Shock

Slide 1 · Shock

Circulatory failure, septic mechanisms, and multiorgan injury

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Define shock as systemic circulatory failure with impaired tissue perfusion.

Distinguish cardiogenic, hypovolemic, and septic shock by mechanism.

Trace immune, endothelial, coagulation, and metabolic pathways in septic shock.

Explain how these pathways culminate in cellular hypoxia and organ dysfunction.

Slide 3 · Shock is circulatory failure with cellular hypoxia

Circulatory failure

Reduced effective tissue perfusion

Cellular hypoxia

The defining lesion is inadequate tissue oxygen delivery and/or utilization.

Slide 4 · Hypoperfusion links the circulation to tissue injury

Impaired blood flow

Oxygen and nutrient deficit

Cell dysfunction

Tissue injury

Shock describes a systemic pathophysiologic state, not one specific etiologic disease.

Slide 5 · Early injury may be reversible

Early shock

Potentially reversible injury

Prolonged hypoperfusion

Irreversible injury

Duration and severity of the perfusion deficit determine cellular fate.

Slide 6 · Major clinical settings that precipitate shock

Massive hemorrhage

Blood-volume depletion

Severe trauma / burns

Fluid loss and inflammatory injury

Myocardial infarction

Loss of pump function

Pulmonary embolism

Obstruction to cardiac outflow

Slide 7 · Three principal etiologic categories

Cardiogenic

Myocardial pump or mechanical outflow failure

Hypovolemic

Inadequate circulating blood or plasma volume

Septic

Dysregulated infection response with vascular and cellular dysfunction

Slide 8 · Cardiogenic shock: Failure of cardiac output

Myocardial / mechanical defect

Reduced cardiac output

Systemic tissue hypoperfusion

A primary cardiac mechanism results in circulatory failure.

Slide 9 · Cardiogenic shock can have distinct causes

Intrinsic myocardial injury

Acute myocardial infarction

Electrical dysfunction

Ventricular arrhythmia

Extrinsic compression

Cardiac tamponade

Obstructed outflow

Massive pulmonary embolism

Slide 10 · Hypovolemic shock starts with volume depletion

Blood or plasma volume loss

Reduced effective circulating volume

Lower cardiac output

Tissue hypoperfusion

Slide 11 · Routes to hypovolemia

Hemorrhage

Loss of whole blood

Vomiting / diarrhea

Extracellular fluid loss

Extensive burns

Plasma and fluid loss

Trauma

Hemorrhage and fluid loss

Slide 12 · Three types of shock: Compare the initiating defect

Type

Dominant initiating disturbance

Examples

Cardiogenic

Pump failure / outflow restriction

MI; tamponade; arrhythmia; PE

Hypovolemic

Insufficient circulating blood / plasma

Bleeding; burns; gastrointestinal fluid loss

Septic

Systemic response to infection

Severe microbial infection

Slide 13 · Sepsis is organ dysfunction from a dysregulated response

Infection

Dysregulated host response

Life-threatening organ dysfunction

The organ injury results from the host–microbe interaction, not simply microbial presence.

Slide 14 · Septic shock denotes a particularly severe sepsis subset

Sepsis

Life-threatening organ dysfunction due to dysregulated infection response

Septic shock

Profound circulatory, cellular, and metabolic abnormalities with increased mortality risk

Slide 15 · SIRS and sepsis are not synonymous

SIRS

Systemic inflammatory response can arise from sterile insults

Sepsis

Requires infection with dysregulated host response and organ dysfunction

Burns, trauma, and pancreatitis can cause nonmicrobial systemic inflammation.

Slide 16 · Uncommon shock mechanisms involve acute vasodilation

Neurogenic shock

Spinal cord injury may produce acute vasodilation

Anaphylactic shock

IgE-mediated hypersensitivity may produce acute vasodilation

Both can cause hypotension and tissue hypoperfusion.

Slide 17 · Classifying shock directs attention to the initiating lesion

CLINICOPATHOLOGIC APPLICATION

A patient with ventricular arrhythmia and low output: Pump failure.

A patient with severe hemorrhage: Volume deficit.

A patient with infection and organ dysfunction: Evaluate the septic pathway.

Which mechanism is responsible for reduced effective perfusion?

Slide 18 · Septic shock reflects several mutually reinforcing processes

Inflammatory activation

Cytokines, leukocytes, complement

Endothelial dysfunction

Leakage, vasodilation, flow disturbance

Procoagulant state

Microvascular fibrin thrombi

Metabolic disturbance

Impaired fuel handling and oxygen use

Slide 19 · Diverse microbial agents can initiate sepsis

Bacteria

Gram-positive and gram-negative infections

Fungi

Fungal infections

Viruses

Certain severe viral infections can cause sepsis

The mechanism depends on shared host-response pathways rather than one pathogen.

Slide 20 · Septic injury extends beyond the infected site

Local microbial infection

Systemic activation of innate immunity

Injury to remote normal tissues

Multiorgan dysfunction

Failure of normal containment permits a generalized, tissue-damaging host response.

Slide 21 · Innate immunity recognizes both microbes and tissue damage

PAMPs

Pathogen-associated molecular patterns derived from microbes

DAMPs

Damage-associated molecular patterns released by injured host cells

Slide 22 · Multiple sensors trigger the septic inflammatory response

Toll-like receptors

Recognize diverse microbial / damage signals

G protein–coupled receptors

Detect some bacterial peptides

C-type lectins (e.g., Dectins)

Detect fungal antigens

Slide 23 · Microbial recognition activates inflammatory gene programs

PAMP/DAMP recognition

Innate receptor signaling

NF-κB nuclear activation

Mediator gene expression

Slide 24 · NF-κB links cell sensing to cytokine production

Receptor ligation

NF-κB activation

Transcription of inflammatory genes

TNF, IL-1, and other mediators

This is one important pathway in a more complex network.

Slide 25 · Major soluble mediators in septic inflammation

Cytokines

TNF; IL-1; IL-12; IL-18

Interferons

IFN-γ

Late alarmin-like mediator

HMGB1

Acute-phase markers

C-reactive protein; Procalcitonin

Slide 26 · Reactive oxygen and lipid mediators amplify injury

Reactive oxygen species

Contribute to cellular and oxidative injury

Prostaglandins

Participate in inflammatory vascular responses

Platelet-activating factor

Promotes vascular and inflammatory activation

Slide 27 · Complement reinforces the systemic inflammatory state

Microbial / proteolytic triggers

Complement activation

C3a, C5a, C3b generation

Vascular and leukocyte responses

Slide 28 · Complement fragments have different effector roles

Fragment

Dominant function

Septic relevance

C3a

Anaphylatoxin

Inflammatory vascular response

C5a

Anaphylatoxin; chemoattractant

Recruitment / activation of leukocytes

C3b

Opsonin

Microbial recognition and clearance

Slide 29 · Innate cells extend and amplify mediator release

Microbial sensing

Macrophages, neutrophils, dendritic cells

Cytokines and chemokines

Recruitment / activation of more cells

Slide 30 · Endothelial–leukocyte signaling propagates inflammation

Inflammatory mediators

Endothelial adhesion molecules

Leukocyte activation / adhesion

Amplified tissue injury

Slide 31 · Inflammation and coagulation activate each other

Inflammatory cytokines

Endothelial and coagulation activation

Widespread thrombin generation

Additional inflammatory signaling

Thrombin can signal through protease-activated receptors.

Slide 32 · Pro- and anti-inflammatory pathways are concurrent

Proinflammatory arm

Microbial clearance signals plus risk of host tissue damage

Counterregulatory arm

Mechanisms limiting inflammation but risking immune dysfunction

Dominance varies with host and pathogen factors.

Slide 33 · Proposed mechanisms of immune suppression

Antiinflammatory mediators

IL-10; Soluble TNF receptor; IL-1 receptor antagonist

Immune-cell loss

Lymphocyte apoptosis

Reduced responsiveness

Cellular anergy

Cytokine shift

Relative shift toward anti-inflammatory responses

Slide 34 · The host response is dynamic rather than uniform

Infection + host factors

Simultaneous activating and suppressive responses

Variable inflammatory balance

Heterogeneous clinical courses

Avoid a rigid model of an exclusively early “hyperinflammatory” phase.

Slide 35 · Endothelial injury is central to septic shock

Barrier dysfunction

Protein-rich vascular leakage

Vasomotor dysfunction

NO and other mediators

Microvascular dysfunction

Uneven capillary flow

Coagulation dysfunction

Loss of anticoagulant restraint

Slide 36 · Cytokines weaken endothelial junctions

Blood-vessel lumen

Endothelial cells and junctions

Extravasated protein-rich fluid → tissue edema

Schematic of increased vascular permeability—not histologic evidence.

Slide 37 · Loss of barrier function causes interstitial edema

Inflammatory endothelial activation

Junctional permeability increases

Protein-rich fluid escapes

Interstitial edema develops

Slide 38 · Edema impairs microvascular exchange

Vascular leakage

Interstitial tissue edema

Nutrient transport / waste removal impaired

Tissue hypoperfusion worsens

Slide 39 · Vasoactive mediators contribute to hypotension

Activated endothelium

Nitric oxide + other mediators

Vascular smooth-muscle relaxation

Systemic hypotension

Slide 40 · Septic capillary flow becomes heterogeneous

Flowing capillary

Intermittent flow

Poorly perfused capillary

Low flow

Schematic depiction of heterogeneous microvascular flow.

Slide 41 · Loss of local autoregulation causes oxygen mismatch

Microvascular dysfunction

Loss of metabolic flow matching

Uneven oxygen supply

Oxygen demand–delivery mismatch

Slide 42 · Four pathways turn the vessel into an injury amplifier

Leakage

Fluid leaves the vascular space

Vasodilation

Effective perfusion pressure declines

Flow heterogeneity

Some beds are underperfused

Thrombosis

Small-vessel lumens are obstructed

Slide 43 · Sepsis produces a systemic procoagulant milieu

Inflammatory activation

Tissue factor ↑; Anticoagulants ↓; Fibrinolysis ↓

Thrombin and fibrin generation

Small-vessel thrombosis

Slide 44 · Tissue factor expression promotes thrombin generation

Proinflammatory cytokines

Monocyte / endothelial tissue factor ↑

Coagulation activation

Fibrin-rich microthrombi

Slide 45 · Anticoagulant pathways are downregulated

TFPI

Reduced tissue factor pathway inhibition

Thrombomodulin

Reduced endothelial anticoagulant activity

Protein C

Reduced anticoagulant protection

Net effect

Thrombin activity favors clot formation

Slide 46 · PAI-1 restricts fibrin removal

Inflammatory signaling

PAI-1 expression ↑

Fibrinolysis suppressed

Fibrin persists in the microcirculation

Slide 47 · NETs are a proposed contributor to thrombosis

Neutrophil activation

Neutrophil extracellular traps

Potential activation of coagulation pathways

Procoagulant amplification

A possible role supported by some studies—not a universally quantified effect.

Slide 48 · Stasis enhances local coagulation

Leakage and tissue edema

Reduced small-vessel flow

Slower clearance of activated factors

Further thrombin generation

Slide 49 · Microthrombi restrict capillary perfusion

Patent vessel

Fibrin-rich obstruction

Downstream low flow

Fibrin

Schematic of septic microvascular thrombosis, not a specimen.

Slide 50 · DIC combines microthrombosis with bleeding

Thrombotic component

Fibrin-rich thrombi impair organ microcirculation

Hemorrhagic component

Consumption of platelets and coagulation factors favors bleeding

DIC is a severe potential complication, not obligatory in every case.

Slide 51 · Coagulation and inflammation form a feedback loop

Inflammation activates coagulation

Thrombin signals to immune cells

Additional inflammatory activation

More endothelial injury

Slide 52 · Metabolic abnormalities compound septic injury

Insulin resistance

Reduced response to insulin

Hyperglycemia

Glucose increases during stress

Lipid abnormalities

Circulating triglycerides may rise

Lactic acidosis

Hypoxia impairs oxidative ATP production

Slide 53 · Inflammatory and stress signals favor hyperglycemia

TNF, IL-1 + stress hormones

Gluconeogenesis ↑

Insulin response impaired

Blood glucose rises

Slide 54 · Impaired insulin action has multiple contributors

Cytokine effects

Inflammation can decrease insulin secretion and responsiveness

Tissue insulin resistance

Abnormal glucose handling in liver and other tissues

The source describes impaired GLUT-4 surface expression as a proposed mechanism.

Slide 55 · Hyperglycemia can worsen antibacterial defense

High circulating glucose

Reduced neutrophil bactericidal function

Less effective microbial control

Ongoing infection risk

Hyperglycemia also promotes endothelial adhesion molecule expression.

Slide 56 · Sepsis can elevate glucose, triglycerides, and lactate

Metabolite

Direction described

Mechanistic interpretation

Glucose

Increased

Inflammatory / stress insulin resistance

Triglycerides

Increased

Systemic metabolic disruption

Lactate

Increased

Reduced oxidative metabolism during hypoxia

Slide 57 · Cellular hypoxia drives lactate accumulation

Inadequate tissue oxygen availability

Oxidative phosphorylation decreases

Anaerobic glycolysis increases

Lactate and acidosis develop

Slide 58 · Adrenal dysfunction may aggravate severe sepsis

Initial stress glucocorticoid surge

Possible later adrenal insufficiency

Reduced glucocorticoid effectiveness

Impaired stress adaptation

In severe DIC, adrenal hemorrhagic necrosis can occur; This is not a universal septic finding.

Slide 59 · Organ failure reflects impaired delivery and utilization

Supply failure

Hypotension, edema, heterogenous flow, thrombosis

Cellular utilization failure

Oxidative stress and mitochondrial damage

Slide 60 · Oxidative mitochondrial injury can limit oxygen use

Inflammation / oxidative stress

Mitochondrial dysfunction

Reduced effective oxygen utilization

Organ-cell dysfunction

Slide 61 · Inflammatory mediators can depress cardiac output

High cytokine / mediator burden

Myocardial contractility decreases

Cardiac output falls

Tissue perfusion worsens

Slide 62 · Endothelial injury can produce pulmonary failure

Pulmonary vascular injury / leakage

Alveolar–capillary barrier dysfunction

Acute respiratory distress syndrome

Severe gas-exchange impairment

Slide 63 · Multiple organs may fail together

Kidneys

Impaired renal function

Liver

Hepatic dysfunction

Lungs

Respiratory injury / ARDS

Heart

Impaired myocardial contraction

Slide 64 · Septic shock integrates four injury mechanisms

Inflammatory injury

Cytokines, innate cells, complement

Vascular injury

Leakage, vasodilation, flow heterogeneity

Microthrombosis

TF, lost anticoagulants, fibrin persistence

Metabolic failure

Hyperglycemia, lactate, mitochondrial dysfunction

Slide 65 · Severity reflects pathogen and host characteristics

Pathogen-related

Infectious burden and virulence

Host-related

Immune state, comorbid conditions, mediator patterns

Outcome reflects interacting processes, not one measurable mediator alone.

Slide 66 · Single-mediator blockade has major limitations

Multiple interconnected pathways

Simultaneous immune suppression

Variable host and pathogen context

Limited success of targeted antagonism

The complexity of septic signaling and its therapeutic consequences.

Slide 67 · Source-described management addresses underlying causes

Treat infection

Antibiotics for the underlying microbial cause

Support circulation

Intravenous fluids and pressors

Limit tissue hypoxia

Supplemental oxygen and supportive measures

Conceptual textbook overview; Not an up-to-date treatment protocol.

Slide 68 · Bacterial superantigens can trigger shock-like syndromes

Bacterial superantigen

Polyclonal T-cell activation

High systemic cytokine release

Rash, vasodilation, hypotension, shock

Slide 69 · Application: Impaired cardiac pump

CLINICOPATHOLOGIC APPLICATION

Clinical setting: Acute myocardial infarction.

Primary abnormality: Intrinsic myocardial dysfunction.

Predicted consequence: Falling cardiac output and systemic hypoperfusion.

Why is this cardiogenic, not hypovolemic, shock?

Slide 70 · Application: Extensive blood loss

CLINICOPATHOLOGIC APPLICATION

Clinical setting: Severe hemorrhage after trauma.

Primary abnormality: Reduced blood volume.

Predicted consequence: Inadequate circulating volume and cardiac output.

Which upstream defect should the explanation identify?

Slide 71 · Application: Infection with organ dysfunction

CLINICOPATHOLOGIC APPLICATION

Clinical setting: Major bacterial infection with worsening organ function.

Mechanism: Dysregulated immune–vascular–coagulation response.

Potential consequences: Hypotension, edema, microthrombi, metabolic injury.

Why is this more than a localized inflammatory response?

Slide 72 · Distinguish the three syndromes mechanistically

Clinical clue

Most fitting type

Why

Acute infarction with pump failure

Cardiogenic

Primary impaired cardiac output

Major fluid or blood loss

Hypovolemic

Reduced effective volume

Infection with systemic organ dysfunction

Sepsis / septic shock spectrum

Dysregulated host response

Slide 73 · Integrated model of septic shock

Microbial insult

Dysregulated host response

Vascular + coagulation + metabolic injury

Tissue hypoxia and multiorgan dysfunction

Slide 74 · References and source boundaries

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026), Chapter 4, pp. 117–120.

The classification follows Table 4.3; pathway concepts follow the septic-shock text and Figure 4.20.

Original editable diagrams are explanatory schematics, not reproductions of textbook figures.

No external clinical guidelines, protocols, or current epidemiologic estimates were added.