This course introduces learners to a variety of infectious diseases using a patient-centered, story-based approach. Through illustrated, short videos, learners will follow the course of each patient’s illness, from initial presentation to resolution. Integrating the relevant microbiology, pathophysiology and immunology, this course aims to engage and entice the learner towards future studies in microbiology, immunology and infectious diseases. The patient-centered videos included in this course were created as part of the Re-imagining Medical Education initiative, led by Charles Prober MD, Senior Associate Dean of Medical Education at the Stanford School of Medicine. This initiative was the first of its kind to explore the collaborative creation of foundational medical education online content by inter-institutional teams of faculty. The content presented in this course was created by faculty from Stanford University School of Medicine, in collaboration with The University of Washington School of Medicine, Duke University School of Medicine, UCSF School of Medicine, and The University of Michigan Medical School. Support for this initiative was provided by the Robert Wood Johnson Foundation and the Burke Family Foundation. PLEASE NOTE: Information provided in this course is for educational purposes only and is not intended to be used for diagnostic and/or treatment purposes.
Gram Negative Sepsis
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來自 Stanford University 的課程
Stories of Infection
666 個評分
從本節課中
Bacterial Infections Part 2
In Module Three, we will explore seven additional cases of infectious disease involving bacteria. We will see how a timely and accurate diagnosis can be vital for a patient's survival. By the end of this module, learners will be able to interpret the clinical presentation of these seven infectious diseases and describe the relevant microbiology, pathophysiology, and immunology.
與講師見面
Maya Adam, MDLecturer
Stanford School of Medicine
Today, we'll be talking about sepsis, a syndrome in which an overwhelming infection
can lead to a widespread inflammatory response that spirals out of control,
as it did in the case of this 51-year-old tech entrepreneur and father, named Chuan Li.
Chuan Li had recently sold his successful software company
and was excited to make the most of his new freedom by spending time with his young son,
learning to cook, and taking up cycling.
At first, when he started feeling more tired than usual,
he thought he was just having trouble adjusting to the long bike rides.
But over the next few weeks, the fatigue got worse.
Not only did Chuan Li have to give up his cycling routine,
but he became so weak that he could barely carry his son upstairs at bedtime.
When he met up for lunch with some former colleagues,
they almost didn't recognize him because they said he looked so pale.
Chuan Li went to see his physician, who ordered some blood work,
and found that he was severely anemic
with a low platelet count but a high white blood cell count.
The physician worried this could be a blood cancer.
So he sent Chuan Li to be admitted to the hospital
where he could quickly receive a blood transfusion for his severe anemia
and a bone marrow biopsy to determine the diagnosis.
Unfortunately, when the pathologist looked at Chuan Li's bone marrow under a microscope,
he saw that it was filled with immature white blood cells.
And Chuan Li was diagnosed with acute myeloid leukemia.
Chuan Li was kept in the hospital,
and he was given a peripherally inserted venous catheter,
extending from a vein in his arm to his superior vena cava,
so he could begin multi-drug chemotherapy to destroy the cancer cells
and allow his normal bone marrow function to return.
Because chemotherapy drugs
often reduce the white blood cell counts to dangerously low levels,
Chuan Li was kept in a private room with extra measures to prevent infection.
Even his little boy was only allowed a few brief visits
and had to wear a mask while visiting his dad.
But in spite of these precautions, five days after beginning chemotherapy,
Chuan Li's temperature spiked to 39.8 degrees Celsius,
and he began complaining of shaking chills.
His heart rate and breathing rate were also elevated.
Around the same time, Chuan Li's morning blood work results came back showing
that he had a dangerously low white blood cell count with almost no neutrophils.
Chuan Li's nurse immediately recognized
that he met the criteria for systemic inflammatory response syndrome or SIRS.
SIRS is as a collection of physical findings like abnormal body temperature,
rapid heart rate and breathing,
and abnormal white blood cell count,
that together suggest widespread dysregulated inflammation throughout the body.
Although SIRS can occur with some noninfectious conditions,
when it occurs as a result of a confirmed infection,
the patient is diagnosed with sepsis.
Because Chuan Li was immunosuppressed from his chemotherapy,
the nurse knew that an infection
was the most likely explanation for these worrisome changes in his vital signs.
She paged the attending physician, who came to the bedside right away.
Because patients with sepsis can deteriorate quickly,
Chuan Li's doctors arranged for transfer to the intensive care unit
for continuous monitoring and treatment.
Meanwhile, they started him on supplemental oxygen through a nasal cannula
and continuously tracked his blood oxygen saturation using a pulse oximeter.
The nurse established multiple routes of intravenous access
so that fluids and medications could more easily be administered.
He was started on IV fluids to improve blood flow to his tissues,
and blood samples from two separate sites, including his PICC line,
were taken and sent for Gram stain and culture.
Gram stain of the blood samples from both sites showed Gram-negative bacilli,
and a diagnosis of Gram-negative sepsis was confirmed.
Chuan Li's doctors also knew that it was important to identify
and treat the specific source of infection, so his PICC line was removed,
since any indwelling catheter is considered a potential culprit.
The doctors also ordered a chest x-ray
and took a urine sample for urinalysis and culture, but these tests all came back normal.
But, on physical exam, they noted that Chuan Li had multiple sores in his mouth,
a common side effect of chemotherapy for AML.
In patients like Chuan Li who are also neutropinic,
this opening in the mucosal barrier
that normally protects us from invading pathogens can be enough to allow bacteria to enter
and infect the bloodstream.
When Gram-negative bacteria invade a person's tissues,
the inflammatory response begins with pattern recognition receptors,
like the toll-like receptor family on the surface of macrophages
which recognize the lipopolysaccharides in the cell wall of the bacteria.
This binding and recognition leads to activation of nuclear factor-kappa B
or NF-kappa B within the macrophage.
Activated NF-kappa B is free to move from the cytoplasm to the nucleus,
where it acts as a transcription factor to induce the expression
of a wide variety of genes involved in theinflammatory response.
These genes include pro-inflammatory cytokines, chemokines, and nitric oxide.
In response to these signals, neutrophils and additional macrophages are activated
and deployed to the site of infection,
where they release more signaling molecules to change the local physiology.
Together these changes result in the cardinal signs of local inflammation:
warmth and redness due to local vasodilation,
and edema due to increased permeability of the small vessels.
Normally, this process is localized at the site of infection but in some patients,
especially those like Chuan Li who have bacteria within the bloodstream,
macrophages become activated
to release high levels of inflammatory cytokines throughout the body.
This unregulated, self-sustaining production of inflammatory cytokines
explains Chuan Li's fever.
The circulating cytokines also decrease the muscle tone of the heart and arteries
and increase the vascular permeability
so that plasma leaks from the blood vessels into the tissues.
Chuan Li's body was working to compensate for these changes
by increasing his heart rate and respiratory rate.
But in cases like this,
if the process is allowed to continue, oxygen delivery to the tissues can be impaired,
and the patient's blood pressure can drop, leading to septic shock.
Despite the initial efforts to support Chuan Li's breathing and tissue perfusion,
his condition had worsened by the time he got to the ICU.
His blood pressure had begun to drop, and he was now lethargic and disoriented.
His oxygen saturation began to decline, so the decision was made to intubate him
and provide mechanical ventilation.
He was promptly started on IV antibiotics, and IV fluids were continued.
Later that night, the nurse noticed that Chuan Li's oxygen saturation was dropping again.
When the physicians examined his lungs, they heard crackles,
and a chest x-ray confirmed
that some of the extra fluids he was receiving were leaking into his lungs
and impairing his ability to oxygenate the blood.
Now, his doctors had a dilemma.
They couldn't give him more fluids without flooding his lungs,
but his blood pressure was still dangerously low.
So he was given norepinephrine,
a drug that constricts the blood vessels to help maintain blood pressure.
Despite all these interventions,
Chuan Li's vital signs remained unstable over the next few days,
and his daily blood tests for liver and kidney function progressively worsened
due to his inability to deliver oxygen to those organs.
His kidney function was especially poor, to the point where he had stopped making urine
and could no longer maintain his blood electrolytes in the normal range.
Throughout Chuan Li's illness,
the team of doctors had maintained an ongoing open discussion
with Chuan Li's wife and parents.
And at this point, they held another family meeting.
They broke the bad news that Chuan Li's organs were failing as a result of his infection,
and that his illness was probably going to take his life,
even with the most aggressive medical care.
After a long difficult discussion,
the family decided to request that Chuan Li's breathing to be removed,
and he died a few hours later, surrounded by his family.
