HEMODYNAMIC DISORDERS

BY Dr. Birhane H (MD)

 Circulatory disorders

COURSE CONTENTS
 Edema – pathophysiology and morphology
 Haemorrhage and coagulation systems
 Thrombosis and Embolism
 Ischemia and infarction
 Shock and DIC
 Introduction
• Organs and cells need intact circulatory
system
 for delivery of :
– oxygen, nutrients,
– hormones,
– electrolytes, water ; and
 for removal of:
– metabolic waste and
– carbon dioxide
• For their normal function cells and tissues
need
 intact circulation
 normal fluid homeostasis => requires:
– Intact vessel wall integrity
– maintenance of intravascular pressure
• 60% of body weight is water
– 2/3 of which is intracellular and the
remainder is in extracellular
 Edema
• Edema is an increased fluid collection in the
interstitial tissue spaces.
• The fluid can be collected in different body
cavities:
– Hydrothorax
– Hydropericardium or
– Hydroperitoneum(ascites)
• Anasarca is a severe and generalized edema
with profound subcutaneous tissue swelling
There are two types of edema fluid:
1. Transudate
– It is a protein-poor fluid
– occur when there is
• under conditions of reduced plasma protein
2. Exudate (inflammatory edema)
– is a protein-rich
– Occurs because of increased vascular
permeability following inflammation
 Pathophysiology of edema
Conditions that result in edema are:
Increased Hydrostatic Pressure
Reduced Plasma Osmotic Pressure
(Hypoproteinemia)
Sodium and Water Retention
Lymphatic Obstruction
Inflammation
Increased Hydrostatic Pressure
Conditions that increase
hydrostatic pressure:
A. Impaired venous return
– congestive heart failure
– constrictive pericarditis
– ascites (liver cirrhosis)
B. Venous obstruction or
compression
– Thrombosis
– external pressure (e.g., mass)
 Reduced Plasma Osmotic Pressure
(Hypoproteinemia)
Causes:-
• Protein-losing glomerulopathies (nephrotic
syndrome)
• Liver cirrhosis
• Malnutrition
• Protein-losing gastroenteropathy
 Sodium and Water Retention
• Increased salt retention =>associated Water
=>increased hydrostatic pressure and
diminished vascular colloid osmotic pressure
(due to dilution).
• Salt retention occurs whenever renal function
is compromised , such as in primary kidney
disorders and in cardiovascular disorders that
decrease renal perfusion
• causes
– Excessive salt intake with renal insufficiency
– Increased tubular reabsorption of sodium
– Renal hypoperfusion
– Increased renin-angiotensin-aldosterone secretion
 Lymphatic Obstruction
• Inflammatory
• Neoplastic
• Postsurgical
• Postirradiation
Edema can involve any body part but most
common sites includes:
• subcutaneous tissues,
• lungs, and
• brain
• Subcutaneous edema can be diffuse (anasarca) or
more prominent in regions with high hydrostatic
pressure
• dependent edema is an edema which is more
prominent in certain body areas with higher effects
e.g. Lower extremities
– It is a prominent feature of cardiac failure
• Edema due to renal dysfunction is generally more
severe than cardiac edema
• It often appears initially in parts of the body
containing loose connective tissue, such as the
eyelids;
 periorbital edema is thus a characteristic finding
Subcutaneous edema can be pitting or
nonpitting
• Pitting edema – is when a finger pressure over
edematous tissue displaces the interstitial
fluid and leaves a finger-shaped depression
• None pitting edema – when finger pressure
leaves no depression
 Effects of edema
• Depends on site of occurrence
• Can be minor or sever.
– pulmonary edema can cause death by interfering
with normal ventilatory function.
– Brain edema is serious and can be rapidly fatal.
 HYPEREMIA AND CONGESTION
• both indicate a local increased volume of
blood in a particular tissue.
• Hyperemia is an active process resulting from
augmented blood flow due to arteriolar
dilation.
– The affected tissue is more red than normal
Congestion is a passive process resulting from
impaired venous return out of a tissue.
• It can be
– local, resulting from an isolated venous obstruction
or
– systemically, as in cardiac failure
• The tissue has a blue-red color (cyanosis)
• congestion and edema commonly occur
together.
 Hemostasis
• Hemostasis a collective term which involves:
• 1. maintenance of blood in a fluid, clot-free
state in normal vessels
• 2 prevent blood loss by inducing the rapid
formation of a localized hemostatic plug at
the site of vascular injury.
 Normal Hemostasis
• sequence of events in hemostasis at a site of
vascular injury :
A. Local vasoconstriction
– This effect is transient and reduce blood flow
– mediated by reflex neurogenic mechanisms and
augmented endothelin,a potent endothelium-
derived vasoconstrictor.
B. Primary hemostasis
– Characterized by platelets aggregation
C. Secondary hemostasis
– Involves activation of the coagulation cascade
clot formation
D. Counter-regulation (fibrinolysis)
– to limit the hemostatic plug to the site of injury
 Platelets
• Platelets play a critical role in hemostasis
– by forming the primary plug that initially seals
vascular defects and
– By providing a surface that binds and concentrates
activated coagulation factors
• On contact with vWF and collagen, platelets
undergo a sequence of reactions that
culminate in the formation of a platelet plug
– Platelet adhesion
– Platelets rapidly change shape
– Secretion (release reaction) of granule contents
 Coagulation Cascade

• is series of amplifying enzymatic reactions

that leads to the deposition of an insoluble
fibrin clot.
 HEMORRHAGE
it is extravasation of blood from vessels into the extravascular
space
The extravasation can be either to the exterior of the body or
into non vascular body spaces

Causes
• Trauma – the most • Congestion
common cause • Aneurysm
• Atherosclerosis • Vitamin C deficiency
• inflammatory erosion of the • spontaneous haemorrhage
vessel wall
• Neoplasm
Terminologies
• Hematoma: accumulation of blood in tissues.
• Petechiae :Minute (1- to 2-mm) hemorrhages
into skin, mucous membranes.
• Purpura :Slightly larger (upto 1 cm) superficial
hemorrhages in the skin
• Ecchymosis: A larger superficial hemorrhage in
the skin
• Hemothorax, Hemoperitoneum,Hemarthrosis,…
– Accumulation of blood at the respective tissue spaces
• Consequence of haemorrhage depends on
– The volume of blood lost
• Greater losses can cause haemorrhagic (hypovolemic)
shock.
– The rate of blood loss – much blood losses can be
tolerated if they appear in long period of time
– The site of haemorrhage is also important
• bleeding in subcutaneous tissues can be insignificant
• if bleeding located in the brain it may cause death
 Thrombosis
• It is blood clot (thrombus) formation in
uninjured vessels or thrombotic occlusion of a
vessel after relatively minor injury
• Both hemostasis and thrombosis involve three
components:
– the vascular wall
– platelets, and
– the coagulation cascade
 Pathogenesis
• There are three factors that predispose to
thrombus formation.
They are called Virchow's triad
• (1) endothelial injury
• (2) stasis or turbulence of blood flow, and
• (3) blood hypercoagulability
 Endothelial Injury
• An intact dry and smooth endothelium is anti
thrombotic (prevent adhesion of platelet and
other blood cells)
• Endothelial injury by itself can lead to
thrombosis
• Physical loss or functional disruption of
endothelium  exposure of sub endothelial
ECM, adhesion of platelets thrombosis
Endothelial dysfunction in the absence of
endothelial cell loss may occur with:
• hypertension,
• turbulent flow over scarred valves, or
• the action of bacterial endotoxins.
• Hypercholesterolemia
• products absorbed from cigarette smoke
• radiation
 Alterations in Normal Blood Flow
• Normal blood flow is laminar.
• Stasis and turbulence :
– Disrupt laminar flow and bring platelets into
contact with the endothelium
• Turbulence contributes to arterial and cardiac
thrombosis by causing endothelial injury or
dysfunction.
• stasis is a major contributor to the
development of venous thrombi.
Conditions that alter blood flow
Turbulence
• Ulcerated atherosclerotic plaques
• Stenosed valves,…
Stasis
• Aneurysms, abnormal aortic and arterial
dilations
• Myocardial infarction
• Atrial fibrillation,…
 Hypercoagulability
• Contributes less frequently to thrombotic states
• Is defined as any alteration of the coagulation
pathways that predisposes to thrombosis.
• Can be primary (genetic) or secondary
(acquired) disorders .
• Of the inherited causes of hypercoagulability,
mutations in the factor V gene and the
prothrombin gene are the most common
Secondary (Acquired) Hypercoagulable States :-
• oral contraceptive use
• Pregnancy
• Cancers
• Smoking and obesity
• Prolonged bed rest or immobilization
• Advanced age,….
 Types of thrombus
Arterial thrombi Venous thrombi
– Arise at the site of – Arise at area of stasis
endothelial injury and – Grow in the direction of
turbulence blood flow from its site
– Grow in a retrograde of attachment.
fashion, against blood – Has loose attachment
flow from its site of – Almost invariably
attachment. occlusive
– Has firm attachment – 90% of occur in lower
– They are usually extremities.
occlusive
• Mural thrombi: thrombi occurring in heart
chambers or in the aortic lumen.
• Vegetations: thrombi on heart valves .
– E.g. infections can cause valve damage, (infective
endocarditis)
– Sterile vegetations can also develop on
noninfected valves in hypercoagulable states.
 Fate of the Thrombus
• Propagation: the thrombus may accumulate
more platelets and fibrin, eventually causing
vessel obstruction.
• Embolization: thrombi may dislodges or
fragment and travel to other sites in the
vasculature.
• Dissolution: removal of thrombi by fibrinolytic
activity
• Organization and recanalization: Thrombi
induce inflammation and fibrosis ,and there will
be formation of capillary channels across the
thrombus, re establishing lumen continuity.
 EMBOLISM
• An embolus is a detached intravascular mass
that is carried by the blood to a site distant
from its point of origin
Causes of embolism:
– Thromboembolism – 99%
– Fat droplets
– Air embolism
– Atherosclerotic debris (cholesterol emboli),
– Tumor fragments,
– Foreign bodies,…
 Thromboembolism
• Emboli lodge in vessels resulting in partial or
complete vascular occlusion  ischemic necrosis
(infarction) of downstream tissue
• The site of impaction of an embolus depends on
the source of the emboli
• Embolism in the pulumonary arteries & their
branches derive from thrombus in systemic veins
or the right side of the heart.
• systemic emboli arise from the left side of the
heart or arteries.
Thromboembolism
• a) Pulmonary thromboembolism (PTE)
• b) Systemic thromboembolism
• c) Crossed embolism
 Pulmonary thromboembolism
• > 95% of venous emboli originate from deep leg
vein thrombi.
• Reach to right side of the heart before entering
the pulmonary vasculature.
• The effect of pulmonary embolism depends on
the size of the embolus and on the state of
pulmonary circulation.
• Depending on the size of the embolus, it may
occlude the
– main pulmonary artery,
– impact across the bifurcation (saddle embolus), or
– pass out into the smaller, branching arterioles .
 C/M
• Most pulmonary emboli (60% to 80%) are
clinically silent because they are small.
• Sudden death, right ventricular failure (cor
pulmonale), or cardiovascular collapse occurs
when 60% or more of the pulmonary
circulation is obstructed with emboli.
• patient who has had one pulmonary
embolus is at high risk of having more.
 Systemic Thromboembolism
• refers to emboli in the arterial circulation
Origins of systemic Thromboembolism :
– intracardiac mural thrombi-80%
• two-thirds of which are associated with left ventricular
wall infarcts and dilated left atria
– aortic aneurysms
– thrombi on ulcerated atherosclerotic plaques,
– fragmentation of valvular vegetations
• In contrast to 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%)
– brain (10%)
– intestines, kidneys, and spleen affected to a lesser
extent
The consequences of embolization depend on:
– vulnerability to ischemia,
– caliber of the occluded vessel, and
– the collateral blood supply
 Crossed embolism
• or paradoxical embolism
• occurs in the presence of interventricular
defect when an embolus transferred from the
right to the left side of the heart, then to
systemic circulation.
 Fat Embolism
• It is due to entry of fat globules in the
circulation.
• It usually follows fracture of bones
• it is asymptomatic in most cases and fat is
removed.
The pathogenesis of fat emboli probably involves
mechanical vascular obstruction by fat emboli
biochemical injury.
– free fatty acid from fat globules cause local toxic
injury to endothelium.
• Fat embolism occur due to inflammation
induced raised tissue pressure at the site of
injury that forces fat in to marrow sinsosoid &
veins
• The features of this syndrome are a sudden
onset of dyspnea, blood stained sputum,
tachycardia, change in mental status
 Air embolism
• Entry of gas bubbles within the circulation that can obstruct
vascular flow
• For example, a very small volume of air trapped in a coronary
artery during bypass surgery , or introduced into the cerebral
circulation by neurosurgery in the “sitting position,” can
occlude flow
• A larger volume of air, generally more than 100 cc, is
necessary to produce a clinical effect in the pulmonary
circulation.

• Air may enter the circulates during:

– Obstetric procedures
– Chest wall injury
– In deep see divers & under water construction workers.
– Neck wounds penetrating the large veins
– Cardio thoracic surgery.
 Amniotic fluid embolism
• It is a grave but un common, unpredictable
complication of labour
• It had mortality rate over 80%.
• The amniotic fluid containing fetal material enters
via the placental bed, the ruptured uterine veins.
• The onset is characterized by sudden severe
dyspnea , cyanosis, hypotensive shock followed
by seizure & coma of the labouring mother.
• 50% cases they will develop DIC due to fetal
material activation of the coagulation cascade.
 Infarction
• An infarct is an area of ischemic necrosis caused
by occlusion of either the arterial supply or the
venous drainage
• 99% of all infarcts result from arterial
thromboembolism
• Mechanism include:
– Local vasospasm
– Expansion of atheroma
– External compression of the vessels. e.g trauma
– Entrapment of vessels at hernial sacks etc.
Factors that determine the size & development
of an infract:
A. The nature of vascular supply
The presence of dual blood supply in the Lung
, Liver, Hand & fore arm offset the occurrence
of infraction rapidly unlike renal & spleenic
circulation, which have end arterial supply.
B: Rate of development occlusion:
slowly developing occlusions  provide time for
collaterals dev’t infraction are less likely
C: Vulnerability or susceptibility to hypoxia
Death of cells after ischemia varies
• Neurons after 3 to 4 minutes
• Myocardial cells die after 20-30min of ischemia
D: Oxygen content of blood
in an anaemic patients even partial obstruction may
lead to tissue infarction
E: The severity & duration of ischemia.
 Types of infarcts
• Infarcts are classified deepening on:
A) The basis of their colour (reflecting the
amount haemorrhages)
– Hemorrhagic (red)
– white(anemic)
B) The presence or absence of microbial
infection
– Septic
– Bland
A. Red infarcts
• It occurs:
– Venous occlusions as in ovarian torsion
– In loose tissues such as lung which allow blood to
collect in infarcts zone
– Tissues with dual circulations (eg. lung), permitting
flow of blood from unobstructed vessel in to necrotic
zone
– In tissues that were previously congested because of
sluggish out flow
– When flow is re established to a site of previous
arterial occlusion & necrosis
B. White infarcts
• It occurs in arterial occlusion or in solid
organs such as heart, spleen, kidney, where
the solidity of the tissue limits the amount of
hemorrage
 Morphology
• Gross
• All infarcts tend to be wedge shaped, with the
occluded vessel at the apex and the periphery of
the organ forming the base.
• Microscopy
• ischemic coagulative necrosis.
• The brain is an exception to this generalization,
where liquifactive
• necrosis is common.
 .
Disseminated intravascular
coagulation (DIC)
Definition: -
• - 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
coagoulopathy.
 Etiology and Pathogensis

• It is a coagulopathy that occurs following various

clinical conditions.
• Two major mechanisms activating the
coagulation pathway to cause DIC are:
• ( 1) release of tissue factor or thromboplastic
substance in to the circulation
• (2) widespread injury to the endothelial cells.
1.Tissue thromboplastin substance sources include:
A: In massive trauma, sever burns & extensive surgery.
– auto infusion of thromboplastin from the tissues
B: In obstetric conditions
– thromboplastines derived from the placenta, dead
retained foetus amniotic fluid may enter the
circulation
C: Cancers such as adenocarcinoma of lung
– release of a variety of mucus like secration which
directly activating factor X ,VII & Proteolytic
enzymes
D: In gram-negative sepsis (an important cause
of DIC),
• bacterial endoxins cause
– increased synthesis and release of tissue factor
from monocytes
2 Endothelial injury:
• Wide spread endothelial injury result from:
– Deposition of antigen antibody complexes as it
occur in systemic lupus erythematosus
– Extreme temperature eg. Heat, stroke, burns
– Hypoxia, acidosis, shock
 Clinical Course

• The two major consequences of DIC

1. widespread deposition of fibrin within the
microcirculation which leads to:
– Ischemia of affected organs and
– Microangiopathic hemolytic anemia
2. platelet consumption and increase
fibrinolysis leading to :
– hemorrhagic diathesis
• Clinically they present with:
– extensive skin & mucus membrane bleeding and
haemorrhage from multiple sites,
– Respiratory symptoms such as dyspnea, cyanosis
may occur.
– convulsion & coma in case of CNS bleeding
– Oligouria if acute renal failure, etc..
 SHOCK
• Failure of the circulatory system to maintain an
appropriate tissue perfusion and oxygen delivery to
organs.
• Shock is not synonymous with low blood pressure
• hypo perfusion (shock)  hypoxic and metabolic
effects  initially cause reversible cellular injury if
persist  irreversible tissue injury and death
• compensatory mechanisms sustain the patient, at
least for a while.
• When these adaptations fail, shock becomes
irreversible.
 Types of Shock
• Cardiogenic shock
• Hypovolemic shock
• Septic shock
• Anaphylactic shock
• Neurogenic shock
 1.Cardiogenic shock:
• Caused by failure of myocardial pump resulting from
– intrinsic myocardial damage,
– extrinsic pressure, or
– obstruction to outflow.
• Inability of the heart to pump  leads to decreased
cardiac output decreased delivery of blood to tissues
• Clinical causes:
-Myocardial infarction, myocarditis
-Ventricular rupture
-Arrhythmia
-Cardiac tamponade
-Pulmonary embolism
 Hypovolemic shock
• Occurs secondary to a pronounced decrease
in blood or plasma volume, caused by loss of
fluid from the vascular compartment.
• Decreased effective blood volume leads to
decreased venous return.
• Causes of hypovolemic shock:
– Hemorrhage
– Fluid loss (e.g., vomiting, diarrhea, burns, or
trauma)
 Neurogenic shock :

• follow acute injury to the brain or spinal cord.

• Which result in loss of vascular tone and
peripheral pooling of blood.
 Anaphylactic shock
• represents systemic vasodilation and
increased vascular permeability as a
consequence of a systemic type I
hypersensitivity reaction
 Septic Shock
• septic shock ranks first among the causes of death in
ICU.
• Have 50% mortality rate.
• a kind of shock caused by systemic microbial infection,
• Septic shock results from the host innate immune
response to infectious organisms .
• Septic shock is most frequently triggered by gram-
positive bacterial infections,
• followed by gram-negative bacteria and fungi.
• Hence, an older synonym, “endotoxic shock”, is no
longer appropriate.
 Pathogenesis of Septic Shock
• Components of microorganisms binds to a
specific receptor on monocytes, macrophages,
and neutrophils intracellular signalling 
cytokines such as IL-1 and TNFat low doses
cytokines localy eradicate the bacteria.
•  if severe infections, and a consequent
augmentation of the cytokine cascade), 
systemic effects of TNF and IL-1 may begin to be
seen, including
– fever,
– increased synthesis of acute-phase reactants, and
– increased production of circulating neutrophils.
• Finally, at higher levels , the syndrome of septic shock
supervenes ; the same cytokine and secondary mediators,
now at high levels, result in .
– Systemic vasodilation (hypotension) ,
– Diminished myocardial contractility
– Widespread endothelial injury and activation, causing systemic
leukocyte adhesion and diffuse alveolar capillary damage in the
lung.
• Activation of the coagulation system, culminating in
disseminated intravascular coagulation (DIC).
• DIC causes multiorgan system failure that affects the liver,
kidneys, and central nervous system, among others.
 Stages of Shock
• Shock is a progressive disorder that if uncorrected
leads to death
1.nonprogressive stage
• An initial stage during which reflex compensatory
mechanisms are activated and perfusion of vital
organs is maintained.
2.progressive stage
• characterized by tissue hypo perfusion and onset of
worsening circulatory and metabolic imbalances
• there is widespread tissue hypoxia.
3.An irreversible stage
• the body has incurred cellular and tissue injury so
severe that even if the hemodynamic defects are
corrected, survival is not possible.
THANKS