Sepsis & Septic Shock

Prepared and presented by
Marc Imhotep Cray, M.D.

Shock Capsule
2
Shock is a clinical condition characterized by a fast pulse rate
(usually > 100 beats/min) and a low blood pressure (systolic blood
pressure usually < 100 mmHg)
Common types of shock are
 hypovolemic (low blood volume, e.g. in hemorrhage),
 cardiogenic (heart pump failure, e.g. in myocardial infarction)
 septic (severe infection) See: Systems-based Pathophysiologic High
Yield Cases-Case 15, Pg. 22.
Less common types are
 anaphylactic (type I hypersensitivity reaction, e.g. penicillin allergy)
 neurogenic (loss of sympathetic vasomotor tone, e.g. spinal cord injury)

Etiology of Circulatory Shock
3
Cardiogenic Shock
Myocardial infarction
Cardiomyopathy
Valvular heart disease
Ventricular rupture
Congenital heart defects
Papillary muscle rupture
Obstructive Shock
Pulmonary embolism
Cardiac tamponade
Tension pneumothorax
Dissecting aortic aneurysm
Hypovolemic Shock
Acute hemorrhage
Dehydration from vomiting, diarrhea
Overuse of diuretics
Burns
Pancreatitis
Distributive Shock
Anaphylaxis
Neurotrauma
Spinal cord trauma
Spinal anesthesia
Sepsis
View Full Presentation: Pathology and Pathophysiology of Shock

Stages of Shock
4
Shock is a progressive disorder that leads to death if underlying causes are not
corrected
 Exact mechanisms of sepsis-related death are still unclear; aside from
increased lymphocyte and enterocyte apoptosis, cellular necrosis is minimal
• Death typically follows the failure of multiple organs usually offer no
morphological clues to explain their dysfunction
King EG, Bauzá GJ, Mella JR, Remick DG. Pathophysiologic mechanisms in septic shock. Lab Invest.
2014;94(1):4-12.
 For hypovolemic and cardiogenic shock pathways leading to a patient’s
demise are reasonably well understood tissue ischemia, acute tubular
necrosis, lactic acidosis severe cellular and tissue injury cardiopulmonary
arrest
 Unless insult is massive and rapidly lethal (e.g., exsanguination from a
ruptured aortic aneurysm), shock tends to evolve through three general
(albeit somewhat artificial) stages…

The 3 Stages of Shock
5
These stages have been documented most clearly in hypovolemic
shock but are common to other forms as well:
 Stage 1 An initial nonprogressive stage during which reflex compensatory
mechanisms are activated and vital organ perfusion is maintained
 Stage 2 A progressive stage characterized by tissue hypoperfusion and onset
of worsening circulatory and metabolic derangement, including lactic
acidosis
 Stage 3 An irreversible stage in which cellular and tissue injury is so severe
that even if hemodynamic defects are corrected, survival is not possible

Comparison of Clinical Findings In Different Types of Shock
6
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.

7
Sepsis, Organ Dysfunction and Septic Shock: Definitions
Sepsis: life-threatening organ dysfunction due to dysregulated host response to infection
Organ dysfunction: an acute change in total Sequential Organ Failure Assessment (SOFA) score
of 2 points or greater secondary to the infection cause
Septic shock: Occurs in a subset of patients with sepsis and comprises of an underlying
circulatory and cellular/metabolic abnormality that is associated with increased mortality
persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm
Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate
volume resuscitation
New 2016 definition, also called Sepsis-3, eliminates requirement for presence of systemic inflammatory
response syndrome (SIRS) to define sepsis, and it removed severe sepsis definition. What was previously called
severe sepsis is now the new definition of sepsis.
Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock
(Sepsis-3). JAMA.

8
Septicemia Capsule:
 Septicemia arises through escape of bacteria from a focus of infection
such as an abscess
 Septicemia is more likely to occur in:
 people with an immunodeficiency disorder, cancer, or diabetes mellitus
 those who take immunosuppressant drugs, and
 drug addicts who inject
 Symptoms include a fever, chills, rapid breathing, headache, and clouding
of consciousness
 Sufferer may go into life-threatening septic shock
 Treatment Glucose and/or saline are given by intravenous infusion, and
antibiotics by bolus injection or IV infusion
 Surgery may be necessary to remove original infection
 If treatment is given before septic shock develops, prognosis is good

Sepsis & Septic Shock
9
Epidemiology
 Sepsis is a leading cause of morbidity and mortality in United
States, with an estimated incidence rate of 300 cases per 100,000
population and a case fatality rate of 20–50%
 Medical costs of sepsis in U.S. > $17 billion
 Rates of sepsis continue to rise secondary to medical advances 
widespread use of indwelling intravascular catheters, increased
implantation of prosthetic material (e.g., cardiac valves and
artificial joints), and administration of immunosuppressive drugs
and chemotherapeutic agents
 These interventions serve to increase risk of infect. & subsequent sepsis

Sepsis & Septic Shock (2)
10
 Sepsis is a continuum of conditions, from infection & bacteremia to sepsis
& septic shock
 Sepsis is life-threatening organ dysfunction caused by a dysregulated
immune response to infection
• Critical care experts have developed a severity score, called Sequential
(Sepsis-related) Organ Failure Assessment (SOFA) score, to predict
which patients are at highest risk of dying of sepsis
o The score is calculated 24 hours after admission to the ICU and every
48 hours thereafter
 Septic shock (“Sepsis-3” definition ) includes pts who, despite fluid
resuscitation, require vasopressor support and exhibit signs of organ
dysfunction (SOFA score ≥2) have a predicted mortality of 40%

11
Another commonly used term is Systemic inflammatory
response syndrome ( SIRS ) is a nonspecific inflammatory
state that may be seen w infection as well as w
noninfectious states (e.g. pancreatitis, pulmonary
embolism, and myocardial infarction)
 Leukopenia and hypothermia, included in SIRS case definition,
are predictors of a poor prognosis when associated w sepsis
NB: Four SIRS criteria are 1) tachycardia (heart rate >90 beats/min); 2) tachypnea
(respiratory rate >20 breaths/min); 3) fever or hypothermia (temperature >38 or
<36 °C), and ; 4) leukocytosis, leukopenia, or bandemia (white blood cells
>1,200/mm3, <4,000/mm3 or bandemia ≥10%)

Marc Imhotep Cray, M.D. 12
Hammer GD & McPhee SJ (Eds.). Pathophysiology of Disease: An Introduction to
Clinical Medicine, 7th Ed. New York, NY: McGraw-Hill Education, 2014.
Clinical definition
of sepsis
(Prior to 2016)

13
Relationship of infection,
systemic inflammatory
response syndrome (SIRS),
sepsis, severe sepsis, and
septic shock
Abbreviations:
ARDS, acute respiratory distress syndrome
CI, cardiac index
DIC, disseminated intravascular coagulation
MODS, multiple-organ dysfunction syndrome Dipiro JT et al, editors: Pharmacotherapy: A Pathophysiologic Approach,
8th Ed. New York: McGraw-Hill, 2011.

14
Etiology
 Although evidence of infection is a diagnostic criterion for
sepsis only 28% of patients w sepsis have bacteremia, and
only 10% will have primary bacteremia, defined as positive
blood cultures w/o an obvious source of bacterial seeding
 Common sites of infection among pts. w sepsis syndrome (in
decreasing order of frequency) include
 respiratory tract
 genitourinary tract
 abdominal sources (gall bladder, colon)
 device-related infections, and
 wound or soft tissue infections

15
Etiology cont.
Bacteriology of sepsis:
 Gram-negative bacteria ( Enterobacteriaceae & Pseudomonas ) ,
previously most common cause of sepsis, have been supplanted
by gram-positive organisms now cause more than 50% of
cases
o Staphylococci are most common bacteria cultured from
bloodstream, b/c of an increase in prevalence of chronic
indwelling venous access devices and implanted prosthetic
material

Pathogenic sequence of
events in septic shock
16
Activation of macrophages by endotoxin
and other proteins leads to release of
inflammatory mediators and immune
modulation resulting in host tissue
damage and, in some cases, death
Hammer GD & McPhee SJ (Eds). Pathophysiology of Disease: An Introduction
to Clinical Medicine, 8th Ed. New York, NY: McGraw-Hill Education, 2018.

17
Pathophysiology of
septic shock
Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.

18
Signs and Symptoms Associated with Sepsis
Early Sepsis
Fever or hypothermia
Rigors, chills
Tachycardia
Tachypnea
Nausea, vomiting
Hyperglycemia
Oliguria
Myalgias
Lethargy, malaise
Proteinuria
Hypoxia
Leukocytosis
Hyperbilirubinemia
Late Sepsis
Lactic acidosis
Oliguria
Leukopenia
DIC
Myocardial depression
Pulmonary edema
Hypotension (shock)
Hypoglycemia
Azotemia
Thrombocytopenia
ARDS
Gl hemorrhage
Coma
 Clinical manifestations of sepsis:
 Those related to systemic
response to infections
(tachycardia, tachypnea,
alterations in temp. & WBC count)
and
 Those related to specific organ
system dysfunction
(cardiovascular, respiratory, renal,
hepatic, and hematologic
abnormalities)

Important to identify any potential source of
infection
19
 Localizing Sn & Sx referable to organ systems may provide useful clues to
etiology of sepsis and are as follows:
 Head and neck infections – Severe headache, neck stiffness, altered
mental status, earache, sore throat, sinus pain/tenderness,
cervical/submandibular lymphadenopathy
 Chest and pulmonary infections – Cough (especially if productive),
pleuritic chest pain, dyspnea, dullness on percussion, bronchial
breath sounds, localized rales, any evidence of consolidation
 Cardiac infections – Any new murmur, especially in patients with a
history of injection or IV drug use

Source of infection (2)
20
 Abdominal and gastrointestinal (GI) infections – Diarrhea, abdominal
pain, abdominal distention, guarding or rebound tenderness, rectal
tenderness or swelling
 Pelvic and genitourinary (GU) infections – Pelvic or flank pain, adnexal
tenderness or masses, vaginal or urethral discharge, dysuria, frequency,
urgency
 Bone and soft-tissue infections – Localized limb pain or tenderness, focal
erythema, edema, swollen joint, crepitus in necrotizing infections, joint
effusions
 Skin infections – Petechiae, purpura, erythema, ulceration, bullous
formation, fluctuance

Investigative Images of
Septic Shock Cases
Source: Kalil, A. Septic Shock. Medscape. Updated: Jan 2019.

Strawberry tongue in a child with staphylococcal toxic shock syndrome. Drage, LE.
Life-threatening rashes: dermatologic signs of four infectious diseases.
Mayo Clin Proc. 1999;74:68-72.

Venn diagram showing the overlap of infection, bacteremia, sepsis, systemic
inflammatory response syndrome (SIRS), and multiorgan dysfunction.
Kalil, A. Septic Shock. Medscape. Updated: Jan 2019.
https://emedicine.medscape.com/article/168402-overview

A 26-year-old woman developed rapidly progressive shock associated with purpura
and signs of meningitis. Her blood culture results confirmed the presence of
Neisseria meningitidis. The skin manifestation seen in this image is characteristic of
severe meningococcal infection and is called purpura fulminans.

Gram stain of blood showing the presence of Neisseria meningitidis.

Acute respiratory distress syndrome (ARDS), commonly observed in septic shock as a
part of multiorgan failure syndrome, results in pathologically diffuse alveolar damage
(DAD). This photomicrograph shows early stage (exudative stage) DAD.

Photomicrograph showing delayed stage (proliferative or organizing stage) of
diffuse alveolar damage (DAD). Proliferation of type II pneumocytes has
occurred; hyaline membranes as well as collagen and fibroblasts are present.

Acute respiratory distress syndrome (ARDS) in a patient who developed
septic shock secondary to toxic shock syndrome.

Bilateral airspace disease and acute respiratory failure in a patient with
gram-negative septic shock. The source of the sepsis was urosepsis.

A 45-year-old woman was admitted to the intensive care unit
with septic shock secondary to spontaneous biliary peritonitis.
She subsequently developed acute respiratory distress
syndrome (ARDS) and multiorgan failure.

An 8-year-old boy developed septic shock secondary to Blastomycosis
pneumonia. Fungal infections are rare causes of septic shock.

Soft-tissue infection secondary to group A streptococci, leading to toxic shock syndrome.

Necrotizing cellulitis of toxic shock syndrome.

Necrosis of the little toe of the right foot and cellulitis of the
foot secondary to group A streptococcal infection.

Group A streptococci cause beta hemolysis on blood agar.

Gram stain of blood showing group A streptococci that was
isolated from a patient who developed toxic shock syndrome.

A 46-year-old man presented with nonnecrotizing cellulitis and
streptococcal toxic shock syndrome. The leg was incised to
exclude underlying necrotizing infection.

streptococcal toxic shock syndrome (same patient as in
previous image). This patient also had streptococcal
pharyngitis.

streptococcal toxic shock syndrome (same patient as in previous
image). The patient had diffuse erythroderma, a characteristic
feature of the syndrome.

A 46-year-old man presented with nonnecrotizing cellulitis and streptococcal toxic shock
syndrome (same patient as in previous image). The patient had diffuse erythroderma, a
characteristic feature of the syndrome. He improved with antibiotics and intravenous
gammaglobulin therapy. Several days later, a characteristic desquamation of the skin
occurred over his palms and soles.

Progression of soft-tissue swelling to vesicle or bullous formation
is an ominous sign and suggests streptococcal shock syndrome.

Extensive debridement of necrotizing fasciitis of the hand.

Healing of the hand after aggressive surgical debridement of necrotizing
fasciitis (same patient as in previous image).

Septic Shock: KEY POINTS
44
 Septic shock results from a severe systemic inflammatory
response to infection
• Gram-negative bacteria, gram-positive bacteria, and fungal infections
are common causes of septic shock
• In gram-negative shock, endotoxins in bacterial cell walls stimulate
massive immune system activation
• Septic shock from any organism is characterized by release of large
numbers of immune mediators (e.g., cytokines) resulting in widespread
inflammation
• The clotting cascade, complement system, and kinin system are
activated as part of immune response

Septic Shock: KEY POINTS
45
 Widespread inflammation leads to profound peripheral vasodilation with
hypotension, maldistribution of blood flow with cellular hypoxia, and
increased capillary permeability with edema formation
 Initially, septic shock is characterized by abnormally high cardiac output
resulting from immune-mediated vasodilation and sympathetic activation
of the heart
• Patient is usually febrile, pink, and warm. Even though cardiac output is high, cellular
hypoxia is present because of maldistribution of blood low
• Reduced cellular oxygen utilization is manifested as a high SvO2
 Therapy for septic shock is aimed at improving distribution of blood flow
and managing infection with antibiotics. Administration of fluid and drugs
to increase cardiac and vascular performance is done to improve
distribution of blood low

Sources and further study:
47
 Copstead LC, Banksia JL. Pathophysiology, 5th Ed. St. Louis, Missouri: Saunders-Elsevier, 2013.
 Dipiro JT et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 8th Ed. New York: McGraw-Hill,
2011.
 Kalil, A. Septic Shock. Medscape. Updated: Jan 2019.
 Kishiyama JL. Ch. 3 Disorders of the Immune System, Pgs. 31-59 and Bloch KC. Ch. 4 Infectious
Diseases, Pgs. 61-87 In: Hammer GD and McPhee eds. JS. Pathophysiology of Disease : An Introduction
to Clinical Medicine, 7th Ed. New York: McGraw-Hill Education, 2014’
 Johnson AG et al. Bacterial Diseases. In: Microbiology and immunology. 4th Ed. Baltimore: Lippincott
Williams & Wilkins, 2010.
eLearning (Cloud)
 Infectious Disease Pathology
 Microbial biology & Immune System
Textbooks:
 Ryan KJ and Ray CG Eds. Sherris Medical Microbiology, 5th Ed. New York: McGraw-Hill, 2010.
 Carroll KC etal. Jawetz, Melnick, & Adelberg’s Medical Microbiology 27th Ed. New York: McGraw-Hill,
2016.

Sepsis & Septic Shock

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Sepsis & Septic Shock

Similar to Sepsis & Septic Shock (20)

More from Imhotep Virtual Medical School

More from Imhotep Virtual Medical School (20)

Recently uploaded

Recently uploaded (20)

Sepsis & Septic Shock