"Death" - help explain it?

[xaero1]

Hi guys, haven't posted in a while as there's been loads going on. Broke up with the girlfriend, been on holiday, and a family member suffered a major heart-attack and has been in a critical state in hospital. A real mix of bad and good stuff then.

With the heart-attack her heart stopped pumping and she was medically dead for 10 minutes before the paramedics were able to restart it. She's now been left brain damaged as a result because parts of her brain effectively died through oxygen starvation. It's a horrible situation and pretty shocking considering she is only 52. She was my uncle's first wife, mother to 3 of my cousins.

I've been thinking back to my education in A-level biology and trying to explain A) what death is, and B) why we cannot simply restart hearts or 'dead' cells. Perhaps you can help me understand it and fill in the gaps.

My understanding is this, every cell in your body performs respiration using oxygen and glucose to stay 'alive' and active. The oxygen and the glucose are supplied to each cell in the blood which of course is pumped around the body by the heart. Simple stuff right? Every cell contains a nucleus with DNA plus a bunch of other organelles like mitochondria, centrioles, ribosomes and vacuoles. These organelles have different functions but in general they keep the cell working and allow it to divide/replicate either by mitosis (normal cells) or meiosis (sex cells).

If you starve a cell of its blood supply it stops to function. It 'dies'. If you stop providing electricity to a computer it shuts down. Fair enough.

However my question is this, if you re-start the blood supply why can't the cells continue to function again? What makes them 'dead'?

Surely 10 minutes is too short a time for the organelles within a cell to degrade?

I'm probably missing a really simple answer here so go easy on me!

Cheers

[GGT]

Sorry about your aunt.

About the "restarting blood supply" and cell death....starving the brain of oxygen makes neurons "die". That doesn't mean CPR can't restore certain functions (breathing, blinking, swallowing) but sections of the brain can be left damaged and "dead". Once the connections are gone, they can't be jump-started like the heart's electrical network. That also happens with spinal cord injuries that sever nerves and cause paralysis.

Same reason why damaging or breaking the information pathways in the brain (a "stroke") can cause limbs (or mouth, throat, speech centers) to become useless, but awareness and cognition might be unaffected. The only time that's not true are near-drownings in super cold water, where everything is slowed so much the brain can "preserve" itself somehow.

Sounds kinda hokey, but think of it like any organic living thing....or a flower in a pot. Starve it of water and some roots will die, no way to water those parts back to blooming. But the plant can be "revived" with water and other roots will feed new blooms.

minx or wiggin can probably give a better explanation.

[Dreadnaught]

That sounds like a rough time, sorry to hear about all of this.

I think the difficulty is explaining what makes a person an individual. Our personalities and memories are a biological system, but we still know little enough about our minds that it's not possible to simply reduce us to our biological parts.

I just finished a book on this two nights ago that I think is worth reading:

http://books.google.com/books?id=nkPj3dNFYwoC

The last chapter is about how/if to use "reductionism" to define our personalities.

[GGT]

Another author to help explain things:

Jill Bolte Taylor (born 1959 in Louisville, Kentucky) is a neuroanatomist who specializes in the postmortem investigation of the human brain. She is affiliated with the Indiana University School of Medicine and is the national spokesperson for the Harvard Brain Tissue Resource Center. Her own personal experience with a massive stroke, experienced in 1996 at age 37, and her subsequent eight-year recovery, has informed her work as a scientist and speaker. For this work, in May 2008 she was named to Time Magazine's list of the 100 most influential people in the world.[1] "My Stroke of Insight" received the top "Books for a Better Life" Book Award in the Science category from the New York City Chapter of the National Multiple Sclerosis Society on February 23, 2009 in New York City.[2]

http://en.wikipedia.org/wiki/Jill_Bo...oke_of_Insight

Quite an interesting book.

[wiggin]

This is a more complex question than can be answered simply, but I'll try to give a brief overview.

Cells aren't like machines; they are dynamic organisms that need a continual input of energy to survive. In most cells of the body, we have a number of ways of making energy to run basic cellular processes. The most common is respiration, where glucose is broken down to produce ATP. As I'm sure you're aware, much of this process is oxygen-dependent (oxygen becomes an electron acceptor at the very end; these redox reactions drive the production of ATP). In the absence of oxygen, the cell shifts energy production to a much less efficient system of glucose metabolism that produces lactic acid as a byproduct. Most cells can also use other energy sources (e.g. fat) in the cell for a brief period, but brain cells in particular can't metabolize anything other than glucose, so they are particularly susceptible to starvation.

There are a bunch of bad things that happen during ischemia (essentially, when a tissue is deprived of blood supply), notably the accumulation of metabolic wastes (like lactic acid and carbon dioxide) as well as the depletion of energy. These can result in two forms of cell death: necrosis, which is an unplanned death of the cell due to damage, and apoptosis, which is the planned death of a cell in response to various signals.

Briefly, it is believed that energy depletion kills a cell thus: There are some very important energy-dependent ion pumps on the cell membrane that maintain certain ion gradients and concentrations inside and outside the cell. These pumps take the lion's share of energy in the cell (I believe I read once a single pump accounts for about 70% of our basal energy expenditure) and are critical for the dynamic functioning of the cell. When these pumps run out of energy, the cell starts falling out of its healthy ion balance. The biggest change that happens is that calcium ions start to leak into the cell (normally calcium levels inside the cell are very low; they are allowed into the cell at very specific, brief periods to drive signaling processes). As calcium ions start pouring into the cell, they start activating a whole cascade of events in the cell, including the activation of proteases, other degrading enzymes, and the production of reactive oxygen species - all very bad for the cell's long term viability. As this process continues, the membranes of the cell and the mitochondria destabilize, which release apoptosis-related proteins called caspases and start programmed cell death.

Bottom line, the cell self-destructs when deprived of energy too long. In brain cells and some other energy-intensive cells, this is on the order of minutes; in other cells, it can take hours. In addition, there is a problem called 'reperfusion injury' where cells that have been ischemic actually get damaged more when blood supply is restored. The details are a bit complicated, but just trust me that cells don't like these dramatic shifts in environment. There are some other tissue-level events that happen as well, but I won't get into them (things like permeability of blood vessels change, which can cause further damage).

So cells don't just 'turn off' when deprived of energy; they undergo a deterioration and eventual complete destruction of the cell due to the destabilization of its homeostatic processes.

I'm sorry to hear about your aunt, but I figured I'd just give you the science and leave it at that.

As an addendum, I should mention that it's possible to keep cells alive for longer without blood supply. The easiest way is to cool cells - in fact, they've been playing with cooling people during strokes/heart attacks/etc. to reduce the extent of the injury. Colder cells have slower metabolic processes, so they use up energy slower (and react slower to adverse events), so it gives you some more time to restore blood supply. If you make the cells really cold - say, freezing them down to -200 C or so - you can keep them viable nearly indefinitely (certainly for months to years; decades for some cell types). There's some fancy footwork you need to do to keep them from dying from the freeze/thaw process, but it can be done.

[CitizenCain]

Perhaps it would help if you think about it from the other side. Death is the absence of life, and life is something we've yet to really explain or understand. Sure, we know the mechanics of how we stay alive, and even the mechanics of how we die, and we can replicate both... but what we cannot do is infuse something with life, even when we can replicate it in an inert state (as some genetic research has done).

"The spark of life," so to speak. We don't know what it is, or why it is. All we know is that once it's gone, we can't bring it back.

[termite]

Magnets

[xaero1]

Hi Wiggin, many thanks for the explanation. I remember a lot of the stuff about respiration and anaerobic respiration, ATP, ADP, proteases etc.. but it's surprising how you need a memory jolt to think about it more clearly. What you say makes a lot of sense now and helps me understand it all better.

[Draco]

Sorry to hear that xaero! Hang in there though buddy