Hemodynamic disorders med- 2011, final ii

HEMODYNAMIC DISORDERS

THROMBOSIS

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

http://cats.med.uvm.edu/cats_teachingmod/pathology/path301/vascpath/vascel/movie_shells/i193.html

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 StatesInherited

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 THROMBITHROMBI 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:

Thrombus(Lines of Zahn)

Layering (Lines of Zahn)

Cardiac Mural Thrombus

Mural ThrombiIn Ventricles (Left) and Aortic Aneurysm (Right)

Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003.

Cardiac Mural Thrombi

Notice underlying endocardial fibrosis

Right

Left

Thrombotic VegetationsMitral 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)TraumaSurgeryBurns3rd Term Pregnancy and PostpartumCancer (migratory thrombophlebitis-Trousseau’s Syndrome)Bed RestImmobilization

Valvular Thrombi (vegetations)

Infective EndocarditisNon-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 thrombiMinute 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 venousthrombi). 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 asmall fibrous‘Lump’ as evidence of a previous thrombus

Propagation Accumulation of more platelet & fibrin and obstruction

EmbolizationEarly & 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

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 cellclumps, 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 ThromboembolismGenerally 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

Thromboembolism

Pulmonary Embolus

Saddle Pulmonary Embolus

Embolization (Embolus)Thromboembolism of Pulmonary Artery

Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th 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) orrarely from soft tissue trauma and burns

10% of cases show clinical findings

Clinically characterized byPulmonary insufficiency, neurologic symptoms, anemia & thrombocytopeniaSymptoms appear 1-3 days after injury

PathogenesisMechanical obstruction in pulmonary & cerebral microcirculation and

chemical injury to endothelium by free fatty acids resulting in skin rash

Bone Marrow EmbolusIn 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)

Clinically characterized by 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 EmbolismTorn placental membrane- amniotic fluid release

Rupture of uterine veins

Infusion of amniotic fluid into maternal venous circulation

Morphologically characterized byLungs show squamous cells, lanugo hair, mucin from GIT & RS

pulmonary edema, diffuse alveolar damage, systemic fibrin thrombi

Clinically characterized bySevere 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)

Clinical Consequences of DIC

Tumor EmbolismTumor Embolism Lymphatics (Carcinoma) Blood vesseles (Sarcoma)

Common sites Liver (Carcinoma) Lung (Carcinoma & Sarcoma) Bone (Prostate, Thyroid, Breast, Kidney, Lung

INFARCTION

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

MYOCARDIAL INFARCTION

Myocardial InfarctionRegional Full-Thickness (Left); Circumferential Subendocardial (Right)


Left VentricleLeft Ventricle

Mural ThrombusOver Myocardial Infarction


Myocardial InfarctionRupture


VentricleVentricle

Myocardial InfarctionChronological Appearance








RENAL INFARCTION

Kidney InfarctionReplaced by Fibrotic Scar (Left)


Lung InfarctWedge Shape...

Infarcted Colon

OK Colon

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

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)

Morphology of Shock

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

HyperemiaHyperemia is an active process resulting from augmented tissue inflow due to arteriolar dilation (e.g. Acute inflammation, Exercising muscles, Blushing, Sexual arousal)

CongestionCongestion 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

Chronic Passive Congestion

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 membranesor serosal surfacesPurpuras are larger (3-5 mm) hemorrhagesEcchymoses are larger (1-2 cm) subcutaneous hematomas (bruises)Hemothorax, Hemopericardium, Hemoperitonium and Hemoarthrosis are bleeding in oneor 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)


HemorrhageWhy 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

ThrombocytopeniaThrombocytopeniaIdiopathic 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

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 VenousHydrostatic Pressure + 36 + 16Osmotic Pressure - 26 - 26Net 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 pressure

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 FailureInability 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 MechanismsRenin-Angiotensin-Aldosterone Axis, Renal Vasoconstriction, Increased ADH

Congestive Heart FailureRenin-Angiotensin-Aldosterone Axis

Renin Aldosterone Renal Na reabsorption

Renal retention of Na + H2O

Plasma volume

Transudation EDEMA

Decreased Renal Perfusion

Congestive Heart FailureRenal Vasoconstriction

Renal Vasoconstriction

Glomerular Filtration Rate (GFR)

Tubular reabsorption of Na + H2O

Plasma volume

Transudation EDEMA



Congestive Heart FailureAnti-Diuretic Hormone

Anti-Diuretic Hormone (ADH)

Renal retention of H2O

Plasma volume

Transudation EDEMA



CentralVenousPressure

Renal

Perfusion

Renin Renal Vasoconstriction

ADH

Congestive Heart Failure

Events Leading to Systemic EdemaSecondary 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.)

AscitesAscites

Portal Hypertension

Sinusoidal Hypertension

Renal

Perfusion

Hepatic LymphOverwhelms

Thoracic DuctAldosterone

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

Angioedema

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

Elephantiasis

Elephantiasis (filariasis)

“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

INCREASEDHYDROSTATICPRESSURE

Congestive Heart Failure

Portal hypertension (Ascites)Venous Obstruction

•HEART•LIVER•KIDNEY

INFLAMMATION Increased permeability

DECREASED ONCOTICPRESSURE

Nephrotic SyndromeCirrhosis (Ascites)Protein Malnutrition

LYMPHATICOBSTRUCTION

InflammatoryNeoplastic

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

Pitting edema

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 Edema

Pulmonary EdemaNormal Lung

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

Brain 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

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Hemodynamic disorders med- 2011, final ii