Hemodynamic

Disorders,
Thromboembolic
disease, and Shock
Gifty B. MD
May 2018
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Edema
- Increased fluid in interstitial tissue spaces or
Is a fluid accumulation in the body cavities in excessive
amount
- Approximately 60% lean body weight is water, 2/3 of which
are intracellular with remainder in extracellular compartment
(most in the interstitial space)

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• Depending on the site, fluid accumulation in body cavities can
be variously designated as:
a) Hydrothorax – fluid accumulation in pleural cavity in a
pathologic amount
b) Hydropericardium – pathologic amount of fluid
accumulated in pericardial cavity .
c) Hydroperitoneum (ascites) – fluid accumulation in
peritoneal cavity.
d) Ansarca – is a severe & generalized edema of the
body with profound subcutaneous swelling.
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- There are four primary forces that determine fluid movement
across the capillary membrane. Each of them categorized
under two basic categories, the hydrostatic pressure & the
oncotic pressure. These four primary forces are known as
Starling forces.

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Pathophysiologic categories of edema
1. Increased hydrostatic pressure
- Local increase in venous pressure may result from impaired
venous outflow eg deep venous thrombosis in lower
extremities
- Generalized increases in venous pressure occur most
commonly in congestive heart failure affecting right
ventricular cardiac function.

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2.Reduced plasma osmotic pressure
It can result from excessive loss or reduced synthesis of
albumin (serum protein most responsible for maintaining
colloid osmotic pressure.
 Nephrotic syndrome
 Protein malnutrition
 Diffuse liver pathology (cirrhosis)

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3. Lymphatic obstruction
- Impaired lymphatic drainage leads to localized edema –
lymphedema
- It can result from inflammatory or neoplastic obstruction
 Filariasis causes massive lymphatic & lymph node fibrosis in
the inguinal region resulting in edema of the external genitalia
& lower limb – Elephantiasis
 Axillary Lymph node infiltrated by cancer removed by surgery
or irradiatd leads to edema of upper extremity

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4. Sodium & water retention
- Salt retention can be a primary cause of edema.
- Increased salt , with obligate accompanying water , causes
both increased hydrostatic pressure & diminished vascular
colloid osmotic pressure.
- Salt & water retention can occur with any acute reduction of
renal function including glomerulonephritis & acute renal
failure

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Hyperemia and Congestion

- Both indicate an increased volume of blood in a particular
tissue

Hyperemia
- Is an active process resulting from an increased or augmented
tissue inflow because of arteriolar vasodilation
- Affected tissues become red as there is engorgement with
oxygenated blood.
- Occur in exercising skeletal muscle or acute inflammation
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commonly.
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Congestion
- is a passive process resulted from impaired out flow from a
tissue.
- Occur systemically as in cardiac failure or
locally in isolated venous obstruction
- Affected tissue appear blue - red due to accumulation of
deoxygenated blood

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Hemorrhage
Definition:
- Extravasations of blood outside the blood vessel.
- Hemorrhage from large vessel is due to vascular injury
including trauma, atherosclerosis, or inflammatory or
neoplastic erosion of the vessel wall

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• An increased tendency to hemorrhage from usually
insignificant injury is seen in clinical disorders called
hemorrhagic diathesis.
 Fragility of blood vessels
 Platelet deficiency or dysfunction
 Coagulation disorders

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Hematoma- accumulation of blood within a tissue
Petechiae – Minute 1 to 2 mm hemorrhages to skin , mucous
membranes or serosal surfaces. It is usually due to low platelet
count (thrombocytopenia)
Purpura- larger hemorrhages (>3mm ) that may be associated
with same causes as petechiae or also may occur secondary to
trauma, vascular inflammation (vasculitis)
-Ecchymosis – larger (> 1 to 2 cm) subcutaneous hematoma &
are characteristically seen after trauma

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- Large accumulation of blood can occur in body cavities & are
called hemothorax, hemopericardium, hemopertonium or
hemarthrosis

Clinical significance
- Volume of bleeding
- Rate of bleeding
- Site of bleeding

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Hemostasis & thrombosis
- Normal hemostasis is the result of a set of well- regulated
processes that accomplish two important functions
They maintain blood in a fluid , clot-free state in normal
vessels
They induce a rapid & localized hemostatic plug at a site of
vascular injury
Thrombosis is inappropriate activation of normal hemostatic
processes such as formation of a blood clot (thrombus) in
uninjured vasculature or after minor injury

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Both hemostasis & thrombosis are regulated by three
components
• Vascular wall
• Platelets
• Coagulation cascade

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Platelet
- Membrane bound smooth discs with a number of
glycoprotein receptors
- After vascular injury, platelets encounter ECM which is
normally sequestered beneath intact endothelium. On contact
with ECM , platelets undergo three general reactions
 Adhesion & shape change
 Secretion (release reaction)
 Aggregation

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Coagulation cascade
- The coagulation cascade is a series of enzymatic conversions,
turning inactive proenzymes into activated enzymes &
resulting in the formation of thrombin . Thrombin then
converts the soluble plasma protein fibrinogen into the
insoluble fibrous protein fibrin

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Clotting is regulated by three types of anticoagulants
 Antithrombins (eg antithrombin III) inhibit the activation of
thrombin & other factors. It is activated by binding to heparin
like molecules on endothelial surface
 Protein C & S – two vitamin K dependent proteins which
inactivate factors Va & VIIIa
 Tissue factor pathway inhibitor (TFPI) – a protein secreted by
endothelium & form complexes with factor Xa & tissue
factor-VIIa & inactivates them

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Fibrinolytic pathway
- It is activated along with coagulation
- This is accomplished by generation of plasmin. Plasmin is
derived from enzymatic breakdown of its inactive circulating
precursor plasminogen by plasminogen activators

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Thrombosis
- Three primary factors predispose to thrombus formation –
Virchow triad
Endothelial injury
Stasis or turbulence of blood flow
Blood hypercoagulability

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Arterial thrombi Venous thrombi
Arise at the site of endothelial injury Arise at area of stasis

Grow in a retrograde fashion, against Grow in the direction of

blood flow from its site of attachment flow towards the heart

They are usually occlusive Almost invariably occlusive

Has firm attachment Has loose attachment i.e, why
propagating tail may
Undergo fragmentation.

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Fate of Thrombus
• Propagation
- The thrombus may accumulate more platelets and fibrin,
propagating to cause vessel obstruction
• Embolization
- Thrombi may dislodges and travel to other sites in the
vasculature

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• Dissolution
- Thrombi may be removed by fibrinolytic activity.
- Activation of fibrinolytic pathways can lead to rapid shrinkage
& even total lyses of recent thrombi in contrast older thrombi
undergo extensive fibrin polymerization renders the thrombus
substantially more resistant to proteolysis and lyses is
ineffectual rather it tends to become organize

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• Organization and recanalization
- Organization refers to the in growth of endothelial cells,
smooth muscle cells, and fibroblasts into fibrin rich thrombus
- Organization accompanied by the formation of capillary
channels across the thrombus, re establishing lumen
continuity to some extent. This is known as recanalization

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Clinical correlations
Thrombi are significant clinically in that:
- They cause obstruction of arteries and veins
- They are possible source of emboli

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Venous Thrombosis (phlebothrombosis)
- Venous thrombosis affects veins of the lower extremity in 90%
of cases
A)Superficial venous thrombosis
- Usually occur in saphenous system particularly when
there are varicosities
- cause local edema, pain, and tenderness, become
symptomatic but rarely embolize
developing a condition known as varicose ulcer

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Deep venous thrombosis
- Are more serious as they may embolize
- Usually start in deep veins within the calf muscles.
- Although they may cause local pain & edema, unlike Superficial
vein thrombosis, they are entirely asymptomatic in
approximately 50% of patients, since deep venous obstruction
rapidly offset or relived by collateral bypass channels.

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Arterial & cardiac thrombosis
- Atherosclerosis is major initiator of thrombosis related to
abnormal vascular flow & loss of endothelial integrity.
- Rheumatic heart disease may result in atrial mural thrombi
due to mitral valve stenosis followed by left atrial dilation
- In addition to obstructive features, arterial thrombi may
embolize to any tissue, but particularly common in the brain,
kidney spleen because of their large volume of in flow of
blood.

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Disseminated intravascular coagulation
- It is an acute or chronic thrombohemorrhagic disorder
occurring as a result of progressive activation of coagulation
pathway beyond physiologic set point secondary to a variety
of diseases resulting in failure of all components of
hemostasis , hence the other term for DIC is consumption
coagulopathy.

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Etiology & pathogenesis
- DIC is not a primary disease but coagulopathy that occurs in
the course of variety of clinical conditions .
- It may result from pathologic activation of extrinsic and/or
intrinsic pathways of coagulation or impairment of clot
inhibiting influences

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Two mechanisms that trigger DIC
 Release of tissue factor or thromboplastin
 Widespread injury to the endothelial cells

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Major disorders associated with DIC
Acute
Obstetric complication
 Placental abruption
 Septic abortion
 Retained dead fetus
 Amniotic fluid embolism
 Toxemia

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Infections
- Gram negative sepsis
- Meningococcemia
- Malaria
Burn, accidental trauma
Chronic
- Neoplasms
- Chronic illness

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Clinical course
- The consequences of DIC are two fold.
- First, there is widespread deposition of fibrin within the
microcirculation . This may lead to ischemia of more severely
affected or more vulnerable organs & hemolytic anemia
resulting from fragmentation of red cells as they squeeze
through narrowed microvasculature (microangiopathic
hemolytic anemia)
Second , hemorrhagic diathesis may dominate the clinical
picture because of consumption of platelets & clotting factors
& increase in fibrinolysis
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-The onset may be fulminant as endotoxic shock, amniotic fluid
embolism,chronic in case of carcinomatosis or retention of
dead fetus. So the clinical presentation varies with stage &
severity of the syndrome. Overall 50% of patients with DIC are
obstetric patients & about 33% of patients have
carcinomatosis.

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- Clinically they may present with extensive skin & mucus
membrane bleeding and hemorrhage
- Respiratory symptoms such as dyspnea, cyanosis may occur.
- They may present convulsion & coma in case of CNS
bleeding or acute renal failure with oligouria, less often they
may present with acrocynosis. Circulatory failure may
appear suddenly & may be progressing.
- The presentations of acute DIC, as it occur in case of trauma
or obstetric conditions, dominated by bleeding diathesis.
Where as chronic DIC ,as it occurs in cancer patients, tends
to present initially with thrombotic complications
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Laboratory manifestations include thromobcytopenia, secondary
to platelets aggregation in the thrombus, , prolonged PT,
PTT, .The cardinal manifestation of DIC which correlates most
closely with bleeding is plasma fibrinogen level, i.e. low

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Embolism
Definition
- An embolism is a detached intravascular solid, liquid or
gaseous mass that is carried by blood to sites distant from its
point of origin.
- Thrombus is source of emboli in 99% of cases

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- Emboli lodge in vessels too small to permit further passage ,
resulting in a partial or complete vascular occlusion. The
potential consequence of this is the ischemic necrosis of distal
tissue known as infarction
- Depending on site of origin, emboli may lodge in the
pulmonary or systemic circulations.

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Pulmonary thromboembolism
- In more than 95% of instance venous emboli originate from deep
leg vein thrombi.
- The effect of pulmonary embolism depends on the size of the
embolus and on the state of pulmonary circulation.
- A large thrombus extending up to the femoral or iliac vein may
become detached & block the out flow tract of the right
ventricle, the main pulumonary trunk, impact across the
bifurcation, also called saddle embolus or both of its branches
causing sudden death by circulatory arrest. sudden death, right
side heart failure (cor pulmonale) or cardiovascular collapse
occur when 60% or more of the pulmonary circulation is
obstructed with emboli.
- Most pulmonary emboli i.e around 60-80% are clinically silent
because they are very small 55
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- Embolic obstruction of medium sized arteries manifest as
pulmonary hemorrhage but usually does not cause infarction
because dual blood inflow to the area from bronchial
circulation.
But in the presence of left side heart failure, infarction could
occur.
- A patient who has had one pulmonary embolus is at high risk
of having more.
- A person with multiple emboli over time may have right sided
heart failure

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Systemic thromboembolism
Refers to emboli travelling within arterial circulation. Most
(80%) arise from intra cardiac mural thrombi, two third of
which are associated with left ventricular wall infarcts and
another quarter with dilated left atria secondary to rheumatic
valvular heart disease.
The remainder from aortic aneurysm, thrombi on ulcerated
athrosclerotic plaques or fragmentation of valvular
vegetation.

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• Unlike venous emboli, which tend to lodge primarily in one
vascular bed (the lung), arterial emboli can travel to a wide
variety of sites.
• The major sites for arteriolar embolization are the lower
extremities (75%) & the brain (10%), with the rest in the
intestines, kidney & spleen.

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crossed embolism
Crossed or paradoxical embolism occurs in the presence of
patent foremen ovale when an embolus is transferred from
the right to the left side of the heart, then to systemic
circulation.

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Infarction
Definition
- An infract is an area of ischemic necrosis caused by occlusion
of either the arterial supply or venous drainage in a particular
tissue.

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- Nearly 99% of all infarcts result from thrombotic or embolic
events& almost all result from arterial occulsion. Other
mechanism include
• Local vasospasm

- Infarction caused by venous thrombosis are more likely to

occur in organs with single venous outflow channels, such
testis & ovary.

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Factors that determine the size & development of an infract.
A. The nature of vascular supply
B. Rate of development occlusion: slowly developing occlusions
are less likely to cause infraction since they provide time for
the development of collaterals.
C. Vulnerability or susceptibility to hypoxia
D. Oxygen content of blood
- Partial obstruction of the flow of blood in an anemic or
cyanotic patient may lead to tissue infarction.

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• Types of infarcts
Infarcts are classified deepening on:
A) The basis of their colour (reflecting the amount
hemorrhages)
1] Hemorrhagic (red)
2]white(anemic)
B) The presence or absence of microbial infection
1]Septic
2]Bland

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Microscopy
- The dominant histologic feature of infarction is ischemic
coagulative necrosis. The brain is an exception to this
generalization, where liquifactive necrosis is common

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Shock
- A state in which the failure of the circulatory system to maintain
adequate cellular perfusion resulting in wide Spread reduction in
delivery of oxygen & other nutrients to tissues

- Regardless of the underlying pathology, shock constitutes systemic

hypoperfusion owing to reduction either in cardiac out put or in the
effective circulating blood volume. The end results are hypotension
followed by impaired tissue perfusion and cellular hypoxia

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Hypovolemic shock
Definition:
• Reduction in circulating blood volume which result in
reduction in preload leading to decreased cardiac output
• Causes of hypovolemic shock include hemorrhage, fluid loss
from burns ,diarrhea & vomiting

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Cardiogenic shock
- It results from myocardial pump failure (severe depression of
cardiac performance).
Causes
a) Acute myocardial infraction
b) Mycocarditis
c) Dilated cardiomyopathy/hypertrophic cardiomyopathy
d) Myocardial depression in septic shock

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Distributive shock
Definition:
- Refers to a group of shock sub types caused by profound
peripheral vasodilatation despite normal or high cardiac
output
Cause:
- Septic shock
- Anaphylactic shock
- Neurogenic shock

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Septic shock
Definition: a kind of shock caused by systemic microbial
infection, most commonly by gram negative infection
(endotoxic shock ) but can also occur with gram positive or
fungal infections.

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Or
Sepsis with
1] Hypotention, arterial blood pressure less than 90mmHg or
40mmHg less than the patients normal BP
2] Organ dysfunction
3] Unresponsive to fluid administration

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Pathogenesis of septic shock:
- It has a mortality rate of over 50% ranking the first among
causes of death in intensive care unit
- It results from spread & expansion of an initially localized
infections like pneumonia in to the blood stream.

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Effects of septic shock
• Systemic vasodilation
• Diminished myocardial contractility
• Wide spread endothelial injury & activation, alveolar
capillary damage – Adult respiratory
distress syndrome
• Activation of the coagulation system result in DIC.

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Neurogenic shock
- Shock may occur in setting of anesthetic accident or spinal
cord injury due to loss of vascular tone & peripheral pooling of
blood
Anaphylactic shock
- It is initiated by a generalized Ig-E mediated hypersensitivity
response , is associated with systemic vasodilation &
increased vascular permeability.

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Stages of shock
Uncorrected shock passes through 3 important stages:
1) An initial non progressive phase
- It is also called a period of early compensatory Period, during which
compensatory mechanisms are activated & perfusion of vital organs
maintained.
2) Progressive stage
-Characterized by tissue hypo perfusion with onset of worsening circulatory &
metabolic imbalances including acidosis.
- There is a wide spread tissue hypoxia.
- Anaerobic glycolysis result in excessive lactic acid production. The lactic acid
reduces tissue PH Anoxic injury to endothelial cells result in DIC.
- Clinically , the patient may become confused & the urine output declines
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3) irreversible stage
- A stage at which, even if hemodynamic disorders are
corrected, survival is not possible
- Widespread cell injury is caused by lysosomal enzyme leakage
- Myocardial contractile function worsens due to nitric oxide
synthesis
- If ischemic bowel allows intestinal flora to enter the
circulation, endotoxin shock may be superimposed
- At this point, the patient has complete renal shutdown due to
acute tubular necrosis

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Clinical course of shock
• Patient may manifest as having, a weak and rapid pulse,
tachypenia & cool, clammy, cyanotic skin. In septic shock, skin
initially be warm & fleshed because of peripheral vasodilation.
The patient may present
with confusion, restlessness, decrease in urine out put coma
and death.

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- The prognosis varies with the origin of shock & its duration.
- 80-90% of young patients with hypovolumic shock survive
where as cardiogenic shock & septic shock carry mortality rate
up to 75%

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• Thank you

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