Medical Year 1, CVS, Shock

S H O C K [CIRCULATORY COLLAPSE]
DEFINITION: It is a catastrophic event caused by wide-spread tissues hypoperfusion due to reduction in
the blood volume or cardiac output or redistribution of blood resulting in an inadequate effective
circulating blood volume.
EFFECTS OF SHOCK
• It is precipitated by any massive insult to the body.
• This led to life threatening homeostatic derangements in all body cells.
• Marked perfusion deficit → insufficient delivery of O2 & nutrients to the cells & tissues
- inadequate clearance of metabolites → cellular hypoxia → shift from aerobic to anaerobic
respiration → lactic acidosis.
• These haemodynamic & metabolic derangement →REVERSIBLE CELL INJURY to progress to
IRREVERSIBLE CELL INJURY

CLASSIFICATION OF SHOCK (PATHOPHYSIOLOGICAL)

I. HYPOVOLEMIC OR HAEMORRHAGIC SHOCK

Principle mechanism: Inadequate blood or plasma or fluid volume

Clinical eg. 1. Profuse Haemorrhage. 2. Crush injuries, Burns, severe trauma. 3 Excessive

Vomiting, diarrhoea (Fluid loss)

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II. CARDIOGENIC SHOCK

Principal mechanism: Failure of myocardial pump due to intrinsic myocardial damage or extrinsic
compression or obstruction to outflow
Clinical Eg. 1. Extensive myocardial infarction
2. Arrhythemias
3. Rupture of Heart
4. Cardiac temponade
5. Massive Pulmonary embolism

III. SEPTIC SHOCK

Principle mech: Peripheral vasodilation & pooling of blood, endothelial activation & injury,
leucocyte induced damage, Disseminated Intravascular Coagulation, activation
of cytokine cascade
Clinical Eg. : 1. Overwhelming microbial infection
2. Gram negative septicaemia (Endotoxic shock)
3. Gram positive septicaemia
4. Fungal sepsis
5. Super antigen

IV. NEUROGENIC SHOCK

Principle mech: loss of vascular tone → vasodilatation, peripheral pooling of blood
Clinical Eg. 1. Anaesthetic accidents. 2. Spinal cord injury

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V. ANAPHYLACTIC SHOCK
Principle mech: Systemic vasodilatation, increased vascular permeability
Clinical e.g. Generalized Type I Hypersensitivity

STAGES OF SHOCK
Shock is a progressive disorder, if uncorrected, is rapidly lethal. It tends to involve 3 stages.
1. INITIAL NONPROGRESSIVE STAGE: Reflex mechanisms are activated and perfusion of vital organ is
preserved.
2. PROGRESSIVE STAGE: Characterized by tissues hypoperfusion, circulatory & metabolic imbalances.
3. IRREVERSIBLE STAGE: Severe cellular & tissues injury.
Hemodynamic defects may be corrected by therapy but, survival is not possible.
• In the early nonprogressive phase of shock, various neurohumoral mechanisms help maintain
cardiac output and blood pressure.
• The net effect is tachycardia, peripheral vasoconstriction, and renal fluid conservation; cutaneous
vasoconstriction causes the characteristic “shocky” skin coolness and pallor.
• Coronary and cerebral vessels are less sensitive to sympathetic signals and maintain relatively
normal caliber, blood flow, and oxygen delivery.
• Thus, blood is shunted away from the skin to the vital organs such as the heart and the brain.
• If the underlying causes are not corrected, shock passes imperceptibly to the progressive phase,
which as noted is characterized by widespread tissue hypoxia.
• In the setting of persistent oxygen deficit, intracellular aerobic respiration is replaced by anaerobic
glycolysis with excessive production of lactic acid.
• The resultant metabolic lactic acidosis lowers the tissue pH, which blunts the vasomotor response;
arterioles dilate, and blood begins to pool in the microcirculation.

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PATHOPHYSIOLOGY OF HYPOVOLEMIC SHOCK

I. CAUSES [ ETIOLOGY]
1. Acute loss of critical portion of blood volume
E.g., Massive haemorrhage due to trauma or splenic rupture → Haemoperitoneum (Hemorrhagic shock)
Severity of shock depend on
1. Rate of blood loss
2. Degree of trauma
3. Haemoglobin level of blood
4. Cardiopulmonary status of patient prior to shock
2. Acute reduction of PLASMA volume & by outpouring of exudates
E.g., Extensive Burns & scalds, severe crushed injuries
3. Extensive depletion of FLUID & ELECTROLYTE: E.g., Severe vomiting and diarrhea in gastroenteritis

II. PATHOPHYSIOLOGY
STAGE I: INITIAL NONPROGRESSIVE OR COMPENSATORY OR EARLY STAGE
1. ACTIVATION OF COMPENSATORY REFLEX MECHANISMS
Preservation of perfusion of vital organs
Mechanism:
Cardiac output remains unchanged & there is no fluid redistribution
Initial vaso-vagal attack due to volume deficit → syncopy
Widespread Vasodilatation of arterioles → decreased blood pressure &decreased cerebral blood flow
→ (transient) loss of consciousness.

2. ACTIVATION OF NEUROHUMORAL MECHANISMS

(1). Stimulation of BARORECEPTORS → Vasoconstriction of arterioles in skin & skeletal muscles
(2). Release of CATECHOLAMINES causing generalized sympathetic activation.
a. Selective arteriolar vasoconstriction of skin, skeletal muscles, salivary glands, intestine, Liver, Spleen,
Kidney
b. In the kidneys → cortical vasoconstriction → blood is redistributed to ward medulla.
c. Vasodilatation of cerebral & coronary arteries
(3). Activation of RENIN - ANGIOTENSIN ALDOSTERONE AXIS
Renin & Angiotensin cause vasoconstriction
Aldosterone causes renal conservation of salt & water

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(4). Release of ACTH → Salt &H2O retension

(5). Release of ADH → Renal conservation of H2O
NET EFFECTS:
1. Increase peripheral resistance
2. Increase force of myocardial contraction
3. Increase blood volume & venous return
4. Shunting of available blood to vital organ (e.g., Heart, brain & Proximal convoluted tubules of
kidney)
Clinical features: Cold, clammy sweaty skin (Cold shock), Cyanosis, Tachycardia, Dry mouth, impaired
digestion, and fall in urine out put.

STAGE II: PROGRESSIVE OR DECOMPENSATORY STAGE

• Volume deficit is still uncorrected
• Persistent hypoxia → aerobic to anaerobic respiration → Metabolic lactic acidosis.
• Resultant metabolic acidosis lowers the pH → impair vasomotor response
• Vasodilatation occur → pooling of blood in microcirculation & splanchnic bed
• Effective circulatory blood volume (hypovolemia) → hypoxic endothelial injury→ D I C (Disseminated
intravascular coagulation)
EFFECT: With wide spread tissues hypoxia → deteriorate the function of vital organ
CLINICAL FEATURES: Mental confusion & Oliguria,
Upto this stage II, removal of cause of hypovolemia & replacement of volume by effective treatment, can
return the patient to normal state.
STAGE III: IRREVERSIBLE SHOCK
• Occurs the following severe cellular & tissues hypoxic injury
• Death usually occurs even if the hemodynamic defects are corrected.
• Widespread cell injury → disruption of cell membrane & leakage of lysosomal enzyme: -
irreversible multiorgan damage & failure
EFFECTS:
• Myocardial depressant factor - worsen the poor cardiac performance & myocardial contractile
dysfunction
• Ischaemic intestinal mucosa - allows intestinal flora to enter the circulation & endotoxic shock may
be superimposed on hypovolemic or cardiogenic shock.
• Kidney - showed complete renal shutdown due to acute tubular necrosis.
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• Hypoxic encephalopathy
• ARDS (Adult/Acute respiratory distress syndrome)
RECOVERY PHASE:
• 80 -90 % healthy young patients
• Timely volume replacement
• Urine formation with diuresis → Loss of water & electrolyte
CLINICAL COURSE
Patient presents hypotension, ashen-gray pallor; cool & clammy cyanotic skin; weak rapid thready pulse,
rapid cardiac & respiratory rates
With uncontrolled sepsis, skin may be warm & flushed due to peripheral vasodilatation
PATHOPHYSIOLOGY OF SEPTIC SHOCK
• Most common cause of death in intensive care unit.
• Results from spread of microbes from uncontrolled initially localized infection (e.g., Urinary tract
infection (UTI), Gastrointestinal tract infection, abscess, peritonitis, pneumonia) into blood stream.
• The incidence is rising, ironically, in part because of improved life support for critically ill patients,
as well as an increase in invasive procedures and the growing numbers of immunocompromised
patients (due to chemotherapy, immunosuppression, or HIV infection) and the increasing
prevalence of multidrug resistant organisms in the hospital setting.

A. CAUSES (ETIOLOGIC AGENTS) OF SEPTIC SHOCK

1. Most frequently caused by G+ve cocci -e.g., Pneumococci, Staph, Strept: G +ve bacteremic shock or
exotoxic shock
They release EXOTOXIN - Peptidoglycans present in bacterial cell wall
Toxic shock syndrome toxin - 1 into circulation
2. G -ve bacilli - E. coli, Klebsiella pneumoniae, Proteus, Pseudomonas aeruginosa, Serratia,
Bacteroides: G-ve bacteremic shock OR endotoxic shock
Source of infection - 1. infected burns
2.Surgical operation or instrumentation on Urogenital, GIT
3. Complication of post abortion or postpartum infection
These organisms release ENDOTOXIN - LIPOPOLYSACCHARIDES when cell walls are degraded.
ENDOTOXINconsists oftoxic lipid A core component & complex lipopolysaccharide coat
3. Fungi
4. Super antigen (Staph aureus)
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B. PATHOGENESIS
Factors involved in the pathophysiology of septic shock include the following:
1. Inflammatory and counter-inflammatory responses.
- In sepsis, various microbial cell wall constituents engage receptors on cells of the innate immune
system, triggering pro-inflammatory responses. Likely initiators of inflammation in sepsis are
signaling pathways that lie downstream of Toll-like receptors (TLRs).
- Upon activation, innate immune cells produce TNF, IL-1, IFN-γ, IL-12, and IL-18, as well as other
inflammatory mediators such as high mobility group box 1 protein (HMGB1).
- Reactive oxygen species and lipid mediators such as prostaglandins and platelet activating factor
(PAF) are also elaborated.
- These effector molecules induce endothelial cells (and other cell types) to upregulate adhesion
molecule expression and further stimulate cytokine and chemokine production.
- The complement cascade is also activated by microbial components, resulting in the production of
anaphylotoxins (C3a, C5a), chemotactic fragments (C5a), and opsonins (C3b).
- Microbial components can activate coagulation directly through factor XII and indirectly through
altered endothelial function.
- The widespread activation of thrombin may further augment inflammation by triggering protease-
activated receptors (PARs) on inflammatory cells.
- The hyperinflammatory state initiated by sepsis also activates counter-regulatory
immunosuppressive mechanisms, which may involve both innate and adaptive immune cells.
- Septic patients oscillate between hyperinflammatory and immunosuppressed states during their
clinical course.
- Mechanisms for the immune suppression include a shift from pro-inflammatory (TH1) to anti-
inflammatory (TH2) cytokines, production of anti-inflammatory mediators (e.g., soluble TNF
receptor, IL-1 receptor antagonist, and IL-10), lymphocyte apoptosis, the immunosuppressive
effects of apoptotic cells, and the induction of cellular anergy.
2.Endothelial activation and injury
- The proinflammatory state and endothelial cell activation associated with sepsis lead to
widespread vascular leakage and tissue edema, which have deleterious effects on both nutrient
delivery and waste removal.
- One effect of inflammatory cytokines is to loosen endothelial cell tight junctions, making vessels
leaky and resulting in the accumulation of protein-rich edema fluid throughout the body.

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- This alteration impedes tissue perfusion and may be exacerbated by attempts to support the
patient with intravenous fluids.
- Activated endothelium also upregulates production of nitric oxide (NO) and other vasoactive
inflammatory mediators (e.g., C3a, C5a, and PAF), which may contribute to vascular smooth
muscle relaxation and systemic hypotension.
3. Induction of a procoagulant state
- Sepsis alters the expression of many factors so as to favor coagulation.
- Proinflammatory cytokines increase tissue factor production by monocytes and possibly
endothelial cells as well, and decrease the production of endothelial anti-coagulant factors, such
as tissue factor pathway inhibitor, thrombomodulin, and protein C.
- They also dampen fibrinolysis by increasing plasminogen activator inhibitor-1 expression.
- The vascular leak and tissue edema decrease blood flow at the level of small vessels, producing
stasis and diminishing the T-lymphocyte activators that induce the release of high levels of
cytokines that result in a variety of clinical manifestations, ranging from a diffuse rash to
vasodilation, hypotension, shock, and death.
C. CLINICAL FEATURES OF SEPTIC SHOCK
Patients present with fever with chills and rigors, confusion, anxiety, difficulty in breathing, fatigue and
malaise and nausea and vomiting.

CARDIOGENIC SHOCK
COMMONEST CAUSE: Myocardial Infarct
OTHER CAUSE Acute arrhythmias
Surgical or spontaneous rupture of cardiac valve
Fulminating myocarditis
Other severe myocardial injury
Cardiac temponade
Massive pulmonary embolism
PATHOPHYSIOLOGY: Similar to hypovolemic shock

NEUROGENIC SHOCK
CAUSES OF NEUROGENIC SHOCK
1. Patient receiving G.A (General anaesthesia), spinal anesthesia or epidural block
2. Following severe pain such as biliary colic or ureteric colic.

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PATHOPHYSIOLOGY
Neuronal control mechanism which maintains the vascular tone -interrupted → Vasodilatation
decreased peripheral resistance → peripheral pooling→ Loss of effective circulating volume & SHOCK

ANAPHYLACTIC SHOCK
Initiated by interaction of Ag (antigen) with Ab (antibodies) → release of pharmacologically active
compounds responsible for characteristic feature of shock $.
Occur after adminstration of heterologous protein in the form of antisera, hormones, enzyme,
polysaccharide & drugs such as penicillin.
Severity varies with level of sensitization. Shock dose of Ag may be small.
Clinical features
Occur within minutes after exposure - itching, hives, skin erythema followed by striking constriction of
bronchioles & appearance of respiratory distress, laryngeal oedema with hoarseness of voice.
Vomiting + Diarrhoea, abdominal cramps, laryngeal obstruction → SHOCK & die within an hour.

ORGAN CHANGES IN SHOCK

Hypoxic failure of multi organ system
1. BRAIN (Ischaemic / anoxic / hypoxic encephalopathy)
Brain is extremely vulnerable to 02 deficit & may suffer wide-spread neuronal injury.
Extent depends on duration & intensity of hypoxia & duration of survival.
Morphological changes may occur in 12 - 24 hr.
GROSS: Brain - enlarged, swollen & muddy discoloration,
Gyri - widened, Sulci - narrowed
C.S - poor demarcation between gray & white matter
HISTO:
(i) EARLY CHANGES (12 - 24) Hrs
Acute neuronal cell change (RED NEURONE) - microvacuolization, eosinophilia of cytoplasm,
nuclear pyknosis & karyorrhexis.
Susceptible cells - neurons of hippocampus, cerebellum & other neurocortex

(ii) SUBACUTE CHANGES (24 hrs - 2 wks)

Necorsis of tissues, influx of macrophages, vascular proliferation, reactive gliosis

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(iii) REPAIR (after 2 wks)

Removal of necrotic tissues, loss of normally organized CNS structure, & gliosis with preservation of
some layers (Pseudolaminar necrosis)
2. HEART
1. Subendocardial hemorrhages & necrosis: range from isolated fibre ischaemic lesion to large areas
– micro & macroinfarcts.
2. Zonal lesion

3. KIDNEY: Acute renal failure - ischaemic acute tubular necrosis SHOCK KIDNEY:
HEMOGLOBINURIC NEPHROSIS
GROSS :
Cortex : enlarged, pale & slightly widened
Medulla : deep red, congested & cyanotic
CMJ : well defined
HISTO:
TUBULE: Ischaemic acute tubular necrosis (TUBULORRHEXIS)
LUMEN: Occlusion of tubular lumina by haline casts
INTERSTITIUM: Interstitial oedema & accumulation of leucocytes
GLOMERULI: Most cases – unaffected
In endotoxic shock - thrombosis (+) in glomerlar capillaries (due to DIC )

4. LUNGS (Shock lung, Adult respiratory distress $, Diffuse alveolar damage)

GROSS: Heavy, firm, red, boggy, secondary bacterial infection - foci of bronchopneumonic
consolidation
HISTO: Pulmonary congestion & intra alveolar hemorrhage
Interstitium & intraalveolar edema & inflammation fibrin deposition
presence of alveolar hyaline membrane (consists of fibrin &necrotic epithelial cells) STIFF
LUNG $, A R D S

5. ADRENAL GLAND: Stress response: depletion of lipids within cortical cells transforming them from
clear vacuolated cell → non-vacuolated compact cells. It begins within zona reticularis & spreading
outward towards the capsule.

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6. INTESTINES: Ischaemic enterocolitis or acute Haemorrhagic enteropathy

GROSS: Oedema & thickening of intestinal wall + Hemorrhagic congestion of. Superficial ulcer
Shedding of mucosa
HISTO: Dilatation of mucosal capillary & venules
Submucosal oedema with haemorrhagic extravasation of RBC
Thrombi within the vessels (+
7. LIVER
FATTY CHANGE& CENTRAL HEMORRHAGIC NECROSISbegin in center of lobule &extending through
entire lobule. Fibrin thrombi (+) within sinusoids

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