CRRT often had severe primary injuries due to blunt trauma. Most of them suffered from secondary multiple organ failure concomitant to AKI.


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