Fluid and Hemodynamic Disorders

Dr. Dexter MD FRC PathUndercover Professor

Department of PathologySGU SOM, Grenada

OBJECTIVES Hemostasis Recanalization

Coagulation

Clot

Thrombosis

Thrombus

Thrombocytopenia

Embolism Hemorrhage

Embolus Occult bleeding

Lines of Zahn Hemosiderin

Organization Hematemesis

Petechia Hemoptysis

Ecchymoses Melena

Purpura Hemarthrosis

Hematoma

Infarct - pale - red - bland - septic

OBJECTIVESHematuria Shock

Hemothorax Hyperemia

Hemopericardium Congestion

Fibrinolysis Congestive heart failure

Thrombolysis edema

Factor V leiden Lymphedema

D-dimer Anasarca

Hypercoagulable state Effusion

Virchow's triad Ascites

Stasis Transudate

Trousseau syndrome Exudate

EDEMA• Recapitulate the factors that govern the fluid exchange

(at the arteriolar and venular ends of the capillaries) between vascular and extravascular space.

• Trace the pathway of fluid from the tissue space to the heart (lymphatics, thoracic duct, left subclavian vein, superior vena cava)

• Define edema as an abnormal accumulation of fluid in interstitial space and serous cavities (hydrothorax, hydropericardium, hydroperitoneum – ascites)

• Define anasarca as severe edema that affects the body in a generalized fashion.

• Distinguish localized edema from generalized edema and list the common causes for each.

EDEMA• Explain the pathogenetic mechanism of edema based

on capillary hydrostatic pressure and colloid osmotic pressure in capillaries and tissues.

• Distinguish the properties of exudates from those of transudate.

• Explain the mechanism of edema in venous blockage, congestive heart failure, lymphatic obstruction, renal disease, liver disease and protein malnutrition.

• Describe the morphology of edema clinically and microscopically.

• Distinguish pitting edema from non-pitting edema• Explain the effects of edema in subcutaneous tissue,

lungs, and brain.• Derive the main lines of management of edema based

on the knowledge of pathology.

Normal Circulation

• Heart• Aorta & Arteries• Microcirculation

– Arterioles– Capillaries– Venules

• Veins & Venules• Lymphatics

Normal capillary filtration

Hydrostatic pressure = 32 mm of Hg

Oncotic pressure = 26 mm of Hg

Colloid osmotic pressure in tissues

Hydrostatic pressure in tissues = 3 mm of Hg • Lymphatics Thoracic duct Left Subclavian Vein • Superior Vena Cava Heart

EDEMA - Definition

• Edema is an abnormal excess accumulation of fluid in the intercellular spaces or body cavities

• Occurs most commonly in - Subcutaneous tissues, lungs and the brain.

EDEMA IS GIVEN DIFFERENT NAMES IN DIFFERENT LOCATIONS:

• Pleural space – pleural effusion (hydrothorax)

• Pericardium – pericardial effusion (hydropericardium)

• Peritoneum – ascites (hydroperitoneum)• Anasarca – severe generalized edema

Classification of Edema• Based on mechanism

– Increased hydrostatic pressure– Decreased plasma oncotic pressure– Lymphatic obstruction– Sodium retention– Altered membrane permeability

• Based on distribution– Localized– Generalized

• Based on content of accumulation– Transudate– Exudate

• Clinocopathological– Congestive Heart Failure– Pulmonary Edema– Cirrhosis Of The Liver– Renal Disease

Increased hydrostatic pressure• Impaired venous

return– Congestive heart

failure– Venous obstruction

or compression• Thrombosis• External pressure

(e.g. tumor)

• Hypervolemia– Sodium retention

(renal failure)• Usually

generalized

Reduced plasma oncotic pressure- hypoproteinemia

• Reduced albumin synthesis –malnutrition, liver disease

• Increased albumin loss – renal disease

• Reduced albumin absorption –protein losing enteropathy

• Usuallygeneralized

Lymphatic obstruction• Inflammatory• Neoplastic• Post

surgical/radiation

• Usuallylocalized

Altered membrane permeability

• Inflammation– Acute– chronic

• Angiogenesis• Burns

Congestive heart failure• Right heart failure

– Increased hydrostatic pressure – edema – Dependent edema (legs, sacrum)

• Left heart failure– Reduced GFR, sodium retention, renin-angiotensin-

aldosterone axis– Pulmonary edema

• Management – Salt restriction, Diuretics– Aldosterone antagonists

Renal disease• Damages basement membrane

– Excess albumin loss – hypoalbuminemia (NephroticSyndrome)

– Decreased plasma oncotic pressure - edema• Glomerulonephritis

– inflammatory damage with clogging of glomerular capillaries – reduced GFR

– Secondary hyperaldosteronism – sodium and water retention

– Generalized edema – initially periorbital edema

Liver disease

• Cirrhosis of liver– Portal hypertension – increased hydrostatic

pressure in splanchnic circulation- ascites– Decreased albumin synthesis – reduced

plasma oncotic pressure

Malnutrition • Reduced serum albumin

• Decreased plasma oncotic pressure

• Decrease in effective plasma volume

• Secondary hyperaldosteronism

• Sodium and water retention

• Edema

Features Transudate ExudateProcess Passive (increased

pressure)Active (inflammation)

Vascular permeability

normal Increased

Plasma protein leak Absent Present

Protein content of fluid

Low S.G.<1012Protein<1.5g/dl

High S.G >1020Proteins> 1.5 g/dl

Fibrin absent Present

Inflammatory cells absent present

Morphology of edema • Skin• M/E – cell swelling,

clearing and separation of the extracellular matrix– Pitting or non pitting

edema (myxedema)

– Impaired wound healing– Thickening– Susceptible to infection

Pulmonary edema – Morphology

• Interstitial – early phase• Alveolar - frothy fluid in alveolar lumen• M/E - severely congested alveolar

capillaries and alveoli filled with homogenous pink-staining fluid

• Clinical features– Cough, dyspnea– Severe cases – frothy sputum, cyanosis

Cerebral edema • 2 Categories

– Vasogenic edema• disruption of blood brain barrier – interstitial edema• Infections, trauma, neoplasms

– Cytotoxic edema – (Gray matter)• Intracellular edema – due to cell injury• Hypoxic-ischemic insult

• Headache, papilledema• Motor/ sensory abnormalities• Treat by intravenous mannitol and steroids

Morphology

• Gross – Flattened gyri

and narrowed sulci

– Compression of ventricular cavities

Herniation • Transtentorial (Uncal) – displacement of the

temporal lobe– presses on III cranial nerve and parasympathetic

fibers – impaired ocular movements, pupillary dilation– Posterior cerebral artery compression – damage to

visual cortex• Tonsillar herniation -Tonsillar herniation through

the foramen magnum– Brain stem compression – respiratory centers in

medulla oblongata– Brain stem herniation – Duret hemorrhages in

midbrain and pons– Death due to cardio-respiratory arrest

Herniation

• Subfalcine herniation – displacement of cingulate gyrus under the falx cerebri– Compression of branches of anterior cerebral

artery– Ischemic injury of primary motor and /or

sensory cortex– Weakness and /or sensory abnormalities in

leg

Hyperemia and Hemorrhage

OBJECTIVES• Distinguish hyperemia as an active process caused by

arteriolar dilation from congestion as a passive phenomenon caused by impaired outflow from veins.

• Elucidate the causes of acute and chronic congestion of lungs, liver and describe the morphological changes.

• Define hemorrhage as extravasation of blood and due to rupture of blood vessels.

• Identify the common causes of hemorrhage (trauma, atherosclerosis, vasculitis, aneurysm, bleeding diathesis)

• Define the different varieties of hemorrhage viz. petechiae, purpura, ecchymosis, hematoma, hemothorax, hemopericardium, hemoperitoneum, hemarthrosis.

• Explain the chronological changes that take place in the extravasated blood in the tissues.

• Recognize that severe blood loss can lead to shock.

Definition • Hyperemia – active increase in the volume of

blood in tissues (red)– Caused by arteriolar dilation– Physiological - blushing, skeletal muscle during

exercise– Pathological - inflammation

• Congestion – passive increase in the volume of blood in tissues (blue-red color); usually also accompanied by edema– Impaired venous flow from tissues e.g. cardiac failure,

venous obstruction– Always pathological

Morphology

• Lung– Acute pulmonary congestion (left ventricular

failure) • Alveolar capillaries engorged• Alveolar septal edema

– Chronic pulmonary congestion (browninduration)

• Thickened fibrous septa• Heart failure cells (hemosiderin laden

macrophages)

Morphology • Liver

– Acute passive venous congestion (right heart failure, Budd-Chiari syndrome)

• Central vein and sinusoids distended with blood• Degeneration of central hepatocytes

– Chronic congestion – NUTMEG LIVER• Central region of hepatic lobule is reddish brown and are

accentuated against the surrounding zones of uncongestedtan liver

• M/E –– centrilobular necrosis– Hemorrhage– Hemosiderin laden macrophages– Long standing cases – fibrosis (cardiac cirrhosis)

Hemorrhage

• Extravasation of blood to the exterior of the body or into nonvascular body space due to rupture of blood vessels

• Trauma, atherosclerosis, aneurysms, bleeding disorders

HEMORRHAGE IS GIVEN DIFFERENT NAMES IN DIFFERENT LOCATIONS:

• Hemothorax, Hemopericardium, Hemoperitoneum, Hemarthrosis

• Soft tissues – hematoma• Petechiae – a pin point hemorrhage in skin

or conjunctiva; represents rupture of capillary or arteriole

• Purpura – diffuse superficial hemorrhage in the skin up to 1 cm in diameter

• Ecchymosis – a larger superficial hemorrhage

Chronological changes that occur to extravasated blood

• Hb (red-blue)

• Bilirubin (blue, green)

• Hemosiderin (brown)

Clinical features of hemorrhage

• Hemoptysis – coughing blood• Hemetemesis – vomiting blood• Malena – passing blood in stool

• Minor petechiae – harmless• If recurrent – iron deficiency anemia• If severe – hypovolemic shock• Brain stem hemorrhage – sudden death

Disseminated intravascular coagulation (DIC)

OBJECTIVES• Define DIC as a serious and often fatal complication of many

illnesses that involves widespread small thrombi in microcirculation and bleeding through out the body. Recognize that it can occur in acute, subacute and chronic forms. Recognize the need to diagnose it early and treat.

• Explain the main mechanism of diffuse endothelial injury that leads to DIC, with examples

• (Gram negative septicemia, immune mediated type II and III hypersensitivity, release of thromboplastic substances into circulation- amniotic fluid, snake bite, acute promyelocyticleukemia, extensive tissue necrosis, proteolytic enzymes and mucin released by carcinomas).

• Recognize that concurrent fibrinolysis proceeds hand in hand with widespread microthrombi.

• Explain the development of lactic acidosis and microinfarcts in DIC.

OBJECTIVES• Explain the pathogenesis of bleeding in DIC based on

consumptive coagulopathy and fibrin degradation products (FDPs) acting as anticoagulants (inhibit thrombin, platelet aggregation and fibrin polymerization).

• Elucidate the clinical features of shock and bleeding in DIC.

• Explain the basis of investigations that can be performed to confirm the diagnosis of DIC (FDPs, D-dimers, coagulation tests)

• Based on the understanding of the pathogenesis of DIC, indicate broad lines of its management (heparin to prevent formation of thrombi, replacement of platelets and plasma)

Disseminated intravascular coagulation (DIC)

• Widespread small thrombi in the microcirculation throughout the body accompanied by simultaneous bleeding

• Acute, subacute, chronic• Serious and often fatal• Not primary but an end point of other

diseases• Recognize early and treat

Causes • Idiopathic• Diffuse endothelial injury

– Gram negative sepsis (endotoxic)– Viral, ricketssiae– Immunologic injury (type II, III, SLE)

• Release of thromboplastic agents in circulation –activation of coagulation– Amniotic fluid embolism– snake bite– Promyelocytic leukemia– Extensive tissue necrosis, burns– Mucin, proteolytic enzymes from carcinoma

PATHOGENESIS OF DICTISSUE INJURY ENDOTHELIAL CELL INJURY

EXTRINSIC INTRINSIC

Intravascular Coagulation

Plasmin

Bleeding

ThromboplastinsContact Activation

Platelet AggregationThromboplastins

Microangiopathic Hemolyticanemia and ischemic

tissue injury

Consumption of Va, VIIIa,Fibrinogen and Platelets Fibrin Microthrombi

Microvascular occlusionCleaves Va, VIIIa, Fibrinogenand Platelet receptors

Fibrinogen andFibrin split products

Inhibit:Platelet aggregation

Fibrin polymerizationThrombin

Endotoxins and D.I.C

• Activate monocytes• Activated monocytes release IL-1, TNF�• IL-1 and TNF� act on endothelial cell

surface and increase the expression of tissue factor and reduce the expression of thrombomodulin

• Injured endothelial cells induce platelet aggregation and activation of intrinsic pathway by exposure of collagen

Effects of D.I.C

• Decreased tissue perfusion – shock, lactic acidosis, microinfarcts

• Bleeding – consumptive coagulopathy

• Diagnosis – FDPs– D-dimers

Management of DIC

• Heparin to prevent formation of thrombi• Replace platelets and plasma

SHOCK

OBJECTIVES• Define shock; recognize the importance of shock in

clinical practice.• Explain the common causes of cardiogenic,

hypovolemic, septic, and distributive varieties of shock and highlight the pathogenesis of shock in each type.

• Identify theoretically the three stages of shock (non progressive, progressive and irreversible) and explain the pathophysiological changes and clinical features at each stage. Distinguish septic shock from hypovolemic shock based on clinical features. Define the lesions that lead to a fatal outcome.

• Describe the morphological changes produced by hypoxic injury in the following organs – brain, heart, kidney, lungs, adrenals, GIT, liver.

Shock

• Is a clinical state characterized by a generalized decrease in perfusion of tissues associated with reduction in effective cardiac output

Causes • Cardiogenic- results from myocardial pump failure.

– intrinsic myocardial damage (infarction), ventricular arrhythmias– extrinsic compression (cardiac tamponade)– outflow obstruction (pulmonary embolism).

• Hypovolemic - results from loss of blood or plasma volume.– Hemorrhage– Fluid loss from severe burns or trauma. – Vomiting, diarrhea

• Septic - caused by systemic microbial infection.– Most commonly, gram-negative infections (endotoxic shock)– Gram-positive and fungal infections.

Causes

• Distributive - imbalance between compartments– Neurogenic

• Simple fainting – peripheral pooling of blood. Fall down – self correct due to recumbent position – increased venous return restores cardiac output.

• Anesthetic – loss of vascular tone, peripheral pooling• Spinal cord injury

– Anaphylactic – generalized IgE mediated response• Systemic vasodilation, increased permeability• Reduced tissue perfusion

Septic shock• Endotoxins are lipopolysaccharides from the

walls of gram negative bacteria• They are released when walls are degraded by

inflammatory response• LPS has a toxic fatty acid (Lipid A) core and a

coat of complex polysaccharides including O Ag.• Similar molecule in walls of gram positive

bacteria, fungi and super antigen of bacterial walls

• LPS plays the dominant role in shock

Septic shock• LPS in low doses

– activates monocytes, macrophages, and neutrophils.– The mononuclear phagocytes respond to LPS by producing TNF, which

in turn induces IL-1 synthesis. – Both TNF and IL-1 act on endothelial cells (and other cell types) to

produce further cytokines (e.g., IL-6 and IL-8) and induce adhesion molecules.

– local acute inflammatory response - improves clearance of the infection• LPS in moderate dose

– Release of NO and PAF - vasodilation– systemic effects of TNF and IL-1 - including fever, increased synthesis

of acute-phase reactants, and increased production of circulating neutrophils

• LPS at higher doses – septic shock syndrome characterized by– Systemic vasodilation (hypotension) – Diminished myocardial contractility – Widespread endothelial injury and activation – Activation of the coagulation system, culminating in DIC

Effects

• Hypotension- due to peripheral pooling secondary to vasodilation

• Impaired tissue perfusion• Cellular hypoxia• Cell injury• Cell death

Stages of shock

• Initial non-progressive• Progressive• Irreversible

Non-progressive stage• Stage of compensation - Compensated by reflex

mechanisms• Baroreceptors –release of catecholamines,

renin, angiotensin, ADH• Generalized sympathetic stimulation –

tachycardia, peripheral vasoconstriction, renal conservation of fluid

• Cutaneous vasoconstriction – cool, pale skin– Septic shock – peripheral vasodilation, flushed and

warm • Coronary, cerebral vessels less sensitive to

sympathetic response so maintain blood flow and oxygen delivery

Progressive stage• Stage of impaired tissue perfusion

– Imbalance between circulation and metabolic needs– Intracellular aerobic respiration replaced by anaerobic

glycolysis– Excess lactic acid production – low pH– Sludging of RBCs– Blunting of vasomotor response– Arterioles dilate and blood pools into microcirculation– Reduced cardiac output, anoxic endothelial injury,

DIC• Patient confused, urine output decreases

Irreversible shock

• Stage of decompensation– Severe widespread cell and tissue injury– Leakage of lysosomal enzymes (aggravate shock)– Perfusion of brain and myocardium at critical level– ATN, ARF (renal uremia)

• Failure of multiple organ systems• Survival difficult even if hemodynamics are

corrected

Morphological changes

• Mainly due to hypoxic injury• Brain, heart, kidney, lungs, adrenals, gut,

liver, pancreas,

Brain

• Ischemic encephalopathy– Edema, mottled discoloration in gray matter– Watershed infarcts – Laminar cortical necrosis – Pyramidal cells of hippocampus, purkinje cells

of cerebellum– Gray white junction blurred– Neuronal necrosis– Hemorrhages

Heart

• Focal and widespread necrosis

• Contraction band necrosis

kidney

• Acute tubular necrosis

Lungs

• Adult respiratory distress syndrome (ARDS)

Gut

• Hemorrhagic enteropathy

• Gastric stress ulcers

Adrenal hemorrhage Liver

• Fatty change• Central hemorrhagic

necrosis

Pancreas

• Necrosis• Pancreatitis

• All organs can recover except for neurons and myocytes

Clinical features• Weak rapid pulse• Tachypnea• Cool clammy cyanotic skin• Septic shock (warm, flushed skin)• Gradual loss of function – cardiac, cerebral,

pulmonary• Electrolyte disturbances, metabolic acidosis• Renal failure• Life threatening : MI, bleeding. sepsis

THROMBOSIS, EMBOLISM, AND INFARCTION

OBJECTIVES• Recapitulate the normal process of coagulation,

fibrinolysis and the factors involved. • Recapitulate the role of endothelial cells in hemostasis.• Define thrombosis, distinguish it from clotting.• Recognize the normal and abnormal situations for

thrombosis to occur.• Enlist the important causes of endothelial cell injury,

loss of laminar blood flow and hypercoagulability of blood which are the main factors that predispose to thrombosis.

• Explain the fate of thrombus 9dissolution, organization and recanalization, propagation, embolization)

OBJECTIVES• Distinguish a postmortem clot from thrombus based on gross and

microscopic features.• Differentiate the sites, predisposing factors and clinical effects of

venous versus arterial thrombosis.• Define and classify embolism (thrombo, fat, air, bone marrow,

tumor, amniotic fluid, atherosclerotic, foreign body, infective) and derive the clinical scenarios.

• Enlist the common situations of arterial and pulmonary thromboemboli.

• Discuss the effects of minor, major and massive pulmonary thromboemboli.

• Explain the role played by cardiac, pulmonary status and collateral circulation in determining the outcome of emboli.

OBJECTIVES• Explain how paradoxical emboli develop.• Define infarction, distinguish arterial and venous infarcts and list

common sites.• Identify the main causes of infarction in a given clinical situation

(obstruction by thrombosis, embolism, hemorrhage into atherosclerotic plaque, torsion of blood vessels, hypo perfusion, vasculitis)

• Explain the difference between the pathogenesis of red and pale infarcts

• Analyze clinical vignettes of commonly occurring ischemic pathologies (as discussed in the lectures) due to thrombosis andembolism to identify mechanisms, pathogenesis, relevant investigations and predict usual outcomes (Pulmonary embolism, stroke, myocardial infarction, gangrene legs, intestinal infarction, pulmonary embolism.

Hemostasis

• Well-regulated processes that maintain blood in a fluid, clot-free state in normal vessels

• Dependent on three general components:– Vascular wall– Platelets– Coagulation cascade

Thrombosis

• Inappropriate activation of normal hemostatic process, such as formation of thrombus in an uninjured vessel or thrombotic occlusion of a vessel after relatively minor injury.

Endothelial cell injury

• Stress induced by hypertension• Bacterial toxins in shock• Hypercholesterolemia• Homocystinuria• Cigarette smoking (CO?)

• All predispose to thrombus formation at the site of endothelial injury

Loss of laminar flow

• Stasis– Endothelial cell hypoxia/ damage– Allows platelets to come in contact with

endothelium– Allows local activation of coagulation factors– Allows buildup of platelets/fibrin– Prevents dilution of activated clotting factors– Reduces flow of clotting inhibitors– Stasis in aneurysms, in leg veins

Turbulence

• Turbulence occurs where there is structural damage to vasculature

• Atherosclerotic plaques, aneurysms• Platelets come in contact with damaged

endothelium

Hypercoagulability of blood

• Hereditary and Acquired• Hereditary – lack of natural anticoagulants

– Factor V mutation (Leiden) – commonest– Anti-thrombin III deficiency– Protein C deficiency– Protein S deficiency

Acquired syndromes

• Terminal cancer– Thrombogenic substances released from

necrotic tumor cells (Trousseau syndrome)• Cardiac failure

– Anoxic damage to tissues, release of Thrombogenic substances

• Severe trauma, burns• Oral contraceptives – increased

production of clotting factors

Morphology of thrombi

• Gross– Dark gray friable mass– Arterial thrombi - pale– Venous thrombi – red

• Microscopy - lines of Zahn– Alternate pale and dark lines– Light – platelet and fibrin– Dark - RBCs

Thrombus versus ClotClot Thrombus

Platelets not involved Platelets involved

Occurs outside vessel (test tube, hematoma) or inside (Postmortem)

Occurs only inside vessel

Red Red (venous), Pale (arterial)

Gelatinous Firm

Not attached to the vessel wall

Attached to the vessel wall

Sites of thrombosis – arterial

• Heart (mural)• Aorta (on

atherosclerotic plaque)

• Aneurysm (mural)• In other arteries

(occlusive)– Coronaries– Carotids, cerebral– Femoral– Mesenteric

Venous thrombosis

• Takes the shape of vessels in which it forms

• Redder than arterial thrombus• Superficial veins of legs (varicosities)• Deep veins of legs (90%)

– Deep calf veins- (at or above the knee) femoral, popliteal, iliac

• Deep leg veins - Edema of ankle and foot, pain, tenderness.

• Asymptomatic in 50%- due to collaterals . • High risk of embolization• Trousseau's Syndrome - Unexplained

thrombophlebitis, recurrent -look for underlying abdominal malignancy like pancreatic cancer ( release of procoagulants)

Effect of thrombi on organs

Venous thrombus

• Edema, congestion • Rarely- the pressure of edema leads to secondaryblock of the artery leadingto infarction• Embolization to lungs

Arterial thrombus

• Acute - Infarct • Slow - atrophy,

fibrosis• Heart - systemic

emboli

Embolism

• Occlusion of a part of vascular tree by a mass (solid, liquid, gas) that is carried by the blood to a site distant from its point of origin

Classification

• 99% of Emboli represent part of dislodged thrombus – Thromboembolism

• Others – Fat– Air/gas bubbles– Bone marrow– Tumor cells– Amniotic fluid– Atherosclerotic plaque debris– Foreign body

Pulmonary Thromboembolism

• Incidence – 65% of all autopsies– Mostly asymptomatic

• The commonest origin is from the deep leg veins and reaches the lungs but most of these are clinically silent

• Major contributor to death in 15% of the hospitalized patients– Usually occurs the first time they get out of the

bed

Classification • Massive

– Sudden obstruction of 60% of pulmonary vasculature; sudden death, no time to develop infarction

• Major– Multiple medium sized vessels occluded – dyspnea,

pain– Infarction only in 10% because of collateral circulation

by bronchial arteries• Minor

– Small vessels obstructed, get lysed, remain asymptomatic

Systemic Thromboembolism

• Thrombi that travel in arterial circulation• Sites of origin

– Heart : mural thrombus (80%)– Aorta : ulcerated atherosclerotic plaques– Venous circulation : paradoxical through ASD,

VSD• Effect : embolize to the lower extremities

(75%) and brain (10%)– they block an end artery leading to infarction

Fat embolism• Trauma to bone, subcutaneous tissue, burns• Fat globules enter the circulation by rupture of

the marrow vascular sinusoids or rupture of venules

• Pathogenesis – Mechanical blockage - Globules enlarge in circulation,

platelets adhere– Biochemical injury – Free fatty acids are released

from adipose tissue in the circulation and are toxic to endothelial cells – DIC, clogged pulmonary and systemic capillaries

Fat embolism

• Fat embolism syndrome –– characterized by pulmonary insufficiency, neurologic

symptoms, anemia, and thrombocytopenia and is fatal in about 10% of cases.

– Typically, the symptoms appear 1 to 3 days after injury, with sudden onset of tachypnea, dyspnea, and tachycardia.

– Neurologic symptoms include irritability and restlessness, with progression to delirium or coma.

Fat embolism

• Diagnosis : fat globules in sputum, urine• Postmortem : frozen section of tissues

since routine processing through alcohol will dissolve the fat

Air embolism• Air may be introduced into the venous circulation

through neck wounds, thoracocentesis, Cut in internal jugular vein, and hemodialysis

• Child birth, abortion • 150 ml of air causes death• Air bubbles tend to coalesce and physically

obstruct the flow of blood in the right ventricle, lungs, and the brain

• Frothy mixture in right ventricle – ineffective ejection, may occlude large vessels

Nitrogen embolism(The bends, Caisson’s disease)

• Deep sea diving without using Caisson’s chamber (exposed to high pressure)

• Scuba diving (deeper than 10 meters)• O2, N2 dissolve in high amounts in blood and tissues due

to high pressure• Sudden resurfacing releases N2, O2

• O2 reabsorbed, N2 bubbles out – ruptures tissues and in vessels it forms emboli

• Platelets adhere to N2 – form secondary thrombi and aggravate the ischemia

• Brain (death), muscles, joints (bends), lungs – edema, hemorrhage (chokes)

• Caisson’s disease – more chronic form with persistent gas emboli in bones

• Necrosis in femur, tibia, humerus

• Treatment – Pressure chamber – slow decompression

Bone marrow embolism

• Seen in small pulmonary vessels after vigorous cardiac resuscitation

• Incidental finding at autopsy

• Not a cause of death

Amniotic fluid embolism• 1 in 50,000 deliveries• Sudden event after

labor• Squames, hair,

meconium in pulmonary vessels

• Usually fatal – DIC, pulmonary edema, diffuse alveolar damage

Atherosclerotic emboli

• Usually an incidental finding at autopsy

• Involves small dislodged fragments of atherosclerosis from main renal artery in to smaller intrarenalbranches producing small infarcts

• No clinical symptoms

Infarction

• Definition – an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue

• 99% of infarcts result from thrombotic or embolic events

Other causes of infarction• Hemorrhage in atherosclerotic plaque• Torsion of blood vessels

– Venous or arterial or both• Hypoperfusion

– Secondary to MI– Severe hemorrhage – Septic shock

• Vasculitis– Rupture– thrombosis

Types of infarcts• White infarcts (pale)

– Little bleeding into the organ affected– Solid organs like kidney, spleen, heart– Arterial occlusion

• Red infarcts– Large amount of bleeding into the organ– Soft organs with tissue spaces - lungs– Tissues with dual blood supply (lungs and small

intestine)– Venous infarcts (congestion followed by infarction)– When flow is reestablished after arterial occlusion and

necrosis

Morphology of infarcts• Gross :

– wedge shaped, with the occluded vessel at the apex and the periphery of the organ forming the base

– Initially congested and ill defined margins– Well defined, rim of hyperemia– Later brown due to hemosiderin

• Micro – Ischemic coagulation necrosis

• Septic – Abscess formation

Factors that influence the development of infarction

• Nature of the vascular supply• Rate of development of occlusion

– Sudden is dangerous and leads to infarction, slow occlusion leads to ischemia, fibrosis

• Tissue vulnerability to hypoxia– Brain versus skeletal muscle, bone

• Oxygen carrying capacity of blood

Nature of the blood supply

• Dual blood supply – less chances of infarction– Lungs, liver– Circle of Willis– Hand (ulnar and radial arteries)

• Collateral circulation– Enlargement of anastomoses in the coronary

circulation reduces the risk of infarction

Evolution of infarct

• Polymorphs, macrophages• Granulation tissue, lymphocytes, plasma

cells• Scar – contraction• Cerebral infarction – initially coagulation

necrosis later liquefactive necrosis followed by reactive astrocytosis

• Importance of age of infarct – medico legal

Pulmonary infarction - etiology

• Pulmonary thromboemboli of medium size

+• Compromised bronchial circulation or

cardiac failure• Medium sized emboli in the presence of

good bronchial circulation – only hemorrhage no infarction

Morphology

• Wedge shaped red infarct with base towards the pleura

• Fibrinous exudate on pleura usually in lower lobes (75%)

Cerebral infarcts

• Most are located in the vertebro-basilar artery territory and are caused by atherosclerosis with superimposed thrombosis

• Thromboembolism is a less common cause of cerebral infarction and is seen mostly in the internal carotid artery territory

Evolution of cerebral infarcts

• 12 hours– Starts as coagulation necrosis– Softening, color changes– May have hemorrhage due to reperfusion

• 48 hours– Edema of the infarcted region, acts like a

intracerebral mass causing raised intracranial pressure

– Microglia engulf necrotic material, Gitter cells

Later evolution of cerebral infarcts

• Further breakdown of the tissue constituents, softening

• Liquefaction necrosis• Cyst formation• Overlying meninges thickened• Surrounding regions of gliosis

Myocardial infarction

• Coronary atherosclerosis with superimposed thrombosis

• Left anterior descending is the commonest involved

• Coagulation necrosis• Initially blotchy, later pale scar tissue• Cardiac enzymes raised in serum• Presents with severe chest pain (angina)