A Man Was Kissed By His Dog. This Is How His Organs Shut Down.
JD is a 63 year old man, presenting to the emergency room with fever and shortness of
breath.
He tells the admitting nurse that purplish spots had developed around his face, starting
3 days ago, and the feeling in his right leg, started going numb.
JD was a healthy 63 year old. He hadn’t been to the hospital recently, and he hadn’t
traveled anywhere.
Whatever was happening to him, was something new.
At examination, bruise-like spots were found all over his legs. There were no cuts or wounds
present.
If you put these together with fever and shortness of breath in someone who was fine a few days
ago, then this kind of looks like an infection.
Good thing he didn’t have a headache with neck stiffness, because if he did, that could
mean meningitis, which is an infection that affects the brain.
A blood test reveals that JD has lymphocytopenia.
Lympho derived from Latin lympha, the goddess of water, and today referring to a type of
white blood cell that fights infection.
Cyto meaning cell.
And Penia meaning deficiency of.
A deficiency of white blood cells that fight infection.
This was combined with an increase in blood markers that indicate that JD has increased
inflammation, meaning that his immune system is now more active than normal.
There was definitely something, going on.
Additional tests revealed JD had thrombocytopenia.
Thrombo from Ancient Greek θρόμβος (thrombus) meaning piece or lump, referring
to a clot of blood.
A deficiency of blood clot cells.
This makes sense, because more markers reveal that he has liver dysfunction.
The liver is supposed to make blood clotting factors that stop you from bleeding when you
get a cut. A dysfunctional liver, means those factors aren’t being made properly. And
this fits with thrombocytopenia, giving the medical team some more clues as to what’s
happening because
It’s found that JD has acute kidney injury. Muscle proteins were found floating around
in his body, meaning that his muscles were breaking down, actually dissolving away. These
muscle proteins get caught in his kidneys and start to damage the tubules. All of this
is only the start of his problems.
When you work out, your muscles produce lactic acid as a metabolic byproduct from increased
activity. But for JD, so much lactic acid was found in him, that he is in acidosis.
And there was no indication that he was doing any strenuous exercise.
Meaning that large parts of his body might not be receiving enough oxygen in compliance
with demand for normal function. Without taking medicines, or any history of other disease,
but a fever and skin reaction, this could point to a possible massive bacteremia, or
bacterial presence in blood.
The fever. The liver dysfunction. The dissolving muscles and kidney failure. All of these add
up to a medical emergency with impending life threatening consequences, as JD is admitted
in to the hospital.
Multiple antibiotics were started empirically. This means that the medical team doesn’t
know exactly what bacteria is floating around in JD’s body at the moment, so they want
to cover as much as they can during this time.
The reason this is done is because figuring out which bacteria is causing his problems,
will take days. Samples need to be collected from the body, and from those samples, bacteria
needs to be grown and cultured to get a measurable amount that can be identified. The days this
will take, are days that JD doesn’t have, because his muscles are dissolving inside
of him, and his organs are shutting down.
As the hours pass, JD’s mental status starts to decline. He becomes disoriented and confused.
This encephalopathy means that his liver isn’t just dysfunctional, he’s now in acute liver
failure.
More monitoring finds that his kidneys are worsening.
His intestines are now obstructed because the muscles of his GI tract have become paralyzed
as the bruising on his skin become a deeper purple color.
As the night continues.
A code is announced on the hospital speakers. JD’s heart has stopped beating.
Doctors, nurses, and pharmacists immediately converge on his room to try and bring him
back.
Several minutes pass. A heart beat comes back and he’s resuscitated.
But his blood pressure is still low.
A tube is placed down his throat and he’s put on mechanical ventilation.
Medicines are administered to him to both constrict his blood vessels, and to promote
the force of his heart contractions.
All of this is done because if his organs are not perfused with blood because of that
low blood pressure, the bad things happening to him, will worsen. But as time continues,
those bad things, continue to worsen.
The kidneys are supposed to filter blood. If they don’t, metabolic waste begins to
build up.
And because he isn’t getting any better,
his kidney failure continues to decline and he’s put on a machine that
does that filtering for him, something called dialysis.
If JD was previously healthy, what is even happening? How can he go from living normal
life one day, to having his heart stop in a hospital bed a few days later?
Blood culture results from the lab return to the medical team. A gram negative rod shaped
bacteria identified as Capnocytophaga canimorsus was found. This bacteria lives in the mouths
of pet dogs and cats. It doesn’t affect canine or feline lifeforms. It doesn’t live
natively inside humans. If a human comes in contact with this bacteria, the immune system
almost always destroys it, protecting our bodies from infection.
But if a human gets a bite from those animals, and that person is immunocompromised, meaning
their immune system isn’t working properly, then this bacteria can proliferate and spill
into bloodstream. And when the body issues a generalized response to this bacteria in
the blood stream, the uncontrolled reaction by the immune system, shuts down the entire
body.
When you get a cut, the surrounding area becomes swollen, red and warm. This inflammation is
the immune system sending white blood cells, sending chemical and protein signals to the
site of injury. The walls of the blood vessels are forced to relax by these mediators so
that more immune cells can enter the site, as fluid rushes in, causing the swelling.
This is similar to what’s happening to JD, except instead of a small localized region,
his entire body’s blood vessels are forced to relax, causing his blood pressure to drop.
Without adequate pressure to push the blood through the organs, it results in Tissue Ischemia.
Isch from an old greek word meaning to restrain
Emia meaning presence of blood.
A restrained presence of blood, in the tissues.
As less oxygen from blood reaches the organs, their dysfunction begins to set in.
The inner lining of the blood vessels in these organs start to develop lesions. This is because
activated white blood cells bind to the cells of this lining, forcing the release of reactive
chemicals (Reactive oxygen species, lytic enzymes and NO, endothelia, PDGF, etc), injuring
them and forming lesions all along this lining.
The result of this cellular insult means that the blood vessel narrows, making it even harder
for blood to pass through the organs. When combined with a low pressure to push that
blood through, the organs aren’t just dysfunctional anymore, they’re all starting to fail.
As less oxygen is delivered to the organs, mitochondrial dysfunction starts to happen
in the cell. Respiratory enzymes that make the mitochondria the powerhouse of the cell
become inhibited, meaning energy is no longer produced properly. Stress begins to build
up, as mitochondrial DNA begins to break down. The same chemical that dilates the blood vessels
(Nitric Oxide btw) in inflammatory response, approaches the inner membrane and the matrix
proteins of the mitochondria, and begins to dissolve the mitochondrial ultrastructure.
Instead of a powerhouse, the mitochondria degrades into a sludge that promotes cellular
death,
And causing all of his organs to shut down. This is called sepsis, and the resulting low
blood pressure, is septic shock.
If the Capnocytophaga canimorsus bacteria is swarming around in his blood and forcing
his immune system to react this way, then where did it come from? And how did it enter
his body?
Closer examination of JD finds no dog bite marks, no scratch marks, so those are ruled
out.
He was previously healthy, meaning he has no history of immunodeficiency or history
of taking medicines that could compromise his immune system.
His family confirmed that JD did love his pet dogs. He was very close with them.
The spleen is an organ that recycles old red blood cells, but it also stores white blood
cells, which are integral to the immune system. If someone doesn’t have a spleen, then they
could be predisposed to an infection from Canocytophaga, but JD’s spleen was functional,
MEANING that all of this points to misfortune and a freak accident, because without a bite
mark, or any predisposing factors that would indicate immunocompromise, it means some degree
of licking and puppy kisses delivered Capnocytophaga Canimorsus from the dog’s mouth, to some
entrance in his body, whether through his mouth or through the pores of his skin, as
this zoonosis was spread all throughout his body.
A Capnocytophaga infection, is rare. In the United States millions of people have dogs,
and the infection isn’t even tracked. In the Netherlands, a record of 0.67 cases per
1 million people happen per year, meaning JD is less than 1 in a million. And among
those who do have a Capnocytophaga infection, the fatality rate is around 25%, meaning because
he is 1 in a million, there’s a chance he could be 1 in 4, too.
Additional antibiotics were added to his regimen. As days pass, JD’s fever clears. Repeat
blood tests find improvements in some markers, but worsening in others.
On the 8th day of hospitalization, a fungus named Candida albicans was found in his blood.
Fungus has nothing to do with the dog. Where did that come from?
Well, some clinical implications need to be accounted for here.
Candida is present in your gut microbiome. This would be all the microscopic organisms
that live inside your stomach and intestines to help you digest. When broad spectrum antibiotics
are given, like in JD’s case, lots of the bacteria in that microbiome are incidentally
eliminated. But candida is a fungus. Antibiotics don’t affect fungus that way. It starts
to take over, reproduce en masse, and cause a fungal overgrowth.
Because JD was in the intensive care unit, a central line was placed. This gives the
medical team access in to his body. Candida lives on your skin. It’s not affecting you
right now because you’re probably not admitted in the intensive care unit. But as the catheter
has a connection directly to a central vein for JD, through his skin, it introduces a
vector for the fungus, to enter his body, and to colonize, increasing his risk for infection
the longer that it’s in place.
An antifungal medicine was added to JD. His skin started blistering and 10 days after
the initiation of antibiotics, signs of systemic infection were still present.
Blood tests seemed to normalize in him. His thrombocytopenia seemed to resolve. His muscles
didn’t seem to be dissolving anymore.
But the next day, the nurse alerts everyone that JD’s fever has returned. More tests
find that inflammatory markers were rising, again.
Typically, if a patient is starting to improve but the fever returns in the intensive care
unit, this could indicate a hospital acquired infection. But in the ICU, most of these parameters
can be controlled, so another antibiotic was added again to JD.
A CT scan of his chest revealed possible pneumonia. This time from a new fungus, aspergillus fumigatus,
as was detected in secretions from his trachea. Antifungal medicine was changed and his antibiotic
regimen was simplified. For the next few days, JD was improving, again.
But 4 days later, an abdominal CT scan revealed that the blood flow to his spleen is now obstructed.
This infarction, a Latin word meaning to stuff or pack into, means that something caused
a blood clot to be stuffed into a vessel of his spleen. The scan confirms a complete infarction
meaning that all blood flow was obstructed, as the organ begins to necrose.
As doctors look at JD, they see that all 4 of his limbs have developed gangrene, meaning
that the blood supply has been cut off from them, and that the tissue is no longer viable.
If he survives this, it’s likely that he won’t have his original limbs to use for
the remainder of his life.
Sepsis has been known to humans for several thousand years now. The ancient Egyptians
used these glyphs to describe a principle, something, that couldn’t be seen by the
eye, that was contained near what we know now as the intestines. This principle, could
travel up to the heart and cause death. We know this principle today as bacteria because
we’re able to see it with microscopes, but Ancient Egyptians didn’t have microscopes,
meaning they knew something from the gut, can cause very bad problems.
The interesting thing about these glyphs, is that the fifth one, is not pronounced.
It indicates that the word or idea presented by the immediate previous glyphs are describing
something disgusting. In the Ancient Egyptian hieroglyph for the brain, that same final
glyph is present, meaning that the Ancients, thought the brain was something disgusting.
But the Greeks developed the Egyptian idea of self-intoxication from something disgusting
stemming from the intestines and the brain. They used the word sepsis (σ̃ηψιζ) which
implied a bad smell, and it was contrasted with pepsis which described a concoction of
some sort. Hippocrates wrote that sepsis was the process by which flesh decays, swamps
generate foul airs and smells, and the process by which wounds fester. Clearly he knew something
he couldn’t see with eyes, was the cause of all these problems.
In western civilization, it took 2000 years to further develop these ideas. In 1684 an
Italian physician Frencesco Redi ran an experiment to see if sepsis really produced small creatures spontaneously,
as written by Aristotle.
He took pots filled with meat, fish or cheese and let them rot in the open. Flies gathered
and laid eggs, creating maggots. He repeated the experiment, this time with a fine gauze
covering the meat, fish or cheese. Flies gathered, but this time, could only lay their eggs on
the gauze. No maggots grew on the baits, meaning that small creatures don’t spontaneously
generate from the process of sepsis.
Today, we know the idea behind these hieroglyphs is bacteria. And even more recently, Capnocytophaga
canimorsus used to be called DF-2 (dysgonic fermenter) in pre 1990 literature, because
it hadn’t been classified as a new species. The first case report was in 1961 California
when a 17 year old boy who had undergone splenectomy 3 years earlier for a football injury had
sustained a dog bite, and fell ill days later. Several reports describing DF-2 are in literature
before 1989, when it was finally given it’s name.
And while germ theory of disease gave a basis for bacteria causing sepsis, it didn’t explain
why patients’ organs still shut down, in cases when the target bacteria was successfully
eliminated from the body. This multi-organ failure, is the same one that’s happening
to JD.
Another CT scan is done on his head. In his brain, severe hypoxia, or low oxygen, was
found along with a swelling of fluid. Because the brain is enclosed in the skull, there
isn’t much room for it to expand when there is a swelling of fluid, meaning that permanent
brain damage is happening to JD.
The medical team meets with his family, and it’s determined that therapy will be de-escalated.
If he comes back from this, he will have permanent brain damage. He won’t have his original
arms and legs to use anymore. There there will be likely loss of normal function for
all his organs.
In septic shock, sometimes it’s not just the bacteria itself that causes the problem,
it’s how the body responds.
Starting with the Tissue Ischemia, almost everything described in the process of the
organs shutting down, was not just caused by the bacteria but also by the human immune
system. The Nitric Oxide dilation of the blood vessels caused low blood pressure. The white
blood cells caused endothelial damage to the lining of the blood vessels and caused microcirculatory
lesions, narrowing the vessel, worsening the decrease in blood flow, in the face of severe
hypotension.
Capnocytophagia canimorsus is one of the most lethal sepsis pathogens described. It’s
right up there with Neisseria meningitidis and Streptococcus pneumoniae. Those names
tell you what they cause. Capnocytophaga can live inside white blood cells after it has
been phagocytosed, or eaten by them. So as the immune system tries to destroy the bacteria,
they hide inside instead. They can do this because they create an enzyme that breaks
down hydrogen peroxide that would have otherwise destroyed them inside the immune cells. Something
called catalase. And as they reproduce, break out and diffuse through the blood stream,
the immune system reacts systemically as Capnocytophaga spills everywhere.
Small blood clots form as the complement system is activated from inflammation before the
liver shuts down. These clots lodge into the extremities, cutting off blood flow to them.
Causing gangrene to develop as the tissue starts to necrose.
Just like what happened to JD.
On day 16 of his admission, the therapy was finished. Days later, he was returned home
to family for processions.
The point of this case, is not to scare anyone of their animals.
The infection is rare enough that it’s not tracked in the United States. If you aren’t immunocompromised,
and are a healthy person with a strong immune system, getting kissed by your dog or cat
probably isn’t going to be a problem.
But the point of this case is to say if you have pets, and are very close with them physically,
if you develop flu like symptoms that’s worse than a simple viral infection, you want
to get that checked out immediately. These flu-like symptoms include things like an intense
fever with bruise-like spots developing under the skin in places that you haven’t bumped.
Big dark spots that rapidly develop.
Or something like a severe shortness of breath, don’t wait. Get it checked out immediately.
I think most folks know of someone in their life, who had a fever, and a couple of days
later, passed in the hospital. There’s a good chance that that was some degree of sepsis
from either waiting too long, or from a freak accident.
And for anyone watching who is in clinical practice or comes into contact with patients,
you know that the clinical course for a patient with bacteremia and sepsis, can decline in
just a couple of hours, and I’m sure you’ve heard or seen situations where when you come
back for your next shift, that patient is no longer with us.
Even if the incidence is less than 1 person per million, there’s more than 300 million
here in the United States, so statistically, around 300 people can get an infection from
a dog licking them, biting them, or anything involving a dog’s mouth, just like in JD’s
case.
So take care of yourself. And Be well.