From Reversible vs. Irreversible Cell/Tissue Injury to Hands-Only CPR 

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From Reversible vs. Irreversible Cell/Tissue Injury to Hands-Only CPR 

By Sandor Szabo, MD, PhD, MPH, DSc (h.c.) 

Professor, School of Medicine, American University of Health Sciences, Signal Hill/Long Beach, CA 

 

The mechanisms of cell and tissue injury often sound exoteric – hence, I will start, as often happens with presenting medical topics, with a real clinical case, as I heard recently on the weekly edition of Radiolab on NPR/KPCC 89.3 FM (1). 

 

While a large family was visiting New York City (NYC) and standing in line to enter a Broadway theatre, an older member of the family suddenly collapsed. Since it looked like heart attack to a family member, after calling 911, they started an improvised CPR (cardiopulmonary resuscitation)… Fortunately, the ambulance arrived in about 5 mins. (apparently, in the busy parts of NYC ambulances always stand by corners or circulate), The ambulance arrived to the nearest hospital in about 15 minutes and the patient was in ICU (Intensive Cre Unit) in about 5 minutes where the professional CPR continued, alternating with electric shocks on the chest, while anxious family members were waiting outside of  ICU… Ten minutes later the doctor in charge came out with the statement that the patient regained heart rhythm. The family rejoiced, became jubilant – but the doctor told them that they ‘still need to do additional tests to be sure that patient is really doing OK’…  Then another anxious wait followed for about 45 minutes, when the ICU doctor came out to tell that the ‘patient heart was beating, lungs were helped with a breathing machine, but his brain cortex was dead,  as CT and MRI images revealed’… Essentially, the patient was brain  dead and it was up to the family to decide how long they wanted to maintain their loved one in this non-communicating vegetative state…  After 3 very difficult days of soul-searching and consultations with neurologists and other medical experts, the family decided to ‘pull the plug’ and the patient was pronounced dead in medical-legal terms. 

Unfortunately, this is a very typical and often seen scenario in emergency rooms (ER) and hospitals. As a pathologist, I have seen this in many cases when the lungs are essentially normal, heart might show small or large areas of infarct (dead cardiac tissue) that would still not functionally destroy the heart – yet the patient was dead, due to the high sensitivity of brain tissue to lack of oxygen delivered by hemoglobin with normal blood flow. Actually, our neurons may suffer a short reversible damage that rapidly may become irreversible if the lack of blood supply (ischemia) lasts longer than 3- minutes. Namely, different tissues (2, 3) have different tolerances to hypoxia, e.g., cells in the brain, heart, kidney and the liver are the most sensitive: 

Brain: About 3 minutes  Heart: 15-20 minutes  Kidney and liver: 20-30 minutes              Skin: About 60 minutes  Skeletal muscle: 60-90 minutes

Table 1-1. Susceptibility of Cells to Ischemic Necrosis    High  Neurons (3 – 5 min)  Intermediate   Myocardium, hepatocytes, renal epithelium   (30 min- 2 hr)  Low   Fibroblasts, epidermis, skeletal muscle (many hours)

Depending on the duration of exposure to cell stressors, like hypoxia, chemical toxins, here is an AI-generated comparison of reversible vs. irreversible cell and tissue injury: A classic example of reversible cell injury is cellular swelling caused by mild hypoxia (oxygen deprivation), where the cell can return to normal function if oxygen supply is restored, while an example of irreversible cell injury is necrosis which occurs when a cell experiences severe prolonged ischemia (lack of blood flow) leading to permanent damage and cell death: other examples include fatty change in the liver (reversible if mild) and myocardial infarction (irreversible) due to prolonged ischemia in the heart muscle.  

• Reversible cell injury:  

• Characterized by cellular swelling, mild mitochondrial changes 

• Can be caused by temporary stressors like mild hypoxia or toxin exposure.  

• Cells can recover to normal function if the stressor is removed.  

• Irreversible cell injury:  

• Characterized by severe membrane damage, mitochondrial dysfunction, nuclear fragmentation, and release of lysosomal enzymes.  

• Occurs when the stressor is severe or prolonged, causing the “point of no return”.  

• Leads to cell death.  

 

 

 

 

Here are the differences, illustrated with more scientific details (2, 3): 

 

The practical healthcare implications should be easily deductible: if a heathy, usually older individual collapses, with apparent heart attack (with no other reasons such as trauma or hypoglycemia due to insulin overdose in diabetic patients), start traditional CPR such as about 15 strong push on the chest, followed by two breath in the open mouth (white nose trill are closed) and repeat this as long as pulses of collapsed persons become palpable, implicating the normal heart function has been restored. The purpose of this is to restore blood flow to the brain, the most sensitive organ to lack of oxygen, delivered by erythrocytes (red blood cells). Despite this obvious need to restore blood circulation as soon as possible, we know from practical experience that CPR is frequently delayed for several reasons, e.g., panic, confusion and being uncomfortable to breathe in the mouth of unfamiliar person (especially if commercial mouth-to-mouth masks were not available).  

Enter thus the hand-only CPR that was developed by ER physicians and emergency medical technician to save more patients with heart attacks on the streets, in homes and at commercial sites. Comparative studies demonstrated that there were no major differences in the survival rate if traditional or hands-only resuscitation were applied. There are multiple videos about this on the Internet; one of the simplest is by the Red Cross (https://www.redcross.org/take-a-class/cpr/performing-cpr/hands-only-cpr). Based on these instructions and my experience, follow these steps: 

• Check the person; tap on shoulder and ask if he or she is OK. If no response call 911 and start hands-only CPR. 

• Be sure that the person is on firm surface (e.g., floor or table) – otherwise the chest compressions are not effective. 

• Push hard and fast with two hands (at least 2 inches deep in chest; 100 to 120 compressions per minute). Some ribs my break – but those will heal if the patient survives… 

• Allow the chest to return to its normal position after each compression. 

• This is a difficult procedure; have another nearby person to help you, e.g., 2-3 alternatives are the best. 

• Check if the pulse on carotid or radial arteries have returned and patient started breathing. 

The bottom line: hands-only CPR is effective, but it’s a hard, physically and emotionally draining procedure; thus, ask for help from nearby persons. 

 

 

References 

1. Radiolab on NPR/KPCC 89.3 FM 
2. Miller M, Zachary JF: Mechanisms and morphology of cellular Injury, adaptation, and death. Pathol. Basis Vet. Dis., 2017, 17:2–43.e19. doi: 10.1016/B978-0-323-35775-3.00001-1 17:2–43.e19. doi: 10.1016/B978-0-323-35775-3.00001-1 
3. Robins Cotran Pathologic Basis of Disease. Kumar V., Abbas A.K., Aster J.C. (eds.) 9th edition. Elsevier Saunders, 2015.