HEMODYNAMIC DISORDER SO much for (1).ppt

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1. HEMODYNAMIC DISORDERS
TEWODROS(M.D)

2. Edema
60% of lean body weight is water; two thirds of
this water is intracellular, remainder is in the
extracellular space, mostly interstitial fluid.
EDEMA signifies increased fluid in the interstitial
tissue spaces.
Depending on the site, fluid collections are
variously designated hydrothorax,
hydropericardium, and hydroperitoneum
(ascites).
Anasarca: severe, generalized edema with
profound subcutaneous tissue swelling.

3. Pathophysiologic Categories of Edema
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
Arteriolar dilation
Heat
Neurohumoral dysregulation

4. Reduced Plasma Osmotic Pressure
(Hypoproteinemia)
Protein-losing glomerulopathies (nephrotic syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
Lymphatic Obstruction
Inflammatory
Neoplastic
Postsurgical
Postirradiation

5. Sodium Retention
Excessive salt intake with renal insufficiency
Increased tubular reabsorption of sodium
Renal hypoperfusion
Increased renin-angiotensin-aldosterone
secretion
Inflammation
Acute inflammation
Chronic inflammation
Angiogenesis

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8. Types of edema
•Transdate: protein poor (<3 gm/dl) fluid with
specific gravity of <1.012 due to imbalances in
normal hemodynamic forces e.g. congestive
heart failure, liver and renal disease etc.
•Exudate - protein rich (>3 gm/dl) fluid with a
specific gravity of >1.020 results from
endothelial damage and alteration of vasular
permeability e.g. inflammatory and
immunologic pathology.

9. Hyperemia & Congestion
•Hyperemia is an active
process resulting from
tissue inflow because of
arteriolar dilation,
•e.g. skeletal muscle during
exercise or at sites of
inflammation.
•The affected tissue is redder
because of the
engorgement of vessels
with oxygenated blood.
•Congestion is a passive
process resulting from
impaired outflow from a
tissue.
• It may be systemic e.g.
cardiac failure, or local e.g.
an isolated venous
obstruction.
•The tissue has a blue-red
color (cyanosis), due to
accumulation of
deoxygenated hemoglobin
in the affected tissues.

10. Morphology: lung
•The cut surfaces are hemorrhagic and wet.
LUNGS:
•Microscopically, acute pulmonary congestion is
characterized by alveolar capillaries engorged
with blood,alveolar septal edema and/or focal
intra-alveolar hemorrhage.
•In chronic pulmonary congestion, the septa are
thickened and fibrotic, and the alveolar spaces
may contain numerous hemosiderin-laden
macrophages (heart failure cells).

11. Morphology: liver
•In acute hepatic congestion: central vein and
sinusoids are distended with blood with or
without central hepatocyte degeneration.
•In chronic passive congestion of the liver: on
cut surface central regions of the hepatic
lobules are red-brown and surrounded by
zones of uncongested tan liver (nutmeg liver).

12. Cont…
Microscopically:
centrilobular necrosis with loss of hepatocytes,
hemorrhage and hemosiderin-laden
macrophages.
Long-standing cases (most commonly associated
with heart failure), hepatic fibrosis (cardiac
cirrhosis) may develope.

13. Hemorrhage
•Hemorrhage generally indicates extravasation
of blood due to vessel rupture
•Hematoma: accumulation of blood within
tissue.
•Petechiae: Minute 1- to 2-mm hemorrhages
into skin, mucous membranes, or serosal
surfaces.

14. CONT..
•Purpura: Slightly larger (≥3 mm)
hemorrhages.
•Ecchymoses: Larger (>1 to 2 cm)
subcutaneous hematomas (i.e., bruises).
•Large accumulations of blood in one or
another of the body cavities are called
hemothorax, hemopericardium,
hemoperitoneum, or hemarthrosis (in joints).

15. Thrombosis
•It represents hemostasis in the intact vascular
system.
•It is a process by which a thrombus is formed.
•A thrombus is a solid mass of blood
constituents which developes in artery or
vein.
•Is intravascular coagulation of blood often
causing sinificant interuption to blood flow.

16. Pathogenesis
Three primary influences predispose to
thrombus formation, the so-called Virchow
triad:
(1)endothelial injury
(2)stasis or turbulence of blood flow
(3)blood hypercoagulability
In other words it results from interaction
platelets, damaged endothelial cells and the
coagulation cascade.

17. Figure 4-13 Virchow triad in thrombosis. Endothelial integrity is the single most important factor. Note that injury to endothelial cells can affect local blood flow and/or
coagulability; abnormal blood flow (stasis or turbulence) can, in turn, cause endothelial injury. The elements of the triad may act independently or may combine to cause
thrombus formation.
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18. Primary (Genetic) Hypercoagulable States
•Mutation in factor V gene (factor V Leiden)
•Mutation in prothrombin gene
•Mutation in methyltetrahydrofolate gene
•Antithrombin III deficiency
•Protein C deficiency
•Protein S deficiency
•Fibrinolysis defects
)

19. Secondary(Acquired)
Hypercoaguable States
High risk for thrombosis
•Prolonged bed rest or immobilization
•Myocardial infarction,Atrial fibrillation
•Tissue damage (surgery, fracture, burns)
•Cancer
•Prosthetic cardiac valves
•Disseminated intravascular coagulation
•Heparin-induced thrombocytopenia
•Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
Lower risk for thrombosis
Cardiomyopathy,Nephrotic syndrome,Hyperestrogenic states
(pregnancy),Oral contraceptive use,Sickle cell anemia,Smoking.

20. Pathogenesis contd. 1) platelets
•- maintain the integrity of the vascular
endothelium.
•-participate in endothelial repair through the
contirbution of PDGF
•-form platelet plugs
•-promote the coagulation cascade through the
platelet phospholipid complex.

21. Pathogenesis contd
2) Endothelial cells
•- are resistant to the thrombogenic influence
of platelets and coagulation proteins. Intact
endothelial cells act to modulate several
aspects of hemostasis and oppose coagulation
after injury by thromboresistance.

22. Pathogenesis contd
3) Coagulation Cascade
•The coagulation cascade constitutes the third
component of the hemostatic process and is a
major contributor to thrombosis.
•The coagulation cascade is essentially a series
of enzymatic conversions, turning inactive
proenzymes into activated enzymes and
culminating in the formation of thrombin.

23. Pathogenesis contd
3) Coagulation Cascade contd.
•Thrombin then converts the soluble plasma
protein fibrinogen precursor into the insoluble
fibrous protein fibrin.
•-intrinsic pathway
•-extrinsic pathway

24. Pathogenesis contd
3) Coagulation Cascade contd.
•Besides inducing coagulation, activation of the
clotting cascade also sets into motion a
fibrinolytic cascade that limits the size of the
final clot.
• This is primarily accomplished by the
generation of plasmin.

25. Con…
•Plasmin is derived from enzymatic breakdown of
its inactive circulating precursor plasminogen,
either by a factor XII-dependent pathway or by
two distinct types of plasminogen activators

26. Fibrinolysis (thrombus dissolution)
•Runs concurrently with thrombogenesis.
•Restores blood flow in vessels occluded by a
thrombus and facilitates healing after
inflammation and injury.
•The proenzyme plasminogen is converted by
proteolysis to plasmin, the most important
fibrinolytic protease.
•Plasmin split fibrin.

27. Thrombotic disorders
•- can be anti-thrombotic (hemorrhagic),
leading to pathologic bleeding states such as
hemophilia, Christmas disease and von
Willebrand disease.
•- can also be prothrombotic, leading to
hypercoagulability with pathologic
thrombosis.

28. Hereditary Thrombophilia
•Is a prothrombotic familial syndrome.
•Charecterized by recurrent venous thrombosis
and thromboembolism
•Can be caused by deficiency of antithrombotic
proteins including antithrombin 3, protein C,
and protien S.

29. Antiphospholipid antibody syndrome
•Is a prothrombotic disorder charecterized by
autoantibodies directed against a number of
protein antigens complexed to phospholipids
•Is further charecterized by recurrent venous
and arterial thromboembolism, fetal loss,
thrombocytopenia and a variety of
neurological manifestations.

30. Antiphospholipid antibody syndrome
•It is most often diagnosed because of an
incidental finding of prolonged PTT.
•It is sometimes associated Systemic Lupus
Erythematosus and so this antibody is also
known as lupus anticoagulant.

31. Disseminated intravascular
coagulation
•Is both prothrombotic and antithrombotic
disorder characterized by widespread
thrombosis and hemorrhage resulting from
the consumption of platelets and coagulation
factors.

32. Morphology of thrombus
•Thrombi may develop anywhere in the
cardiovascular system, the cardiac chambers,
valve cusps, arteries, veins, or capillaries.
•They vary in size and shape, depending on the
site of origin.
•Arterial or cardiac thrombi usually begin at a
site of endothelial injury (e.g., atherosclerotic
plaque) or turbulence (vessel bifurcation)
•Venous thrombi characteristically occur in
sites of stasis.

33. Arterial & Venous Thrombi
•Arterial thrombi grow in a retrograde
direction from the point of attachment
•Venous thrombi extend in the direction of
blood flow (i.e., toward the heart).
•The propagating tail of either thrombi may
not be well attached (particularly in veins) is
prone to fragmentation, creating an embolus.

34. Thrombi (cont.)
•When formed in the heart or aorta, thrombi
may have grossly (and microscopically)
apparent laminations, called lines of Zahn;
•these are produced by alternating pale layers
of platelets admixed with some fibrin and
darker layers containing more red cells.

35. Cont…
•When arterial thrombi arise in heart chambers or
in the aortic lumen, they usually adhere to the
wall of the underlying structure and are termed
mural thrombi.

36. Arterial thrombi
•are usually occlusive
•most common sites in descending order, are
coronary, cerebral, and femoral arteries.
•It is usually superimposed on an
atherosclerotic plaque and are firmly
adherent to the injured arterial wall and are
gray-white and friable, composed of a tangled
mesh of platelets, fibrin, erythrocytes, and
degenerating leukocytes.

37. Venous thrombosis
•Also called phlebothrombosis, is almost
invariably occlusive
•the thrombus often takes the shape of the vein.
•Because these thrombi form in a relatively static
environment, they contain more enmeshed
erythrocytes and are therefore known as red, or
stasis thrombi.
•Phlebothrombosis most commonly affects the
veins of the lower extremities (90% of cases).

38. Postmortem clots
•At autopsy, postmortem clots may be confused
for venous thrombi.
•Postmortem clots are gelatinous with a dark red
dependent portion where red cells have settled
by gravity and a yellow chicken fat supernatant
resembling melted and clotted chicken fat.
•They are not attached to the underlying wall.
•Red thrombi are firmer, almost always have a
point of attachment, and on transection reveal
vague strands of pale gray fibrin.

39. Thrombi on Heart Valves
•Bacterial or fungal blood-borne infections may result in the
development of large thrombotic masses on heart valves,
called as vegetations (infective endocarditis).
•Sterile vegetations can also develop on noninfected valves in
patients with hypercoagulable states, so-called nonbacterial
thrombotic endocarditis.
•Less commonly, noninfective, verrucous (Libman-Sacks)
endocarditis attributable to elevated levels of circulating
immune complexes may occur in patients with systemic lupus
erythematosus

40. Figure 4-15 Potential outcomes of venous thrombosis.
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Fate of thrombus

41. EMBOLISM
•An embolus is a detached intravascular solid,
liquid, or gaseous mass that is carried by the
blood to a site distant from its point of origin.
•Almost all emboli represent some part of a
dislodged thrombus, hence the commonly
used term thromboembolism.

42. Embolism (cont.)
•The emboli ultimately lodge in vessels too
small to permit further passage, resulting in
partial or complete vascular occlusion leading
to ischemic necrosis of distal tissue,
(infarction). Depending on the site of origin,
emboli may lodge in the pulmonary or
systemic circulations.

43. PULMONARY THROMBOEMBOLISM
•Depending on size of embolus, it may occlude
main pulmonary artery, or impact across the
bifurcation (saddle embolus), or pass out into
the smaller, branching arterioles
•Rarely, embolus may pass through an
interatrial or interventricular defect to gain
access to the systemic circulation (paradoxical
embolism).

44. PULMONARY THROMBOEMBOLISM (cont.)
•Most pulmonary emboli (60% to 80%) are
clinically silent because they are small. Sudden
death, right heart failure (cor pulmonale), or
CVS occurs when 60% or more of the
pulmonary circulation is obstructed with
emboli.
•Embolic obstruction of small end-arteriolar
pulmonary branches may result in infarction.

45. SYSTEMIC THROMBOEMBOLISM
•refers to emboli traveling within the arterial circulation.
•Most (80%) arise from intracardiac mural thrombi.
•The major sites for arteriolar embolization are the lower
extremities (75%) and the brain (10%).
•The consequences of systemic emboli depend on the extent
of collateral vascular supply in the affected tissue, the tissue's
vulnerability to ischemia, and the caliber of the vessel
occluded; in general, arterial emboli cause infarction of
tissues supplied by the artery

46. FAT EMBOLISM
•Microscopic fat globules may be found in the
circulation after fractures of long bones
(which have fatty marrow) or, rarely, in soft
tissue trauma and burns.
•Fat is released by marrow or adipose tissue
injury and enters the circulation through
rupture of the blood vessels.
•Less than 10% of patients with fat embolism
have any clinical findings.
•Fat embolism syndrome is characterized by
pulmonary insufficiency, neurologic symptoms,
anemia, and thrombocytopenia.

47. AIR EMBOLISM
•Gas bubbles within the circulation can
obstruct vascular flow (and cause distal
ischemic injury) acting as thrombotic masses.
Bubbles may coalesce to form frothy masses
sufficiently large to occlude major vessels.
•Air may enter the circulation during obstetric
procedures or as a consequence of chest wall
injury.
•An excess of 100 cc is required to have a
clinical effect.

48. Decompression sickness
•Occurs when individuals are exposed to sudden
changes in atmospheric pressure.
•Scuba and deep sea divers, underwater
construction workers, and individuals in
unpressurized aircraft in rapid ascent are all at
risk.

49. Decompression sickness (cont.)
•When air is breathed at high pressure (e.g.,
during a deep sea dive), increased amounts of
gas (particularly nitrogen) become dissolved in
the blood and tissues. If the diver then
ascends (depressurizes) too rapidly, the
nitrogen expands in the tissues and bubbles
out of solution in the blood to form gas
emboli.
•‘Bends’ and ‘chokes’.

50. AMNIOTIC FLUID EMBOLISM
•A grave and uncommon complication of labor
and the immediate postpartum period,
characterized by sudden severe dyspnea,
cyanosis, and hypotensive shock, followed by
seizures and coma.
• If the patient survives the initial crisis,
pulmonary edema develops, along with DIC,
owing to release of thrombogenic substances
from amniotic.

51. AMNIOTIC FLUID EMBOLISM (cont.)
•Caused by infusion of amniotic fluid or fetal
tissue into the maternal circulation via a tear
in the placental membranes or rupture of
uterine veins.
•Microscopy: presence in the pulmonary
microcirculation of squamous cells shed from
fetal skin, lanugo hair, fat from vernix caseosa,
and mucin derived from the fetal respiratory
or gastrointestinal tract. Marked pulmonary
edema and diffuse alveolar damage are also
present. Systemic fibrin thrombi indicative of
DIC can also be seen.

52. INFARCTION
•An infarct is an area of ischemic necrosis caused
by occlusion of either the arterial supply or the
venous drainage in a particular tissue e.g.
myocardial, cerebral, pulmonary and bowel
infarction.
•Most infarcts result from thrombotic or embolic
events, and almost all result from arterial
occlusion. Although venous thrombosis may
cause infarction, it more often merely induces
venous obstruction and congestion.

53. Morphology
•Infarcts are classified on the basis of their
color (reflecting the amount of hemorrhage)
and the presence or absence of microbial
infection.
•Therefore, infarcts may be either red
(hemorrhagic) or white (anemic) and may be
either septic or bland.

54. Red Infarcts
Red (hemorrhagic) infarcts occur
•with venous occlusions (such as in ovarian
torsion)
•in loose tissues (such as lung), and in tissues
with dual circulations (e.g., lung and small
intestine), permitting flow of blood from the
unobstructed vessel into the affected zone

55. White Infarct
•White (anemic) infarcts occur with arterial
occlusions in solid organs with end-arterial
circulation (such as heart, spleen, and kidney),
where the solidity of the tissue limits the
amount of hemorrhage that can seep into the
area of ischemic necrosis from adjoining
capillary beds.

56. Morphology
•Gross: Most infarcts are wedge-shaped, with the
occluded vessel at the apex and the periphery of
the organ forming the base.
•Micro: An inflammatory response begins along
the margins of infarcts within a few hours and is
usually well defined within 1 or 2 days, followed
by gradual degradation of the dead tissue with
phagocytosis of the cellular debris by neutrophils
and macrophages. Most infarcts are ultimately
replaced by scar tissue.

57. Septic Infarct
•Septic infarctions may develop when
embolization occurs by fragmentation of a
bacterial vegetation from a heart valve or
when microbes seed an area of necrotic
tissue. The septic infarct is converted into an
abscess, with a correspondingly greater
inflammatory response

58. Infarct (cont.)
•The consequences of a vascular occlusion can
range from no or minimal effect, all the way
up to death of a tissue or even the individual.
The major determinants include: (1) the
nature of the vascular supply; (2) the rate of
development of the occlusion; (3) the
vulnerability of a given tissue to hypoxia; and
(4) the blood oxygen content.

59. SHOCK
•Shock, or cardiovascular collapse, is the final
common pathway for a number of potentially
lethal clinical events, including severe
hemorrhage, extensive trauma or burns, large
myocardial infarction, massive pulmonary
embolism, and microbial sepsis.

60. In shock there is
•systemic hypoperfusion caused by reduction
either in cardiac output or in the effective
circulating blood volume.
•The end results are hypotension, followed by
impaired tissue perfusion and cellular hypoxia.
•Initially the cellular injury is reversible,
persistence of shock eventually causes
irreversible tissue injury.

61. Types of shock.
•Cardiogenic shock results from myocardial pump
failure e.g intrinsic myocardial infarction,
ventricular arrhythmias.
•Hypovolemic shock results from loss of blood or
plasma volume e.g. hemorrhage, fluid loss from
severe burns, or trauma.
•Septic shock is caused by systemic microbial
infection. Most commonly due to gram-negative
infections (endotoxic shock), but it can also occur
with gram-positive and fungal infections.

62. •Neurogenic shock: anesthetic accident or
spinal cord injury can lead to loss of vascular
tone and peripheral pooling of blood.
• Anaphylactic shock: initiated by a generalized
IgE-mediated hypersensitivity response, is
associated with systemic vasodilation and
increased vascular permeability.

63. Septic/Endotoxic Shock
•Septic shock results from spread and expansion
of an initially localized infection (e.g., abscess,
peritonitis, pneumonia) into the bloodstream.
•Most cases of septic shock (approximately 70%)
are caused by endotoxin-producing gram-
negative bacilli. Endotoxins are bacterial wall
lipopolysaccharides (LPSs) that are released when
the cell walls are degraded (e.g., in an
inflammatory response).

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65. Stages of Shock
If uncorrected, leads to death. Unless insult is massive and
lethal (e.g. a massive hemorrhage), shock tends to evolve
through three general phases.
•A nonprogressive phase: reflex compensatory mechanisms
are activated and perfusion of vital organs is maintained
•A progressive stage: tissue hypoperfusion and onset of
worsening circulatory and metabolic imbalances, including
acidosis
•An irreversible stage: sets in after body has incurred cellular
and tissue injury so severe that even if the hemodynamic
defects are corrected, survival is not possible.

66. Morphology
•The cellular and tissue changes induced by
shock are essentially those of hypoxic injury,
since shock is characterized by failure of
multiple organ systems, the cellular changes
may appear in any tissue.
•They are particularly evident in brain, heart,
lungs, kidneys, adrenals, and gastrointestinal
tract.

67. Morphology of shock (cont.)
•brain - ischemic encephalopathy
•heart - coagulation necrosis, may exhibit subendocardial
hemorrhage and/or contraction band necrosis.
•kidneys - tubular ischemic injury (acute tubular necrosis,
therefore oliguria, anuria, and electrolyte disturbances
constitute major clinical problems.
•lungs are seldom affected in pure hypovolemic shock because
they are resistant to hypoxic injury. When shock is caused by
bacterial sepsis or trauma, however, changes of diffuse
alveolar damage may appear, the so-called shock lung

68. Clinical Course.
•In hypovolemic and cardiogenic shock, the
patient presents with hypotension;
• a weak, rapid pulse; tachypnea; and cool,
clammy, cyanotic skin. In septic shock, the skin
may initially be warm and flushed because of
peripheral vasodilation.
•As shock progresses, electrolyte disturbances and
metabolic acidosis (lactic acidosis) complicate the
situation followed by progressive fall in urine
output.

69. Prognosis
•The prognosis varies with the origin of shock
and its duration.
•80% to 90% of young, otherwise healthy
patients with hypovolemic shock survive with
appropriate management, whereas
cardiogenic shock associated with extensive
myocardial infarction and gram-negative
shock carry mortality rates of up to 75%, even
with the best care currently available.