First Shift PATHOLOGY
Pathology Lecture 2:
Fluid and Hemodynamics
Edema
- Under normal conditions, fluid flowing out of
arterial ends > reabsorbed at venular ends
Edema is usually prevented by draining
through lymphatic channels
- Due to higher oncotic pressure compared to
hydrostatic pressure at the venular end and low
oncotic pressure of interstitial fluid
- When lymphatics are unable to drain off excess
fluids
- Edema is usually due to:
Increased Hydrostatic Pressure
- Increased fluid flowing out into the arterial
end + decreased reabsorption at the
venular end
- Lymphatics must increase the drainage
capacity, but only at a certain capacity
- Remaining fluid will flow to the interstitium
or other cavities of the body = EDEMA
- Ex. Congestive Heart Failure (generalized)
Localized edema may occur in deep
venous thrombosis
Decreased Oncotic Pressure
- Increased filtration + less reabsorption at
venular end (accumulation of plasma
proteins)
- Ex. Liver cirrhosis production of albumin
from the liver is decreased
Could also affect the kidneys in nephrotic
syndrome, where glomerular capillaries
are leaky leading to loss of albumin
Increased Vascular Permeability
- During inflammation
- Capillary, venous, and arterial end >
increased but inadequate lymphatic
drainage
Lymphatic Obstruction
- Lymphedema, caused by tumors in the
lymphatic system
- Ex. Chylothorax lung becomes
atelectatic d/t the fluid edema
- Ex. Parasitic infection in filariasis
affecting LE and external genitalia lymph
nodes
Sodium and Water Retention
- Retaining sodium, water follows
- Increased hydrostatic pressure (d/t
intravascular vol expansion) and reducing
plasma osmotic pressure
- Ex. renal diseases like glomulonephritis
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Clinically Important Forms of Edema
- Cerebral edema is the most fatal or any
intracranial edema
Flattened gyri and narrowed sulci
Shiny brain surface
Spaces appear in between the parenchyma
- Anasarca (generalized edema)
- Pitting edema
- Facial edema
- Laryngeal edema
- Pulmonary congestion and edema
White, frothy exudate caused by air and
water = bubbling
Congestion
- Seen hand in hand with edema (HHWW)
- Both types are due to localized, increased blood
volume in a tissue
- Active Congestion/Hyperemia
Increased blood flow from arterial or arteriolar
circulation
Seen in acute inflammation
Blood vessels are dilated and engorged with
blood become redder
Tissue edema due to increased vascular
permeability
- Encephalitis
- Bacterial pneumonia
- Viral pneumonia
- Passive Congestion/Congestion
Obstruction to venous outflow
Usually have an abnormal blue-red color as in
cyanosis (accumulation of deO2 hemoglobin
in the area)
Localized (LV failure) lungs
Systemic (RV failure) liver, spleen, and
other systemic organs
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Clinical Manifestations of Congestion
- Pulmonary Congestion
Edema, hemorrhage, heart failure cells, brown
induration on gross findings
Acute
- Alveolar sacs filled with blood alveolar
septal wall with congested capillaries
Chronic
- Leakage of RBCs in alveolar sacs
- Due to longstanding obstruction to venous
outflow
Septa thickened by edema and fibrosis
- Hemosiderin-laden macrophages heart
failure cells (seen in Prussian blue)
Dead cells that leak out RBCs
- Liver Congestion
Fatty changes, centrilobular necrosis and liver
cirrhosis
Atrophy of surrounding hepatocytes around
central vein Zone 3 (Chronic Passive
Congestion)
- Central veins and hepatic sinuses of the
centrilobular regions which are distended
with blood
- Atrophy of centrilobular hepatocytes due to
increased pressure in the hepatic veins
- Dilated sinusoids distended by RBCs,
appear red
Gross appearance of the liver: pale, deep red
- Nutmeg Liver yellow-brown zone of
uncongested liver substance and blue-red
zone of congested liver substance
Ex. cardiac cirrhosis (long standing CPC)
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- Splenomegaly in Long-Standing HTN
Congested spleen
Hemorrhage
- Extravasation of blood due to ruptured blood
vessels
- Risk of hemorrhage is increased in a variety of
clinical disorders, hemorrhagic diatheses
- Ex. esophageal varices vomiting out blood
Hematemesis is a manifestation
- v.s. hemoptysis coughing
Clinical Manifestations of Hemorrhage
- Hematemesis, hemoptysis
- Large bleeds in the body cavity
Hemothorax
Hemopericardium could cause cardiac
tamponade
Hemoperitoneum
Hemarthrosis in joints
- Petechia very small bleeding foci at 1-2mm
Purpura slightly larger at 3-5mm
Ecchymoses largest at 1-2cm
- Subgaleal Hemorrhage, Scalp Contusions d/t
blunt head trauma blood between aponeurosis
and skull
- Hematuria blood in the tubules, excreted in
the urine
- Hematoma large collection of blood in tissue
(bruise)
- Intracerebral hemorrhage most likely due to
systemic hypertension; fatal
Thrombosis
- Formation of a solid clot within the vessels or
heart
- Resultant mass is called the thrombus
Normal Hemostatic Process
1. Vasoconstriction
Release of endothelin at the site of injury
2. Primary Hemostasis
Formation of the platelet plug at the site of
injury
Substances exposed include vWF, to which
platelets stick
Platelets also change shape to accommodate
plugging the area
- ADP and TXA2 recruit more platelets
3. Secondary Hemostasis
Stabilization of the clot
Release of tissue factor, phospholipid complex
expression, and thrombin activation
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4. Anti-thrombotic Counterregulation Composition of Thrombus

Release of tPA and thrombomodulin - Platelets
Blocks the coagulation cascade and allows - Fibrin
dissolution of the platelet plug - Entrapped red cells

Fate of the Thrombus

- Organization
Through recanalization re-establishing
continuity of the lumen
- Propagation
- Embolization

Complications
- Vessel occlusion
- Embolization dislodged thrombus

Predisposition to Thrombosis (Virchows Triad)
- Increased coagulability of blood
Ex. a lot of cells in the blood that could cause
clumping Polycythemia
- Damage to endothelium
Ex. Atherosclerosis endothelium is
disrupted; thrombus may overlie the area of
the plaque
- Slow flow/stasis
Ex. Aneurysm dilated portion of the vessel
> more areas of the blood to go > slowing
of blood flow + turbulence
Diabetes some vessels are smaller due to
the atherosclerotic lesion
Prolonged bed rest/immobilization cancer
Endothelial Injury
- Ulcerative atherosclerosis
- Transmural myocardial infarction
- Vasculitis
- Trauma
- Radiation
- Bacterial toxins
Alterations in Normal Blood Flow
- Platelets activated in more contact with
endothelium
- Slowed flow retards the dilution of activated
clotting factors and hepatic clearance
- Does not allow contact of cellular portion to the
endothelial wall
Normally, center: blood cells; periphery:
proteins
- Stasis or turbulence retards the inflow of
inhibitors
- Turbulence may also induce injury

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Hypercoagulable States
- Primary (genetic)
Antithrombin III
Protein C and S deficiency
Other combined deficiencies
Factor V Leiden (mutation)
Heparin-induced thrombocytopenia syndrome
Antiphospholipid antibody syndrome
- Secondary (acquired)
Prolonged bed rest (high risk)
Atrial fibrillation (low risk)
MI
Tissue damage
Acute leukemia
Disseminated intravascular coagulation (DIC)
- Consumptive coagulopathy
*Review of the Coagulation Cascade
Common pathway: Factor X
Prothrombin > thrombin
Fibrinogen > fibrin
Platelet prostaglandin pathway
- From arachidonic acid
- COX
- Prostacyclin (inhibits platelet agg) and
thromboxane (stimulates platelet agg)
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Thrombus Formation
- Platelet fibrin thrombus is formed > platelet
factor 3 is released
- Plate factor 3 acts as a co-factor in the activation
of the coagulation cascade
Fibrolipid Plaque in Atheroma
- Visualized in a specialized stain in the blood
vessel wall
- Predisposes to thrombus formation
- Stain: oil red with haemelum(?)
Cholesterol clefts can be found in the lesion
*Thrombi can also form on top of already
atherosclerotic vasculature
> Opened coronary artery with mild
atherosclerotis slowing of blood flow
narrowing of vessel
Lines of Zahn
- Only seen in a true thrombus
To differentiate from a post-mortem clot
- Gelatinous, has a dark dependent portion
and a yellow chicken fat upper portion
- Alternating red and light pink
Pale pink bands of fibrin and red bands of
RBCs
Organized Thrombi with beginning Recanalization
- Form smaller channels of thrombus in a vessel
- Even with recanalization > not enough
Bleeding Atheromatous Plaque
- Common cause of sudden occlusion
Mural Thrombus
- In the large chamber of the heart or a large
vessel
- Caused by aneurysmal vessels
- Ex. aortic aneurysm in the abdominal aorta
- Atherosclerotic leads to mural thrombosis
or aneurysmal rupture > stasis
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Infarction Embolism
- Process of tissue necrosis resulting from - Intravascular mass in a vessel carried far away
interference of blood supply by the circulation
- Types: - Throw off particular area of the thrombus
Red/Hemorrhagic Ex. Carotid artery embolus > brain
- Venous occlusions embolism
- Loose tissues with lumen Ex. Venous embolus from DVT in the LE >
- Tissue with dual circulations pulmonary embolism
- Tissues previously congested, with re- - Can be anything other than a thrombus
established blood flow Air embolism
- Ex. Pulmonary infarct - Can obstruct vascular flow
- Ex. Liver infarction can have both red - Due to
and white infarcts because of dual blood Carelessly done IV procedures
supply Obstetric procedures
- Small intestine superior mesenteric Chest wall injury
artery occlusion (hemorrhagic necrosis on Decompression sickness (sudden
microscopy) decrease in atmospheric pressure)
White/Pale Amniotic fluid embolism in the peripartum
- D/t arterial occlusions stage (while giving birth)
- In firm, compact tissue - Occurs in 1/50,000 deliveries
- Usually wedge-shaped, but size depends - 80% mortality rate
on which vessel is occluded - Some amniotic fluid may be found in the
Bigger or smaller branches maternal circulation
- Ex. Renal infarct d/t polyarteritis nodosa - May go into the pulmonary system
Coagulative necrosis Fat embolism
- Ex. Splenic infarct - Can be due to fractured long bones (90%),
burns, and severe fatty liver
Etiology Bone marrow contains fat, which can
- Intrinsic occlusion of vessels form an embolus
Ex. thrombosis, embolism or expansion of - Pulmonary insufficiency and neurologic
atheroma symptoms may be seen
- Vasospasm
- Extrinsic compression Thromboembolism
Ex. twisting of vessels ovarian cyst - Pulmonary
enlarging, twists the assoc. vessels Large emboli
- Instantaneous death (large saddle
Morphology of Infarct pulmonary embolus)
- Shape: wedge-shaped, segmental, irregular Small emboli
- Nature of necrosis - May be clinically silent, seen in patients
In brain, liquefactive necrosis without CV failure
In heart or kidney, coagulative necrosis - Blood flow from bronchial arteries (collateral
- Types: red and white infarcts circulation)
- LM: Between large and small
Ischemic coagulative necrosis - Pulmonary hemorrhage
Anemic infarct with few RBC Multiple emboli
Hemorrhagic infarct has engorgement and - Pulmonary HTN
hemorrhage

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First Shift PATHOLOGY First Cluster Exam

Shock Stages of Shock (Robbins)

- Condition of inadequate perfusion of multiple 1. Non-Progressive Stage
organs in the body Reflex compensatory mechanisms are
- May be due to decreased CO or venous return activated
- May lead to complications such as fever, brain Perfusion to vital organs*
death, etc. - Coronary and cerebral blood vessels are
less sensitive to sympathetic stimulation to
Hypovolemic Shock* maintain normal caliber and blood flow
- Low ECV > low cardiac output delivery
Ex. massive hemorrhage or fluid loss from Cutaneous vasoconstriction*
burns, trauma Neurohormonal mechanisms are activated to
maintain cardiac output and blood pressure
Shock d/t Internal Fluid Loss
- Burns 2. Progressive Stage
- Anaphylactic shock If underlying causes not corrected, leads to
- Endotoxemia this phase
- Trauma Worsening of circulatory and metabolic
> cause increased vascular permeability, imbalances
decreasing the ECV Persistent O2 deficit will trigger intracellular
aerobic respiration to be replaced by
Cardiogenic Shock* anaerobic glycolysis > excessive production
- Pumping action of the heart is impeded > low of lactic acid
cardiac output - Lactic acidosis stops vasomotor
Ex. myocardial infarct, myocarditis, cardiac response
tamponade - Arterioles dilate, blood pools in
microcirculation > worsens cardiac output
Neurogenic Shock - Puts endothelial cells at risk with
- Due to anesthetic accident or spinal cord injury subsequent DIC

Anaphylactic Shock 3. Irreversible Stage

- Through IgE-mediated hypersensitivity reaction
Septic Shock*
- From systemic immune response to microbial
infection
- Systemic arterial and venous dilation leads to
tissue hypoperfusion
- Gram-positive bacterial infection is the most
common cause
Reflected by lysosomal enzyme leakage,
further aggravating the shock state
Myocardial contractile function worsens d/t
accumulation of NO
Ischemic bowel may allow intestinal flora to
enter circulation > bacteremic shock
Culminates in death

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Disseminated Intravascular Coagulopathy

- An acquired syndrome characterized by systemic activation of blood coagulation, which results in the
formation of intravascular fibrin thrombi and multiple organ failure due to impaired perfusion
- Hyperstimulation of the coagulation cascade
Massive tissue destruction > release of tissue thromboplastin > activation of extrinsic pathway
Endothelial injury > activation of contact factors > activation of intrinsic coagulation pathways >
thrombin generation
- Manifests as coagulation problems, causing widespread microthombi formation
- Commonly seen in shock, acute renal failure, and acute respiratory failure
- Vascular thrombi and focal tissue infarction common

References:
- Robbins
- Pathology Lecture (Dr. Caja)
- LAM Notes 2015

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First Shift PATHOLOGY First Cluster Exam

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