What is the pathophysiology of acute radiation syndrome (ARS)?

From the Guidelines

The pathophysiology of acute radiation syndrome (ARS) is primarily driven by the damage caused to the most replicative cells in the body, including spermatocytes, lymphohematopoietic elements, and intestinal crypt cells, which are highly sensitive to radiation 1.

Clinical Components of ARS

The clinical components of ARS include:

• Hematopoietic syndrome: characterized by the development of lymphopenia, granulocytopenia, or thrombocytopenia
• Gastrointestinal syndrome: marked by symptoms such as headache, nausea, vomiting, or diarrhea
• Cerebrovascular syndrome: which can lead to severe damage to the central nervous system

Phases of ARS

Each syndrome can be divided into four phases:

• Prodromal phase: initial symptoms
• Latent phase: temporary improvement
• Manifest illness phase: severe symptoms
• Recovery or death phase: outcome depending on the dose and severity of radiation exposure The time course and severity of these clinical signs and symptoms vary depending on the dose range of whole-body or significant partial-body exposure, as outlined in Figure 1 1.

From the Research

Pathophysiology of Acute Radiation Syndrome (ARS)

The pathophysiology of ARS is complex and involves damage to multiple organ systems. Key aspects include:

• Damage to DNA, protein, and lipids in mammalian cells, as well as increased mitochondria-dependent generation of reactive oxygen species (ROS) 2
• Activation of signaling networks, including DNA non-homologous end-joining (NHEJ) and homologous recombination (HR), and signaling pathways containing ataxia telangiectasia mutated (ATM) 2
• Radiation-induced cytocidal effects on parenchymal cells of hierarchically organized tissues, leading to organ failure 3
• Systemic inflammatory response mediated by released pro-inflammatory cytokines, contributing to multi-organ involvement 3

Organ-Specific Effects

ARS can affect multiple organ systems, including:

• Hematopoietic system: bone marrow failure, lymphopenia 2, 3, 4
• Gastrointestinal system: nausea, vomiting, diarrhea, GI syndrome 2, 3, 4
• Neurovascular system: neurovascular syndrome, cardiovascular/central nervous system syndromes 3, 4
• Skin: damage, hair loss 2, 4
• Reproductive system: damage to spermatogenic cells 2

Clinical Manifestations

The clinical manifestations of ARS include:

• Prodromal phase: nausea, vomiting, anorexia, lymphopenia, diarrhea 4
• Latent phase: temporary clinical improvement 4
• Organ-specific syndromes: bone marrow, GI, cardiovascular/central nervous system syndromes 3, 4
• Triad of early emesis, hair loss, and bone marrow failure 4

Diagnosis and Assessment

Diagnosis of ARS is based on:

• Clinical presentation: unexplained emesis, bone marrow failure, hair loss 4, 5
• Laboratory tests: serial blood counts, chromosome analysis, dicentric count 4
• Radiation exposure history 4
• Assessment of severity: guidelines for assessing severity and managing ARS victims 5