Hemodynamic disorders med- 2011, final ii

DEFINITION:
It is the process of formation of solid mass in the
circulation from the constituents of flowing blood.
It may be within a blood vessel or cardiac chamber, in a
living organism.
Always formed ante-mortem.
The mass itself is called Thrombus.

COMPOSITION OF THROMBUS
Fibrin, Platelets, RBC's
(Hemostatic plug formation: endothelial injury, platelet aggregation, fibrin meshwork )
LOCATION OF THROMBI
Arteries, veins, heart chambers, heart valves
TYPES OF THROMBI
Arterial vs. venous;
bland vs. septic

PATHOGENESIS OF THROMBOSIS
(Predisposing Factors)
Virchow’s Triad
– Endothelial injury
– Stasis or turbulence of blood flow
– Blood hypercoagulability

Endothelial Injury
– Tissue Damage (Surgery, Fractures, Burns)
– Atherosclerosis
– Hypertension
– Toxic Products

Abnormal Blood Flow
• Turbulence of Blood Flow
– Swirls, Eddies and increased pressure are injurious
– These changes occur in arteries and the heart
– Atherosclerosis, Aneurysms, Myocardial Infarction, Cardiac Valve Lesions
– Hyperviscosity Syndromes e.g. Sickle Cell Anemia, Polycythemia
• Stasis of Blood Flow
– More commonly a problem on the venous side leading to Venous Thrombosis
– Can occur in the heart (Atrial Fibrillation or Infarction)
– Pregnancy, long plane ride, immobility after surgery
• Turbulence and Stasis :
– Disrupt normal laminar flow and bring platelets in contact with endothelium
– Prevent dilution of activated clotting factors
– Retard the inflow of clotting factor inhibitors and permit thrombi build-up
– Promote endothelial cell activation

Hypercoagulability
Any alterations of the coagulation pathways that predispose to
Thrombosis
Primary (Genetic) or Secondary (Acquired) Disorders
• Factor V Leiden mutation is the most common inherited cause of
hypercoagulability, it is resistant to the anti-coagulant effect of Activated
Protein C
• Lack of Protein S, Protein C and Antithrombin III, patients present with
venous thrombosis and recurrent thromboembolism in adolescence and early
adulthood
• Lupus ‘Anticoagulant’ with Lupus Erythematosus is associated with arterial
and venous thrombosis & recurrent abortion
• Smoking, Obesity, Oral Contraceptives (BCP)

Hemostasis & Thrombosis
• Hemostasis is the normal, rapid formation of a
localized “plug” at the site of vascular injury
• Thrombosis is the pathologic formation of a blood
clot within the non-interrupted vascular system in
a living person

Hypercoagulable States
Inherited
Abnormality Approximate Rate
Factor VLeiden - APCR (Caucasion) 15-30%
Prothrombin Gene Mutation 8-13%
Protein C Deficiency 5-6%
Protein S Deficiency 5 - 6%
Antithriombin Deficiency < 1%
Hyperhomocysteinemia 3 - 5%
Rogers: Am J Hem 41: 113, 1992

EFFECTS OF THROMBI
Stenosis or blockage of arterial lumen
ischemia, infarction
Venous occlusion
local congestion and edema and/or pulmonary embolism (travels)
Left heart valve & chamber thrombi
systemic embolism

MORPHOLOGY OF THROMBI
THROMBI DEVELOP
IN THE CARDIOVASCULAR SYSTEM
Lines of Zahn:
Alternating Pale Layers of Platelets & Fibrin With Darker Layers of Rbc’s
(seen in areas with active blood flow like heart, aorta & large arteries not in veins)
*Postmortem clots are gelatinous with a dark red dependent portion & yellow “chicken fat”
supernatant, usually not attached to the underlying wall
*Thrombi in heart chamber/aortic lumen are applied to the underlying structure, mural
thrombi (non-occlusive)
• *Arterial thrombi are Occlusive/Non-occlusive, begin at site of endothelial injury and
grow along flow of blood & typically are firmly adherent to the injured arterial wall
(atherosclerotic plaque)
• *Venous thrombi are almost always Occlusive- 85-90% of venous thrombi form in lower
extremities

Atheroma with Thrombosis:Atheroma with Thrombosis:

Mural Thrombi
In Ventricles (Left) and Aortic Aneurysm (Right)
Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7th
ed., Saunders, Philadelphia, 2003.

Cardiac Mural Thrombi
Notice underlying endocardial fibrosis
Right
Left

Thrombotic Vegetations
Mitral Valve
Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

CLINICAL SETTING FOR CARDIAC /ARTERIAL
THROMBUS FORMATION
Myocardial Infarction (MI)
Rheumatic Heart Disease
Atherosclerosis
Rare large round thrombus obstructing mitral valve is called “ ball-valve thrombus”
Thrombi formed in ventricles just before death composed of mainly fibrin (Agonal thrombi)

VENOUS THROMBOSIS
Superficial Veins of the Lower Extremities
– Cause Pain, Swelling - Rarely Embolize
– Associated With Varicosities Abnormally Dilated, Tortuous Veins
– Increased Risk of Infections
– Increased Risk of Varicose Ulcers
Deep Veins of the Lower Extremities
– Thrombi in Deep Veins (Popliteal, Femoral, Iliac Veins) More Likely
to Embolize
– About 50% Are Asymptomatic (Formation of Collaterals)
– May Produce Edema, Pain and Tenderness

• Phlebothrombosis
It is due to stasis of blood in un-inflamed veins,
particularly the calf veins.
• Thrombophlebitis
It is related to inflammation of the vein walls.

PHLEBOTHROMBOSIS THROMBOPHLEBITIS
Main cause Stasis Inflammation
Primary thrombus Small Larger-depends on extent
of phlebitis.
Propagated clot Long/poorly anchored Usually none-if present
short and well-anchored
Emboli Common, may be massive Rare unless infective
Sterile
Site Usually calf veins Anywhere
Clinical Often silent Pain
Signs of inflammation

CLINCAL SETTING FOR VENOUS
THROMBUS FORMATION
Cardiac Failure (CHF)
Trauma
Surgery
Burns
3rd Term Pregnancy and Postpartum
Cancer (migratory thrombophlebitis-Trousseau’s Syndrome)
Bed Rest
Immobilization

Valvular Thrombi (vegetations)
Infective Endocarditis
Non-bacterial Thrombotic Endocarditis (NBTE)
-Seen in patients dying of chronic debilitating diseases- advanced cancer (50% cases) &
other end stage diseases (cachectic, marantic or terminal endocarditis)
Atypical Verrucous Endocarditis (Libman-sacks)
-Seen in 50% of acute SLE, Systemic sclerosis, Collagen diseases
Capillary thrombi
Minute thrombi composed mainly of packed red cells in vasculitis & DIC

FATE OF THROMBOSIS
Resolution (Dissolution)
Recent thrombi can undergo total lysis by activation of fibrinolytic system (mostly small venous
thrombi). After the first 2-3 h, thrombi won’t undergo lysis.
Organization and recanalization
Replacement by granulation tissue followed by recanalaization or healing totally to leave only a
small fibrous‘Lump’ as evidence of a previous thrombus
Propagation
Accumulation of more platelet & fibrin and obstruction
Embolization
Early & infected thrombi may detache from site of origin and may block distal vesseles
Hyalinization & Calcification
(Degraded thrombus with superadded bacterial infection may lead to mycotic aneurysm)

Thrombus Propagated into the
Inferior Vena Cava

CLINICAL SIGNIFICANCE:
Obstruction of arteries or veins can cause
ischemia, infarction, or may embolize
Venous thrombi may lead to congestion, poor wound
healing, skin ulcers and painful thrombosed veins
Microthrombi in microcirculation (capillaries) may
cause DIC

DIAGNOSIS:
• Clinical signs are unreliable.
• Phlebography using a contrast medium.
• Radioactive iodine-labelled fibrinogen test.
• Doppler ultrasound.

EMBOLISM
It is the process of carrying an abnormal mass (embolus)
in the blood stream to a point distant from its origin.
*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

TYPES OF EMBOLI
Gas
(air, nitrogen , other gases)
Liquid
(amniotic fluid, radiographic contrast material, fat after soft tissue trauma / fracture, bone marrow )
Solid
(thrombus-- most common, foreign body- bullet, catheter; also atheroematous material, tumor cell
clumps, tissue fragments, parasites, bacterial clumps etc.
99% are dislodged thrombus
Rarely: Bullets, Fat, Air, Atherosclerotic Fragments, Tumor Fragments, Bone Marrow
Emboli can be Bland (sterile) or Septic (infected)

• ORIGIN & SITES OF EMBOLIZATION:
• Venous: Systemic veins Pulmonary arteries
• Arterial: Heart or aorta Systemic circulation
• Paradoxic: Systemic veins (through septal defect in heart or
AV shunts in heart) systemic circulation
*Retrograde: Embolus traveling against the flow of blood (metastatic deposits in spine from
carcinoma prostate due to retrograde embolism through intraspinal veins from large
thoracic & abdominal veins due to increased pressure in body cavities: during coughing or
straining)

EFFECTS OF EMBOLISM
Ischemia
Infarction
Sepsis if infected
(example: pulmonary embolism with pulmonary infarction)

Thromboembolism
A detached thrombus or part of thrombus constitutes the most
common type of embolism
*Arterial (systemic) thromboembolism
(from within heart & arteries)
*Venous thromboembolism Pulmonary thromboembolism
(from veins of lower legs & upper limbs, pelvic vein, cavernous sinus of brain, right side of
heart)

Systemic Thromboembolism
• Emboli traveling within the arterial circulation
• 80% arise from intra-cardiac mural thrombi (myocardial infarction)
• Vegetations on the heart valves (mitral/aortic) & prosthetic heart valves may
embolize to the systemic circulation
• Infective endocarditis, Cardiomyopathy & CHD may be cause
• Emboli developing in relation to atherosclerotic plaques, aortic aneurysms,
pulmonary veins and paradoxic emboli
• Major site of embolization are lower extremities (75%), brain (10%), intestine,
kidney & spleen
• Leads to infarction of the affected organs, gangrene, arteritis & mycotic
aneurysm, myocardial infarction and sudden death.

Pulmonary Thromboembolism
Generally originate from deep leg veins (popliteal, femoral & iliac)
Usually pass through the right heart Into pulmonary vasculature
60% Pulmonary Arterial obstruction usually leads to sudden death, RVF
Most pulmonary emboli (60-80%) are clinically silent because of small size
• May occlude main pulmonary artery, across the bifurcation (Saddle
Embolus) or pass into the smaller branching arterioles
• Embolic obstruction of medium-sized arteries may result in hemorrhage
without infarction because of intact bronchial circulation. If bronchial
circulation is compromised as in left heart failure it results in infarction
• Emboli obstructing small end-arteriolar pulmonary branches usually result in
associated infarction
• Multiple pulmonary emboli over time may cause pulmonary hypertension
and right heart failure

Embolization (Embolus)
Thromboembolism of Pulmonary Artery
ed., Saunders, Philadelphia, 2003; . Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

Fat embolism syndrome
Microscopic fat globules derived from long bone fractures (fatty marrow) or
rarely from soft tissue trauma and burns
10% of cases show clinical findings
Clinically characterized by
Pulmonary insufficiency, neurologic symptoms, anemia & thrombocytopenia
Symptoms appear 1-3 days after injury
Pathogenesis
Mechanical obstruction in pulmonary & cerebral microcirculation and chemical
injury to endothelium by free fatty acids resulting in skin rash

Bone Marrow Embolus
In Pulmonary Vessel

Air embolism
Gas bubbles within the circulation can obstruct vascular flow to cause distal
ischemic injury
Air can enter the circulation during
Chest wall injury, Operation on neck & head, Obstetrical operation & trauma, Intravenous
infusion, Sudden atmospheric pressure changes in scuba & deep sea divers, underwater
construction workers and in individual in unpressurized aircraft in rapid ascent
(Decompression sickness- Caisson disease)
Bends due to rapid gas bubble formation within skeletal muscle & about joint
Chokes due to respiratory distress caused by edema, hemorrhage, focal atelectasis, emphysema
CNS & CV effects due to focal ischemia
Multiple foci of ischemic necrosis specially in heads of femur, tibia, humerus etc
Clinical effects observed with air in excess of 100 ml

Amniotic Fluid Embolism
Torn placental membrane- amniotic fluid release
Rupture of uterine veins
Infusion of amniotic fluid into maternal venous circulation
Morphologically characterized by
Lungs show squamous cells, lanugo hair, mucin from GIT & RS
pulmonary edema, diffuse alveolar damage, systemic fibrin thrombi
Severe dyspnea, cyanosis, hypotensive shock, seizures, coma & DIC
Mortality rate> 80%

Disseminated Intravascular Coagulation (DIC)
• Sudden widespread fibrin deposition in microcirculation
• Rapid consumption of platelets and coagulation proteins
• Secondary massive fibrinolysis, all the little thrombi dissolve
• Clotting Disorder Turns Into a Bleeding Disaster
Sepsis is common cause of DIC (30-50% of patients with gram negative sepsis)

Tumor Embolism
Tumor Embolism
Lymphatics (Carcinoma)
Blood vesseles (Sarcoma)
Common sites
Liver (Carcinoma)
Lung (Carcinoma & Sarcoma)
Bone (Prostate, Thyroid, Breast, Kidney, Lung

INFARCTION
An infarct is a localized area of ischemic necrosis caused by
occlusion of either the arterial supply or venous drainage in a
particular tissue
• 90-99% of all infarcts due to arterial thrombotic or embolic events
Less common causes of infarction are vasospasm, hemorrhage in atheromatous plaque, twisting
of vessel, extrinsic compression or traumatic rupture of blood supply
• Coagulative necrosis is characteristic of hypoxic death in all tissues except CNS
• All infarcts tend to be wedge-shaped, with the occluded vessel at the apex

TYPES OF INFARCTS:
•Bland vs. Septic
(assumed to be bland unless specified as “septic”)
•Arterial (usually white/pale) vs. Venous (red/hemorrhagic);
•Bland and arterial most common

MORPHOLOGY OF INFARCTS
White/Pale:
Occur with arterial occlusion or in solid organs with single blood supply (ex: kidneys, spleen)
Red/Hemorrhagic:
Occur with venous occlusion, in loose tissues, tissues with dual circulation.
All infarcts are wedge shaped, poorly defined & hemorrhagic in initial stage, later margins are
better defined revealing hyperemia, become pale & sharply defined in solid organs and firmer &
browner in spongy organs
Microscopic evidence is visible after (12-18) hours if patient survives
Characterized by coagulative / liquefactive necrosis surrounded by inflammatory zone, later
there is evidence of regeneration & repair. Most infarcts are ultimately replaced by scars tissue.
Septic infarction results from embolization of infected vegetation from heart valve or if microbes
seed area of necrosis →abscess →organization

FACTORS AFFECTING INFARCTS:
• Nature of the vascular supply (dual arterial supply)
• Collateral circulation
• Rate of development of occlusion
• Duration of occlusion
• Metabolic needs of the tissue/organ
• Vulnerability of the tissue to hypoxia
Brain - < 3 minutes
Heart – 0.5-2 hours
Kidney – 2-3 hours
Skin fibroblasts - < 24 hours
• Oxygen content of blood

Hemorrhagic Lung Infarct Pale Splenic Infarct

Myocardial Infarction
Regional Full-Thickness (Left); Circumferential Subendocardial (Right)
Left VentricleLeft Ventricle

Mural Thrombus
Over Myocardial Infarction

Rupture
VentricleVentricle

Chronological Appearance

Kidney Infarction
Replaced by Fibrotic Scar (Left)

CLINICAL SIGNIFICANCE OF INFARCTION
•Usually cause pain;
•May cause loss of function (example: myocardial infarct may
cause heart failure);
•May cause hemorrhage or sepsis (examples: lung infarct causes
hemoptysis, bowel infarct causes GI bleeding or sepsis).

SHOCK
It is defined as systemic hypo-perfusion due to reduction either in
Cardiac Output or Effective Circulating Blood Volume.
The End Results are:
• Hypotension, followed by
• Impaired Tissue Perfusion and Cellular Hypoxia
• Reversible Cellular Injury→ Irreversible Tissue Injury→ Death
• Non-Progressive Stage, Progressive Stage, Irreversible Stage

TYPES OF SHOCK
Three Main Categories:
Cardiogenic,
Hypovolemic, and
Septic
Others:
Neurogenic Shock (anesthetic and spinal cord injury) & Anaphylactic
Shock

CARDIOGENIC SHOCK
Results From Severe Myocardial Failure Due to:
– Intrinsic myocardial damage (myocardial infarction, ventricular
rupture, arrhythmia)
– Extrinsic Compression (cardiac tamponade)
– Outflow Obstruction (pulmonary embolism)

HYPOVOLEMIC SHOCK
Results From Loss of Blood or Plasma Volume:
- Hemorrhage
- Fluid Loss (severe burns, trauma, vomiting, diarrhea etc.)

SEPTIC (ENDOTOXIC) SHOCK
• Most common cause of death in ICU’s in the US
• Dissemination of infection into the vasculature
• Caused by overwhelming systemic microbial infection, most
often by Gram-negative infection (Endo-toxic Shock) but can
also occur with Gram-positive and fungal infections
• Spread & expansion of localized infection (abscess, peritonitis,
pneumonia) into the blood stream.

Pathogenesis Of Septic Shock
• Endotoxins are bacterial wall lipopolysaccharides (LPS) which
consists of a toxic fatty acid (Lipid A) core and a complex
polysaccharide coat (unique to each species). Gram-positive
bacteria and fungi have analogus molecules.
• High quantities of LPS → (TNF & IL-1→ IL6 & IL8)
-Systemic vasodilation (hypotension),
-Diminished cardiac contractility,
-Widespread endothelial injury and activation (SLA, ARDS, DAD),
-Activation of coagulation system (DIC)
• Multi-organ system failure and death

Effects of Shock on Tissues
• Brain -- ischemic encephalopathy --> confusion, obtundation;
• Heart -- subendocardial ischemia, infarction; contraction band
necrosis --> decreased output
• Kidneys -- acute tubular necrosis --> oliguria, anuria and electrolyte
disturbances
• Lungs -- diffuse alveolar damage (DAD) --> Adult respiratory
distress syndrome (ARDS) --> hypoxia
• GI tract -- mucosal necrosis, hemorrhages
• Liver -- central necrosis, fatty change
• Coagulation system -- disseminated intravascular coagulation (DIC)

Clinical Course of Shock
• Hypotension
• Weak, rapid pulse, tachycardia
• Rapid shallow respiration
• Drowsiness, confusion & irritability
• Cool, clammy skin
– In septic shock the skin is initially warm and flushed
secondary to peripheral vasodilation
• Multi-organ failure ensues if shock continues

Hyperemia & Congestion
Increased volume of blood in an area compared to normal
Hyperemia
Hyperemia is an active process resulting from augmented tissue inflow
due to arteriolar dilation (e.g. Acute inflammation, Exercising muscles,
Blushing, Sexual arousal)
Congestion
Congestion is a passive process resulting from impaired outflows from a
tissue (cardiac failure-systemic or venous obstruction-local)
Both can be Local or Diffuse

MORPHOLOGY OF HYPEREMIA &
CONGESTION
– Hyperemia: tissue is red or purple, engorged with oxygenated blood,
swollen, often edematous. Examples- Lungs.
– Congestion: tissue is blue-red in color due to accumulation of
deoxygenated hemoglobin in the affected tissues. Later on tissue becomes
brownish (iron deposition) & indurated (fibrosis).
Examples – Liver, Legs, Lungs

PULMONARY CONGESTION
– Acute Pulmonary Congestion: engorged alveolar capillaries, alveolar septal edema, focal
minute intra-alveolar hemorrhage
– Chronic Pulmonary Congestion: thickened & fibrotic septa along with presence of
numerous hemosidrin–laden macrophages (Heart Failure Cells)
HEPATIC CONGESTION
– Acute Hepatic Congestion: central vein and sinusoids are distended with blood, central
hepatocytes may show degeneration & peripheral hepatocytes may develop fatty change
– Chronic Passive Congestion of Liver: central regions of hepatic lobules are grossly red-
brown, slightly depressed & surrounding uncongested zones reveal fatty change (nutmeg
liver). Microscopically there is centrilobular necrosis with hepatocyte drop out and
hemorrhage & hemosidrin containing macrophages. Hepatic fibrosis (cardiac cirrhosis)
may be seen in heart failure.

Hyperemia in PneumoniaHyperemia
Infection
(Pneumonia)

Liver - Chronic Passive Congestion

“Nutmeg” Liver
Cross Section of a Nutmeg“Nutmeg” Liver

SIGNIFICANCE OF CONGESTION
If diffuse, usually indicates Heart failure;
If local, usually indicates a blockage upstream toward the
heart;
Cirrhosis can cause Varices in esophagus

HEMORRHAGE
Extravasation of blood due to rupture of blood vessels
– Rupture of a large vessel: Trauma, Atherosclerosis, Inflammatory or
Neoplastic Erosion
– Rupture of small vessels: hemorrhagic diathesis
Hematoma is blood enclosed within tissue (red-blue → blue-green → golden brown)
Petechiae are minute (1-2 mm) hemorrhages into skin, mucous membranes
or serosal surfaces
Purpuras are larger (3-5 mm) hemorrhages
Ecchymoses are larger (1-2 cm) subcutaneous hematomas (bruises)
Hemothorax, Hemopericardium, Hemoperitonium and Hemoarthrosis are bleeding in one
or other body cavities.
Hematochezia- bright red blood per rectum, Melena - dark black blood per rectum
Hematuria - blood, gross or microscopic in urine
Hemoptysis - coughing up of blood , Hematemesis - vomiting up of blood

CAUSES OF HEMORRHAGE
– Trauma
– Vascular diseases with rupture (atherosclerosis, arteritis,
aneurysms, etc.).
– Low platelets (below 10-15,000/cu mm)
– Coagulopathy (factors less than 10% activity)
– Ulcers, tumors, coagulation factors, infarcts,

MORPHOLOGY OF HEMORRHAGE
Acute –
Red or purple collection of blood in tissue
Chronic or old –
Brown or maroon pasty material

EFFECTS OF HEMORRHAGE
Effects of hemorrhage depends on following factors:
Location
Rate
Duration
Co-morbid diseases
(emphysema, anemia, heart disease)

Hemorrhage
Why do bruises change color
as they Resolve?
• The RBC’s in a hemorrhage are broken down:
– hemoglobin (red) → bilirubin (blue-green) →
hemosiderin (golden-brown)

Intracerebral Hemorrhage

PurpuraPurpuraColonic PetechiaeColonic Petechiae
ThrombocytopeniaThrombocytopenia
Idiopathic Thrombocytopenic PurpuraIdiopathic Thrombocytopenic Purpura

Clinical Effects of Hemorrhage
• <20% blood loss, little health effect in otherwise healthy individuals
– That’s why donating blood is OK
– But suppose you have heart or lung disease - mild blood loss could decrease
critical oxygen carrying capacity and → ‘heart attack’
• >20% blood loss → hemorrhagic shock
• Bleeding into the brain stem is fatal while same blood loss from a
finger cut is trivial
• Chronic recurrent bleeding can lead iron deficiency anemia!

Anemia from Blood Loss
• This may be the only hint of Occult Cancer
– Carcinoma of the Colon
– Gastric Carcinoma (less common)

EDEMA
Excess accumulation of fluid in the interstitial tissue spaces.
• A transudate (protein-poor fluid -specific gravity <1.012)
or
• An exudate (protein-rich fluid -specific gravity >1.020)

SPECIAL TYPES OF EDEMA
• Pleural effusion (hydro-thorax)
• Pericardial effusion (hydro-pericardium)
• Ascites (edema in peritoneal cavity)
• Anasarca (widespread edema)
• Cerebral edema (in brain, intra- and extracellular)

Normal Microcirculation
Capillary Arterial Venous
Hydrostatic Pressure + 36 + 16
Osmotic Pressure - 26 - 26
Net filtration Pressure + 10 mmHg - 9 mm Hg
(leak-out) (Reabsorb)

Homeostasis is maintained by the opposing effects of
vascular hydrostatic pressure and plasma colloid osmotic

Pathophysiologic Categories of Edema
I. Increased Hydrostatic Pressure
II. Reduced Plasma Osmotic Pressure
III. Lymphatic Obstruction
IV. Sodium Retention
V. Inflammation

Increased Hydrostatic Pressure
A. Congestive Heart Failure
B. Portal Hypertension
C. Venous Thrombosis

Congestive Heart Failure
Inability of Heart to Pump blood in systemic circulation
↓
Blood backing up into the lungs
↓
Blood backing up into the venous circulation
↓
Increasing Central Venous Pressure (CVP)
↓
Increased capillary pressure (Hydrostatic Pressure)
↓
Edema
↓
↓ Cardiac Output → Decreased Arterial blood volume → Decrease Renal perfusion
↓
Activates the Renal Defense Mechanisms
Renin-Angiotensin-Aldosterone Axis, Renal Vasoconstriction, Increased ADH

Renin-Angiotensin-Aldosterone Axis
Renin Aldosterone
Renal Na
reabsorption
Renal retention of
Na + H2O
Plasma volume
Transudation EDEMA
Decreased Renal Perfusion

Renal Vasoconstriction
Renal
Vasoconstriction
Glomerular Filtration
Rate (GFR)
Tubular
reabsorption of
Na + H2O
Plasma volume
Transudation EDEMA
Renal retention of
Na + H2O

Anti-Diuretic Hormone
Anti-Diuretic
Hormone (ADH)
Renal retention of
H2O
Plasma volume
Transudation EDEMA
Renal retention of
Na + H2O

Central
Venous
Pressure
Renal
Perfusion
Renin Renal
Vasoconstriction
ADH

Events Leading to Systemic Edema
Secondary to Primary Heart Failure

Clinically initially cardiac edema can be demonstrated in legs or sacrum

Portal Hypertension
• Portal Hypertension is “Increased resistance to portal blood flow”
• The most common cause of Portal Hypertension is CIRRHOSIS
• Results in Ascites
• Pathogenesis of Ascites is complex
– Increased Portal Pressure (hydrostatic pressure) leads to increased liver sinusoidal
hypertension. Fluid moves into the Space of Disse then into lymphatics
• The hepatic lymph percolates into the peritoneal cavity
– Normal thoracic duct lymph = 1 Liter/d
– In cirrhosis, hepatic lymph flow far exceeds Thoracic duct capacity
Cirrhosis → hypoalbuminemia → decrease in plasma osmotic pressure → ascites →
decrease in blood volume → decreased renal perfusion → secondary hyperaldosteronism
(increased renin etc.)

Portal Hypertension
Sinusoidal
Hypertension
Renal
Perfusion
Hepatic Lymph
Overwhelms
Thoracic Duct
Aldosterone
ASCITES
Cirrhosis
Serum
Albumin

Venous Thrombosis
• Impaired venous outflow increases hydrostatic pressure

Reduced Plasma Osmotic Pressure
• Albumin is the serum protein MOST responsible for the maintenance of
colloid osmotic pressure.
• A decrease in osmotic pressure can result from increased protein loss or
decreased protein synthesis
• Increased albumin Loss:
– Nephrotic Syndrome
• Increased protein permeability of the glomerular basement membrane
– Protein losing gastroentropathy
• Reduced albumin synthesis
– Cirrhosis
– Protein malnutrition

Inflammation
• Both Acute and Chronic Inflammation are associated with Edema
• Generalized edema in systemic infections, poisoning, certain drugs
& chemicals, anaphylactic reactions and anoxia
• Localized edema in infections, allergic reactions, insect bite,
irritant drugs & chemical and Angioneurotic edema*
*It involves skin of face & trunk and may involve lips, larynx, pharynx, lung etc

Lymphatic Obstruction
• Impaired lymphatic drainage with resultant lymphedema, usually localized
• Commonly due to inflammation or neoplastic obstruction, may be post-surgical
& post-radiation in patient undergoing treatment for Breast Cancer
Both Acute and Chronic Inflammation are associated with EDEMA
Filariasis: A parasitic infection causing massive lymphatic & lymph nodes fibrosis in inguinal
region resulting in edema of external genetalia & lower limbs called elephantiasis
Carcinoma of breast with obstruction of superficial lymphatics can lead to an
unusual appearance of the breast- “peau d’orange” (orange peel)
Resection and/or radiation to axillary lymphatics can lead to arm edema

“peau d’orange” appearance in breast cancer

Sodium & Water Retention
• Contributory factors in several forms of edema
• Salt retention may be primary cause of edema
Post-streptococcal glomerulonephritis & Acute Renal failure
• Increased salt with accompanying water cause increase hydrostatic pressure
and decreased vascular colloid osmotic pressure leading to edema

EDEMA
INCREASED
HYDROSTATIC
PRESSURE
Portal hypertension
(Ascites)
Venous Obstruction
•HEART
•LIVER
•KIDNEY
INFLAMMATION
Increased permeability
DECREASED
ONCOTIC
PRESSURE
Nephrotic Syndrome
Cirrhosis (Ascites)
Protein Malnutrition
LYMPHATIC
OBSTRUCTION
Inflammatory
Neoplastic
SALT & WATER RETENTION

GENERALIZED EDEMA
• HEART
• LIVER
• KIDNEY

Edema Morphology
• Edema of the Subcutaneous Tissue is most easily detected Grossly (not
microscopically)
• Push your finger into it and a depression remains (pitting)
• Swelling and wetness of the tissues
• Subtle cell swelling with clearing and separation of extracellular elements
• Dependent Edema is a prominent feature of Congestive Heart Failure (legs in
standing & sacrum in recumbent position)
• Periorbital edema is often the initial manifestation of Nephrotic Syndrome,
later affecting all parts of body

Pulmonary Edema
• Pulmonary Edema is most frequently seen in Congestive Heart Failure (LVF)
– May also be present in Mitral Stenosis, Cardiac Surgery, Renal failure,
Adult Respiratory Distress Syndrome (ARDS), Pulmonary Infections,
Inhalation of toxic substances, Aspiration, Radiation injury, Shock, Uremia,
High altitude edema and Hypersensitivity reactions.
• The Lungs are typically 2-3 times normal weight
• Cross sectioning causes an outpouring of frothy, sometimes blood-tinged fluid
representing mixture of air, edema fluid & extravasated red cells
• Microscopically alveolar capillaries are congested and there is collection of
eosinophilic, granular and pink proteinaceous material (edematous fluid) in
interstitial and alveolar spaces

Pulmonary Congestion
and Edema

Edema of the Brain
• Localized: Abscess, Neoplasm
• Generalized: Encephalitis, Hypertensive crises, Obstruction of
venous outflow, Trauma
• In Generalized edema brain is grossly swollen with narrowed
sulci and distended gyri showing flattening against skull
• Vasogenic & Cytotoxic edema

Clinical Correlation
• Subcutaneous Edema-Annoying but Points to Underlying Disease
– However, it can impair wound healing or clearance of Infection
• Pulmonary Edema-May cause death by interfering with Oxygen
and Carbon Dioxide exchange & Creates a favorable environment
for infection
• Edema of Brain-The big problem is: There is no place for the fluid to
go! Herniation into the foramen magnum will kill or brain stem
vascular supply can be compressed and damage vital centers

Hemodynamic disorders med- 2011, final ii

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Hemodynamic disorders med- 2011, final ii