FLUID AND

HEMODYNAMICS
Ella C. Lim, M.D., DPSP
 EDEMA

 Definition: Extravasation of fluid from

vessels into interstitial spaces or body
cavities; the fluid may be protein poor
(TRANSUDATE) or may be protein
rich (EXUDATE).

 Hydrothorax, hydroperitoneum
(ascites), hydropericardium, anasarca
 EDEMA

 Causes: (table 4-1 Pathophysiologic categories

of edema)
 INCREASED HYDROSTATIC
PRESSURE
Caused by a reduction in venous return
(heart failure)
 DECREASED COLLOID OSMOTIC
PRESSURE caused by reduced
concentration of plasma albumin
(decreased synthesis – liver
 EDEMA

Causes:
 LYMPHATIC OBSTRUCTION that
impairs interstitial fluid clearance
(e.g., scarring, tumors- pMRM,
infection - filariasis)

 PRIMARYRENAL SODIUM
RETENTION (renal failure)

 INCREASED VASCULAR
 Lymphatic obstruction from
filariasis


Pitting edema of the leg
 Edema


 HYPEREMIA & CONGESTION

 Hyperemia – active process

resulting from augmented tissue
inflow because of arteriolar dilation
(e.g., exercise, inflammation);
oxygenated blood - erythema

 Congestion – passive process

resulting from impaired outflow from
a tissue; deoxygenated blood -
cyanosis.
Lung, acute pulmonary congestion
& edema – medium power


                                                

                       
 Lung, acute pulmonary
congestion & edema – medium
power
 Identify:
 Congested alveolar septa

 Intra-alveolar transudate

 The alveolar septa are prominent, due

to marked congestion of the
capillaries.
 The alveolar lumens contain pale-
staining edema fluid. Compare this
form of pulmonary congestion with
chronic passive congestion in the next
 What is the pathogenesis of
pulmonary edema?
 Pathogenesis of Pulmonary
Edema
 MI – LVF (left ventricular failure) -
pump failure - impaired blood flow
from lung to LA (left atrium) –
Increased hydrostatic pressure in
pulmonary alveolar capillaries -
transudation of fluid into alveoli.

 Pulmonary edema in other cases may

also result from damage to alveolar
capillaries (eg, ARDS).
 How does this type of edema differ
from that seen in acute
inflammation?
 The fluid in pulmonary edema is a
transudate (ie, it is protein poor,
has low specific gravity, and does not
contain inflammatory cells).

 Edema in inflammation is an
exudate.
Lung, chronic passive venous
congestion – gross


                                                

                       
 Lung, chronic passive venous
congestion – gross
 Identify:
 Hilus
 Pleura

 Cut surface

 This is caused by any chronic

condition that retards the outflow of
pulmonary venous blood from the
lungs to the left side of the heart (eg,
chronic mitral valve stenosis).
 Lung, chronic passive venous
congestion – gross
 Pooling of blood in the lung capillaries
and associated microhemorrhages
produce a dark brown discoloration,
noted here.
 In addition, septal fibrosis causes the
lung to become stiff. The fibrosis
causes the lung to feel firm to the
touch; also, the fibrosis causes the cut
edges to be raised or to stand up.
 This gross appearance is also called
 Lung, Chronic Passive
Congestion

 What is the brown pigment that is

derived from hemoglobin?

 What are heart failure cells?

 Lung, Chronic Passive
Congestion

 Hemosiderin

 Hemosiderin laden macrophages

Lung, chronic passive venous
congestion – high power


                                                

                       
 Lung, chronic passive venous
congestion – high power
 Identify:
 Alveolar
septa
 Macrophages with hemosiderin

 Are the alveolar septa normal in

thickness?
 Lung, Chronic Passive
Congestion

 They are thickened, due to edema

and reactive fibrosis.

 What effect would such a histologic

picture have on gaseous exchange in
the lung?
 Lung, Chronic Passive
Congestion

 It would be markedly impaired.

 What might the symptoms be?

Lung, Chronic Passive
Congestion

 Dyspnea
 Orthopnea

 Paroxysmal nocturnal
dyspnea
 Cough
 Liver, chronic passive venous
congestion – gross, cut surface


                                                

                       
 Liver, chronic passive venous
congestion – gross, cut surface
 This condition is caused by resistance or
obstruction to the outflow of venous
blood from the liver, as may occur in
chronic right heart failure (congestive
heart failure).
 The area surrounding the central veins
(centrizonal) becomes intensely
congested, and the hepatocytes in the
central zone may even become necrotic
due to hypoxia.

 Liver, chronic passive venous
congestion – gross, cut surface
 The alternating pale areas represent
the periportal hepatocytes, which have
sustained a lesser degree of hypoxia.
 This gross appearance is also called
NUTMEG LIVER.
 Remember that in the hepatic lobules,
blood flows from the periportal to the
central zones, and hence the
centrilobular areas are more
vulnerable to hypoxia than are the
 NUTMEG


 NUTMEG


Liver, chronic passive venous
congestion – medium power


                                                

                       
 Liver, chronic passive venous
congestion – medium power
 Identify:
 Portal triads
 Congestion

 The congestion and accompanying

sinusoidal dilatation are maximum in
and around central veins and
decrease progressively toward portal
triads. This is due to back pressure
opposite to the direction of normal
blood flow in the hepatic lobule.
 HEMORRHAGE

 Hemorrhage vs. Congestion –

extravasation of blood due to vessel
rupture

 Hematoma – accumulation of blood

w/in tissue
 Petechiae (1-2 mm)
 Purpura (3 mm)
 Ecchymoses (>1 to 2 cm)
 Hemothorax, hemopericardium,
 HEMATOMA


 PETECHIAE & PURPURA


 ECCHYMOSES


 HEMOSTASIS
 Endothelial Injury
 Vasoconstriction – Endothelin
 Primary Hemostasis – Platelet
adhesion (vWF) – shape change –
granule release (ADP, TXA2) -
recruitment – aggregation (1º
hemostatic plug)
 Secondary Hemostasis – TF &
phospholipids (coagulation cascade) –
thrombin activation – fibrin
polymerization – 2º hemostatic plug
 COAGULATION CASCADE

 Coagulation Cascade
 Intrinsic Pathway – Factor XII (Hageman
factor)
 Extrinsic Pathway – Tissue Factor
 Common Pathway – Factor IX –
Thrombin – Fibrin

 Fibrinolytic Cascade
 Plasminogen - Plasmin
 COAGULATION CASCADE

 Three natural anticoagulants:

 (1) Proteins C & S - generates
active protein C that inactivates
cofactors Va and VIIIa. Protein C itself
is activated by thrombin after the
latter binds to thrombomodulin on
the endothelium.

 (2)Antithrombin is activated by
binding to heparin-like molecules on
the endothelium; activated
 COAGULATION CASCADE

 (3) Tissue factor pathway inhibitor

(TFPI) – a protein secreted by
endothelium (and other cell types),
complexes to factor Xa and to tissue
factor VIIa and inactivates them to
rapidly limit coagulation.
 THROMBOSIS
 Definition: A thrombus is an
intravascular mass attached to the
vessel wall & is composed of
coagulation factors/fibrin, RBCs, &
platelets.

 Thrombi may propagate, resolve,

become organized, or embolize.

 Thrombosis causes tissue injury by

local vascular occlusion or by distal
Heart, coronary atherosclerosis
with thrombosis - gross


                                                

                       
Heart, coronary artery thrombosis
–
low power


                                                 

                      
Heart, coronary artery
thrombosis –
low power
 Identify:

 Intima

 Thrombus

 Recanaliza
tion
 Media

 Adventitia
 Heart, coronary artery
thrombosis
 This cross section of the coronary
artery in the previous image shows
marked concentric thickening of the
intima, due to intimal damage and
subsequent deposition of fibrous
tissue.
 On one side, a fresh thrombus is
attached to the damaged
endothelium. In some parts of the
thrombus, there is formation of new
capillary channels. This process, called
 THROMBOSIS
 Thrombus development depends on the
relative contribution of the components of
Virchow’s triad:
 ENDOTHELIAL INJURY (toxins,

hypertension, inflammation, metabolic

products)
 ABNORMAL BLOOD FLOW – stasis or
turbulence (aneurysms, atherosclerotic
plaques)
 HYPERCOAGULABILITY – either primary
(factor V Leiden, increased prothrombin
synthesis, antithrombin III deficiency) or
 THROMBOSIS
 Prevent venous thrombus with
heparin/warfarin

 Prevent arterial thrombus with

aspirin

 Postmortem clot vs thrombus:

resembles chicken fat (gelatinous,
rubbery, dark red at the ends and
yellowish elsewhere) without
 Postmortem clot vs. Thrombus


 Lines of Zahn
 Postmortem clot


 THROMBOSIS

 What causes arterial thrombosis?

...venous thrombosis?
 THROMBOSIS
 Arterial thrombosis is caused by
ENDOTHELIAL DAMAGE (eg,
atherosclerosis or vasculitis).

 Venous thrombosis is caused by

STASIS (sluggishness) of blood
flow.

 Both types of vessels are affected in

HYPERCOAGULABLE STATES such as
ANTITHROMBIN DEFICIENCY or
Venous thrombi – gross, cross
section

                                                

                       
Venous thrombi – gross, cross
section

 The thrombi are red due to

entrapped erythrocytes and have
a laminated appearance,
reflecting varying composition of
the thrombus, which relates to
the rate of blood flow at the time
the thrombus was forming.
 THROMBOSIS

 What are the various fates of

thrombi?
 THROMBOSIS

 Propagation
 Embolization

 Dissolution

 Organization with
recanalization
 EMBOLISM

 An embolus is any detached solid,

liquid, or gaseous mass carried by the
blood to a site distant from its origin;
the vast majority are part of a
dislodged thrombus.

 Pulmonary emboli derive primarily

from lower extremity deep vein
thrombosis; their effect (sudden
death, right heart failure, pulmonary
hemorrhage, or infarction) depends on
the size of the embolus.
 EMBOLISM
 Systemic emboli derive primarily
from cardiac mural or valvular
thrombi, valve vegetation, atrial
myxoma, aortic aneurysms, or
atherosclerotic plaque; whether
an embolus causes tissue infarction
depends on the site of the
embolization and collateral
circulation.

 Atrial fibrillation predisposes to atrial

Heart, view of the tricuspid valve from
the right atrial side - gross

                                                

                       
 EMBOLISM
 Fat embolism – from traumatic
fracture of the long bones and pelvis
 CNS damage – ischemia, hemorrhage
 Respiratory failure – hypoxemia

 Thrombocytopenia – platelet consumption

in thrombi

 Amniotic fluid embolism

 sudden onset dyspnea, cyanosis,
hypotensive shock
 DIC
 EMBOLISM
 Decompression sickness (Caisson
disease)
 Rapid ascent from diving forces nitrogen
gas bubbles to develop in tissues and
lumen of blood vessels
 Pain in joints, muscles, bone
 Hemiparesis, bladder & bowel
dysfunction
 Pneumothorax – dyspnea & pleuritic
chest pain from rupture of subpleural
bleb
 Pulmonary embolus
 INFARCTION
 Infarcts are areas of ischemic, usually
coagulative necrosis, caused by occlusion of
arterial supply or less commonly venous
drainage.

 Infarcts are most commonly caused by

formation of occlusive arterial thrombi, or
embolization of arterial or venous thrombi.

 Infarcts caused by venous occlusion, or in

loose tissues with dual blood supply,
are typically hemorrhagic (red) whereas
Heart, myocardial infarct: acute
vs. healed – gross, cross section

                                                

                       
 Heart, myocardial infarct:
acute vs. healed – gross, cross
section
 Identify:
 Acute infarct: coagulative necrosis

 Acute infarct: hyperemia

 Heart, myocardial infarct:
acute vs. healed – gross, cross
section
 The well-defined pale area in the
acute myocardial infarct represents
coagulative necrosis.
 It is surrounded by a red area of
reactive hyperemia.
 (In contrast, the ill-defined pale area
in the old myocardial infarct
represents a fibrous scar.)
Brain, cerebral infarct: acute vs.
chronic – gross, coronal section


                                                

                       
 Brain, cerebral infarct: acute
vs. chronic – gross, coronal
section
 Identify: Acute hemorrhagic infarct

 The well-defined hemorrhagic area in

the acute cerebral infarct represents
hemorrhagic liquefactive necrosis.
 INFARCTION

 What are the major similarities

between a myocardial and a cerebral
infarct?
 INFARCTION
 The major similarity is in the etiology.
 Both types of infarcts are commonly
caused by THROMBOTIC OCCLUSION
of the arteries supplying them.
 Thrombi usually form on the same
underlying disease process (ie,
atherosclerotic arterial disease).

 Also, the early histologic reactions,

such as neutrophilic infiltration and
granulation tissue formation, are
 INFARCTION

 What are the major differences

between a myocardial and a
cerebral infarct?
 INFARCTION

 A MYOCARDIAL INFARCT typically

features COAGULATIVE NECROSIS,
which heals by fibrosis and leaves
behind a FIBROUS SCAR.

 In contrast, a CEREBRAL INFARCT is

typically LIQUEFACTIVE NECROSIS,
in which dead tissue is digested
without being replaced by fibrosis,
leaving behind a CYSTIC, CAVITARY
Lung, pulmonary infarct – gross,
cut surface

                                                 

                      
Lung, pulmonary infarct – gross,
cut surface
 Identify:
 Infarct
 Pleura

 This image shows a triangular,

peripheral, subpleural area that is
solid and airless. This is the typical
appearance of a pulmonary infarct.

 It represents an area of coagulative

necrosis resulting from loss of
Lung, pulmonary infarct – gross,
cut surface
 The anoxia (ischemia) is most
commonly due to a detached venous
thrombus that is carried from the leg
veins to the right side of the heart
and ultimately occludes a pulmonary
arterial branch (pulmonary
thromboembolism).

 The infarct appears red because of

hemorrhage into the necrotic area.
Hemorrhage is favored by the dual
Lung, infarct - medium power

                                                

                       
 Lung, infarct - medium power

 On the left side, air spaces and alveolar

septa can be seen; however, the right
half looks solid and eosinophilic.
 On careful examination, it is possible to
see faint outlines of the alveoli, but
otherwise the tissue looks
structureless. These features are
typical of coagulative necrosis,
which in this case resulted from
occlusion of a pulmonary vessel by a
thrombus that originated from the
Lung, infarct – high power

                                                

                       
 Lung, infarct – high power
 Note that the outlines of the
pulmonary alveoli can be seen, but
the structural details have been
obscured in this area of coagulative
necrosis.
 There are no intact nuclei. The
pulmonary airspaces seem filled with
debris, derived in this case from
remnants of red blood cells (ie, there
was hemorrhage in this area of
necrosis). This appearance is typical
of pulmonary infarcts.
 SHOCK

 Definition: Shock is reduced perfusion

of tissue, which results in impaired
oxygenation of tissue.
 Shock causes systemic hypoperfusion due to
either reduced cardiac output or reduced
circulating blood volume.

 Most common causes/types:

 Cardiogenic (cardiac pump failure
due to MI)
 Hypovolemic (blood loss, >20%
 SHOCK
 Septic shock results from the host
innate immune response to bacterial
or fungal cells molecules (endotoxin),
with systemic production of cytokines
(TNF, IL-1), that affect endothelial &
inflammatory cell activation.

 Hypotension, DIC, and metabolic

acidosis constitute the clinical triad of
septic shock.
 SHOCK

 Other complications:
 Multi-organ dysfunction – most
common COD

 Ischemic Acute Tubular Necrosis

– coagulation necrosis of tubular cells
leading to renal failure
Kidney, renal tubular necrosis due
to shock – gross, outer & cut
surfaces


                                                

                       
Kidney, renal tubular necrosis due
to shock – gross, outer & cut
surfaces
 Identify:
 Cortex

 Medulla

 Calyces

 In this image, note that the cortex is

very pale and bloodless.
 By comparison, the medulla looks
darker red and congested.
Kidney, acute tubular necrosis
due to shock – high power


                                                

                       
 Kidney, acute tubular necrosis
due to shock – high power
 Identify:
 Glomeruli

 Tubules with necrotic epithelium

 Tubules with intact epithelium

 The glomeruli are normal. Note the

Bowman space and the nuclei of the
glomerular cells. Several of the
proximal tubules show necrosis of the
epithelium.
 Kidney, acute tubular necrosis
due to shock – high power
 In these tubules, the normal cuboidal
epithelium has been replaced by
eosinophilic, structureless debris in
which cellular outlines as well as the
nuclei are obscured.

 These tubules may be compared with

normal (uninjured) tubules. These have
a well-preserved layer of epithelial
cells that show distinct nuclei.
 What are the major morphologic
changes in multiple organ failure
in a patient who dies of shock?
Major morphologic changes in Multiple
Organ Failure in a patient who dies of
Shock
 Kidneys: Acute tubular necrosis.

 Brain: Laminar cortical necrosis.

 Lungs: Shock lung (diffuse alveolar

damage) with hyaline membranes
(seen mainly in septic shock).
 Heart: Foci of necrosis, hemorrhage,
contraction band necrosis.
 GI: Hemorrhages.

 Liver: Central hemorrhagic necrosis,

fatty change.
Brain, cortical laminar necrosis –
gross, coronal section


                                                

                       
 Brain, cortical laminar necrosis
–
gross, coronal section
 Identify:
 Normal cortex

 Cortex with laminar necrosis

 Compare the thinned and discolored

cerebral cortex on the left side to the
relatively preserved cortex on the right
side. Neurons in different areas of the
brain have different susceptibilities to
global ischemic damage, such as may
Brain, cortical laminar necrosis
–
gross, coronal section
 Most patients with shock who are
diagnosed and treated early suffer
no or only mild ischemic damage to
the brain, which may result only in a
confusional state.

 However, more severe, prolonged,

and irreversible shock can lead to
laminar cortical necrosis.
 How does this picture differ from a
thrombotic/embolic infarct?
 A thrombotic/embolic infarct in
the brain is a localized lesion
present in the area supplied by the
occluded vessel.

 In contrast, laminar cortical

necrosis is due to global hypoxic
change as in shock, and hence
affects a large part of the cortical
ribbon.
The END