Chocolate, Pigs, and Greatness

I read Mark 10:35-45 the other day and it absolutely crushed me. Are you ready?

The passage starts off hilarious. "Then James and John, the sons of Zebedee, came to [Jesus]. 'Teacher,' they said, 'we want you to do for us whatever we ask.' "

What?

Where do you get off making such ridiculous demands to anyone like that?

It sounds like something my two year old son would say to me. The other day he came running up to my wife and threw his hand at her and demanded, "Mommy, I want choco-lot." He repeats his original demand and begins to use his free hand to point to the center of his outstretched hand, "Right there Mommy, put it right there." Not even a 'Hello'. Not a 'Please.' Heck, he didn't even try to butter her up with something cute.

My son's message was plain and simple, "Give me the chocolate and no one gets hurt."

John and James swagger up to Jesus, thrust out their hands, "Jesus, give me the chocolate right here. Put it right here Jesus."

I imagine Jesus had to summon some supernatural power in order to suppress his laughter. If a snort didn't sneak out he at least had to crack a smile as he replied in verse 36, "What do you want me to do for you?"

The brothers go on to ask for a seat at the right and left hand of God. Now that's some serious chocolate.

A few lines later, the other disciples get ticked off at James and John. They have good reason for it too right? Surely the other disciples get it, surely they know better than speak to Jesus in such a way, to ask for such things, right? Apparently not; Jesus stands in the midst of a pack of chocolate hogs all squealing, ruttin', and snorting about who should get the chocolate. (Similar scenes re-enacted in Luke 9:46-48 and 22:20-30.)

Jesus's response is stunning. Like a caring parent and teacher he gently raises his hands to hush the snorting beasts and motions them in. The piggy pack trots over and Jesus says, "You know that those who are regarded as rulers of the Gentiles lord it over them, and their high officials exercise authority over them. No so with you. Instead, whoever wants to become great among you must be your servant and whoever wants to be first must be slave of all."

Then he delivers the coup de grâce.

"For even the Son of Man did not come to be served, but to serve, and to give his life as a ransom for many." Ouch.

The silence in the room must have been deafening as Jesus cut with surgical precision to the heart of the matter, greatness.

Pork and sweets aside, I don't know if this made Jesus laugh or mad or something else entirely. And I don't really think so lowly of the disciples as if I have something figured out. Truth be told, I am the child with an outstretched palm to God making ridiculous demands. Most days I have the spiritual understanding and maturity of a two year old. Tears rest upon my eyes as I type; I confess that with utmost sincerity.

Entire books could be written about this passage but I think the main issue here is greatness: God's greatness, what I like to call Kingdom Greatness (KG), versus Worldly Greatness (WG).

Let's look at what John and James originally ask for (v37) "Let one of us sit at your right and the other at your left in your glory." Because we already briefly discussed the end of the passage we know that John and James are not after KG but WG. They want what we all want, or at least what we secretly fantasize about (or not so secretly for some) - to be the next American Idol.

Now the folks that I really admire on that show are the rejects. Now I am not talking about the ones who may have a decent voice but aren't quite superstar material. I am talking about the screeching train wrecks that we all love to watch crash and burn. Now they have guts.

They actually get up in front of God and everybody and let it all hang out. I can barely do that in the privacy of my own truck as I barrel down the highway each day. I may fantasize about being the next American Idol as I belt out the latest tune in my pickup but you wouldn't find my crow-voice singing for anybody, much less millions of Americans only to be forever memorialized as a singing whack-job on YouTube.

Seriously though, it's not just American Idol but there is a cult in our culture devoted to celebrity and fame. Pick up any magazine or check out the top news feeds on any major news site like CNN. There is this obsession with other people's lives, an obsession with greatness. I'd love to throw my nose up in the air and declare my superiority over this craze for greatness but I can't.

I have the most bizarre fantasies about being great. In all seriousness, I, the great cackling crow of the pickup truck, actually fantasize about being some superstar on American Idol. (I thought about including a MP3 of my 'talents' but withdrew it over fear of being targeted by Al-Qaeda; yes, I'm that bad.) My fantasies don't stop there. I dream of becoming somebody great that will change the world, become filthy rich in the process, and have a throng of loyal followers, devoted to me, I mean my noble causes, of course.

If I'm honest, I have this deep seated desire to be 'great'. I am not talking about doing a good job and being the best you can be. But the desire to be distinguished, eminent, noticed, affirmed, desired - to be greater or 'better' than other people and for those 'other' people to recognize it.

John and James asked to 'sit', to share in 'God's glory.' Jesus hits the nail on the head at the end of the passage though. They weren't after KG, they were after WG. In the Jewish culture, in that period of time, many Jews anticipated the coming of a leader to free them from the Romans who ruled over them.

And that's exactly what John and James were driving at. They wanted to ride in on the big war horses galloping next to Jesus as he stormed the Roman Empire with cold steel and hard blows. But Jesus's idea of greatness was exactly the opposite.

In verse 38, he flat out tells them, 'You have no idea what you are asking for.' John and James were thinking of glory and honor. Jesus had a different 'cup' of tea in mind.

"Can you drink the cup I drink or be baptized with the baptism I am baptized with? (V38 continued) " Jesus has already established that they are clueless. The brothers greedily elbow each other in the side and exchange eager glances, "Oh yeah, we can drink it baby! " (V39, with a slight paraphrase.)

The 'cup' Jesus spoke of and the 'baptism' he spoke of was much more than his death. Fast-forward to Mark 14:35-36, the hours before Jesus's death, Jesus prays that if it is his father's will that 'this cup' may pass from him. Jesus is asking to be saved from death.

Think of the most painful and horrible moments in your life. Without fail, every single one of them centers on some aspect of a relationship gone wrong (be it with God, someone else, or yourself). The wounds we receive and dish out in relationships are the most devastating, darkest, and most forsaken parts of our hearts and existence. That was the 'cup' that Jesus is talking about.

Jesus immersed (i.e. baptized) himself into everything that is wrong with the world - everything that is broken in our relationships. On the cross He baptized Himself, He immersed Himself in the wretchedness and horror of every child abuse, the forsakenness and plague of fatherlessness, the scraping desperation of loneliness and depression...every shattered and bleeding corner of relationship that is marred by sin, Jesus covered Himself with, He immersed Himself in that gulf of darkness like a man plunged to the darkest and deepest depths of the Pacific. Not only did He immerse and cover Himself with our problems and our brokeness, He did so knowing that it would cost Him everything with His own dad. He would not only be covered in our mistakes and become wretched and disgusting but he would have to go it alone. That was his cup.

This was not the cup that James and John were asking to take a sip from. They still wanted the chocolate. They wanted WG.

It's hard for me to go on because this is me! I kneel and pray, "God use me to do something great for your kingdom!" What I really mean is, "God I want the glory. I want to win. I want to be the hero on the shining white stallion that everybody adores. I want a beautiful happy and healthy family. I want to be rich, I want to be powerful."

But sometimes I really fool myself into thinking that I really do mean it. That I am really saying, "Lord! Help me to do something 'great' to change the world," while I harbor dishonest notions that I don't really want fame or fortune. What I really do is kneel and spit on God's feet and ask for the cup of Worldly Greatness.

I have never asked that God would hand me the cup that Jesus drank from. I have never asked or meant for God to 'baptize' me into the 'baptism' of Jesus. We think that suffering and hardship is for missionaries and super-spiritual-saints in far-off lands. But that is not the via delarosa, the Way of Suffering, i.e. the path that Christ blazed for us to follow. Christ said point blank, "He who would follow me must deny himself, pick up his cross, and follow me." If you're going to follow Jesus there is a 'cup' you must drink from.

You have to deny the cup of WG, immerse yourself into the death and wretchedness of broken relationships that is the cross, and follow Christ into a new and different kind of life. My prayers are pathetic. My requests and demands to Jesus are much baser and dumber than anything John or James ever said or thought.

Does Jesus tell us to drink that same cup he drank?

Jesus goes on in the following verses and sets up the comparison between Worldly Greatness versus Kingdom Greatness. In their day and especially within the Jewish culture, greatness was a function of your position of power, e.g. the religious/political leaders of the day. Jesus notes that brand of 'greatness' (i.e. fame, fortune, and power) exists and you can chase after it but 'not so with you' v43.) Not so for those who would be apart of the kingdom and embrace kingdom greatness.

All that to say, 'greatness' aint about being 'great'. At least, not for a Christian. Kingdom Greatness is about something else entirely. Kingdom Greatness is about being servanthood. "Whoever wants to be become great among you must be your servant, and whoever wants to be first must be slave of all." (vv43-44.)

KG means serving the needs of others. This is so simple on the surface but so incredibly hard to apply. At work when someone cuts you down to size in front of the group, does it serve the needs of that group, of that person to respond in kind or to respond in Truth? That doesn't mean we become weak or pushovers. In fact I think it means the exact opposite.

How much harder and how much more courage does it take to say what needs to be said to someone or to a group of people in a situation? It is dang tough. That is real strength, not cowardice or 'playing nice'. What about when a group of co-workers start bashing what you believe and they don't know you're a Christian? Easier to go along with the jokes or controversy or easier to stand up and speak 100% Truth with 100% Love? As my coach used to say in high school, T-U-F,, 'TOUGH!"

Does your friend who's heading the wrong way in life need you to look the other way? Does he need some half-hearted and unrealistic encouragement? Or does that friend need you to cry with him? Does she need you to confront her? Does he need you to pray for him and with him?

Service to others comes in every relational situation. What about your spouse? Does it serve your spouse when you watch 4 hours of television when you get home and dont take time to make a meaningful relational connection? What about your children, how are you serving their needs for a meaningful relationship with a Father or a Mother?

Kingdom Greatness, is about looking into the heart of relationship and asking, "What does this person need?" And that is, usually, never easy to do. So to answer the question above, I think that being a Christian does mean drinking from the cup of Jesus and immersing ourselves into the hurt, the wretchedness, the loneliness, the bitterness, and the hard and forsaken places of relationship and to bring the healing, the love, the forgiveness, the grace, and the Truth that Christ has for those situations. Talk about a stiff drink.

The 'service' that Christ slaved himself to, what He saw as our greatest need was redemption of our relationship with God, with each other, and ourselves. He knew we would be best served if He would redeem relationship and break the powerful curse and grip of sin that reigns down terror and destruction on our relationships. And because He saw that great need in our lives, He took that cup, drank, and gave "His life as a ransom for many" (v45.)

That's greatness.

Digoxin

Okay, so Digoxin is one of those topics in medicine that has always been a little nebulous to me. It didn't help that my pharm profs were about as interesting as bingo night at the community center. That and I'm half retarded.

So here is my review of Dig. It is by no means exhaustive. Please post your thoughts or corrections.

This is probably more aggressive med-student, intard (half intern, half retard), or other resident oriented.

Digoxin

1. Digoxin -- What is it?

Digoxin is a cardiac glycoside. Glyco-who? Yeah, my cards attending didnt even know what that meant. 'Glycoside' is a throwback to Organic chemistry. Basically a glycoside is a sugar group attached to a non-carbohydrate group. There's a decent review of glycosides on wikipedia. So a glycoside is basically a O-chem description of it's basic structure and 'cardiac' is there to direct our attention to where its primary effects play out.

So 'cardiac glycoside' really means some O-chem weirdness that interfaces within the cardio-sphere.

You can increase your geek power with the following trivia and history: Cardiac glycosides have actually been in use for thousands of years and come in many shapes and forms throughout nature. Squill, Oubain, Oleander, et cetera are other glycosides that have been used for various purposes throughout history. Digoxin (aka Dig, Lanoxin, Lanoxicaps, Digitek, 12-Hydroxydigitoxin) got its start with William Withering in 1785 and was originally thought to be an effective treatment for 'Dropsy' (the old school term for 'edema').

But we know that Dig is a cardiac glycoside with positive ionotropy = Dig is some type of O-chem thing that increases the strength of cardiac contractions.

2. Mechanism of Action (MOA)/Pathophys

What's important here is that my review of the pathophys is by NO means utterly complete. My review is more on the short yellow bus side of things. There is a pretty intense review of it on emedicine here (http://emedicine.medscape.com/article/154336-overview). Also, the BRS Physiology book has some pretty helpful pics too.

I found it helpful to think about the MOA in three arms.

• Na+/K+ ATPase poison which eventually leads to positve ionotropy
  
• Enhances the parasympathetic arm of the nervous system (increases vagal tone and thus inihibits the AV node and thus decreases heart rate)
  
• Increases automaticity of cardiac cells (the chance/likelihood that cardiac cells will spontaneously depolarize/contract on their own and apart from the SA node)

The Na+/K+ ATPase poison MOA is actually clinically relevant. Sigh.

The abbreviated version is as follows and a bit more detailed explanation follows:

1. Dig = Na+/K+ ATPase poison via competitive inhibition with K+
2. Increasing Na+ concentration in the cell (via #1) stops the expulsion of calcium from the heart by abolishing the gradient that the Na+/Ca++ exchanger uses
3. (#2) causes increased calcium in the cardiac cells which increases strength of contraction
   

The cardiac cells have these large sodium and potassium exchangers to help maintain electroneutrality, concentration gradients, and all that other physiology crap that we try to cram in the night before the exam right? So in the cardiac cells, the sodium and potassium pump moves sodium out of the cell and potassium into the cell from the extracellular space. Digoxin competes with K+ for binding spots on the pump. When digoxin binds, that said pump is rendered worthless for a time. So if you stop pumping Na+ out and K+ in then you start changing the concentration of Na+ and potassium in the cell right? More Na+ inside the cells and more potassium outside the cell.

Now we move to the Na+/Ca++ exchanger located within that same cell. This exchanger helps to regulate the amount of calcium in cardiac cells by kicking calcium out of the cell and pulling sodium into the cell. It doesn't use ATP to exchange, though. It relies on the low/high concentration of Na+ inside/outside the cell to drive the transport of calcium out of the cell. Thus, if you increase sodium on the inside of the cell then you basically spank that exchanger on it's big protean fanny (i.e. abolish the concentration gradient) and you get more calcium in the cell.

More calcium means stronger contractions. (This is done by several mechanisms which will not be discussed here.)

If you follow the above link, there is also some discussion as to how Digoxin increases automaticity. My cave-man brain didn't find that information as clinically useful to remember so I refer you elsewhere for that explanation.

And if anyone knows how Digoxin enhances parasympethetic activity, I would really like to know. My cards attending, who is wicked smart, and cards fellow were both clueless about that particular MOA. Anyone know? Please post a reference if you know.

What I do know is that Dig enhances parasympethetic activity and thus increases vagal tone (among other things) and that contributes a large part to the AV node inhibition that Dig is known for.

3. Metabolism

A couple of important points to keep in mind here.

1. Digoxin winds up in urinal (i.e. renal excretion)
2. Thyroid status, age, and meds will alter serum levels

Digoxin is renally excreted. This absolutely clutch to keep in mind. Folks that come in with various degrees of renal failure can have a wide array of dig-toxic findings (discussed below.)

Other things that affect Dig metabolism:

• Thyroid. Hyperthyroid patients chew through their dig faster so they will need increased concentrations. Hypothyroid are the exact opposite and will require less.
  
• Age -- them older peeps are kind of like hypothyroid patients; i.e. less is better. This is probably due to decreased GFR in older folks more than anything else.
  
• Meds -- there are mega-lists of drugs that affect the serum levels of digoxin. The general trend is for meds to increase serum levels of digoxin. A few drugs that I keep in mind are Amio (increases dig levels), Erythromycin/Clarithro (and some other Abx increases dig), Captopril (increases dig), and cholecystyramine (and other binding resins decrease the amount of dig in your system). That is just to name a few.

4. Uses

This section is probably one of the weaker ones. I am an ED resident so starting Dig and all the nuances/trials related to its uses are not as pertinent to me. But here is a very brief review of how and when Dig is used and not used.

A) Rate Control -- Digoxin can be used as a rate control for Afib and Aflutter and other atrial tachyarrythmias (though my familiarity is with the former two primarily). This is not acute action and requires dig loading followed by maintenance doses. This is accomplished through Dig's AV node blocking MOA.

B) CHF -- the long of the short of it, as I understand it, is that Dig does NOT affect morbidity or mortality CHF patients but does improve symptoms in select patients.

There have been many trials but two of the big ones are the RADIANCE trial which compared stopping dig in CHF patients on diuretics and ACE-inhibitors versus not-stopping it. People that were discontinued from Dig had worsening CHF, etc.

The DIG trial was the good ol' randomized, double-blind daddio that showed no mortality benefit but symptomatic improvement with Digoxin in CHF. Digoxin, from this trial, benefited patients with severe/class IV symptoms, cardiomegaly on CXR, and/or ejection fraction <25%. dig =" bad" style="font-weight: bold;">

5. Digoxin Toxicity

1. Toxicity is dose dependent but don't depend on serum levels. Go with the clinical picture.
   
2. Get an ECG. There are 3 classic arrythmias. 3 you never see. And everything else in between.
   
3. There are a wide array of symptoms, the primary being decreased CNS, increased visual, increased GI, and cardiac arrythmia and arrest badness.
4. Treatment depends on clinical context. Know your K+ level (NO Calcium!), use atropine early, digibind, activated charcoal on a case-by-case basis
   
5. Digibind has 5 indications for use.

Digoxin has a scary narrow therapeutic window. So it's not hard to get dig-toxic. And toxicity is dose dependent which seems simple enough right? Wrong.

It takes 6-12 hours post-dig ingestion for a serum dig level to reflect actual levels in the body. So when someone presents with acute dig toxicity, a dig level may be helpful if it's elevated but is otherwise worthless.

I.e. patients can be dig toxic with a normal dig level.

The clinical picture trumps lab values. And that's not a bad approach to medicine in general; treat the patient and not the number.

Dig toxicity can do just about anything to a person clinically. I've seen a few people turned into weird animals, others declared me a genius, and some actually thought ol' Presidente GW Bush was a phenonemal public speaker.

There are five things that I think are helpful to remember about symptoms and dig toxicity.

1) Dec CNS symptoms -- drowsy, fatigue, lethargy, etc
2) Inc GI symptoms -- nausea, vomiting, diarrhea (very common)
3) Visual symptoms -- yellow discoloration (Xanthopsia is the fancy medical term for all you purists out there) blue discoloration, flashing halo's, and other visual changes
4) Cardiac badness -- tachycardia, bradycardia, arrest, and everything else in between

ECG findings. If you find yourself getting pimped on a ECG and your attending wants a differential for 'what could cause this type of arrythmia' a great answer is 'Digoxin'. Digoxin can literally cause every type of arrythmia except for the following three: irregularly irregular Atrial fibrillation, Atrial flutter, and a Mobitz 2 (I am not positive about the Wenkebach). You will NEVER see the above three rhythms (plus or minus a Mobitz 1 (anyone know?)) with Dig toxicity.

The three classic rhythms with dig toxicity are a PAT with AV block, biventricular tachycardia, and slow and regular afib; this ECG will have no p waves but will be regular as the day is long (because a junctional escape rhythm keeps the ventricles beating), and it will generally be fairly bradycardic due to the junctional pace. I have seen the slow/reg Afib twice, and both patients were dig-toxic and symptomatically bradycardic.

The most common ECG finding is PVCs which sucks because that is so freaking non-specific.

And every other type of arrythmia is fair game for digoxin except for the three noted above.

Treating a dig-toxic patient has several steps. First and always most important is hemodynamically stability. But that is not necessarily dig-specific.

So the first dig-specific treatment issue is Potassium. Hypokalemic patients will have an exagerrated effect because there is less K+ to compete with Dig. So in effect you have more dig. So check a K+ and replete aggresively. The same goes for Mg++, because Mag is a cofactor for the Na+/K+ ATPase. Replete K+/Mg+ level aggresively.

BUT if a patient is hyperkalemic that could be catastrophic.

Hyperkalemia is bad prognostic sign in dig-toxic patients.

Severe dig-toxicity causes hyperkalemia because the Na+/K+ ATPase is so poisoned that serum potassium is now being elevated which compounds predisposition for arrythmia nasty. So what do hyperK+ cardiac unstable patients need? Calcium right? You wanna push that calcium gluconate or pound them with Ca-Chloride?

Congratulations doctor you just killed your patient, somebody call a lawyer. NO calcium for dig-toxic patients! Their myocardium is already loaded with calcium. More calcium is going to lock those myofibrils down and create the 'stone heart'. Either that or they are going to go into some aweful arrythmia that will not respond to anything.

So what does the hyperK+ dig-toxic patient need? Hemodialysis and if the K+>5, it is a true emergency and is generally fatal unless treated. This brings up another great point. Hemodialysis is really not a great modality to eliminate digoxin in dig-toxicity; digoxin has a high volume of distribution (ie it's all up in the tissues and thus not as amenable to being cleared from the blood by dialsysis). These patients need Digibind.

Digibind is a monocolonal antibody that binds digoxin. This renders digoxin ineffective and then they ride that wonderful golden stream right out of the body and into the white porcelain god bound ever-so-tightly like two star-crossed lovers.

Digibind has specific indications though. The five I know of are as follows: (1) >.1mg/kg or >4mg ingestion in peds or >10mg ingestion in adults (2) Dig serum > 5 (3) K+ >5 (4) Cardiac badness (ie arrythmia) (5) rapid progression of symptoms.

The only other two things I would think about are atropine and activated charcoal.

If your going to use atropine, use it early.

Activated charcoal is not recommend, by the American Academy of Toxicologists, for routine use. But if you have a known ingestion that is very acute. Then you may want to consider it.

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There's always more but that's what helped me understand the nuts and bolts of Digoxin in a Sesame Street sort of way. I hope it helps you.

I used DynaMed, NEJM, eMedicine, wikipedia, and other sources to educate my brain on the matter. My thanks and acknowledgement goes out to those higher lifeforms for their extensive scholarship on the matter.