Hemodynamic

Disorders,
Thromboembolism and
Shock
Kinde Bussa (MD, Pathologist)
Normal fluid homeostasis

Vessel wall
integrity

Intravascular
Osmolarity
pressure
Edema

 Edema is an accumulation of interstitial fluid within

tissues.

 Effusion - accumulations of fluid in the body cavities

 Hydrothorax - pleural cavity

 Hydropericardium – pericardial cavity

 Hydroperitoneum (ascites) - peritoneum

 Anasarca – severe and generalized edema

Pathophysiologic mechanisms
1. Increased hydrostatic pressure

2. Decreased oncotic pressure

3. Lymphatic obstruction

4. Sodium and water retention

5. Increased vascular permeability

Increased hydrostatic pressure
Impaired venous return   
 Congestive heart failure
 Constrictive pericarditis   
 Ascites (liver cirrhosis)
 Venous obstruction or compression
 Thrombosis     
 External pressure (e.g., mass)     
 Lower extremity inactivity with prolonged dependency
Reduced plasma osmotic pressure
(Hypoproteinemia)

 Any condition that lowers plasma albumin level

 Nephrotic syndrome –albuminuria

 Chronic liver disease – decreased synthesis of albumin

 Protein malnutrition

 Protein-losing gastroenteropathy
Lymphatic Obstruction

 Inflammatory

 Neoplastic

 Postsurgical

 Postirradiation
Sodium and water retention

 Increased salt with accompanying water causes increased

hydrostatic pressure and diminished vascular osmotic
pressure
 Excessive salt intake with renal insufficiency
 Increased tubular reabsorption of sodium
 Renal hypoperfusion
 Increased renin-angiotensin-aldosterone secretion
Vascular permeability

 Increased vascular permeability usually occurs in acute

inflammation which subsequently leads to protein
exudation
Morphology of edema

 Microscopically – subtle cell swelling, clearing and

separation of the extracellular matrix

 Most commonly changes are encountered in subcutaneous

tissues, lungs and brain.
Subcutaneous tissue

 Typically influenced by gravity and termed as dependent

Eg.- legs when standing, sacrum when recumbent

 Pitting edema

 Periorbital edema common in renal cases

 Edema due to Hypoproteinemia –affects all parts of the body

Pulmonary edema

 Increased fluid in the alveolar spaces and interstitium of

the lung

 Typically occur in the setting of left ventricular failure,

pulmonary infections, ARDS. . .

 Lungs are 2-3 times than normal weight

 Sectioning reveals frothy blood tinged fluid

Edema of the brain

 May be localized to the site of injury (abscess or

neoplasm) or generalized

 Grossly, brain is soft and heavy, gyri are flattened and

sulci are narrowed

 Severe cerebral edema leads to herniation of the cerebral

tonsils
 Hyperemia and congestion

 Both indicate a locally increased volume of blood

in a particular tissue
 Hyperemia
 active process resulting from increased inflow of blood
into a tissue due to arteriolar vasodilatation

E.g. Skeletal muscle during exercise and in acute

inflammation.

 The affected tissue is more red due to engorgement of

vessels with oxygenated blood.
In hyperemia, increased
inflow leads to
engorgement with
oxygenated blood,
resulting in erythema.
 Congestion

 A passive process resulting from impaired outflow from a

tissue.

 May be systemic as in cardiac failure or local from isolated

venous obstruction.

 The tissue has a blue red color due to accumulation of

deoxygenated blood (cyanosis).
 Congestion of capillary beds is closely related to the
development of edema.

 In chronic passive congestion stasis of poorly oxygenated

blood causes chronic hypoxia which can result in parenchymal
cell degeneration and death.

 Capillary rupture in such sites can result in small hemorrhages

In congestion,
diminished outflow leads
to a capillary bed swollen
with deoxygenated
venous blood and
resulting in cyanosis.
Morphology of hyperemic and congested tissues

Grossly

 Cut surfaces of hyperemic or congested tissues are

hemorrhagic and wet.
Lungs

 Acute pulmonary congestion :- alveolar capillaries engorged with

blood, alveolar septal edema, and focal minute intraalveolar
hemorrhage.

 Chronic pulmonary congestion:- septa become thickened and

fibrotic, alveolar spaces contain hemosiderin laden macrophages
resulting in the appearance termed as brown indurations.

 Heart failure cells are the hemosiderin laden macrophages seen

when congestion is associated with CHF.
liver
 Acute:- central vein and sinusoids are distended
-central hepatocyte degeneration.

 Chronic:- nutmeg liver.

 Hemosiderin laden macrophages are seen.

 In severe and longstanding hepatic congestion (associated

with heart failure) - hepatic fibrosis [cardiac cirrhosis].
Liver with chronic passive congestion and hemorrhagic necrosis

Central areas are red and Centrilobular necrosis with

slightly depressed compared degenerating hepatocytes,
with the surrounding tan viable hemorrhage, and sparse acute
parenchyma( "nutmeg liver“). inflammation
 Hemorrhage

 Caused by damaged to blood vessels or defective clot

formation.

 Increased tendency to bleed occurs in conditions called

hemorrhagic diatheses.
 Acquired or inherited defect in vessel wall, plts and
coagulations factors
 Hemorrhage can be external or hematoma
 Haematoma – haemorrhage enclosed within a tissue or a
cavity.

 Petechiae – minute (1-2mm) hemorrhages into skin, MM

or serosal surfaces. This is typically seen in association
with locally increased IV pressure and thrombocytopenia.

 Purpura – slightly larger (>3mm) hemorrhages usually

occurring due to trauma or vasculitidis, or increased
vascular fragility.

 Ecchymoses – larger (>1 -2cm) subcutaneous hematomas

typically occurs in trauma.
Punctate petechial hemorrhages
of colonic mucosa, due to thrombocytopenia
Ecchymoses:
 Accumulations in body cavities are called

 Hemothorax – pleural cavity

 Hemopericarium – pericardial cavity

 Hemoperitoneum – peritoneal cavity

 Hemarthrosis – joint cavity

 Clinical significance of hemorrhage depends on the rate
and amount of blood loss.

 If > 20% of the total volume of blood is lost rapidly, it

leads to hypovolemic shock and death.

 Chronic loss of blood leads to iron deficiency anemia.

 Site of hemorrhage is also important factor determining
the clinical outcome of hemorrhage.

 Trivial hemorrhage on the skin may kill the if it occur in

brain parenchyma.
Fatal intracerebral bleeding (has a fatal outcome)
 Hemostasis

 Hemostasis is a vital process that maintains blood in a

clot-free fluid state under normal conditions and yet,
following endothelial injury, rapidly forms a clot to
prevent further bleeding and initiate healing.
 It is a well-regulated and balanced process; tipping this
balance in either direction leads to pathology.

 Too little - bleeding disorders.

 Too much -thrombosis

 Hemostasis is effected by three general components :-

a) Vascular wall(Endothelium)

b) Platelets

c) Coagulation system
Hemostasis:
BV Injury

Tissue
Neural Factor

Blood Vessel Platelet Coagulation

Constriction Activation Activation
Primary hemostatic
plug
Reduced
Plt-Fusion Thromibn,
Blood
Fibrin
flow

Stable Hemostatic Plug

Primary hemostasis

 Mediated by Platelets
Platelets
Production of Platelets
Disorders of primary hemostasis

 Stem from quantitative or qualitative defect in platelets

 Prolonged bleeding time and thrombocytopenia

 Normal PT/PTT
 Qualitative defects may be

 Acquired - uremia and and after aspirin ingestion

 Inherited- von Willebrand disease and other rare congenital

disorders.

 The clinical signs of inadequate platelet function include easy

bruising, nosebleeds, excessive bleeding from minor trauma, and
menorrhagia.
von Willebrand Disease

 Genetic vWF deficiency, AD disorder

 Most common inherited coagulation disorder
 Compound defects in platelet function and coagulation
 Multiple types
 Can be qualitative or quantitative abnormality
 Abnormal restocetin platelet agglutination test
Immune Thrombocytopenic Purpura (ITP)
 Chronic ITP is a common disorder that tends to affect
women between the ages of 20 and 40 years.
 Acute ITP is a self-limited form seen mostly in children
after viral infections
 IgG against platelet membrane glycoproteins IIb/IIIa or
Ib/IX complexes
 The spleen is an site of anti-platelet IgG production and
the major site of destruction of the IgG-coated platelets
Heparin-Induced Thrombocytopenia

 Caused by IgG antibodies that bind to platelet factor 4 on

platelet membranes in a heparin-dependent fashion

 Resultant activation of the platelets induces their

aggregation, thereby exacerbating the condition that
heparin is used to treat—thrombosis
Thrombotic Microangiopathies: TTP and HUS

 X-zed by pentad of
 Fever,

 Thrombocytopenia,

 Microangiopathic hemolytic anemia (MAHA),

 Transient neurologic deficits, and
 Renal failure
Secondary Hemostasis
Coagulation Cascade
 It is a series of enzymatic conversions turning inactve
proenzymes to active forms.
 The end stage of blood coagulation is the conversion of
fibrinogen into insoluble fibrin polymer.
 This is mediated by two pathways
- Intrinsic pathway
- Extrinsic pathway
 Activation of coagulation cascade needs

 Exposure of subendothelial contact factors

 Phospholipids

 Ca++
Intrinsic system Extrinsic system

Contact Endothelial
activation injury

Hagman Factor Tissue Factor

activation

Factor X

Final common
pathway

Prothrombin

Thrombin

Fibrinogen

64

Fibrin
Fibrinolysis
 Hemostatic plugs must be removed once healing is
completed(Hemostasis is secured).

 Blood contains an enzymatic system which lyses fibrin and

blood clots – the fibrinolytic system.

 This system includes plasminogen which can be activated

to plasmin by plasminogen activators (t-PA).
Regulation of Coagulation

 There are positive feedbacks and amplifications in the

coagulation pathway, which if unchecked would continue
until all the fibrinogen in plasma is converted to fibrin

 Important inhibitors includes : antithrombin III, the

protein C/protein S system , thrombomodulin and tissue
factor pathway inhibitor.
Endothelium

 The balance between the anticoagulant and procoagulant

activities of endothelium often determines whether clot
formation, propagation, or dissolution occurs
 Normal endothelial cells express a multitude of factors
that inhibit the procoagulant activities of platelets and
coagulation factors and that augment fibrinolysis

 These factors act in concert to prevent thrombosis and to

limit clotting to sites of vascular damage.
Platelet inhibitory effects

 Normal endothelium serve as a barrier that shields

platelets from subendothelial vWF and collagen.

 Secrete Prostacyclin (PGI2), nitric oxide (NO), and

adenosine diphosphatase

 Endothelial cells bind and alter the activity of thrombin

Anticoagulant effects

 Normal endothelium shields coagulation factors from

tissue factor in vessel walls

 Thrombomodulin, endothelial protein C receptor, heparin-

like molecules, and tissue factor pathway inhibitor (TFPI).
Fibrinolytic effects

 Normal endothelial cells synthesize t-PA

 Plasmin – cleaves coagulation factors, fibrin and

fibrinogen and inhibit platelet aggregation
 Summary

Intact endothelial cells serve primarily to inhibit platelet

adhesion and blood clotting. Injury or activation of
endothelial cells, however, results in a procoagulant
phenotype that augments local clot formation.
Disorders of secondary hemostasis

 Due to defect in coagulation cascade

 Ussually cause Deep tissue, joint and post surgical hge is

common

 Prolonged PTT/PT

 Normal bleeding time and platelet count

Hemophilia

 Can be Hemophilia A—Factor VIII Deficiency or Hemophilia

B—Factor IX Deficiency

 X linked recessive

 Prolonged PTT, normal PT

Acquired causes of coagulation cascade

 Vitamin K deficiency

 Liver failure

 Large volume transfusion

DISSEMINATED INTRAVASCULAR
COAGULATION (DIC)

 DIC occurs as a complication of a wide variety of

disorders; it is caused by the systemic activation of
coagulation and results in the formation of thrombi
throughout the microcirculation.

 Consumptive coagulopathy
Major Disorders Associated With DIC

 Obstetric Complications

 Infections/ Sepsis

 Neoplasms (adenocarcinoma and APC)

 Massive Tissue Injury

lab. findings

 Thrombocytopnia

 Prolonged PT/PTT

 Decreased fibrinogen

 Microangiopathic hemolytic anemia (MAHA)

 Eleveted fibrin split product (D-dimer)

Thrombosis
Thrombosis
 Defn – the formation of a solid or semisolid mass from the
constituents of the blood with in the vascular system
during life.

 THROMBUS – is an clot of coagulated blood containing

platelets , fibrin and entrapped cellular elements of
blood attached at the site of its formation in the blood
vessel.
Pathogenesis of Thrombosis
 More than 100 years ago, Rudolf Virchow first organized
pathogenetic concepts of thrombosis around the following
triad:

1. Endothelial injury

2. Alteration in blood flow

3. Hypercoagulability

Rudolf Virchow
1821-1902
1. Endothelial Injury
 Most important factor in thrombus formation and can
result in thrombosis by itself.

 Damage to endothelial cells exposes the thrombogenic

subendothelium (disturbs anticoagulant properties of
vessel wall), which initiates thrombosis.

 Particularly important in thrombus formation in the heart

and arterial circulation.
 Endothelial injury:

o Endocardial injury in myocardial infarction

o Severe hypertension and scarred valves
o Vascular inflammation (vasculitis)
o Bacterial endotoxin and
o Cigarette smoking.
 The final event is exposure of the highly thrombogenic
subendothelial extracellular matrix, mainly collagen and
tissue factors.

 Platelets adhere, aggregate and degranulate

 The extrinsic pathway of blood coagulation is activated

and results in fibrin formation.
2. Abnormal blood flow
 Under physiologic conditions blood flow is laminar, the
cellular elements flow centrally in the vessel lumen
separated from the endothelium by slowly moving clear
zone of plasma.

 Normal blood flow is the best prevention against

thrombosis.

 Sluggish blood flow (Stasis) or Turbulence favors

thrombosis
Stasis and Turbulence
 Disrupt the laminar flow and bring platelets into contact with the
endothelium

 Prevent dilution of activated clotting factors by freshly flowing blood

 Retard the inflow of clotting factor inhibitors and permit the build up
of thrombi

 Turbulence causes reduction in endothelial PGI2 and t-PA

 Turbulence – contributes to arterial and cardiac
thrombosis by mostly causing direct endothelial injury.

 Stasis – a major factor in the development of venous

thrombi.
 Examples include

I. Ulcerated atherosclerotic plaque result in local

turbulence.
II. Aneurysms are favoured sites of stasis.
III. Myocardial infarction
IV. Mitral valve stenosis
V. Hyperviscosity syndrome like polycythemia
3. Hypercoagulability

 Any alteration of the coagulation pathway that

predisposes to thrombosis

 It is a less common cause of thrombosis

 Causes can be Primary (genetic)or Secondary (acquired)

Primary causes

 Mutation in factor V(Leiden factor)

 Prothrombin mutation

 Antithrombin III deficiency

 Protein C or S defciency
Secondary causes – High risk

 Immobilization
 Myocardial Infarction
 Tissue damage
 Disseminated Intravascular Coagulation
 Prosthetic cardiac valves
Secondary causes – Low risk

 Atrial fibrillation
 Cardiomyopathy
 Nephrotic syndrome
 Smoking
 Oral contraceptives
 pregnancy
Morphology of Thrombi

 May develop anywhere in the cardiovascular system:

cardiac chambers, valve cusps, arteries, veins and
capillaries.

 Usually have area of attachment to the underlying

vessel(endothelium) and Lines of Zahn
lines of Zahn
Mural thrombi

 Thrombi in the heart chambers or in aortic lumen, and are

usually adherent to underlying structures.

 Do not usually cause obstruction

 Cardiac mural thrombi (e.g. in Mitral stenosis) and Aortic

mural thrombi (e.g. atherosclerosis )
Arterial versus Venous Thrombi
Arterial Thrombi
 Arise at the site of
endothelial injury
 Grow in a retrograde
fashion
 Has firm attachment
 Usually occlude the blood
flow
 Common sites are coronary,
cerebral, femoral aa.
Venous Thrombi
 Arise at the area of stasis
 Grow in the direction of
blood flow
 Loose attachment-embolism
is common
 Almost invariably occlusive
 Most commonly affect the
veins of the lower
extremity
At autopsy (postmortem) clots may confuse with thrombi

Postmortem True thrombi

 More firm
 Gelatinous
 Usually have point of
 Have dark red
attachment
dependent portion of
RBC  Transection reveal
vague strands of pale
 Overlying yellowish
gray fibrin
supernatant
Under special circumstances thrombi on heart valves may be infected
Infective endocarditis
Fate of thrombi

1. Propagation
 Accumulate more platelets and fibrin - vessel obstruction
2. Embolization
 Dislodge and travel to other sites in the vasculature
3. Dissolution
 Thrombi may be removed by fibrinolytic activity
4. Organization and recanalization
 Ingrowth of endothelial cells, smooth muscle cells and
fibroblasts into the fibrin rich thrombus
Potential outcomes(Fate) of venous thrombosis
Clinical effect of thrombosis

Thrombi are significant clinically because:-

1. They Cause obstruction of arteries and veins

2. They are Possible sources of emboli

Venous thrombosis (Phlebothrombosis)

 Mainly occur in either superficial or deep veins of the legs.

 Superficial usually occur in the saphenous system with

varicosities.
 May cause local congestion, swelling and pain but
rarely embolize.
 Deep vein thrombosis(DVT) - asymptomatic in ~ 50% of
patients.
 DVT in leg veins is a common source of PTE

 DVT occurs in stasis, reduced physical activity (trauma,

surgery, burn) and in hypercoagulable state

 In tumors release of tumor associated procoagulant

release (migratory thrombophlebitis, Trousseau
syndrome)
Arterial thrombosis

 May cause myocardial or cerebral infarction

 Embolization can cause compromization of the blood

supply especially of the brain, kidney and spleen.
 Embolism

 Embolus: any solid, liquid, or gaseous matter that travels along

the bloodstream.

 It will impact and lodge somewhere => partial or complete

vascular occlusion => infarction

 Embolism is the clinical syndrome of having one or more emboli

 Most emboli are dislodged thrombi i.e., thromboemboli
 Can be pulmonary or systemic thromboembolism
Pulmonary thromboembolism (PTE)

 > 95% of pulmonary emboli come from the deep leg veins
(DVT)
 A paradoxical embolus is one from the systemic veins that
passes through a right-to-left intracardiac shunt to
occlude a systemic artery.
 The size & the cardiopulmonary status of the patient
determine the outcome
Outcomes of Pulmonary thromboembolism

1. 60-80% are asymptomatic because they are small =>

organization

2. Sudden death, right heart failure or cardiovascular

collapse occurs when 60% or more of the pulmonary
circulation is obstructed

3. Pulmonary hemorrhage - obstruction of medium sized

arteries
4. Pulmonary infarction in a patient with left sided heart
failure

5. Multiple emboli over time may cause pulmonary

hypertension
PTE
Saddle Pulmonary thromboembolism
Systemic thromboembolism

 Emboli traveling within the systemic arterial circulation

 80% arise from intracardiac mural thrombi & 10-15% origin

unknown

 No artery is immune, though the majority (75%) go to the

lower extremities, 10% brain
 In contrast to pulmonary emboli, systemic emboli almost
always produce infarcts.

 Note that the emboli of bacterial endocarditis are laden

with micro-organisms, and the abscess formation is likely

 The consequence depends on the extent of collateral

vascular supply, the tissue vulnerability to ischemia & the
caliber of the vessel occluded
FAT EMBOLISM
 After fractures of bones, globules of fat are released into
the circulation.

 Occurs 1-3 days after injury with heavy fat embolization

 <10% are symptomatic

 Mechanical & biochemical injury

FAT EMBOLISM
Air Embolism
 Gas in the circulation

 > 100cc produce clinical effect by forming bubbles

 Causes: ruptured uterine veins & chest trauma etc

 Decompression sickness (deep-water divers ascended

rapidly with nitrogen coming out of solution ) => acute &
chronic forms
Air in jugular veins autopsy
Amniotic Fluid Embolism
 It occurs in 1 out of 50,000 deliveries
 Amniotic fluid, which is full of baby's debris, enters the
systemic circulation
 Respiratory difficulty and shock are followed by DIC
 The pathologist finds squamous cells and other debris in
the pulmonary vasculature.
 20-50% mortality rate
AMNIOTIC FLUID EMBOLISM
AMNIOTIC FLUID EMBOLISM
Other types of emboli

 Atheroemboli are bits of debris from inside atherosclerotic

plaques.

 Bone marrow emboli with fractures ribs

 Tumor emboli are bits of cancer that invaded a vein and

then broke off eg. Renal cell carcinoma
Atheroemboli
Bone marrow emboli
 INFARCTION
An infarct is a localized area of necrosis due to
ischemia
Infarction
 Infarction means ‘stuffed full’

 >99% caused by thrombotic or embolic events => almost

all from arterial occlusion

 Venous infarction is seen in testes & ovaries because of

single venous outflow
Morphology of infarct
 Vary in appearance depending on the time
 Within 24hrs no direct evidence
 1-2days inflammation
 Red (hemorrhagic) or white (anemia)
 Septic or bland
 Red (hemorrhagic) infarcts occur

1. With venous occlusions e.g ovarian torsion

2. In loose tissues e.g lung & small bowel
3. In tissues with dual circulation e.g lung
4. In tissues that were previously congested
5. When flow is re-established (reperfusion)
 White (anemic) infarcts occur

1. With arterial occlusions in solid organs with end arterial

circulation e.g heart, kidney, spleen
2. When the solidity of the tissue limits the amount of
hemorrhage
 Most infarcts tend to wedge shaped, with the apex
pointed at the focus of arterial occlusion especially in
spleen, and kidney

 The lateral margins are irregular

 Margins better defined with time by a narrow rim of

hyperemia(inflammation)
 Mic: ischemic coagulative necrosis

 Most infarcts replaced by scar tissue following

organization

 The brain is an exception & results in liquefactive necrosis

Coagulative necrosis, renal
infarction
Spleen infarct
Large recent myocardial
infarction
Mic: Myocardial infarction
Myocardial infarction 2-3days
Myocardial infarction 1-2wks
Myocardial fibrosis following
infarction
Pulmonary infarct
Pulmonary infarct
Pulmonary infarct
Small bowel infarct (gangrene)
Bowel infarction
Cerebral infarct
Factors that influence development of an infarct

1. Nature of vascular supply e.g liver Vs kidney (end artery

e.g retinal artery)
2. Rate of development of occlusion e.g slowly developing
occlusion is less likely to cause infarction
3. Vulnerability of a tissue to hypoxia e.g. Neurons 3-
4min, myocardial cells 20-30 min, fibroblasts many hrs
4. The blood oxygen content e.g anemia, cyanotic or
congestive heart failure
 Shock
“Cardiovascular collapse”

Systemic hypoperfusion
inability to adequately perfuse the whole body, for any
reason
Shock

 Caused by reduction either in cardiac output or in

effective circulating blood volume
 Hypotension, impaired tissue perfusion & cellular hypoxia
 Clinically manifested by
 Hemodynamic disturbances
 Organ dysfunction
 Reversible => irreversible cellular injury
 Shock is likely to deteriorate into a vicious cycle of organ
failure and subsequent exacerbation of shock
Types of shock

1. Cardiogenic shock (i.e., pump failure)

Examples: massive myocardial infarct, rupture (ventricle,
valve), cardiac temponade, arrhythmias
2. Hypovolemic shock
 Bleeding: Externally or Internally (GI bleeds,
hemoperitoneum)
 Other fluid loss: sweating, vomiting, diarrhea, Burns
 Third-space losses (i.e., into effusions)
3. Distributive shock
 Septic shock (i.e., from bacterial breakdown products
and especially cytokine production by way of nitric
oxides)
 Anaphylaxis: IgE mediated hypersensitivity response
(generalized mast-cell degranulation)
 Neurogenic: certain poisons (notably war gases),
Profound anaesthesia, Spinal cord injury, Vasovagal
(i.e., extreme pain, emotion)
Pathophysiologic mechanism of septic shock

 Septic shock is caused by the host response to bacterial (gram

+ve and –ve) or fungal infections

 It is characterized by endothelial cell activation, vasodilation,

edema, disseminated intravascular coagulation, and metabolic
derangements.
 Peripheral vasodilation and pooling of blood; endothelial
activation/injury; leukocyte-induced damage; DIC; activation of
cytokine cascades
Stages of shock: Shock is a progressive disorder if uncorrected leads to death

 Three phases
1. Nonprogressive phase (compensated shock): reflex
compensatory mechanism activated & perfusion of vital
organs maintained
 Baroreceptor reflexes, release of catecholamines,
activation of renin angiotensin axis, antidiuretic
hormone release, & generalized sympathetic stimulation
 Blood is shunted away from the kidneys, gut, skin, and
muscles in order to perfuse the brain and heart.
 Patients may be oliguric from reduced blood flow to the
kidneys ("prerenal azotemia"), and have dry mouth and
skin from reduced blood flow to these organs
2. Progressive stage (decompensated shock): tissue
hypoperfusion & onset of worsening circulatory &
metabolic imbalances, blood pressure and cardiac
output decline
 Lactic acidosis lowers the tissue pH & arteriolar
dilatation => blood pools in microcirculation => decrease
CO & endothelial injury => DIC
 Survivors typically have reversible necrosis of the renal
tubules
 "shock lung" or "adult respiratory distress syndrome”
3. Irreversible stage: severe cellular injury (lysosomal
enzyme leakage) & myocardial contractile function
worsens & ischemic bowel allows bacteria to enter
circulation
 Correction of the deficient cardiac output and volume
deficit by any means fail to reverse shock
 Blood pressure and pH continue to drop
 Death due to multiple organ failure (MOF)
Morphology

 Tissue injury is hypoxic injury any tissue

 Diffuse hypoxic injury to the brain ("respirator brain")

 Subendocardial necrosis

 Widespread contraction band necrosis in the heart

 Acute tubular necrosis (ATN) of the kidneys
 Stressed adrenals, i.e., cortical hyperplasia, lipid
depletion
 Bleeding points ("stress ulcers") in the stomach and
duodenum
 Necrosis of, and bleeding into, portions of the small
intestine (especially when dopamine has been
administered)
 fatty change of the liver and centrilobular necrosis
.

 .
Shock lung: Diffuse alveolar damage
Thank You!!!