Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Cellular Injury II: Classification01:21

Cellular Injury II: Classification

Cellular injury is any process that disrupts a cell’s ability to maintain homeostasis, leading to structural or functional changes. It is broadly classified based on etiology (cause) and mechanism of damage.Classification by EtiologyCellular injury may result from several causes. Hypoxic injury happens due to reduced oxygen delivery, most commonly from inadequate blood supply, such as arterial obstruction; for example, coronary artery thrombosis can cause myocardial infarction. Chemical injury...
Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
Toxic Reactions: Overview01:26

Toxic Reactions: Overview

When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Acute Pancreatitis II: Pathophysiology01:21

Acute Pancreatitis II: Pathophysiology

The pathophysiology of acute pancreatitis centers on injury to pancreatic acinar cells, which initiates a cascade of harmful intracellular events.This injury leads to premature activation of trypsinogen to trypsin in the pancreas. Trypsin then activates other digestive enzymes, such as chymotrypsin, elastase, and phospholipase A2, which begin breaking down pancreatic tissue. The resulting autodigestion causes local inflammation, tissue swelling, hemorrhage, and fat necrosis.Injured acinar cells...
Cellular Injury I: Introduction01:00

Cellular Injury I: Introduction

Cellular injury occurs when a cell cannot maintain homeostasis or adapt to stressors such as hypoxia, toxins, or trauma. Depending on severity and duration, injury may be reversible, allowing recovery, or irreversible, leading to cell death.General Mechanisms of Cell InjuryAlthough causes vary, most cellular injuries arise from a few key mechanisms that disrupt essential functions and often amplify one another. Cell survival depends on the extent and balance of these disturbances.ATP depletion...
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Ultrasound-guided in-plane and Out-of-plane Techniques Versus Landmark Technique for Internal Jugular Vein Catheterization in Adult Cardiac Surgery Patients.

Kathmandu University medical journal (KUMJ)·2026
Same author

Abdominal Wall Scar Endometrioma.

Kathmandu University medical journal (KUMJ)·2021
Same author

Comment on: Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and American Hernia Society.

The British journal of surgery·2020
Same author

Peritoneal Dialysis or Haemodialysis for Kidney Failure?

JNMA; journal of the Nepal Medical Association·2018
Same author

Inguinal Hernia Repair: Principles and Practice in the United Kingdom.

JNMA; journal of the Nepal Medical Association·2016
Same author

Management of Acute Lower Gastrointestinal Bleeding: Principles and Current Practice in the United Kingdom.

JNMA; journal of the Nepal Medical Association·2016
Same journal

Foreign Body Migration from Subglottis to Bronchus in a Tracheostomised Child: A Case Report.

JNMA; journal of the Nepal Medical Association·2026
Same journal

Validation of the Nepalese Version of the Quality of Recovery-15 Questionnaire in Patients Undergoing Elective Surgery.

JNMA; journal of the Nepal Medical Association·2026
Same journal

Evaluation of Preference of Pain Scale in Children using Novel Animated Emoji Scale in Nepal: An Observational Study.

JNMA; journal of the Nepal Medical Association·2026
Same journal

Mucinous Ovarian Cancer in a Young Woman: A Case Report.

JNMA; journal of the Nepal Medical Association·2026
Same journal

Conundrum of Cholesterol Management and Health Implications of Low Cholesterol Levels: A Narrative Review.

JNMA; journal of the Nepal Medical Association·2026
Same journal

Clinical Profile and Management of Pleural Effusion at Tertiary Hospital of Nepal: An Observational Study.

JNMA; journal of the Nepal Medical Association·2026
See all related articles

Related Experiment Video

Updated: Jul 2, 2026

Pseudofracture: An Acute Peripheral Tissue Trauma Model
10:08

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Published on: April 18, 2011

Two-hit hypothesis and multiple organ dysfunction syndrome.

I Butt1, B M Shrestha

  • 1Sheffield Kidney Institute, Sheffield, UK.

JNMA; Journal of the Nepal Medical Association
|August 19, 2008
PubMed
Summary
This summary is machine-generated.

Severe injury or infection can prime the immune system, making a minor subsequent insult lead to a dangerous overreaction. This "two-hit hypothesis" (THH) explains multiple organ dysfunction syndrome (MODS) and mortality, especially in intensive care.

More Related Videos

Study of Experimental Organ Donation Models for Lung Transplantation
08:56

Study of Experimental Organ Donation Models for Lung Transplantation

Published on: March 15, 2024

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
10:42

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models

Published on: October 22, 2012

Related Experiment Videos

Last Updated: Jul 2, 2026

Pseudofracture: An Acute Peripheral Tissue Trauma Model
10:08

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Published on: April 18, 2011

Study of Experimental Organ Donation Models for Lung Transplantation
08:56

Study of Experimental Organ Donation Models for Lung Transplantation

Published on: March 15, 2024

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models
10:42

Bioluminescence Imaging of NADPH Oxidase Activity in Different Animal Models

Published on: October 22, 2012

Area of Science:

  • Immunology
  • Critical Care Medicine
  • Pathophysiology

Background:

  • The
  • two-hit hypothesis
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,
  • ,

Observation:

  • A severe insult primes the immune system.
  • A subsequent, minor insult causes an exaggerated immune response.
  • This response can lead to multiple organ dysfunction syndrome (MODS) and death.

Findings:

  • The "two-hit hypothesis" (THH) describes a two-stage process.
  • Priming occurs after severe injury or sepsis.
  • A second, lesser insult triggers a hyperinflammatory response.

Implications:

  • Understanding THH is vital for preventing MODS.
  • THH is a significant factor in critical care settings.
  • Further research into THH pathophysiology is needed.